Thursday, March 5, 2009
Transient elastography Fibroscan for non-invasive assessment of liver fibrosis
Author's objectives The aim of this report is to assess the available information on the use of transient elastography (FibroScan) for non-invasive assessment of liver fibrosis. Author's conclusions Liver fibrosis is associated with significant morbidity and mortality. The major cause is hepatitis C, which affects 240,000 Canadians. Assessing the degree of liver fibrosis is critical to its management. Liver biopsy, an invasive procedure, is considered to be the diagnostic gold standard. FibroScan is a rapid, non-invasive technology that uses low frequency vibration and ultrasound to assess the stiffness of liver tissue. The diagnostic performance of FibroScan is good for identifying severe fibrosis or cirrhosis, but it is less accurate for milder presentations. FibroScan is a promising technology, but large multi-centre trials comparing a range of emerging non-invasive fibrosis staging technologies are required. Structure abstract from Health Technology Assessment Database
Usefulness of radiofrequency ablation of liver tumors
Author's objectives The aim of this review was to assess the efficacy and safety of radiofrequency ablation (RFA) of liver tumors. Author's conclusions Most malignant liver tumors can not be surgically removed because of their extension, systemic involvement, comorbidities or tumor size. RFA is proposed as an alternative for patients with primary hepatocellular tumors or liver metastases of colorectal cancer, when surgery is not possible. When assessing the evidence, it is observed that in all cases tumor resection is the treatment of choice. When this is not possible, RFA shows more effectiveness than most alternative treatments. However, it is worth mentioning that the differences found are mainly in the rates of local recurrence and length of hospital stay, but there are no differences in survival. In addition, complications, although not evaluated by many authors, would be fewer than in other treatment alternatives (experts suggest a complication rate of 3% to 5%), with a mortality rate lower than 1%. To use this treatment, it is recommended that a multidisciplinary team including a liver surgeon performs a patient selection and that it is performed under ultrasound or topography guidance. The requirements that must be met to use RFA in patients with liver tumor are: - not candidates for surgical tumor resection (either because there is local involvement, or because of tumor location or comorbidities) - metastases of an isolated colorectal cancer or a hepatocarcinoma - no systemic or extrahepatic disease - identification images (ultrasound or computed tomography) - tumors less than 4 cm in diameter. Those tumors of other origins which are treated with RFA or which are treated for palliative treatment are considered investigational. Structured abstract from Health Technology Assessment Database
Surgical Treatment of Hydatid Disease of the Liver
Ahmet A. Balik, MD; Mahmut Basoglu, MD; Fehmi Çelebi, MD; Durkaya Ören, MD; K. Yalçin Polat, MD; S. Selçuk Atamanalp, MD; Müfide N. Akçay, MD
Arch Surg. 1999;134:166-169.
Hypothesis To review the results of different modalities of treatment of hydatid disease of the liver.
Design Retrospective study of 304 patients.
Setting A university hospital in Turkey.
Patients Three hundred four patients with hepatic hydatid disease who underwent operation between 1981 and 1996.
Main Outcome Measures Mortality and morbidity.
Results Two hundred thirty-eight patients had a cyst on the right lobe, 41 patients had a cyst on the left lobe, and 25 patients had a cyst on both lobes. Forty-five patients had multiple hepatic cysts and 18 patients had coexisting cysts in other intra-abdominal organs. Surgical procedures were tube drainage, capitonnage, omentoplasty, cystectomy, segmentectomy, and cystoenterostomy. Of the patients with tube drainage, 36 developed an infection of the remaining cavity, 10 developed long-lasting biliary fistula, 8 developed cholangitis, and 6 developed septicemia. Four patients died of unreleated complications. Of the patients with capitonnage, 7 developed cholangitis and 3 developed an infection of the remaining cavity. Of the patients with omentoplasty, 1 developed an infection of the remaining cavity and 1 developed cholangitis. One patient who underwent segmentectomy developed pulmonary complications. Of the patients with cystoenterostomy, 1 developed cholangitis, 1 developed septicemia, and 1 developed pulmonary complications.
Conclusion For management of hydatid disease of the liver, capitonnage, omentoplasty, cyst excision, segmentectomy, or cystoenterostomy are all superior to tube drainage.
From the Department of General Surgery, Atatürk University School of Medicine, Erzurum, Turkey.
Arch Surg. 1999;134:166-169.
Hypothesis To review the results of different modalities of treatment of hydatid disease of the liver.
Design Retrospective study of 304 patients.
Setting A university hospital in Turkey.
Patients Three hundred four patients with hepatic hydatid disease who underwent operation between 1981 and 1996.
Main Outcome Measures Mortality and morbidity.
Results Two hundred thirty-eight patients had a cyst on the right lobe, 41 patients had a cyst on the left lobe, and 25 patients had a cyst on both lobes. Forty-five patients had multiple hepatic cysts and 18 patients had coexisting cysts in other intra-abdominal organs. Surgical procedures were tube drainage, capitonnage, omentoplasty, cystectomy, segmentectomy, and cystoenterostomy. Of the patients with tube drainage, 36 developed an infection of the remaining cavity, 10 developed long-lasting biliary fistula, 8 developed cholangitis, and 6 developed septicemia. Four patients died of unreleated complications. Of the patients with capitonnage, 7 developed cholangitis and 3 developed an infection of the remaining cavity. Of the patients with omentoplasty, 1 developed an infection of the remaining cavity and 1 developed cholangitis. One patient who underwent segmentectomy developed pulmonary complications. Of the patients with cystoenterostomy, 1 developed cholangitis, 1 developed septicemia, and 1 developed pulmonary complications.
Conclusion For management of hydatid disease of the liver, capitonnage, omentoplasty, cyst excision, segmentectomy, or cystoenterostomy are all superior to tube drainage.
From the Department of General Surgery, Atatürk University School of Medicine, Erzurum, Turkey.
Nexavar Granted FDA Priority Review For Treatment Of Liver Cancer
Bayer HealthCare Pharmaceuticals (NYSE: BAY) and Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today announced that the supplemental New Drug Application (sNDA) for Nexavar(R) (sorafenib) tablets for the treatment of patients with hepatocellular carcinoma (HCC), the most common form of liver cancer, has been accepted for review and granted Priority Review status by the U.S. Food and Drug Administration (FDA). Nexavar is currently approved in more than 50 countries for the treatment of patients with advanced kidney cancer.
Priority Review designation is intended to expedite the regulatory review process for investigational agents or uses that address unmet medical needs. Based on this designation, the FDA reviews the application with a goal of taking action within six months of the date on which they received the sNDA.
“This Priority Review underscores the potential of Nexavar to be a significant advance in the treatment of liver cancer,” said Susan Kelley, M.D., vice president, Therapeutic Area Oncology, Bayer HealthCare Pharmaceuticals. “If approved, Nexavar would be the first FDA-approved therapy for patients battling this devastating disease.”
The sNDA submission, completed in June 2007, was based on data from the Phase 3 SHARP trial which demonstrated that Nexavar extended overall survival by 44 percent in patients with HCC (HR=0.69; p=0.0006) versus placebo. There were no significant differences in serious adverse event rates between the Nexavar and placebo-treated groups with the most commonly observed adverse events in patients receiving Nexavar being diarrhea and hand-foot skin reaction. Based on this data, the companies also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMEA) in June.
“The incidence of liver cancer continues to rise in the United States and around the world, highlighting the significant need for new therapies,” said Hank Fuchs, executive vice president and chief medical officer of Onyx. “Our comprehensive development program continues to identify new areas where Nexavar’s unique combination of multi-targeted activity, tolerability and oral dosing may meet additional unmet needs in cancer.”
HCC, the most common form of liver cancer, is responsible for about 90 percent of the primary malignant liver tumors in adults.(1,2) Liver cancer is the sixth most common cancer in the world and the third leading cause of cancer-related deaths globally.(3) Over 600,000 cases of liver cancer are diagnosed globally each year(3) (about 19,000 in the United States(4) and 32,000 in the European Union(5)) and in 2002 approximately 600,000 people (about 13,000 Americans and 57,000 Europeans) died of liver cancer.(6)
Priority Review designation is intended to expedite the regulatory review process for investigational agents or uses that address unmet medical needs. Based on this designation, the FDA reviews the application with a goal of taking action within six months of the date on which they received the sNDA.
“This Priority Review underscores the potential of Nexavar to be a significant advance in the treatment of liver cancer,” said Susan Kelley, M.D., vice president, Therapeutic Area Oncology, Bayer HealthCare Pharmaceuticals. “If approved, Nexavar would be the first FDA-approved therapy for patients battling this devastating disease.”
The sNDA submission, completed in June 2007, was based on data from the Phase 3 SHARP trial which demonstrated that Nexavar extended overall survival by 44 percent in patients with HCC (HR=0.69; p=0.0006) versus placebo. There were no significant differences in serious adverse event rates between the Nexavar and placebo-treated groups with the most commonly observed adverse events in patients receiving Nexavar being diarrhea and hand-foot skin reaction. Based on this data, the companies also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMEA) in June.
“The incidence of liver cancer continues to rise in the United States and around the world, highlighting the significant need for new therapies,” said Hank Fuchs, executive vice president and chief medical officer of Onyx. “Our comprehensive development program continues to identify new areas where Nexavar’s unique combination of multi-targeted activity, tolerability and oral dosing may meet additional unmet needs in cancer.”
HCC, the most common form of liver cancer, is responsible for about 90 percent of the primary malignant liver tumors in adults.(1,2) Liver cancer is the sixth most common cancer in the world and the third leading cause of cancer-related deaths globally.(3) Over 600,000 cases of liver cancer are diagnosed globally each year(3) (about 19,000 in the United States(4) and 32,000 in the European Union(5)) and in 2002 approximately 600,000 people (about 13,000 Americans and 57,000 Europeans) died of liver cancer.(6)
Treatment options for nonalcoholic fatty liver disease
Shivakumar Chitturi
Australian National University Medical School, Gastroenterology and Hepatology Unit, Canberra Hospital, Australian Capital Territory, Australia, shiv.chitturi@act.gov.au
Nonalcoholic fatty liver disease comprises a range of disorders from steatosis and steatohepatitis through to cirrhosis. Nonalcoholic steatohepatitis can progress to cirrhosis and liver-related death. Therefore, managing this common disorder is becoming an important public health issue. Lifestyle measures are commonly suggested but robust data are lacking. Trials with antioxidants (vitamin E, betaine) as well as cytoprotectants (ursodeoxycholic acid) have been disappointing. While data for insulin sensitizers such as metformin are less conclusive, thiazolidinediones appear promising. However, not all patients respond to thiazolidinediones. Moreover, issues related to weight gain, cardiovascular risk need to be addressed. The use of endocannabinoid antagonists and insulin secretagogues are novel strategies to combat this disorder.
Key Words: fatty liver • insulin sensitizers • nonalcoholic steatohepatitis • nonalcoholic fatty liver disease • endocannabinoids • thiazolidinediones • ursodeoxycholic acid • vitamin E • lifestyle intervention • physical activity
Australian National University Medical School, Gastroenterology and Hepatology Unit, Canberra Hospital, Australian Capital Territory, Australia, shiv.chitturi@act.gov.au
Nonalcoholic fatty liver disease comprises a range of disorders from steatosis and steatohepatitis through to cirrhosis. Nonalcoholic steatohepatitis can progress to cirrhosis and liver-related death. Therefore, managing this common disorder is becoming an important public health issue. Lifestyle measures are commonly suggested but robust data are lacking. Trials with antioxidants (vitamin E, betaine) as well as cytoprotectants (ursodeoxycholic acid) have been disappointing. While data for insulin sensitizers such as metformin are less conclusive, thiazolidinediones appear promising. However, not all patients respond to thiazolidinediones. Moreover, issues related to weight gain, cardiovascular risk need to be addressed. The use of endocannabinoid antagonists and insulin secretagogues are novel strategies to combat this disorder.
Key Words: fatty liver • insulin sensitizers • nonalcoholic steatohepatitis • nonalcoholic fatty liver disease • endocannabinoids • thiazolidinediones • ursodeoxycholic acid • vitamin E • lifestyle intervention • physical activity
treatment of liver disease
Southwest College of Naturopathic Medicine: 2140 East Broadway Rd. Tempe, AZ 85282, USA. lupers@cwix.com
Botanicals have been used traditionally by herbalists and indigenous healers worldwide for the prevention and treatment of liver disease. Clinical research in this century has confirmed the efficacy of several plants in the treatment of liver disease. Basic scientific research has uncovered the mechanisms by which some plants afford their therapeutic effects. Silybum marianum (milk thistle) has been shown to have clinical applications in the treatment of toxic hepatitis, fatty liver, cirrhosis, ischemic injury, radiation toxicity, and viral hepatitis via its antioxidative, anti-lipid peroxidative, antifibrotic, anti-inflammatory, immunomodulating, and liver regenerating effects. Picrorhiza kurroa, though less well researched than Silybum, appears to have similar applications and mechanisms of action. When compared with Silybum, the hepatoprotective effect of Picrorhiza was found to be similar, or in many cases, superior to the effect of Silybum.
Botanicals have been used traditionally by herbalists and indigenous healers worldwide for the prevention and treatment of liver disease. Clinical research in this century has confirmed the efficacy of several plants in the treatment of liver disease. Basic scientific research has uncovered the mechanisms by which some plants afford their therapeutic effects. Silybum marianum (milk thistle) has been shown to have clinical applications in the treatment of toxic hepatitis, fatty liver, cirrhosis, ischemic injury, radiation toxicity, and viral hepatitis via its antioxidative, anti-lipid peroxidative, antifibrotic, anti-inflammatory, immunomodulating, and liver regenerating effects. Picrorhiza kurroa, though less well researched than Silybum, appears to have similar applications and mechanisms of action. When compared with Silybum, the hepatoprotective effect of Picrorhiza was found to be similar, or in many cases, superior to the effect of Silybum.
Treatment of Colorectal Liver Metastases
Liver metastases from colorectal cancer (CRC) have a poor prognosis. Despite recent advances in the management of advanced disease with chemotherapy, liver resection remains the only hope for cure for patients with colorectal liver metastases. Approximately 15% of patients with stage IV CRC referred to specialist centers have metastatic liver disease deemed to be resectable at presentation. Over the last five years, combination chemotherapeutic regimens, namely 5-fluorouracil/folinic acid with irinotecan or oxaliplatin and, more recently, integrating targeted monoclonal antibodies, have been shown to downsize the tumour burden to an extent that sometimes allows initially unresectable metastases to be excised. Five-year survival rates following liver resection range between 25% and 55% compared with 0% and 5% for non-operated patients. Beyond liver resection, the rationale for “pseudo-adjuvant” chemotherapy lacks scientific evidence, despite some promising data. However, perioperative chemotherapy for resectable lesions is gaining ground in current practice. In this article we review the state of the art treatment for CRC liver metastases and, considering the results of recent trials, try to determine the appropriate role of chemotherapy.
Liver Cancer Prognosis - Treatment
Can your liver cancer prognosis be improved? Karon Beattie, a cancer survivor, has compiled a cancer treatment reference book detailing over 350 alternative cancer treatments that have been used by thousands of people who beat cancer. Although liver cancer is not highly responsive to conventional cancer treatments, Beattie gives numerous accounts of people surviving liver cancer by alternative treatments. She states that these treatments are not covered by the FDA and usually not patentable by drug companies, resulting in poor knowledge among doctors.
Specifically in relation to liver cancer, Beattie's book, "Natural Cancer Treatments That Work", describes a treatment that heats tumors without damaging surrounding tissue. She cites survival rates of 78.1% at four years after diagnosis of liver cancer with cirrhosis of the liver, for patients who had failed to respond to chemotherapy and radiation. This seems an astonishing outcome for a cancer given a poor prognosis by oncologists.
Beattie goes on to detail a Stanford University study that found a common antibiotic was successful in eliminating liver cancer. In 2004, Stanford scientists were able to "turn off" a cancer-causing gene in mice suffering liver cancer, turning cancer cells back to normal. In addtion, the author provides 104 first-hand accounts of people who beat liver cancer using natural and alternative treatments. If stories like this are true, why are they not a standard treatment for liver and other cancers?
According to Beattie, the creators of the gentle and non-toxic treatments detailed in her book, are respected Nobel Prize winners, doctors, biochemists, scientists and Ph.D.'s pre-eminent in their fields. She believes that many doctors may not be aware of these treatments because they can only prescribe, and indeed are trained to prescribe treatments that are regulated by the FDA. Many of the alternative treatments she lists involve herbs and vitamins that are outside the jurisdiction of the FDA.
Cancer sufferers and their loved ones will find these compelling accounts hard to ignore in their quest to survive cancer and reclaim their lives.
Specifically in relation to liver cancer, Beattie's book, "Natural Cancer Treatments That Work", describes a treatment that heats tumors without damaging surrounding tissue. She cites survival rates of 78.1% at four years after diagnosis of liver cancer with cirrhosis of the liver, for patients who had failed to respond to chemotherapy and radiation. This seems an astonishing outcome for a cancer given a poor prognosis by oncologists.
Beattie goes on to detail a Stanford University study that found a common antibiotic was successful in eliminating liver cancer. In 2004, Stanford scientists were able to "turn off" a cancer-causing gene in mice suffering liver cancer, turning cancer cells back to normal. In addtion, the author provides 104 first-hand accounts of people who beat liver cancer using natural and alternative treatments. If stories like this are true, why are they not a standard treatment for liver and other cancers?
According to Beattie, the creators of the gentle and non-toxic treatments detailed in her book, are respected Nobel Prize winners, doctors, biochemists, scientists and Ph.D.'s pre-eminent in their fields. She believes that many doctors may not be aware of these treatments because they can only prescribe, and indeed are trained to prescribe treatments that are regulated by the FDA. Many of the alternative treatments she lists involve herbs and vitamins that are outside the jurisdiction of the FDA.
Cancer sufferers and their loved ones will find these compelling accounts hard to ignore in their quest to survive cancer and reclaim their lives.
MESOTHELIOMA INFORMATION - ABOUT MESOTHELIOMA"Mesothelioma (cancer of the mesothelium) is a disease in which cells of the mesothelium become abnormal
"Mesothelioma (cancer of the mesothelium) is a disease in which cells of the mesothelium become abnormal and divide without control or order. They can invade and damage nearby tissues and organs. Cancer cells can also metastasize (spread) from their original site to other parts of the body. Most cases of mesothelioma begin in the pleura or peritoneum." - National Cancer Institute
Mesothelioma is a serious cancer that occurs in individuals exposed to asbestos. Mesothelioma victims have either inhaled or swallowed asbestos fibers which then travel through the lung and become lodged in the pleura (the thin, saran wrap-type membrane lining the lungs). Mesothelioma can also develop in the abdominal (peritoneal) area of the body. Each year 2,500 to 4,000 patients in the U.S. are diagnosed with mesothelioma.
The only known cause of mesothelioma is exposure to asbestos. Even small amounts of asbestos and infrequent exposure can cause injuries.
Exposure to asbestos fibers usually occurs in at-risk workplace environments. Those at the highest risk for developing mesothelioma include workers handling or installing insulation, roofers, electricians, miners, and others (more about occupational hazards).
Asbestos fibers are so toxic, that industrial and trade worker’s families may be exposed to mesothelioma through particles that cling to the worker’s clothing, shoes, skin and hair. This type of “second-hand” exposure to asbestos is known as Para occupational exposure.
Exposure to asbestos can also occur in the home. Asbestos exposure in the home could have occurred when renovation or repair work was performed. The majority of building products manufactured today do not contain asbestos, however those frequently used prior to 1970 do carry exposure risks. Products such as joint compounds, wallboards, gaskets, fireproofing, pipe covering, cements, floor tiles, ceiling tiles and boiler insulation often contained asbestos. If these products were mixed, grinded, cut, sawed, sprayed, removed or otherwise manipulated, banged or damaged, they could have released significant asbestos fibers into your home. The inhalation of these airborne fibers can create the risk of developing mesothelioma, even 15-30 years later.
Mesothelioma Was Preventable
Scores of corporations that manufactured and profited from the sale of asbestos-containing products knew the health hazards as early as the 1920's. If you worked in a high-risk industry and have been diagnosed with mesothelioma, or you have lost someone to an asbestos-related illness, it is your right to seek compensation from those responsible for your situation.
Mesothelioma is a serious cancer that occurs in individuals exposed to asbestos. Mesothelioma victims have either inhaled or swallowed asbestos fibers which then travel through the lung and become lodged in the pleura (the thin, saran wrap-type membrane lining the lungs). Mesothelioma can also develop in the abdominal (peritoneal) area of the body. Each year 2,500 to 4,000 patients in the U.S. are diagnosed with mesothelioma.
The only known cause of mesothelioma is exposure to asbestos. Even small amounts of asbestos and infrequent exposure can cause injuries.
Exposure to asbestos fibers usually occurs in at-risk workplace environments. Those at the highest risk for developing mesothelioma include workers handling or installing insulation, roofers, electricians, miners, and others (more about occupational hazards).
Asbestos fibers are so toxic, that industrial and trade worker’s families may be exposed to mesothelioma through particles that cling to the worker’s clothing, shoes, skin and hair. This type of “second-hand” exposure to asbestos is known as Para occupational exposure.
Exposure to asbestos can also occur in the home. Asbestos exposure in the home could have occurred when renovation or repair work was performed. The majority of building products manufactured today do not contain asbestos, however those frequently used prior to 1970 do carry exposure risks. Products such as joint compounds, wallboards, gaskets, fireproofing, pipe covering, cements, floor tiles, ceiling tiles and boiler insulation often contained asbestos. If these products were mixed, grinded, cut, sawed, sprayed, removed or otherwise manipulated, banged or damaged, they could have released significant asbestos fibers into your home. The inhalation of these airborne fibers can create the risk of developing mesothelioma, even 15-30 years later.
Mesothelioma Was Preventable
Scores of corporations that manufactured and profited from the sale of asbestos-containing products knew the health hazards as early as the 1920's. If you worked in a high-risk industry and have been diagnosed with mesothelioma, or you have lost someone to an asbestos-related illness, it is your right to seek compensation from those responsible for your situation.
MESOTHELIOMA DIAGNOSIS - MESOTHELIOMA INFORMATION
The early detection of mesothelioma is critical to the patient outlook and in determining applicable treatment options. However, mesothelioma is often difficult to diagnose for a variety of reasons. Because mesothelioma is a rare disease, many doctors are not familiar with it. In addition, the non-specific nature of patient symptoms can be indicators of other medical conditions. The extended length of time between asbestos exposure and a patient's symptomatic responses, often between 15-50 years, further hinders immediate detection of mesothelioma. Despite these difficulties there are many procedures available for the accurate diagnosis of mesothelioma.
Initial Evaluation
The initial patient evaluation(s) are critical in identifying patients at risk for developing mesothelioma. To establish risk factors and the presence of symptoms, your physician will complete a medical history that includes questions to help determine the timeframe and environment in which you may have been exposed to asbestos. Communication between the patient and doctor is important so that the earliest possible detection of mesothelioma can be made. Make certain that you have shared all relevant information regarding previous work history and possible asbestos exposure with your physician.
In addition to constructing a medical profile and detailed medical history, a complete physical examination will be performed. During a physical exam your doctor may look for the following:
*
Breath Sounds: listening to the chest cavity as the patient inhales/exhales there may be an absence of breath sounds, or these sounds may be muted. The absence of, or muted nature of, these breath sounds may be an indication of fluid in the chest cavity, or of pleural effusions.
*
A doctor may listen to the chest cavity while having the patient make vowel sounds - comparing the sound resonance in the right and left chest cavities. Muted, or dull, sounds between the cavities could be an indicator of a buildup of fluid.
*
By percussing, or tapping, on the chest area a doctor may notice a dull, solid thumping sound, rather than a hollow resonance. This may also indicate the presence of fluid, or a mass, in the chest cavity.
*
A physical examination will also check for enlarged lymph nodes.
There are often very few signs during an initial physical exam that would identify the presence of mesothelioma. On the basis of patient symptoms, medical history, the presence of specific risk factors (work environment, asbestos exposure), and a complete physical examination, the doctor can use one or more of the methods described below to determine if the disease is present.
Diagnostic Tests
Doctors use a variety of diagnostic procedures to determine if a patient has mesothelioma. Comparing results from imaging scans, tissue biopsies, pulmonary function tests, and other diagnostic techniques, the presence of mesothelioma can be identified.
* Imaging Techniques
There are many available technologies that allow doctors to view, or image, organs and tissue that might show the presence of fluid or tumors.
A chest x–ray may show an unusual thickening of the pleura, lowering of the lung fissures (spaces between the lobes of the lungs), an accumulation of fluid in the lungs (pleural effusion), and/or an irregular mass in the chest cavity.
A CT (computed tomography) scan uses x-ray and computers to give more sophisticated and detailed pictures of the insides of our body than conventional x-rays. A rotating x-ray beam is used to take a series of pictures of the body from different angles. A computer combines the series of pictures to produce a detailed cross-sectional image of a specific part of the body. The CT scan allows a radiologist to see distinct aspects of the lungs and pleura.
Magnetic Resonance Imaging (MRI) uses a strong magnetic field and radiowaves to scan the body. There is no radiation involved. This imaging method produces a series of cross-sectional pictures. MRI scans are useful for viewing 'soft tissues' in the body and can show the extent of mesothelioma. New MRI techniques where surface imaging techniques are combined with quick breath-holding sequences and gadolinium contrast medium give images, which detect tumor growth in the pleura and thoracic wall better than the previous methods. MRI images tend to be quite clear and are superior to routine x–ray images.
Positron Emission Tomography (PET) scans use a camera that produces powerful images of the body’s biological functions. Because cancers and other disease processes metabolize sugars at a higher rate than normal tissues or organs, the PET scan uses tracers to indicate where there is abnormal metabolic activity and can pinpoint the regions of active disease. PET scans can also identify extremely small cancerous cells, indicate benign or malignant cells, and help determine whether treatment therapies are working.
*
Pathological Tests
Mesothelioma is diagnosed by pathological examination. Tissue is removed, put under the microscope, and a pathologist makes a definitive diagnosis, and issues a pathology report.
A tissue sample of a pleural or pericardial tumor can be obtained using a relatively new technique called thoracoscopy. A thoracoscope (telescope-like instrument connected to a video camera) is inserted through a small incision into the chest. The doctor can see the tumor through the thoracoscope and can use special forceps to take a tissue biopsy.
A laparoscopy can be used to see and obtain a biopsy of a peritoneal tumor. In this procedure, a flexible tube is attached to a video camera that is inserted into the abdominal cavity via small incisions. Fluid can also be collected during thoracoscopy or laparoscopy.
A bronchoscopy may be performed if pleural mesothelioma is suspected. In this process, the doctor inserts a flexible lighted tube down the trachea, and into the bronchi to check for masses in the airway. At that time, small samples of abnormal-appearing tissue may also be removed for testing.
Lymph nodes are collections of immune system cells that help the body fight infection. By examining the lymph nodes, the doctor can determine if the cancer has spread. During a mediastinoscopy, a patient has a lighted tube inserted under the sternum (chest bone) at the neck level and then moved down into the chest. The surgeon can see the lymph nodes and take tissue samples to check for cancer. This procedure can also help the physician determine if you have lung cancer or mesothelioma.
* Pulmonary Function Tests (PFT’s)
PFTs encompass a wide variety of tests that evaluate the entire respiratory system. The tests are useful in the assessment and diagnosis of pulmonary disease and aid in determining a course of treatment. PFTs can be a simple peak flow measurement, or complex body plethysmography and ventilation/perfusion scans which are performed in hospitals and clinics. PFTs can also be useful in monitoring patient response to treatment.
Although Mesothelioma can often be difficult to initially detect, the above medical procedures and diagnostic tests can lead to a clear diagnosis. Early medical diagnosis is one of the primary variables affecting long-term prognosis. Click here to learn more about available treatment options.
Staging is a method of evaluating the progress of cancer in a patient. It looks at the mesothelioma and the extent to which it has developed and its possible spread to other parts of the body. Click here to learn more about the staging of mesothelioma.
Initial Evaluation
The initial patient evaluation(s) are critical in identifying patients at risk for developing mesothelioma. To establish risk factors and the presence of symptoms, your physician will complete a medical history that includes questions to help determine the timeframe and environment in which you may have been exposed to asbestos. Communication between the patient and doctor is important so that the earliest possible detection of mesothelioma can be made. Make certain that you have shared all relevant information regarding previous work history and possible asbestos exposure with your physician.
In addition to constructing a medical profile and detailed medical history, a complete physical examination will be performed. During a physical exam your doctor may look for the following:
*
Breath Sounds: listening to the chest cavity as the patient inhales/exhales there may be an absence of breath sounds, or these sounds may be muted. The absence of, or muted nature of, these breath sounds may be an indication of fluid in the chest cavity, or of pleural effusions.
*
A doctor may listen to the chest cavity while having the patient make vowel sounds - comparing the sound resonance in the right and left chest cavities. Muted, or dull, sounds between the cavities could be an indicator of a buildup of fluid.
*
By percussing, or tapping, on the chest area a doctor may notice a dull, solid thumping sound, rather than a hollow resonance. This may also indicate the presence of fluid, or a mass, in the chest cavity.
*
A physical examination will also check for enlarged lymph nodes.
There are often very few signs during an initial physical exam that would identify the presence of mesothelioma. On the basis of patient symptoms, medical history, the presence of specific risk factors (work environment, asbestos exposure), and a complete physical examination, the doctor can use one or more of the methods described below to determine if the disease is present.
Diagnostic Tests
Doctors use a variety of diagnostic procedures to determine if a patient has mesothelioma. Comparing results from imaging scans, tissue biopsies, pulmonary function tests, and other diagnostic techniques, the presence of mesothelioma can be identified.
* Imaging Techniques
There are many available technologies that allow doctors to view, or image, organs and tissue that might show the presence of fluid or tumors.
A chest x–ray may show an unusual thickening of the pleura, lowering of the lung fissures (spaces between the lobes of the lungs), an accumulation of fluid in the lungs (pleural effusion), and/or an irregular mass in the chest cavity.
A CT (computed tomography) scan uses x-ray and computers to give more sophisticated and detailed pictures of the insides of our body than conventional x-rays. A rotating x-ray beam is used to take a series of pictures of the body from different angles. A computer combines the series of pictures to produce a detailed cross-sectional image of a specific part of the body. The CT scan allows a radiologist to see distinct aspects of the lungs and pleura.
Magnetic Resonance Imaging (MRI) uses a strong magnetic field and radiowaves to scan the body. There is no radiation involved. This imaging method produces a series of cross-sectional pictures. MRI scans are useful for viewing 'soft tissues' in the body and can show the extent of mesothelioma. New MRI techniques where surface imaging techniques are combined with quick breath-holding sequences and gadolinium contrast medium give images, which detect tumor growth in the pleura and thoracic wall better than the previous methods. MRI images tend to be quite clear and are superior to routine x–ray images.
Positron Emission Tomography (PET) scans use a camera that produces powerful images of the body’s biological functions. Because cancers and other disease processes metabolize sugars at a higher rate than normal tissues or organs, the PET scan uses tracers to indicate where there is abnormal metabolic activity and can pinpoint the regions of active disease. PET scans can also identify extremely small cancerous cells, indicate benign or malignant cells, and help determine whether treatment therapies are working.
*
Pathological Tests
Mesothelioma is diagnosed by pathological examination. Tissue is removed, put under the microscope, and a pathologist makes a definitive diagnosis, and issues a pathology report.
A tissue sample of a pleural or pericardial tumor can be obtained using a relatively new technique called thoracoscopy. A thoracoscope (telescope-like instrument connected to a video camera) is inserted through a small incision into the chest. The doctor can see the tumor through the thoracoscope and can use special forceps to take a tissue biopsy.
A laparoscopy can be used to see and obtain a biopsy of a peritoneal tumor. In this procedure, a flexible tube is attached to a video camera that is inserted into the abdominal cavity via small incisions. Fluid can also be collected during thoracoscopy or laparoscopy.
A bronchoscopy may be performed if pleural mesothelioma is suspected. In this process, the doctor inserts a flexible lighted tube down the trachea, and into the bronchi to check for masses in the airway. At that time, small samples of abnormal-appearing tissue may also be removed for testing.
Lymph nodes are collections of immune system cells that help the body fight infection. By examining the lymph nodes, the doctor can determine if the cancer has spread. During a mediastinoscopy, a patient has a lighted tube inserted under the sternum (chest bone) at the neck level and then moved down into the chest. The surgeon can see the lymph nodes and take tissue samples to check for cancer. This procedure can also help the physician determine if you have lung cancer or mesothelioma.
* Pulmonary Function Tests (PFT’s)
PFTs encompass a wide variety of tests that evaluate the entire respiratory system. The tests are useful in the assessment and diagnosis of pulmonary disease and aid in determining a course of treatment. PFTs can be a simple peak flow measurement, or complex body plethysmography and ventilation/perfusion scans which are performed in hospitals and clinics. PFTs can also be useful in monitoring patient response to treatment.
Although Mesothelioma can often be difficult to initially detect, the above medical procedures and diagnostic tests can lead to a clear diagnosis. Early medical diagnosis is one of the primary variables affecting long-term prognosis. Click here to learn more about available treatment options.
Staging is a method of evaluating the progress of cancer in a patient. It looks at the mesothelioma and the extent to which it has developed and its possible spread to other parts of the body. Click here to learn more about the staging of mesothelioma.
MESOTHELIOMA SYMPTOMS
Mesothelioma is often difficult to diagnose, primarily due to the non-specific nature of patient symptoms. The onset of mesothelioma symptoms is usually very slow, and may not appear until 30 to 50 years after exposure to asbestos. The following symptoms are frequently reported by those with mesothelioma, but are also associated with other medical conditions.
The following symptomatic responses MAY BE caused by mesothelioma, or by other less serious medical problems. Early symptoms of mesothelioma are often similar to pneumonia. This information is provided for your information only, and should NOT take the place of a full medical diagnosis. If you are experiencing any of the below symptoms, consult your doctor right away.
Symptoms of Pleural Mesothelioma
* Pleural Effusions
One of the most common symptoms of mesothelioma is a pleural effusion, or an accumulation of fluid between the lining of the lung and the chest cavity. As the volume of fluid increases, shortness of breath, known as "dyspnea", and sometimes pain may occur.
* Shortness of Breath
Difficulty breathing (dyspnea) can be caused by a buildup of fluid in the pleural area of the lungs, and/or the presence of a tumor(s) in the pleural lining. Both conditions can restrict the proper functioning of the lungs, resulting in shortness of breath.
* Chest / Back Pain
A buildup of fluid in the pleural lining of the lungs can create a feeling of fullness and pressure, causing areas of localized pain in the chest cavity and sometimes in the lower back area. Chest pain occurs more often on the right side of the body, as mesothelioma affects the right lung 60% of the time. Only 5% of patients have mesothelioma in both lungs.
* Chronic Hoarseness / Difficulty Swallowing / Coughing up Blood
Chronic hoarseness, difficulty swallowing (dysphagia), and/or the coughing up of blood (hemoptysis) are symptoms that are exhibited in less than 1% of undiagnosed mesothelioma sufferers.
* Swelling of the Face and Arms
The swelling of the face or neck areas can indicate a spreading of the cancer beyond the mesothelium.
* Other reported symptoms include fever, muscle weakness and sensory loss, and nausea.
Symptom % exhibiting
Shortness of breath and/or chest pain 90%
Weight loss 29%
Cough, weakness, fever, loss of appetite 3%
Hemoptysis (coughing up blood), hoarseness, dysphagia (difficulty swallowing). less than 1%
Pleural Effusions 84%
Asymptomatic 3%
(source: "Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective
study of 332 patients." P Ruffie et al. Journal of Clinical Oncology Aug 1 1989: 1157-1168.)
The following symptomatic responses MAY BE caused by mesothelioma, or by other less serious medical problems. Early symptoms of mesothelioma are often similar to pneumonia. This information is provided for your information only, and should NOT take the place of a full medical diagnosis. If you are experiencing any of the below symptoms, consult your doctor right away.
Symptoms of Pleural Mesothelioma
* Pleural Effusions
One of the most common symptoms of mesothelioma is a pleural effusion, or an accumulation of fluid between the lining of the lung and the chest cavity. As the volume of fluid increases, shortness of breath, known as "dyspnea", and sometimes pain may occur.
* Shortness of Breath
Difficulty breathing (dyspnea) can be caused by a buildup of fluid in the pleural area of the lungs, and/or the presence of a tumor(s) in the pleural lining. Both conditions can restrict the proper functioning of the lungs, resulting in shortness of breath.
* Chest / Back Pain
A buildup of fluid in the pleural lining of the lungs can create a feeling of fullness and pressure, causing areas of localized pain in the chest cavity and sometimes in the lower back area. Chest pain occurs more often on the right side of the body, as mesothelioma affects the right lung 60% of the time. Only 5% of patients have mesothelioma in both lungs.
* Chronic Hoarseness / Difficulty Swallowing / Coughing up Blood
Chronic hoarseness, difficulty swallowing (dysphagia), and/or the coughing up of blood (hemoptysis) are symptoms that are exhibited in less than 1% of undiagnosed mesothelioma sufferers.
* Swelling of the Face and Arms
The swelling of the face or neck areas can indicate a spreading of the cancer beyond the mesothelium.
* Other reported symptoms include fever, muscle weakness and sensory loss, and nausea.
Symptom % exhibiting
Shortness of breath and/or chest pain 90%
Weight loss 29%
Cough, weakness, fever, loss of appetite 3%
Hemoptysis (coughing up blood), hoarseness, dysphagia (difficulty swallowing). less than 1%
Pleural Effusions 84%
Asymptomatic 3%
(source: "Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective
study of 332 patients." P Ruffie et al. Journal of Clinical Oncology Aug 1 1989: 1157-1168.)
MESOTHELIOMA & ASBESTOS STATISTICS
* Each year 2,500 to 4,000 patients in the U.S. are diagnosed with mesothelioma and asbestos-related diseases.
* Mesothelioma has a long latency (inactive) period of anywhere between 15 – 50 years.
* Experts predict that mesothelioma diagnoses will continue to increase in the United States for at least another 10 to 20 years.
* While many countries have banned certain forms of asbestos, an estimated 5,000 asbestos-containing products exist today. (See a list of dangerous products)
Article/Commentary: A Ban on Asbestos Must be Based on a Comparative Risk Assessment. (Canada)
* As many as 8 million people in the U.S. have already been exposed to asbestos and it continues to pose a serious threat to workers in certain occupations. (Click here for a list of at risk occupations)
* One study of asbestos insulation workers reported a mesothelioma death rate up to 344 times higher than the general population.
* Most mesothelioma victims die within 18 months of diagnosis. Mortality is swift not because the cancer is fast-growing but because it usually is far advanced by the time it is detected.
Read about the development of a blood test for Mesothelioma diagnosis; Visit our Mesothelioma Articles.
*
Poor prognostic variables include: nonepithelial histology, older age (greater than 75 years), pleural primary, chest pain at presentation, poor performance status, and elevated platelet count (greater than 400,000/mcL).
*
By the year 2030 there are estimates that asbestos will have caused 60,000 instances of mesothelioma and around 250,000 other cancers that result in death.
* Over half a million asbestos and mesothelioma injury claims have been filed to date. Over 50,000 were filed in 1998 alone.
* Mesothelioma has a long latency (inactive) period of anywhere between 15 – 50 years.
* Experts predict that mesothelioma diagnoses will continue to increase in the United States for at least another 10 to 20 years.
* While many countries have banned certain forms of asbestos, an estimated 5,000 asbestos-containing products exist today. (See a list of dangerous products)
Article/Commentary: A Ban on Asbestos Must be Based on a Comparative Risk Assessment. (Canada)
* As many as 8 million people in the U.S. have already been exposed to asbestos and it continues to pose a serious threat to workers in certain occupations. (Click here for a list of at risk occupations)
* One study of asbestos insulation workers reported a mesothelioma death rate up to 344 times higher than the general population.
* Most mesothelioma victims die within 18 months of diagnosis. Mortality is swift not because the cancer is fast-growing but because it usually is far advanced by the time it is detected.
Read about the development of a blood test for Mesothelioma diagnosis; Visit our Mesothelioma Articles.
*
Poor prognostic variables include: nonepithelial histology, older age (greater than 75 years), pleural primary, chest pain at presentation, poor performance status, and elevated platelet count (greater than 400,000/mcL).
*
By the year 2030 there are estimates that asbestos will have caused 60,000 instances of mesothelioma and around 250,000 other cancers that result in death.
* Over half a million asbestos and mesothelioma injury claims have been filed to date. Over 50,000 were filed in 1998 alone.
MESOTHELIOMA & ASBESTOS STATISTICS
* Each year 2,500 to 4,000 patients in the U.S. are diagnosed with mesothelioma and asbestos-related diseases.
* Mesothelioma has a long latency (inactive) period of anywhere between 15 – 50 years.
* Experts predict that mesothelioma diagnoses will continue to increase in the United States for at least another 10 to 20 years.
* While many countries have banned certain forms of asbestos, an estimated 5,000 asbestos-containing products exist today. (See a list of dangerous products)
Article/Commentary: A Ban on Asbestos Must be Based on a Comparative Risk Assessment. (Canada)
* As many as 8 million people in the U.S. have already been exposed to asbestos and it continues to pose a serious threat to workers in certain occupations. (Click here for a list of at risk occupations)
* One study of asbestos insulation workers reported a mesothelioma death rate up to 344 times higher than the general population.
* Most mesothelioma victims die within 18 months of diagnosis. Mortality is swift not because the cancer is fast-growing but because it usually is far advanced by the time it is detected.
Read about the development of a blood test for Mesothelioma diagnosis; Visit our Mesothelioma Articles.
*
Poor prognostic variables include: nonepithelial histology, older age (greater than 75 years), pleural primary, chest pain at presentation, poor performance status, and elevated platelet count (greater than 400,000/mcL).
*
By the year 2030 there are estimates that asbestos will have caused 60,000 instances of mesothelioma and around 250,000 other cancers that result in death.
* Over half a million asbestos and mesothelioma injury claims have been filed to date. Over 50,000 were filed in 1998 alone.
* Mesothelioma has a long latency (inactive) period of anywhere between 15 – 50 years.
* Experts predict that mesothelioma diagnoses will continue to increase in the United States for at least another 10 to 20 years.
* While many countries have banned certain forms of asbestos, an estimated 5,000 asbestos-containing products exist today. (See a list of dangerous products)
Article/Commentary: A Ban on Asbestos Must be Based on a Comparative Risk Assessment. (Canada)
* As many as 8 million people in the U.S. have already been exposed to asbestos and it continues to pose a serious threat to workers in certain occupations. (Click here for a list of at risk occupations)
* One study of asbestos insulation workers reported a mesothelioma death rate up to 344 times higher than the general population.
* Most mesothelioma victims die within 18 months of diagnosis. Mortality is swift not because the cancer is fast-growing but because it usually is far advanced by the time it is detected.
Read about the development of a blood test for Mesothelioma diagnosis; Visit our Mesothelioma Articles.
*
Poor prognostic variables include: nonepithelial histology, older age (greater than 75 years), pleural primary, chest pain at presentation, poor performance status, and elevated platelet count (greater than 400,000/mcL).
*
By the year 2030 there are estimates that asbestos will have caused 60,000 instances of mesothelioma and around 250,000 other cancers that result in death.
* Over half a million asbestos and mesothelioma injury claims have been filed to date. Over 50,000 were filed in 1998 alone.
If I Smoked Cigarettes, Can I Still File A Claim Against The Asbestos Companies?
Asbestos alone can cause lung cancer. If you smoked in the past or are presently smoking, and have been diagnosed with lung cancer, asbestos may also be a cause of your cancer. For smokers, asbestos and tobacco act together, greatly increasing the risk of lung cancer. The combination of smoking and asbestos can increase the risk factor of lung cancer.
Smoking does not cause mesothelioma or asbestosis. Therefore, if you have been diagnosed with mesothelioma or asbestosis, it was caused by your asbestos exposure, and has no relationship to your smoking.
Mesothelioma Was Preventable
Scores of corporations that manufactured and profited from the sale of asbestos-containing products knew the health hazards as early as the 1920's. If you worked in a high-risk industry and have been diagnosed with mesothelioma, or you have lost someone to an asbestos-related illness, it is your right to seek compensation from those responsible for your situation.
Smoking does not cause mesothelioma or asbestosis. Therefore, if you have been diagnosed with mesothelioma or asbestosis, it was caused by your asbestos exposure, and has no relationship to your smoking.
Mesothelioma Was Preventable
Scores of corporations that manufactured and profited from the sale of asbestos-containing products knew the health hazards as early as the 1920's. If you worked in a high-risk industry and have been diagnosed with mesothelioma, or you have lost someone to an asbestos-related illness, it is your right to seek compensation from those responsible for your situation.
ABOUT MESOTHELIOMA & ASBESTOS EXPOSURE
WHAT IS MESOTHELIOMA? - Mesothelioma is a serious cancer that occurs in individuals exposed to asbestos. Mesothelioma victims have either inhaled or swallowed asbestos fibers which then travel through the lung and become lodged in the pleura (the thin, saran wrap-type membrane lining the lungs.) Each year 2,500 to 4,000 patients in the U.S. are diagnosed with mesothelioma and asbestos-related diseases.
WHO IS AT RISK FOR MESOTHELIOMA? - While many uses for asbestos were banned in the mid-1970’s, the risk from exposure continues today due to mesothelioma’s long latency (inactive) period of anywhere between 15 – 50 years. Today, asbestos continues to be a threat to workers exposed through their occupations and in buildings that were erected prior to the ban. Experts predict that mesothelioma diagnoses will continue to increase in the United States for at least another 10 to 20 years.
Asbestos fibers are so toxic, that industrial and trade worker’s families may be exposed to mesothelioma through particles that cling to the worker’s clothing, shoes, skin and hair. This type of “second-hand” exposure to asbestos is known as Para occupational exposure.
WHO IS AT RISK FOR MESOTHELIOMA? - While many uses for asbestos were banned in the mid-1970’s, the risk from exposure continues today due to mesothelioma’s long latency (inactive) period of anywhere between 15 – 50 years. Today, asbestos continues to be a threat to workers exposed through their occupations and in buildings that were erected prior to the ban. Experts predict that mesothelioma diagnoses will continue to increase in the United States for at least another 10 to 20 years.
Asbestos fibers are so toxic, that industrial and trade worker’s families may be exposed to mesothelioma through particles that cling to the worker’s clothing, shoes, skin and hair. This type of “second-hand” exposure to asbestos is known as Para occupational exposure.
Cancer Asbestos Settlement Lawsuit Mesothelioma Attorney
Mesothelioma Fact - Alarming Truth
By Kirsten Hawkins, Thu Dec 8th
Lately many people have been looking for mesothelioma fact andinformation. The startling mesothelioma fact is thatMesothelioma Cancer is a rare cancer but every year about 2,000new cases of mesothelioma are diagnosed in the United States andthis number has been continuously increasing for the past 20years. Initially mesothelioma was recognized as a tumor of thepleura, peritoneum and pericardium. Later on, the doctorsstudied the fact linking mesothelioma cancers to asbestosexposure. J.C.Wagner wrote the first on mesothelioma by, andemphasized its linkage to asbestos exposure in about 32 cases ofworkers in the "Asbestos Hills" in South Africa.
Thereon the fact about relationship between mesothelioma andasbestos exposure was confirmed in different research studiesaround the world. Mesothelioma is caused because of asbestosexposure and inhalation of asbestos particles. Asbestos waswidely used in industrial and manufacturing processes andbuilding materials. Construction materials such as cement,tiles, roofing shingles, pipes, insulating material and manymore, contained asbestos materials. The shocking mesotheliomafact is that almost all American buildings constructed before1970s contain asbestos material that could pose risk for theoccupants.
Mesothelioma Applied Research Foundation has released a factthat, though since 1970s the protections
By Kirsten Hawkins, Thu Dec 8th
Lately many people have been looking for mesothelioma fact andinformation. The startling mesothelioma fact is thatMesothelioma Cancer is a rare cancer but every year about 2,000new cases of mesothelioma are diagnosed in the United States andthis number has been continuously increasing for the past 20years. Initially mesothelioma was recognized as a tumor of thepleura, peritoneum and pericardium. Later on, the doctorsstudied the fact linking mesothelioma cancers to asbestosexposure. J.C.Wagner wrote the first on mesothelioma by, andemphasized its linkage to asbestos exposure in about 32 cases ofworkers in the "Asbestos Hills" in South Africa.
Thereon the fact about relationship between mesothelioma andasbestos exposure was confirmed in different research studiesaround the world. Mesothelioma is caused because of asbestosexposure and inhalation of asbestos particles. Asbestos waswidely used in industrial and manufacturing processes andbuilding materials. Construction materials such as cement,tiles, roofing shingles, pipes, insulating material and manymore, contained asbestos materials. The shocking mesotheliomafact is that almost all American buildings constructed before1970s contain asbestos material that could pose risk for theoccupants.
Mesothelioma Applied Research Foundation has released a factthat, though since 1970s the protections
Mesothelioma Lawyers - Important Information for Patients
By Michael Horwin, MA, JD*
Deciding to pursue legal recourse and selecting an attorney to represent you in a mesothelioma or asbestos lawsuit are important decisions that should be made carefully. I have seen some families receive $500,000 and others be awarded nearly $30 million. I have seen some lawyers reject a case only to have another firm accept it and make a big success of it. And I have seen some families wait nearly three years to receive their first check while others received large checks within three months of filing a claim. The main reasons for these differences are the facts of the patient's situation and the law firm chosen.
The Facts of Your Situation
Some mesothelioma patients know they worked around asbestos, but many do not know how they were exposed or how often. In fact, many people are not sure if they were ever near this carcinogen. Unfortunately, there have been thousands of products that contained asbestos - cigarette filters, hair dryers, brakes, basement and roof materials, pipes, boilers, insulation, and many other products found throughout the home and at work. If you were diagnosed with mesothelioma it is more than likely that you were exposed to asbestos multiple times in your life and that this happened decades before your diagnosis.
In general, the value of your case depends on how many asbestos containing products you were exposed to, the number of identifiable defendants that still exist (many have declared bankruptcy), your age and earning capacity. And the speed of your case can depend on a number of variables including the state where you worked and lived when you were exposed to asbestos.
The Law Firm You Choose
When you have been given the news about this terrible disease, you may not feel that you have the time to deal with the legal questions - Should I talk to a lawyer? Should I file a claim? However, you should not wait too long to learn about your legal rights for at least three reasons:
1. Statutes of Limitations - There are statute of limitations which means you only have a limited time to file your case after diagnosis. The statute of limitations time period is set by individual states and varies. The clock usually starts ticking on the day of diagnosis.
2. Financial Pressure - A mesothelioma diagnosis can bring financial stress, less income, more expenses, and treatments that are not covered by insurance. Knowing that money may be on the way from filing a claim can bring financial relief.
3. Lawyers Can be Excellent Resources - The more experienced mesothelioma lawyers and law firms can often be excellent sources of information about various doctors and treatment options available for this disease.
But, picking a lawyer is serious business and you should not use TV ads as the reason to hire an attorney. Actual credentials are what counts. For example, what type of accomplishments has the law firm achieved? How committed are they to mesothelioma/asbestos cases? Are these cases a substantial part of their practice or just a small piece? How many other cases like yours have they handled?
Also, make sure you understand the fees being charges. Contingency is the term that means that the lawyer gets paid only after they collect money for you. The amount of the contingency fee that your lawyer can charge varies and is usually between 33% and 40%. It is important to discuss fees openly, ask what services they cover, how they are calculated, and whether there will be any extra charges.
Finally, for something as important as a mesothelioma lawsuit, your attorney should not only be experienced, skilled, and dedicated, but also a trusted partner who understands that your health needs always take precedence. The best lawyers are those that are not only expert at what they do, but are also caring, supportive, thoughtful and compassionate.
Below are experienced mesothelioma law firms you can contact. If you would like additional information on choosing a reputable mesothelioma law firm please feel free to call me at 1-619-599-3112.
Deciding to pursue legal recourse and selecting an attorney to represent you in a mesothelioma or asbestos lawsuit are important decisions that should be made carefully. I have seen some families receive $500,000 and others be awarded nearly $30 million. I have seen some lawyers reject a case only to have another firm accept it and make a big success of it. And I have seen some families wait nearly three years to receive their first check while others received large checks within three months of filing a claim. The main reasons for these differences are the facts of the patient's situation and the law firm chosen.
The Facts of Your Situation
Some mesothelioma patients know they worked around asbestos, but many do not know how they were exposed or how often. In fact, many people are not sure if they were ever near this carcinogen. Unfortunately, there have been thousands of products that contained asbestos - cigarette filters, hair dryers, brakes, basement and roof materials, pipes, boilers, insulation, and many other products found throughout the home and at work. If you were diagnosed with mesothelioma it is more than likely that you were exposed to asbestos multiple times in your life and that this happened decades before your diagnosis.
In general, the value of your case depends on how many asbestos containing products you were exposed to, the number of identifiable defendants that still exist (many have declared bankruptcy), your age and earning capacity. And the speed of your case can depend on a number of variables including the state where you worked and lived when you were exposed to asbestos.
The Law Firm You Choose
When you have been given the news about this terrible disease, you may not feel that you have the time to deal with the legal questions - Should I talk to a lawyer? Should I file a claim? However, you should not wait too long to learn about your legal rights for at least three reasons:
1. Statutes of Limitations - There are statute of limitations which means you only have a limited time to file your case after diagnosis. The statute of limitations time period is set by individual states and varies. The clock usually starts ticking on the day of diagnosis.
2. Financial Pressure - A mesothelioma diagnosis can bring financial stress, less income, more expenses, and treatments that are not covered by insurance. Knowing that money may be on the way from filing a claim can bring financial relief.
3. Lawyers Can be Excellent Resources - The more experienced mesothelioma lawyers and law firms can often be excellent sources of information about various doctors and treatment options available for this disease.
But, picking a lawyer is serious business and you should not use TV ads as the reason to hire an attorney. Actual credentials are what counts. For example, what type of accomplishments has the law firm achieved? How committed are they to mesothelioma/asbestos cases? Are these cases a substantial part of their practice or just a small piece? How many other cases like yours have they handled?
Also, make sure you understand the fees being charges. Contingency is the term that means that the lawyer gets paid only after they collect money for you. The amount of the contingency fee that your lawyer can charge varies and is usually between 33% and 40%. It is important to discuss fees openly, ask what services they cover, how they are calculated, and whether there will be any extra charges.
Finally, for something as important as a mesothelioma lawsuit, your attorney should not only be experienced, skilled, and dedicated, but also a trusted partner who understands that your health needs always take precedence. The best lawyers are those that are not only expert at what they do, but are also caring, supportive, thoughtful and compassionate.
Below are experienced mesothelioma law firms you can contact. If you would like additional information on choosing a reputable mesothelioma law firm please feel free to call me at 1-619-599-3112.
NEW BRAIN TUMOR TREATMENTS EXTEND LIFE
SAN DIEGO—The term complete remission is never used for the deadliest of brain tumors, but new and ongoing studies reported at the 41st Annual Meeting of the American Society of Clinical Oncology are offering hope that in some cases, novel treatment modalities can extend survival.
During a special session on central nervous system tumors, Stuart Grossman, MD, said that a look at the survival in the group with the worst prognosis—patients with glioblastoma multiforme—indicates that it has changed little. Nevertheless, “This has been a year where there have been genuine advances in this disease, some surprises, and some significant implications for both clinical care and research.” Dr. Grossman is a medical oncologist at Johns Hopkins University in Baltimore, former President of the Society for Neuro-Oncology, and Chairman of the Eastern Cooperative Oncology’s Brain Tumor Working Group.
According to Dr. Grossman, “a whirlwind of the last 30 years” still shows that surgery and radiation therapy do help patients, and that radiotherapy plus daily oral temozolomide has been shown to increase median survival to 14.6 months as opposed to 12.1 months for patients given only radiotherapy. Furthermore, the two-year survival rate was 26.5% for radiotherapy plus temozolomide versus only 10.4% for radiotherapy alone, in a group of 573 glioblastoma patients.
SUBHEAD GOES HERE
The study results Dr. Grossman referred to were reported in the March 10 New England Journal of Medicine by Stupp and colleagues. In another study in that same issue, Hegi and colleagues determined that temozolomide worked best in patients with a methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter. They determined the patient’s status in this regard by polymerase chain reaction analysis.
“One of the interesting things about this study was that two-year survival was only 2% in those who got radiotherapy alone,” Dr. Grossman said. “And in the patients who had a methylated MGMT promoter, it was 22%.” He noted, however, that in other studies, the response rate for temozolomide alone was only 10%.
Nevertheless, the radiotherapy-temozolomide combination has now become “the standard therapy for patients with newly diagnosed glioblastoma, and rightly so,” he said—though he cautioned that physicians should not get so comfortable with this new standard that they fail to refer patients to experimental therapies. “Even with new treatments, 75% of our patients are dead in two years, and that is not a comfortable stopping point.”
Dr. Grossman also remarked that drug adverse events must be considered with any new type of therapy for individual patients. “We have learned that there is a tremendous interaction with the P-450 anticonvulsants. If you give [temozolomide] orally or by IV to a patient on an anticonvulsant drug, you are not guaranteed to get the blood levels you would expect in other tumors.” In addition to that caveat, there is the problem of the blood-brain barrier. “We had taken it on faith that the drug gets through the blood-brain barrier, but now we know that is not always the case.”
While temozolomide has been shown to work in some patients, he added, there are still questions to be answered, such as the optimal amount to give to individual patients. “Our challenge is to continue to develop new therapies, to be very careful about our trial designs, and to be sure we are actually delivering drug to the tumor,” he concluded.
OTHER REPORTS
• Jan C. Buckner, MD, Chair of Medical Oncology at the Mayo Clinic in Rochester, Minnesota, and his group are also looking at the drug CCI-779, a small-molecule inhibitor of the mammalian target of rapamycin, as a “rational therapeutic target” for recurrent glioblastoma multiforme. Early studies have shown it to be well tolerated and that high levels of phosphorylated p70s6 kinase predicted a good response to this treatment.
Dr. Buckner also said that while temozolomide has been shown to work in some patients, other therapeutic remedies should continue to be explored, including nitrosourea-based options, such as BCNU (carmustine) or procarbazine and vincristine. “There is also some evidence that irinotecan and the platins may be active in this disease group,” he noted.
• Jonathan P. S. Knisely, MD, Assistant Professor in the Department of Radiology at Yale University, New Haven, and colleagues reported a phase III study by the Radiation Therapy Oncology Group that analyzed the results of a trial with thalidomide in combination with radiation therapy for patients with multiple brain metastases. The drug did not increase survival.
• Howard Fine, MD, Chief of the Neuro-Oncology Branch at the National Cancer Institute, reported that the investigational drug enzastaurin reduced blood flow to tumors in 92 patients with glioblastoma, in most cases causing tumors to shrink. The drug also inhibited the cell-signaling pathways PKC-beta and P13/kinase, thus having both antiangiogenic and apoptotic effects. A phase III trial of this drug is under way.
• Another drug, erlotinib—an epidermal growth factor antagonist—has shown a promising response rate and has improved median survival in recurrent glioblastoma multiforme, although the numbers are still small, according to Timothy Cloughesy, MD, Director of the Neuro-Oncology Program at the University of California, Los Angeles.
• Martin J. van den Bent, MD, PhD, Head of the Neuro-Oncology Unit at Erasmus University in Rotterdam, the Netherlands, reported that in patients with anaplastic oligodendrogliomas, six cycles of adjuvant PCV (procarbazine, lomustine, vincristine) chemotherapy after radiotherapy prolonged progression-free survival from 13 to 24 months but did not improve overall survival.
• Lynn S. Ashby, MD, a neurologist in Phoenix, studied 95 patients with oligodendrogliomas and 44 patients with oligoastrocytomas and found that improved survival did not correlate with the type of treatment—whether it was radiotherapy, chemotherapy, or a combination. Although these patients would be expected to survive longer than patients with high-grade tumors, “high proliferative activity or the presence of enhancement on MRI is associated with shortened survival.” Also, 1p deletion is a powerful prognostic tool, she said.
During a special session on central nervous system tumors, Stuart Grossman, MD, said that a look at the survival in the group with the worst prognosis—patients with glioblastoma multiforme—indicates that it has changed little. Nevertheless, “This has been a year where there have been genuine advances in this disease, some surprises, and some significant implications for both clinical care and research.” Dr. Grossman is a medical oncologist at Johns Hopkins University in Baltimore, former President of the Society for Neuro-Oncology, and Chairman of the Eastern Cooperative Oncology’s Brain Tumor Working Group.
According to Dr. Grossman, “a whirlwind of the last 30 years” still shows that surgery and radiation therapy do help patients, and that radiotherapy plus daily oral temozolomide has been shown to increase median survival to 14.6 months as opposed to 12.1 months for patients given only radiotherapy. Furthermore, the two-year survival rate was 26.5% for radiotherapy plus temozolomide versus only 10.4% for radiotherapy alone, in a group of 573 glioblastoma patients.
SUBHEAD GOES HERE
The study results Dr. Grossman referred to were reported in the March 10 New England Journal of Medicine by Stupp and colleagues. In another study in that same issue, Hegi and colleagues determined that temozolomide worked best in patients with a methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter. They determined the patient’s status in this regard by polymerase chain reaction analysis.
“One of the interesting things about this study was that two-year survival was only 2% in those who got radiotherapy alone,” Dr. Grossman said. “And in the patients who had a methylated MGMT promoter, it was 22%.” He noted, however, that in other studies, the response rate for temozolomide alone was only 10%.
Nevertheless, the radiotherapy-temozolomide combination has now become “the standard therapy for patients with newly diagnosed glioblastoma, and rightly so,” he said—though he cautioned that physicians should not get so comfortable with this new standard that they fail to refer patients to experimental therapies. “Even with new treatments, 75% of our patients are dead in two years, and that is not a comfortable stopping point.”
Dr. Grossman also remarked that drug adverse events must be considered with any new type of therapy for individual patients. “We have learned that there is a tremendous interaction with the P-450 anticonvulsants. If you give [temozolomide] orally or by IV to a patient on an anticonvulsant drug, you are not guaranteed to get the blood levels you would expect in other tumors.” In addition to that caveat, there is the problem of the blood-brain barrier. “We had taken it on faith that the drug gets through the blood-brain barrier, but now we know that is not always the case.”
While temozolomide has been shown to work in some patients, he added, there are still questions to be answered, such as the optimal amount to give to individual patients. “Our challenge is to continue to develop new therapies, to be very careful about our trial designs, and to be sure we are actually delivering drug to the tumor,” he concluded.
OTHER REPORTS
• Jan C. Buckner, MD, Chair of Medical Oncology at the Mayo Clinic in Rochester, Minnesota, and his group are also looking at the drug CCI-779, a small-molecule inhibitor of the mammalian target of rapamycin, as a “rational therapeutic target” for recurrent glioblastoma multiforme. Early studies have shown it to be well tolerated and that high levels of phosphorylated p70s6 kinase predicted a good response to this treatment.
Dr. Buckner also said that while temozolomide has been shown to work in some patients, other therapeutic remedies should continue to be explored, including nitrosourea-based options, such as BCNU (carmustine) or procarbazine and vincristine. “There is also some evidence that irinotecan and the platins may be active in this disease group,” he noted.
• Jonathan P. S. Knisely, MD, Assistant Professor in the Department of Radiology at Yale University, New Haven, and colleagues reported a phase III study by the Radiation Therapy Oncology Group that analyzed the results of a trial with thalidomide in combination with radiation therapy for patients with multiple brain metastases. The drug did not increase survival.
• Howard Fine, MD, Chief of the Neuro-Oncology Branch at the National Cancer Institute, reported that the investigational drug enzastaurin reduced blood flow to tumors in 92 patients with glioblastoma, in most cases causing tumors to shrink. The drug also inhibited the cell-signaling pathways PKC-beta and P13/kinase, thus having both antiangiogenic and apoptotic effects. A phase III trial of this drug is under way.
• Another drug, erlotinib—an epidermal growth factor antagonist—has shown a promising response rate and has improved median survival in recurrent glioblastoma multiforme, although the numbers are still small, according to Timothy Cloughesy, MD, Director of the Neuro-Oncology Program at the University of California, Los Angeles.
• Martin J. van den Bent, MD, PhD, Head of the Neuro-Oncology Unit at Erasmus University in Rotterdam, the Netherlands, reported that in patients with anaplastic oligodendrogliomas, six cycles of adjuvant PCV (procarbazine, lomustine, vincristine) chemotherapy after radiotherapy prolonged progression-free survival from 13 to 24 months but did not improve overall survival.
• Lynn S. Ashby, MD, a neurologist in Phoenix, studied 95 patients with oligodendrogliomas and 44 patients with oligoastrocytomas and found that improved survival did not correlate with the type of treatment—whether it was radiotherapy, chemotherapy, or a combination. Although these patients would be expected to survive longer than patients with high-grade tumors, “high proliferative activity or the presence of enhancement on MRI is associated with shortened survival.” Also, 1p deletion is a powerful prognostic tool, she said.
Brain tumor 3. Advance in embryo cell tumor treatment.
Accession number;99A0415693
Title;Brain tumor 3. Advance in embryo cell tumor treatment.
Author;MATSUTANI MASAO(Saitama Med. Sch.)
Journal Title;Annual Review Shinkei
Journal Code:L1628A
ISSN:
VOL.1999;NO.;PAGE.204-211(1999)
Figure&Table&Reference;FIG.1, TBL.4, REF.25
Pub. Country;Japan
Language;Japanese
Abstract;
Title;Brain tumor 3. Advance in embryo cell tumor treatment.
Author;MATSUTANI MASAO(Saitama Med. Sch.)
Journal Title;Annual Review Shinkei
Journal Code:L1628A
ISSN:
VOL.1999;NO.;PAGE.204-211(1999)
Figure&Table&Reference;FIG.1, TBL.4, REF.25
Pub. Country;Japan
Language;Japanese
Abstract;
Duke University Will Study Pediatric Brain Cancer
By Bonnie Rochman, The News & Observer, Raleigh, N.C. Knight Ridder/Tribune Business News
Jun. 6--DURHAM, N.C.--Duke University's cancer center has established the country's first pediatric brain tumor institute with a $6 million grant from the Asheville-based Pediatric Brain Tumor Foundation, the largest foundation gift the center has ever received.
The Pediatric Brain Tumor Foundation Institute will research childhood brain tumors, the most deadly of pediatric cancers, officials said Thursday. About 60 percent of children with brain tumors survive at least five ...
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Jun. 6--DURHAM, N.C.--Duke University's cancer center has established the country's first pediatric brain tumor institute with a $6 million grant from the Asheville-based Pediatric Brain Tumor Foundation, the largest foundation gift the center has ever received.
The Pediatric Brain Tumor Foundation Institute will research childhood brain tumors, the most deadly of pediatric cancers, officials said Thursday. About 60 percent of children with brain tumors survive at least five ...
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Video: Pediatric Brain Tumor Foundation Gives $6 Million Grant to Duke
To: MEDICAL EDITORS
Contact: Mary O. Ratcliffe of Pediatric Brain Tumor Foundation, +1-800-253-6530, mratcliffe@curethekids.org
ASHEVILLE, N.C., May 14 /PRNewswire-USNewswire/ -- The Pediatric Brain Tumor Foundation (PBTF) is giving an additional $6 million grant to its research institute at Duke University, bringing total funding for the program to $12 million.
To view the Multimedia News Release, go to:
http://www.prnewswire.com/mnr/pbtf/32347/
Duke will use the funds to continue to sharpen its research focus on pediatric brain tumors, which are the leading cause of cancer death in children ...
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Contact: Mary O. Ratcliffe of Pediatric Brain Tumor Foundation, +1-800-253-6530, mratcliffe@curethekids.org
ASHEVILLE, N.C., May 14 /PRNewswire-USNewswire/ -- The Pediatric Brain Tumor Foundation (PBTF) is giving an additional $6 million grant to its research institute at Duke University, bringing total funding for the program to $12 million.
To view the Multimedia News Release, go to:
http://www.prnewswire.com/mnr/pbtf/32347/
Duke will use the funds to continue to sharpen its research focus on pediatric brain tumors, which are the leading cause of cancer death in children ...
Read all of this article with a FREE trial to HighBeam Research
Advances in brain-tumor treatment hailed
Brain tumors 25 years ago were cut out. Then the area was treated with radiotherapy.
Surgery's still a staple of treatment, but it's more apt to be followed immediately by molecular analysis and genotyping these days, according to Dr. Greg Cairncross, professor of clinical neurosciences and oncology at the University of Calgary in Canada.
Physicians and researchers, including Cairncross, say that if they can figure out the genetic signature of a person's brain tumor, they can select treatments that are most apt to work on it specifically. Not all brain tumors are alike -- not even all brain ...
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Surgery's still a staple of treatment, but it's more apt to be followed immediately by molecular analysis and genotyping these days, according to Dr. Greg Cairncross, professor of clinical neurosciences and oncology at the University of Calgary in Canada.
Physicians and researchers, including Cairncross, say that if they can figure out the genetic signature of a person's brain tumor, they can select treatments that are most apt to work on it specifically. Not all brain tumors are alike -- not even all brain ...
Read all of this article with a FREE trial to HighBeam Research
Targeted Brain Tumor Treatment: Current Perspectives
Ningaraj N.S1, Salimath B.P2, Sankpal U.T1, Perera R1 and Vats T1
1Department of Pediatric Neurooncology and Molecular Pharmacology, Hoskins Center, Curtis and Elizabeth Anderson Cancer Institute, Memorial Health University Medical Center, Mercer University Medical School, 4700 Waters Avenue, Savannah, GA 31404, U.S.A. 2Department of Biotechnology, University of Mysore, Mysore 570006, Karnataka, India.
Abstract:
Brain tumor is associated with poor prognosis. The treatment option is severely limited for a patient with brain tumor, despite great advances in understanding the etiology and molecular biology of brain tumors that have lead to breakthroughs in developing pharmaceutical strategies, and ongoing NCI/Pharma-sponsored clinical trials. We reviewed the literature on molecular targeted agents in preclinical and clinical studies in brain tumor for the past decade, and observed that the molecular targeting in brain tumors is complex. This is because no single gene or protein can be affected by single molecular agent, requiring the use of combination molecular therapy with cytotoxic agents. In this review, we briefly discuss the potential molecular targets, and the challenges of targeted brain tumor treatment. For example, glial tumors are associated with over-expression of calcium-dependent potassium (KCa) channels, and high grade glioma express specific KCa channel gene (gBK) splice variants, and mutant epidermal growth factor receptors (EGFRvIII). These specific genes are promising targets for molecular targeted treatment in brain tumors. In addition, drugs like Avastin and Gleevec target the molecular targets such as vascular endothelial cell growth factor receptor, platelet-derived growth factor receptors, and BRC-ABL/Akt. Recent discovery of non-coding RNA, specifically microRNAs could be used as potential targeted drugs. Finally, we discuss the role of anti-cancer drug delivery to brain tumors by breaching the blood-brain tumor barrier. This non-invasive strategy is particularly useful as novel molecules and humanized monoclonal antibodies that target receptor tyrosine kinase receptors are rapidly being developed.
Abbreviations:
BBB: blood-brain barrier; BTB: blood-tumor barrier; KCa: calcium-dependent potassium channels; NS-1619/NS 004: 1,3-dihydro-1-5-(trifl uoromethyl)-2H benzimidazol-2-one; HBMVEC: human brain microvascular endothelial cells; FACS: fluorescence activated cell sorting; PDGFR: platelet-derived growth factor receptor; RTKIs: receptor tyrosine kinase inhibitors; EGFR: epidermal growth factor receptor; EGFRvIII: variant III of the human EGFR; gBK channel: glioma specific spice variant of KCa channel gene; KATP: ATP sensitive potassium channels; Minoxidil sulfate (MS: KATP channel agonist);Trastuzumab (Herceptin, Her-2 inhibitor, Genentech Inc.).
1Department of Pediatric Neurooncology and Molecular Pharmacology, Hoskins Center, Curtis and Elizabeth Anderson Cancer Institute, Memorial Health University Medical Center, Mercer University Medical School, 4700 Waters Avenue, Savannah, GA 31404, U.S.A. 2Department of Biotechnology, University of Mysore, Mysore 570006, Karnataka, India.
Abstract:
Brain tumor is associated with poor prognosis. The treatment option is severely limited for a patient with brain tumor, despite great advances in understanding the etiology and molecular biology of brain tumors that have lead to breakthroughs in developing pharmaceutical strategies, and ongoing NCI/Pharma-sponsored clinical trials. We reviewed the literature on molecular targeted agents in preclinical and clinical studies in brain tumor for the past decade, and observed that the molecular targeting in brain tumors is complex. This is because no single gene or protein can be affected by single molecular agent, requiring the use of combination molecular therapy with cytotoxic agents. In this review, we briefly discuss the potential molecular targets, and the challenges of targeted brain tumor treatment. For example, glial tumors are associated with over-expression of calcium-dependent potassium (KCa) channels, and high grade glioma express specific KCa channel gene (gBK) splice variants, and mutant epidermal growth factor receptors (EGFRvIII). These specific genes are promising targets for molecular targeted treatment in brain tumors. In addition, drugs like Avastin and Gleevec target the molecular targets such as vascular endothelial cell growth factor receptor, platelet-derived growth factor receptors, and BRC-ABL/Akt. Recent discovery of non-coding RNA, specifically microRNAs could be used as potential targeted drugs. Finally, we discuss the role of anti-cancer drug delivery to brain tumors by breaching the blood-brain tumor barrier. This non-invasive strategy is particularly useful as novel molecules and humanized monoclonal antibodies that target receptor tyrosine kinase receptors are rapidly being developed.
Abbreviations:
BBB: blood-brain barrier; BTB: blood-tumor barrier; KCa: calcium-dependent potassium channels; NS-1619/NS 004: 1,3-dihydro-1-5-(trifl uoromethyl)-2H benzimidazol-2-one; HBMVEC: human brain microvascular endothelial cells; FACS: fluorescence activated cell sorting; PDGFR: platelet-derived growth factor receptor; RTKIs: receptor tyrosine kinase inhibitors; EGFR: epidermal growth factor receptor; EGFRvIII: variant III of the human EGFR; gBK channel: glioma specific spice variant of KCa channel gene; KATP: ATP sensitive potassium channels; Minoxidil sulfate (MS: KATP channel agonist);Trastuzumab (Herceptin, Her-2 inhibitor, Genentech Inc.).
American Brain Tumor Association Gives 21 New Research Awards
DES PLAINES, Ill., April 8 /U.S. Newswire/ -- The Des Plaines- based American Brain Tumor Association recently committed $1.3 million in research funding for fourteen fellowships, five translational grants, and two small project grants. Award recipients are brain tumor investigators at institutions throughout the United States and Canada.
Qualified applications are peer-reviewed by the Association's distinguished Scientific Advisory Council. Award determinations are made by their Board of Directors based on the Advisors' recommendations.
The spectrum of funded research is vast. It ranges ...
Read all of this article with a FREE trial to HighBeam Research
Qualified applications are peer-reviewed by the Association's distinguished Scientific Advisory Council. Award determinations are made by their Board of Directors based on the Advisors' recommendations.
The spectrum of funded research is vast. It ranges ...
Read all of this article with a FREE trial to HighBeam Research
Neuroimaging Clinics of North America: Advances in Brain Tumor Imaging and Therapy
James M. Provenzale, guest editor. Vol 12, No 4, WB Saunders; Philadelphia, PA: 699 pages, 78 illustrations. $45.00.
In the preface to this issue of Neuroimaging Clinics of North America, James Provenzale states that advances in brain tumor treatment will necessitate changes in imaging techniques and strategies. The dual goals of this monograph are to provide radiologists and other clinicians with knowledge of these new (or potential) treatment options and the imaging tools needed to evaluate them. To a large extent, the monograph succeeds, although some of the presentations are not for the faint of heart.
The editor has organized many of the chapters in pairs dealing with a treatment approach (and the science that underlies it) and a means of imaging it. This organization is somewhat artificial. It works for some topics (eg, tumor hypoxia and hypoxia imaging), but not for others. The chapter on perfusion imaging is superb, but not particularly relevant to the chapter on anti-antigenic agents. It is best to view the chapters as stand-alone presentations.
Four chapters provide excellent reviews of current state of the art and future directions for imaging techniques already in use in tumor management at major centers. The discussions of dynamic susceptibility contrast-enhanced MR imaging (perfusion imaging), positron-emission tomography (PET), and MR spectroscopy are thorough and informative. The perfusion discussion reviews the specific challenges to performing perfusion imaging in the presence of disruption of the blood-brain barrier and tumor vascularity. The PET presentation provides an excellent review of FDG imaging and the use of fusion of MR and PET data to improve detection of lesions near the corticomedullary junction that typically have uptake similar to that of gray matter. The use of newer ligands is discussed as well. The chapter on MR spectroscopy deals almost exclusively with multivoxel imaging. This technique is rapidly replacing single-voxel MR spectroscopy in the assessment of tumors for the altogether important reason that gliomas are extremely heterogeneous and are unlikely to be well characterized by a single measurement. The emphasis in interpretation has shifted from viewing individual spectra to assessment of the distribution of metabolites within the lesion. MR spectroscopy data are interpreted with other MR parameters (T2, enhancement, and diffusion). Considering that single voxel MR spectroscopy is still being used, it would have been helpful for the authors to have provided a short discussion and a few illustrations of individual spectra for each glioma grade. There are no chapters devoted specifically to diffusion imaging or functional MR. Diffusion tensor imaging (anisotropy measures and tractography) does show some promise in identifying and assessing the extent of tumor infiltration. This topic is covered in the final chapter, on intraoperative MR imaging, in which the role of functional MR imaging is also discussed. These chapters provide an excellent review of the current state of the art and near future developments in physiologic imaging of brain tumors. Each chapter assumes that the reader has some knowledge of these techniques and should therefore prove most useful to fellowship-trained neuroradiologists and nonradiologists (eg, neurologists, neurooncologists, and neurosurgeons) engaged in the management of brain tumors.
The chapters dealing with the various therapeutic alternatives are extremely informative. The presentations on viral delivery of gene therapy and immunotherapy are noteworthy for their clarity and completeness. The presentation on the molecular abnormalities in tumors offers an excellent review of the genetics of glial tumors and the implications of this genetic information for treatment. This material may seem to have little practical value for radiologists, but as the editor states, radiologists must develop at least a passing knowledge of these topics if they are to design and perform the imaging studies in glioma patients. Practicality aside, the topics discussed in these chapters should be fascinating to anyone dealing with brain tumors. Of course, there is always the risk that more detail than is necessary is provided for the "casual reader." At times, I did get a bit overwhelmed, but it is was easy enough to skim some of the specific details on gene variations and well worth the effort to gain an understanding of tumor biology and how it can be manipulated for therapeutic advantage.
In conclusion, this monograph accomplishes the goals set out by the editor. It provides radiologists (and other interested clinicians) with an excellent review of current physiologic imaging and a superb introduction to the biology of brain tumors and treatment options.
In the preface to this issue of Neuroimaging Clinics of North America, James Provenzale states that advances in brain tumor treatment will necessitate changes in imaging techniques and strategies. The dual goals of this monograph are to provide radiologists and other clinicians with knowledge of these new (or potential) treatment options and the imaging tools needed to evaluate them. To a large extent, the monograph succeeds, although some of the presentations are not for the faint of heart.
The editor has organized many of the chapters in pairs dealing with a treatment approach (and the science that underlies it) and a means of imaging it. This organization is somewhat artificial. It works for some topics (eg, tumor hypoxia and hypoxia imaging), but not for others. The chapter on perfusion imaging is superb, but not particularly relevant to the chapter on anti-antigenic agents. It is best to view the chapters as stand-alone presentations.
Four chapters provide excellent reviews of current state of the art and future directions for imaging techniques already in use in tumor management at major centers. The discussions of dynamic susceptibility contrast-enhanced MR imaging (perfusion imaging), positron-emission tomography (PET), and MR spectroscopy are thorough and informative. The perfusion discussion reviews the specific challenges to performing perfusion imaging in the presence of disruption of the blood-brain barrier and tumor vascularity. The PET presentation provides an excellent review of FDG imaging and the use of fusion of MR and PET data to improve detection of lesions near the corticomedullary junction that typically have uptake similar to that of gray matter. The use of newer ligands is discussed as well. The chapter on MR spectroscopy deals almost exclusively with multivoxel imaging. This technique is rapidly replacing single-voxel MR spectroscopy in the assessment of tumors for the altogether important reason that gliomas are extremely heterogeneous and are unlikely to be well characterized by a single measurement. The emphasis in interpretation has shifted from viewing individual spectra to assessment of the distribution of metabolites within the lesion. MR spectroscopy data are interpreted with other MR parameters (T2, enhancement, and diffusion). Considering that single voxel MR spectroscopy is still being used, it would have been helpful for the authors to have provided a short discussion and a few illustrations of individual spectra for each glioma grade. There are no chapters devoted specifically to diffusion imaging or functional MR. Diffusion tensor imaging (anisotropy measures and tractography) does show some promise in identifying and assessing the extent of tumor infiltration. This topic is covered in the final chapter, on intraoperative MR imaging, in which the role of functional MR imaging is also discussed. These chapters provide an excellent review of the current state of the art and near future developments in physiologic imaging of brain tumors. Each chapter assumes that the reader has some knowledge of these techniques and should therefore prove most useful to fellowship-trained neuroradiologists and nonradiologists (eg, neurologists, neurooncologists, and neurosurgeons) engaged in the management of brain tumors.
The chapters dealing with the various therapeutic alternatives are extremely informative. The presentations on viral delivery of gene therapy and immunotherapy are noteworthy for their clarity and completeness. The presentation on the molecular abnormalities in tumors offers an excellent review of the genetics of glial tumors and the implications of this genetic information for treatment. This material may seem to have little practical value for radiologists, but as the editor states, radiologists must develop at least a passing knowledge of these topics if they are to design and perform the imaging studies in glioma patients. Practicality aside, the topics discussed in these chapters should be fascinating to anyone dealing with brain tumors. Of course, there is always the risk that more detail than is necessary is provided for the "casual reader." At times, I did get a bit overwhelmed, but it is was easy enough to skim some of the specific details on gene variations and well worth the effort to gain an understanding of tumor biology and how it can be manipulated for therapeutic advantage.
In conclusion, this monograph accomplishes the goals set out by the editor. It provides radiologists (and other interested clinicians) with an excellent review of current physiologic imaging and a superb introduction to the biology of brain tumors and treatment options.
Each year, more than 100,000 Americans are told they have a brain tumor. It is not clear why many of these tumors occur. Those that originate in the brain, primary brain tumors, may be due to genetic or environmental factors. Others, called secondary brain tumors, are the result of cancer that has spread from other parts of the body.
There are many different types of brain tumors, which are generally categorized as benign or malignant. Benign brain tumors, while slow growing and non-cancerous, may be inoperable. And unlike benign tumors in other parts of the body, benign brain tumors often recur. Malignant brain tumors grow quickly and are life-threatening. Generally, neither type spreads beyond the brain or spinal cord, meaning that they are unlikely to affect other body organs or systems.
Through the use of neurological exam; sophisticated imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI); and biopsy, doctors are able to provide a specific diagnosis as to the type of brain tumor a person has. Below are descriptions of some brain tumors and their treatment options.
Craniopharyngiomas are tumors near the brain's pituitary gland and most commonly affect infants and children. Because the pituitary gland releases chemicals essential for growth and metabolism, a craniopharyngioma may result in a child's stunted growth. The patient's vision may also be affected. These tumors develop from cells left over from early fetal development.
Treatment: Treatment for these tumors usually includes surgery and fractionated stereotactic radiation therapy. The treatment goal is to gain maximum resection of the tumor while maintaining vision and pituitary function. Dr. Carmel has published the largest series in North America of patients undergoing surgery for craniopharyngioma.
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Ependymomas develop from cells that line chambers of the brain or the canal containing the spinal cord. Most of these tumors are benign. Ependymomas often occur in children, where they typically develop at the brain's base.
In addition to headache and vomiting, ependymomas can cause swelling of the optic nerve, involuntary, jerky eye movement known as nystagmus, and neck pain.
Treatment: Surgery followed by radiation therapy is the usual treatment for these tumors. Chemotherapy may be used in the case of recurrent tumors. However, stereotactic radiation therapy may improve tumor control while limiting the side effects of radiation, especially in children.
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Gliomas account for about half of all primary brain tumors and nearly one-fifth of all primary spinal cord tumors. They originate from nerve cells called glial cells. Gliomas occur most often in the cerebral hemispheres, but also are found in the optic nerve, the brain stem, and especially among children, the cerebellum.
There are many types of gliomas, including:
Astrocytomas
Most gliomas are astrocytomas, which develop from star-shaped glial cells called astrocytes. These tumors can occur in different parts of the brain, and thus, produce varying symptoms. For example, if the astrocytoma is located in the cerebellum (as is commonly the case with children), balance and coordination may be affected. The result of increased intracranial pressure may be headache, vomiting, and visual problems.
Doctors categorize these tumors by grades. Grading occurs after biopsy, when a pathologist examines the brain tissue for breakdown of cell structure. While there are different systems used to assign grades, in general, they are as follows:
Grade I tumors are slow growing; their cells are near-normal in appearance; and are not malignant.
Grade II tumors have cells that are slightly abnormal in appearance and can spread to surrounding tissue.
Grade III tumors grow quickly, contain abnormal cells, and spread to surrounding tissue.
Grade IV tumors contain aggressive, abnormal cells that reproduce quickly. These are the most malignant of brain tumors.
The types of graded astrocytomas include:
Well-differentiated
These Grade I and II, or low-grade, astrocytomas contain relatively normal cells and are less malignant than the other two grades. While well-differentiated astrocytomas often can be completely removed through surgery, those that are inaccessible to the surgeon may be life-threatening.
Anaplastic
These Grade III astrocytomas contain cells with some malignant traits.
Treatment: Surgery followed by radiation, and some chemotherapy, is used to treat anaplastic astrocytomas.
Glioblastoma multiforme
These tumors, sometimes called high-grade or grade IV astrocytomas, grow rapidly, invade nearby tissue, and contain cells that are very malignant. Glioblastoma multiforme is among the most common and devastating primary brain tumors that strike adults. Doctors usually treat glioblastomas with surgery followed by radiation therapy. Chemotherapy may be used before, during or after radiation.
Treatment: For both anaplastic gliomas and glioblastomas , functional image-guided surgery (FIGS) may be helpful in resecting as much tumor as safely possible. Gliadel®, dime-sized chemotherapeutic wafers that are implanted following tumor resection, may be considered for patients with tumors that recur after other treatment.
Gangliogliomas
A rarely occurring and slow-growing form of glioma, gangliogliomas can be found in the brain or spinal cord.
Treatment: These tumors are usually treated with surgery. Functional image-guided surgery may optimize the safety and completeness of surgical resection.
Brain Stem Gliomas
Like their name suggests, brain stem gliomas are located at the base of the brain. They occur more frequently in children than in adults. Brain stem gliomas can range in grade, from slow growing and benign to fast-growing and malignant.
Treatment: Brain stem gliomas occur in a vulnerable location, so surgery is rarely performed to remove them. Radiation therapy can reduce symptoms and improve the patient's chance of survival by slowing tumor growth.
Mixed Gliomas
Mixed gliomas contain more than one type of glial cell; one of them usually being astrocytes. For reasons that are not known, mixed gliomas most commonly occur in young men.
Mixed gliomas often produce symptoms common to many brain tumors-headache, vomiting, and visual problems. Depending on the tumor's location, there may be paralysis on one side of the body, memory difficulties, and personality changes.
Treatment: Treatment focuses on the most malignant cell type found within the tumor and often involves surgical resection. Functional image guided surgery may be used for tumors near the " eloquent" areas of the brain. Radiation therapy is another possibility.
Optic Nerve Gliomas
Optic nerve gliomas can interfere with vision, causing "crossed" eyes, or strabismus; bulging eyeballs, or loss of sight. People with neurofibromatosis, a condition where fiber-like growths affect the nerves, may be susceptible to these types of tumors.
Treatment: Treatment may include surgery, radiation or chemotherapy. Stereotactic radiation therapy may control the tumor while avoiding radiation injury to the uninvolved portions of the optic chiasm.
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Medulloblastomas, which are malignant, represent more than one-fourth of all childhood brain tumors. They belong to a class of tumors called primitive neuroectodermal tumors, or PNETS, and tend to grow quickly. Medulloblastomas can spread throughout the nervous system and, while not a common occurrence, to other parts of the body.
Some symptoms of medulloblastomas include vomiting, headache, and visual problems. As most of these tumors are located in the cerebellum, muscle coordination-particularly during walking-may be affected. There may also be speech difficulties and weakness in the muscles.
Treatment: Medullobastomas, like other PNETs, are difficult to totally remove through surgery because their cells often spread in a scattered, patchy pattern. Doctors usually remove as much tumor as possible with surgery, then prescribe chemotherapy and/or radiation. Children under age three generally do not receive radiation treatment because of possible long-term side effects. However, stereotactic radiation therapy may be an option, especially for young children without widespread disease; this technique does not produce the same effects as of conventional radiation on the developing brain.
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Meninges are thin membranes that cover the brain and the spinal cord. Meningiomas, tumors originating from these membranes, account for about 15 % of all brain tumors and about one-fourth of all spinal cord tumors. These slow-growing tumors rarely become malignant or spread, but about 5 % of the time, malignancy does occur.
Treatment: Surgery is the preferred treatment for accessible meningiomas and is more successful for these lesions than for most tumor types. Recurrent meningiomas may require additional treatment including radiation therapy. In some cases, stereotactic radiosurgery alone may be a good treatment for patients with meningiomas; in others, a strategy of resection plus adjuvant radiosurgery may be ideal. Tumors close to the optic chiasm may be treated with stereotactic radiation therapy, as the high single doses of radiosurgery may injure the chiasm in such cases.
These are malignant tumors that have spread from elsewhere in the body.
Treatment: If only one lesion is present in the brain, functional image-guided surgery (FIGS) or stereotactic radiosurgery may be employed. For patients with more than one metastastic brain tumor, radiosurgery is a better option. Whole-brain radiation therapy is usually prescribed as well.
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These tumors are relatively rare, and when they do occur, are slow growing. Young adults are most commonly affected by oligodendroglimas.
Treatment: Doctors often treat these tumors with surgery alone. As a complete resection may result in a cure, functional image-guided surgery (FIGS) may be indicated.
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Tumors near the pineal gland, a small structure deep within the brain, can be of about 17 different types. Some are malignant, like the germinoma, and others are not. That is why, when possible, biopsy is used to confirm the tumor type.
Treatment: Benign pineal tumors can often be removed surgically; radiation, chemotherapy, or both, can be the course of treatment for malignant pineal tumors. Patients with the most common types of pineal-region tumors-gliomas, germinomas, and PNET-have been treated successfully with stereotactic radiosurgery. Larger tumors can be treated with stereotactic radiation therapy
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The pituitary gland, a small oval-shaped structure located at the base of the brain, releases several chemical messengers known as hormones, which help control the body's other glands and influence the body's growth, metabolism, and maturation. Tumors that affect the pituitary gland account for about 10% of brain tumors. Doctors classify pituitary adenomas into two groups: secreting and non-secreting. Secreting tumors release unusually high levels of pituitary hormones, triggering a constellation of symptoms, which can include impotence, amenorrhea (cessation of the menstrual period), galactorrhea (milk flow unrelated to childbirth or nursing), abnormal body growth, Cushing's syndrome, or hyperthyroidism depending on which hormone is involved. Other tumors that are non-secreting cause symptoms due to their size and so-called "mass effect" on surrounding structures.
Treatment:
Prolactinoma: Currently, patients with prolactin-secreting tumors are often treated with a medication called bromocriptine (brandname: Parlodel) or similar agents such as pergolide or dosinex (a longer-acting preparation), which must be taken lifelong to prevent tumor recurrence. Progressive visual loss, the inability to tolerate the medication, or the chance of a surgical cure may indicate surgical resection. Young women seeking to bear children and to avoid lifelong medication may opt for surgery especially if they have a microprolactinoma (less than 10 mm in height on MRI scan) and a serum prolcatin level less than 300 ng/mL. Such patients may have an excellent chance of cure with surgery. Stereotactic radiosurgery-and in some cases radiation therapy-may play a role in certain patients who have large tumors and cannot tolerate bromocriptine or its related medications.
Acromegaly: This condition is due to oversecretion of growth hormone by a pituitary tumor. If the tumor develops during adolescence the patient may grow to unusual height, a condition known as gigantism. While this may not be inherently a problem, acromegaly, which occurs after growth stops, can be disabling and ultimately lethal. Diabetes, high blood pressure, heart disease, and severe joint abnormalities may ensue. Growth of facial bones may be unsightly. Total resection of a growth-hormone secreting tumor may be curative; other treatments may include stereotactic radiosurgery and/or radiation therapy, which can be highly effective in controlling the disease. Medications such as octreotide or bromocriptine may control the disease to some extent but not nearly as well as in the case of prolactinomas.
Cushing's Disease: Tumors that secrete adrenocorticotrophic hormone (ACTH) stimulate the body's adrenal glands (situated just above the kidneys) to make excessive amounts of cortisol, a steroid that the body normally makes and needs for daily life. However, overproduction of this hormone leads to Cushing's disease, a condition that often is lethal if untreated. Patients develop weight gain due to central obesity, a round-faced appearance, fragile skin, diabetes, and high blood pressure. Surgery is the ideal treatment, especially for those patients with small tumors. Occasionally the entire pituitary gland may need to be removed to achieve a cure, although this should only be done after careful testing confirms that the pituitary is the origin of the problem. Medical therapy with ketoconazole, for instance, may be used as an adjunct. The role of radiation therapy is unclear, although radiosurgery may be useful if surgery is not curative.
Non-secreting tumors: Many patients with pituitary tumors do not suffer from excess hormone production. Rather, their symptoms are due to the "mass effect" of the tumor - i.e., pressure on the optic nerves may cause decreased vision, or the pituitary gland may underproduce normal hormones resulting in problems such as hypothyroidism or decreased sexual drive. If such tumors are found "incidentally", that is, on a scan done for other reasons, treatment may not be needed, especially if the tumor is small. However, if visual loss is present or if MRI demonstrates pressure on the optic nerves, then surgery is often indicated. Radiation therapy or stereotactic radiosurgery can control these tumors but are probably best used as adjuvant treatments after surgery.
Other secreting tumors are much rarer than those listed above, and include:
TSH-producing tumors: Patients with these tumors will have hyperthyroidism because of overproduction of thyroid-stimulating hormone, or TSH (most people with hyperthyroidism have a problem in the thyroid gland itself). The ideal treatment is surgery but radiation therapy or radiosurgery may be needed if TSH levels remain high.
FSH or LH-producing tumors: Follicle stimulating hormone (FSH) or luteinizing hormone (LH) are normally involved in maintenance of sexual function and sexual characteristics in men and women. Their overproduction can alter bodily appearance and interfere with menstrual cycling and pregnancy. The ideal treatment is surgery, but radiation therapy or radiosurgery may be needed if hormonal levels remain high.
Surgery for pituitary tumors: Since pituitary adenomas are underneath the brain, most often they can be surgically approached through the nose and the sphenoid sinus, which lies behind the nose-hence the term "transsphenoidal" surgery. Sometimes an incision under the lip or inside the nose is used to facilitate this surgery, but with the use of modern endoscopic techniques, a nasal incision can be avoided. The tumor itself is removed with the aid of an operating microscope or possibly with the endoscope alone.
The transsphenoidal approach may not be advisable in every case; at times an operation through the head (i.e. "craniotomy") may be preferable if the tumor is unusually large.
Stereotactic radiosurgery for pituitary tumors: Conventional radiation therapy is an effective treatment for many patients with pituitary adenomas. However, large areas of the scalp and brain will also be irradiated. Stereotactic methods make it possible to treat the lesion itself with minimal radiation delivered to surrounding structures. If the tumor is small enough, stereotactic radiosurgery (SRS), may be possible. If the optic nerves or optic chiasm (where the optic nerves meet) are close to the tumor edge, then SRS may not be safe, as the high dose of radiation used would be delivered to these sensitive nerves. If this is the case, then fractionated radiosurgery is advisable.
Stereotactic radiation therapy should be used for the treatment of patients requiring radiation for large pituitary tumors. Radiosurgery may be considered if the lesion is small enough so that injury to the optic chiasm is unlikely to occur from treatment.
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Primitive neuroectodermal tumors (PNETs) usually affect children and young adults. Many scientist believe these tumors originate from primitive cells left over from early nervous system development. PNETs are usually very malignant, growing rapidly and spreading easily within the brain and spinal cord. In rare cases, they spread outside the CNS.
Treatment: Chemotherapy and stereotactic radiation therapy are often used in treatment.
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These tumors, while usually benign, can affect balance, hearing, and speech. Facial paralysis may occur if the tumor involves the seventh cranial nerve. Also known as vestibular schwannomas or acoustic neuromas, these tumors may grow on one or both sides of the brain.
Symptoms may include tinnuitis-ringing in the ear-; ear pain; and dizziness. Headache and problems with walking can also occur.
Treatment: For most patients, surgical resection by a combined skull base approach is the ideal treatment. Patients who are elderly, medically infirm, or refuse surgery may be treated with stereotactic radiosurgery. Clinical trials show that stereotactic radiation therapy yields excellent tumor control and has a minimal complication rate.
Even after treatment for the tumor, some people may continue to have a hearing loss.
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These rare, benign tumors arise from excess growth of blood vessels of the brain. They usually occur in the cerebellum , which is located at the back of the brain. The most common vascular tumor is the hemangioblastoma, which has been associated with von Hippel-Lindau disease, a genetic disorder. Hemangioblastomas do not usually spread.
Because the cerebellum controls balance, people with vascular tumors often walk uncoordinatedly or have difficulty staying steady. Increased pressure within the skull can result in vomiting and headache, as well as visual problems.
Treatment: Surgery is curative. A screening evaluation is recommended to rule out renal cancer, adrenal tumors, and retinal abnormalities. Stereotactic radiosurgery has been shown to control the growth of these tumors.
Brain Cancer Prognosis - Treatment
Can your brain cancer prognosis be improved? Oncologists consider brain cancer to be one of the deadliest cancers, but Karon Beattie, a cancer survivor, has compiled a reference book containing in excess of 350 alternative cancer treatments that thousands of cancer patients have used to overcome their condition, including brain cancer.
Beattie gives accounts of people surviving brain cancer by natural treatments. She states that these treatments are not within the FDA's jurisdiction, resulting in low awareness among doctors.
In one example, Beattie reports that some physicians have used a nutritional supplement to achieve complete remission of aggressive, stage IV cancers that had metastasized.
Specifically in regard to brain cancer, her book, "Natural Cancer Treatments That Work", describes how a British doctor successfully treated a Grade 4 brain tumor with a herbal mixture. The patient is alive two years later, long after oncologists had predicted.
Beattie also details a patient whose brain tumor vanished completely after taking a combination of nutritional supplements known to stop the spread of cancer cells, preventing metastasis. This seems an astonishing outcome for a cancer given a poor prognosis by oncologists.
Further, Beattie gives 131 first-hand accounts of people who beat brain and spinal cord cancers using alternative and natural treatments. If stories like these are factual, why are the treatments not used more widely for brain and other cancers?
According to Beattie, even though the creators of the treatments listed in her book are respected health scientists, few of the treatments have been formally assessed in human clinical trials. Why? There is little financial incentive for drug companies in natural treatments that they cannot patent, yet thousands have successfully used the treatments. Beattie also suggests that many doctors may not know of these treatments because they are only familiar with treatments regulated by the FDA. Many of the alternative treatments she lists involve herbs and vitamins that are beyond the FDA's jurisdiction.
These intriguing accounts will be hard to ignore for cancer sufferers and their loved ones in their efforts to survive cancer and retake their lives.
Beattie gives accounts of people surviving brain cancer by natural treatments. She states that these treatments are not within the FDA's jurisdiction, resulting in low awareness among doctors.
In one example, Beattie reports that some physicians have used a nutritional supplement to achieve complete remission of aggressive, stage IV cancers that had metastasized.
Specifically in regard to brain cancer, her book, "Natural Cancer Treatments That Work", describes how a British doctor successfully treated a Grade 4 brain tumor with a herbal mixture. The patient is alive two years later, long after oncologists had predicted.
Beattie also details a patient whose brain tumor vanished completely after taking a combination of nutritional supplements known to stop the spread of cancer cells, preventing metastasis. This seems an astonishing outcome for a cancer given a poor prognosis by oncologists.
Further, Beattie gives 131 first-hand accounts of people who beat brain and spinal cord cancers using alternative and natural treatments. If stories like these are factual, why are the treatments not used more widely for brain and other cancers?
According to Beattie, even though the creators of the treatments listed in her book are respected health scientists, few of the treatments have been formally assessed in human clinical trials. Why? There is little financial incentive for drug companies in natural treatments that they cannot patent, yet thousands have successfully used the treatments. Beattie also suggests that many doctors may not know of these treatments because they are only familiar with treatments regulated by the FDA. Many of the alternative treatments she lists involve herbs and vitamins that are beyond the FDA's jurisdiction.
These intriguing accounts will be hard to ignore for cancer sufferers and their loved ones in their efforts to survive cancer and retake their lives.
Report of the Brain Tumor Progress Review Group
INTRODUCTION
Brain tumors represent a unique challenge in that they affect the organ that is the essence of the "self." Furthermore, because each area of the brain serves a different but vital function, the therapy that is most effective for other cancers--surgical removal of either the entire organ or the tumor with a generous surround of normal tissue--cannot be used to cure brain tumors. Unfortunately, most brain tumors are relatively insensitive to other cancer treatment, including radiation and chemotherapy.
Coupled with the difficulty in treating brain tumors is the unique biology of the brain:
• Brain tumors occur in an organ that is enclosed in a bony canal that allows little room for growth of the tumor without compressing and damaging normal brain.
• Many brain tumors extensively invade normally functioning brain, making complete surgical removal impossible.
• In their early stages, brain tumors are protected behind a blood-brain barrier; even when this barrier is disrupted in the bulk of the tumor, infiltrating tumor cells at the growing edge remain protected.
• Disruption of the blood-brain barrier leads to edema, which the brain tolerates poorly because of the limited intracranial space and the lack of lymphatics to rid itself of the products of edema and other debris.
• The brain itself is rich in expressed genes and therefore is a fertile field for the growth of both primary tumors and metastases.
• The brain and brain tumors appear to be less susceptible to attack by the immune system than are tumors in other organs. Even the term brain tumor, which suggests a single type of tumor, can be misleading. There are a bewildering variety of central nervous system tumors; the World Health Organization lists 126. Many of these tumors are not, strictly speaking, in the brain but arise from structures intimately associated with that organ, such as tumors of the covering membranes (meningiomas) and adjacent cranial and paraspinal nerves (schwannomas). Brain tumors range from benign (most meningiomas) to highly aggressive (glioblastomas). They affect both adults and children (although the distribution of tumors varies) and are often highly resistant to treatment.
The term brain cancer is also misleading. Most cancers that arise elsewhere in the body cause damage by metastasizing to other organs (including the brain). Primary brain tumors, however, rarely metastasize, although they may widely infiltrate the nervous system. Conversely, many cancers metastasize to the brain, making metastatic brain tumors much more common than primary brain tumors.
Throughout this document, the term brain tumor is used to refer to all tumors that grow inside the skull. The issues discussed in this document, however, also extend to tumors growing within the spinal canal.
STRUCTURE AND PROCESS OF THE PRG MEETING
For the reasons described in the introduction to this report, the Brain Tumor Progress Review Group (BT-PRG) required input from participants with much more diverse expertise than was needed in previous PRGs. In addition to experts on cancer biology and genetics, the BT-PRG required expertise in neurobiology, including areas such as progenitor cells, cellular migration, and blood-brain barrier function. Clinically, expertise was required from both oncology and the clinical neurosciences, including neurosurgery and neurology. In addition, to ensure inclusion of the wide diversity of brain tumors, breakout sessions were held not only for those topics that apply to all solid tumors, including brain tumors, but also (different from other PRGs) for specific types of brain tumors (i.e., intraaxial tumors, extraaxial tumors, pediatric tumors, and metastases). A total of 16 breakout groupswere therefore convened (see box). Each participant attended three breakout sessions.
STRUCTURE OF THE BT-PRG BREAKOUT GROUPS
Basic Biology
Clinical Biology
Specific Tumors
• Models
• Cancer Biology and Etiology
• Neurobiology: Progenitor Cells
• Neurobiology: Migration and Trafficking
• Cancer Genetics
• Tumor Immunology
• Detection, Diagnosis, and Prognosis
• Epidemiology, Prevention, and Outcomes
• Imaging
• Radiation Biology
• Therapeutic Targeting: Blood-Brain Barrier, Gene Therapy, and Vascular Biology
• Treatment
• Extraaxial Tumors
• Intraaxial Tumors
• Pediatric Tumors
• Metastases
The participants in each of these 16 breakout sessions were asked to identify three important research priorities in their assigned areas. It was recognized that it might not be possible to place all of the research priorities formulated by the groups into an overall hierarchy. Although all of the priorities included in the appendices are important and meritorious, some arose in multiple breakout sessions and therefore appear to be of overarching importance. This report delineates those priorities considered by the BT-PRG to be overarching. The appendix contains the full reports of the individual breakout sessions and their priorities.
This report is divided into two sections. Section I, "Scientific Priorities," describes the overarching priorities in both the basic and the clinical sciences. These scientific research priorities are hypothesis driven. To meet them will require the scientific resources described in Section II. The resource priorities in Section II can be considered as hypothesis generating in that their development will generate hypotheses for further research.
SECTION I: SCIENTIFIC PRIORITIES
Three separate sets of breakout sessions addressed the scientific priorities. One set was devoted to fundamental biology and included sessions on models, neurobiology of progenitor cells and of cellular migration and dispersal, cancer biology, immunobiology, and cancer genetics. Another set of sessions was related to clinical issues, ranging from detection and diagnosis to treatment and outcomes. A third set was devoted to specific tumors. Several overarching scientific priorities emerged from all of these sessions and are described here.
Basic Biology
Brain tumors are phenotypically and genotypically heterogeneous. Significant gaps exist in current understanding of the molecular pathways involved in the genesis, progression, and biological and clinical behavior of brain tumors. Brain tumors are unique among human cancers because of their complex interaction with the brain itself, which greatly complicates the use of existing therapies as well as the development of novel ones.
A cardinal feature of the most common malignant brain tumors--their diffuse infiltration into the surrounding brain--presents substantial barriers to the effective delivery of therapeutic agents and increases the possibility of therapeutic toxicity to a vital organ whose function greatly affects the patient's quality of life. Other obstacles to effective therapy include the blood-brain barrier and the difficulties it creates for therapeutic delivery, as well as the relative lack of information on the unique immunological aspects of brain tumors and the cerebral environment.
The biology of brain tumors is distinct from that of many other human tumors. Although tumors are named as though their lineage were understood (e.g., astrocytoma from astrocytes), the cells of origin for most human brain tumors remain enigmatic, complicating the interpretation of data that require a comparison between brain tumor cells and their "normal" counterparts. Highlighting these issues are childhood brain tumors, especially primitive neuroectodermal tumors that arise during brain development. Insights into the normal and aberrant regulation of neurodevelopmental genes may be significant in understanding the etiology of both childhood and adult brain tumors. Likewise, elucidating the genetic alterations in brain tumors may yield new insights into brain development. Achieving significant advances in the diagnosis, prognosis, therapy, and prevention of brain tumors requires unraveling and understanding many aspects of the cellular and molecular biology of brain tumors and their interactions with normal brain elements. These advances must proceed along a number of different fronts and will require the interaction of several disciplines in order to achieve the greatest chance of success (see "Communication" in Section II of this report).
Many of the priorities generated by the breakout sessions of the BT-PRG overlapped, particularly those concerning needed resources (see Section II). The highest scientific priorities in basic biology identified by such overlap are as follows:
• Understand the complex biology of brain tumors, both primary and metastatic, and their interaction with normal brain elements as they relate to oncogenesis, progression, tumor cell dispersal, and heterogeneity.
-- Define the genetic changes and molecular pathways involved in brain tumor initiation and maintenance.
-- Characterize the interactions of brain tumor cells with the normal brain. • Provide a detailed molecular classification of the cells of origin for distinct tumor types and define their lineage associations, as well as the signal transduction pathways that regulate cell fate and the mechanisms by which the local environment of the brain influences cell migration and differentiation.
• Understand genotypic influences on phenotypic behavior, tumor type, age at onset, anatomical position, cell of origin, and cellular biology.
• Isolate the genes that predispose to human brain tumors and understand their relationship to the genes that regulate normal development.
• Identify the genes that regulate patients' responses to chemotherapy and radiotherapy and those that mediate tumor chemoresistance and radioresistance.
• Characterize both central nervous system and systemic immune responses in patients with brain tumors.
• Understand the blood-brain barrier and its regulation.
• Understand the mechanisms underlying the spread and establishment of metastases in the central nervous system.
Epidemiology
Little is known about the epidemiology of brain tumors. Germ line mutations (familial brain tumor syndromes) account for no more than 7% of patients. The only unequivocally established risk factors for nonfamilial brain tumors--therapeutic irradiation to the brain and chronic immunosuppression (e.g., AIDS)--are also infrequent causes of brain tumors. Other suggested etiologies, such as nonionizing radiation (e.g., from cellular telephones or high-tension wires), viral agents, household chemicals, or foods, have not been established as causal. In addition, little is known about the interaction of genetic factors and environmental toxins in the genesis of brain tumors.
Because identification of the risk factors for brain tumors may aid prevention and suggest effective treatments, high-quality epidemiological studies are extremely important. Factors that inhibit epidemiological studies include the relatively small number of patients affected by brain tumors and the large number of histopathological types of these tumors. These factors complicate the design of research protocols and limit the statistical power of the data collected. In addition, existing tumor registries are neither linked nor structured to facilitate the collection of large numbers of samples for meaningful epidemiological research. Important epidemiological scientific priorities, therefore, include the following:
• Support the linking of existing databases to provide larger numbers of samples for epidemiological studies.
• Expand and enhance databases to include all primary brain and spinal tumors--malignant and nonmalignant, adult and pediatric--and to have the flexibility to accommodate new histological and molecular classifications of tumors.
• Develop epidemiological studies of patients' susceptibility to the toxic effects of current treatment modalities and investigate risk and protective factors with study designs that incorporate biological measures.
• Use validated animal models (see "Models," Section II) to study the potential causal factors of brain tumors and of treatment-induced neurotoxicity.
Detection and Diagnosis
Because brain tumors are an extraordinarily heterogeneous group of lesions, accurate diagnosis is essential to proper management. Current imaging techniques provide a sensitive means for delineating the anatomical features of brain tumors but have not provided an effective means for early detection. Early detection could also be complicated by the ethical problems created by presymptomatic diagnosis of tumors for which there may not be effective treatment, and in an organ whose proper function is essential to quality of life. Nonetheless, early detection of brain neoplasms, particularly in the pediatric population, where these lesions are often treatable, could be facilitated by appropriate education of pediatricians, parents, school officials, and other caregivers.
The diagnosis of brain tumors is currently based on histological examination of brain tumor tissues after radiological characterization and surgical biopsy. These approaches are successful in classifying and grading most cases, but in many situations they do not allow accurate prediction of therapeutic responses or of prognosis. The situation may be further complicated by the small size of some diagnostic biopsy samples. There is therefore a critical need to improve the diagnosis of brain tumors in order both to improve current therapeutic management strategies and to form a basis for the evaluation of novel approaches.
The ability to characterize tumors comprehensively at the molecular level raises the possibility that diagnosis could be based on molecular profiling, either alone or with histological examination, rather than on histological phenotype alone. Once such techniques become possible and practical, molecular profiling could be accomplished by tissue analysis or imaging. In the future, molecular markers could also form the basis for screening at-risk individuals or populations. In light of such possibilities, the following priorities in the detection and diagnosis of brain tumors were identified:
• Develop a molecular- and imaging-based classification scheme for brain tumors that can be used to predict tumor behavior and to guide treatment decisions more accurately and objectively than is possible with current histopathological methods.
• Develop techniques that can reliably detect brain injury related to tumor or treatment and use such techniques to assess the efficacy of neuroprotective interventions.
Treatment
Treatment options for patients with brain tumors have been limited and, for most types of tumors, have provided only modest benefits. Some of the likely reasons for these limitations (see "Introduction") include the unique structural and physiological aspects of the central nervous system, especially its vulnerability to damage from many therapies as well as from neoplastic processes themselves. Research in the treatment of brain tumors has been hampered by the lack of clinically predictive model systems; by a minimal understanding, until quite recently, of fundamental tumor biology; and by a narrow range of available therapeutic agents for testing that have had little expected specificity for brain tumors. The major challenge for the future is to develop more effective techniques to treat brain tumors without damaging the brain.
Marked progress is currently being made in dissecting the molecular mechanisms of neoplasia in the brain and elsewhere. These advances are enabling the rapid identification of relevant molecular targets, and the result is a vast array of potential therapeutic approaches and agents in the development pipeline. At the same time, advances in neuroimaging are raising the tantalizing possibility of clinically assessing the capacity of an agent to alter its intended target. It therefore seems reasonable to expect an improved rate of success in research on the treatment of brain tumors. Because the special characteristics of these tumors will continue to present problems and challenges, however, the following priorities were identified:
• Facilitate the development of novel therapeutic agents and approaches for adult and pediatric brain tumors. These approaches should include, but not be limited to, chemotherapeutic, immunologic, antiangiogenic, genetic, and viral agents.
• Increase knowledge about the mechanisms of existing therapies for both adult and pediatric brain tumors.
• Improve the therapeutic index of new agents that are specifically relevant to the central nervous system.
• Enhance the therapeutic ratio for radiation therapy for brain tumors. (Overcome radioresistance of primary brain tumors; overcome normal tissue toxicity such as necrosis/edema and functional deficits.)
• Develop novel drug targeting systems that enhance the uptake by brain tumors of small- and large-molecule diagnostic and therapeutic agents.
• Develop clinical consortia for immunotherapy that are similar to those for radiation and chemotherapy.
• Develop therapies that are less toxic than existing therapies to both the mature and the immature nervous system.
Outcomes
Traditional outcome measurements used in brain tumor studies have included overall and recurrence-free patient survival and, in some instances, radiological response to therapy. Such measurements, however, largely ignore crucial issues relating to quality of life and biological endpoints of response. These issues are of particular importance in tumors for which effective therapies may not exist and in pediatric tumors, for which effective tumor control may be associated with significant long-term morbidity. For these reasons, there is an immediate and crucial need for better measurement tools and surrogate markers to assess patient quality of life and tumor response to therapy. Such outcome markers would facilitate the assessment of neurotoxicity, thereby providing an opportunity to discard potentially neurotoxic therapies sooner. They would also facilitate more accurate assessment of therapeutic response, thereby allowing effective therapies to be continued while ineffective therapies are discontinued. The following priorities were therefore identified:
• Improve techniques for measurement of quality of life and include such measurements in all clinical trials of brain tumor.
• Refine the ability to detect response to existing therapies, such as radiation, and to novel treatments, using surrogate markers measured either by imaging or in biological fluids (e.g., serum or cerebrospinal fluid).
• Establish clinical and imaging markers of neurotoxicity from existing therapies, such as radiation, and from novel treatments.
• Extend the use of such markers to preclinical evaluations in animal models.
Brain tumors represent a unique challenge in that they affect the organ that is the essence of the "self." Furthermore, because each area of the brain serves a different but vital function, the therapy that is most effective for other cancers--surgical removal of either the entire organ or the tumor with a generous surround of normal tissue--cannot be used to cure brain tumors. Unfortunately, most brain tumors are relatively insensitive to other cancer treatment, including radiation and chemotherapy.
Coupled with the difficulty in treating brain tumors is the unique biology of the brain:
• Brain tumors occur in an organ that is enclosed in a bony canal that allows little room for growth of the tumor without compressing and damaging normal brain.
• Many brain tumors extensively invade normally functioning brain, making complete surgical removal impossible.
• In their early stages, brain tumors are protected behind a blood-brain barrier; even when this barrier is disrupted in the bulk of the tumor, infiltrating tumor cells at the growing edge remain protected.
• Disruption of the blood-brain barrier leads to edema, which the brain tolerates poorly because of the limited intracranial space and the lack of lymphatics to rid itself of the products of edema and other debris.
• The brain itself is rich in expressed genes and therefore is a fertile field for the growth of both primary tumors and metastases.
• The brain and brain tumors appear to be less susceptible to attack by the immune system than are tumors in other organs. Even the term brain tumor, which suggests a single type of tumor, can be misleading. There are a bewildering variety of central nervous system tumors; the World Health Organization lists 126. Many of these tumors are not, strictly speaking, in the brain but arise from structures intimately associated with that organ, such as tumors of the covering membranes (meningiomas) and adjacent cranial and paraspinal nerves (schwannomas). Brain tumors range from benign (most meningiomas) to highly aggressive (glioblastomas). They affect both adults and children (although the distribution of tumors varies) and are often highly resistant to treatment.
The term brain cancer is also misleading. Most cancers that arise elsewhere in the body cause damage by metastasizing to other organs (including the brain). Primary brain tumors, however, rarely metastasize, although they may widely infiltrate the nervous system. Conversely, many cancers metastasize to the brain, making metastatic brain tumors much more common than primary brain tumors.
Throughout this document, the term brain tumor is used to refer to all tumors that grow inside the skull. The issues discussed in this document, however, also extend to tumors growing within the spinal canal.
STRUCTURE AND PROCESS OF THE PRG MEETING
For the reasons described in the introduction to this report, the Brain Tumor Progress Review Group (BT-PRG) required input from participants with much more diverse expertise than was needed in previous PRGs. In addition to experts on cancer biology and genetics, the BT-PRG required expertise in neurobiology, including areas such as progenitor cells, cellular migration, and blood-brain barrier function. Clinically, expertise was required from both oncology and the clinical neurosciences, including neurosurgery and neurology. In addition, to ensure inclusion of the wide diversity of brain tumors, breakout sessions were held not only for those topics that apply to all solid tumors, including brain tumors, but also (different from other PRGs) for specific types of brain tumors (i.e., intraaxial tumors, extraaxial tumors, pediatric tumors, and metastases). A total of 16 breakout groupswere therefore convened (see box). Each participant attended three breakout sessions.
STRUCTURE OF THE BT-PRG BREAKOUT GROUPS
Basic Biology
Clinical Biology
Specific Tumors
• Models
• Cancer Biology and Etiology
• Neurobiology: Progenitor Cells
• Neurobiology: Migration and Trafficking
• Cancer Genetics
• Tumor Immunology
• Detection, Diagnosis, and Prognosis
• Epidemiology, Prevention, and Outcomes
• Imaging
• Radiation Biology
• Therapeutic Targeting: Blood-Brain Barrier, Gene Therapy, and Vascular Biology
• Treatment
• Extraaxial Tumors
• Intraaxial Tumors
• Pediatric Tumors
• Metastases
The participants in each of these 16 breakout sessions were asked to identify three important research priorities in their assigned areas. It was recognized that it might not be possible to place all of the research priorities formulated by the groups into an overall hierarchy. Although all of the priorities included in the appendices are important and meritorious, some arose in multiple breakout sessions and therefore appear to be of overarching importance. This report delineates those priorities considered by the BT-PRG to be overarching. The appendix contains the full reports of the individual breakout sessions and their priorities.
This report is divided into two sections. Section I, "Scientific Priorities," describes the overarching priorities in both the basic and the clinical sciences. These scientific research priorities are hypothesis driven. To meet them will require the scientific resources described in Section II. The resource priorities in Section II can be considered as hypothesis generating in that their development will generate hypotheses for further research.
SECTION I: SCIENTIFIC PRIORITIES
Three separate sets of breakout sessions addressed the scientific priorities. One set was devoted to fundamental biology and included sessions on models, neurobiology of progenitor cells and of cellular migration and dispersal, cancer biology, immunobiology, and cancer genetics. Another set of sessions was related to clinical issues, ranging from detection and diagnosis to treatment and outcomes. A third set was devoted to specific tumors. Several overarching scientific priorities emerged from all of these sessions and are described here.
Basic Biology
Brain tumors are phenotypically and genotypically heterogeneous. Significant gaps exist in current understanding of the molecular pathways involved in the genesis, progression, and biological and clinical behavior of brain tumors. Brain tumors are unique among human cancers because of their complex interaction with the brain itself, which greatly complicates the use of existing therapies as well as the development of novel ones.
A cardinal feature of the most common malignant brain tumors--their diffuse infiltration into the surrounding brain--presents substantial barriers to the effective delivery of therapeutic agents and increases the possibility of therapeutic toxicity to a vital organ whose function greatly affects the patient's quality of life. Other obstacles to effective therapy include the blood-brain barrier and the difficulties it creates for therapeutic delivery, as well as the relative lack of information on the unique immunological aspects of brain tumors and the cerebral environment.
The biology of brain tumors is distinct from that of many other human tumors. Although tumors are named as though their lineage were understood (e.g., astrocytoma from astrocytes), the cells of origin for most human brain tumors remain enigmatic, complicating the interpretation of data that require a comparison between brain tumor cells and their "normal" counterparts. Highlighting these issues are childhood brain tumors, especially primitive neuroectodermal tumors that arise during brain development. Insights into the normal and aberrant regulation of neurodevelopmental genes may be significant in understanding the etiology of both childhood and adult brain tumors. Likewise, elucidating the genetic alterations in brain tumors may yield new insights into brain development. Achieving significant advances in the diagnosis, prognosis, therapy, and prevention of brain tumors requires unraveling and understanding many aspects of the cellular and molecular biology of brain tumors and their interactions with normal brain elements. These advances must proceed along a number of different fronts and will require the interaction of several disciplines in order to achieve the greatest chance of success (see "Communication" in Section II of this report).
Many of the priorities generated by the breakout sessions of the BT-PRG overlapped, particularly those concerning needed resources (see Section II). The highest scientific priorities in basic biology identified by such overlap are as follows:
• Understand the complex biology of brain tumors, both primary and metastatic, and their interaction with normal brain elements as they relate to oncogenesis, progression, tumor cell dispersal, and heterogeneity.
-- Define the genetic changes and molecular pathways involved in brain tumor initiation and maintenance.
-- Characterize the interactions of brain tumor cells with the normal brain. • Provide a detailed molecular classification of the cells of origin for distinct tumor types and define their lineage associations, as well as the signal transduction pathways that regulate cell fate and the mechanisms by which the local environment of the brain influences cell migration and differentiation.
• Understand genotypic influences on phenotypic behavior, tumor type, age at onset, anatomical position, cell of origin, and cellular biology.
• Isolate the genes that predispose to human brain tumors and understand their relationship to the genes that regulate normal development.
• Identify the genes that regulate patients' responses to chemotherapy and radiotherapy and those that mediate tumor chemoresistance and radioresistance.
• Characterize both central nervous system and systemic immune responses in patients with brain tumors.
• Understand the blood-brain barrier and its regulation.
• Understand the mechanisms underlying the spread and establishment of metastases in the central nervous system.
Epidemiology
Little is known about the epidemiology of brain tumors. Germ line mutations (familial brain tumor syndromes) account for no more than 7% of patients. The only unequivocally established risk factors for nonfamilial brain tumors--therapeutic irradiation to the brain and chronic immunosuppression (e.g., AIDS)--are also infrequent causes of brain tumors. Other suggested etiologies, such as nonionizing radiation (e.g., from cellular telephones or high-tension wires), viral agents, household chemicals, or foods, have not been established as causal. In addition, little is known about the interaction of genetic factors and environmental toxins in the genesis of brain tumors.
Because identification of the risk factors for brain tumors may aid prevention and suggest effective treatments, high-quality epidemiological studies are extremely important. Factors that inhibit epidemiological studies include the relatively small number of patients affected by brain tumors and the large number of histopathological types of these tumors. These factors complicate the design of research protocols and limit the statistical power of the data collected. In addition, existing tumor registries are neither linked nor structured to facilitate the collection of large numbers of samples for meaningful epidemiological research. Important epidemiological scientific priorities, therefore, include the following:
• Support the linking of existing databases to provide larger numbers of samples for epidemiological studies.
• Expand and enhance databases to include all primary brain and spinal tumors--malignant and nonmalignant, adult and pediatric--and to have the flexibility to accommodate new histological and molecular classifications of tumors.
• Develop epidemiological studies of patients' susceptibility to the toxic effects of current treatment modalities and investigate risk and protective factors with study designs that incorporate biological measures.
• Use validated animal models (see "Models," Section II) to study the potential causal factors of brain tumors and of treatment-induced neurotoxicity.
Detection and Diagnosis
Because brain tumors are an extraordinarily heterogeneous group of lesions, accurate diagnosis is essential to proper management. Current imaging techniques provide a sensitive means for delineating the anatomical features of brain tumors but have not provided an effective means for early detection. Early detection could also be complicated by the ethical problems created by presymptomatic diagnosis of tumors for which there may not be effective treatment, and in an organ whose proper function is essential to quality of life. Nonetheless, early detection of brain neoplasms, particularly in the pediatric population, where these lesions are often treatable, could be facilitated by appropriate education of pediatricians, parents, school officials, and other caregivers.
The diagnosis of brain tumors is currently based on histological examination of brain tumor tissues after radiological characterization and surgical biopsy. These approaches are successful in classifying and grading most cases, but in many situations they do not allow accurate prediction of therapeutic responses or of prognosis. The situation may be further complicated by the small size of some diagnostic biopsy samples. There is therefore a critical need to improve the diagnosis of brain tumors in order both to improve current therapeutic management strategies and to form a basis for the evaluation of novel approaches.
The ability to characterize tumors comprehensively at the molecular level raises the possibility that diagnosis could be based on molecular profiling, either alone or with histological examination, rather than on histological phenotype alone. Once such techniques become possible and practical, molecular profiling could be accomplished by tissue analysis or imaging. In the future, molecular markers could also form the basis for screening at-risk individuals or populations. In light of such possibilities, the following priorities in the detection and diagnosis of brain tumors were identified:
• Develop a molecular- and imaging-based classification scheme for brain tumors that can be used to predict tumor behavior and to guide treatment decisions more accurately and objectively than is possible with current histopathological methods.
• Develop techniques that can reliably detect brain injury related to tumor or treatment and use such techniques to assess the efficacy of neuroprotective interventions.
Treatment
Treatment options for patients with brain tumors have been limited and, for most types of tumors, have provided only modest benefits. Some of the likely reasons for these limitations (see "Introduction") include the unique structural and physiological aspects of the central nervous system, especially its vulnerability to damage from many therapies as well as from neoplastic processes themselves. Research in the treatment of brain tumors has been hampered by the lack of clinically predictive model systems; by a minimal understanding, until quite recently, of fundamental tumor biology; and by a narrow range of available therapeutic agents for testing that have had little expected specificity for brain tumors. The major challenge for the future is to develop more effective techniques to treat brain tumors without damaging the brain.
Marked progress is currently being made in dissecting the molecular mechanisms of neoplasia in the brain and elsewhere. These advances are enabling the rapid identification of relevant molecular targets, and the result is a vast array of potential therapeutic approaches and agents in the development pipeline. At the same time, advances in neuroimaging are raising the tantalizing possibility of clinically assessing the capacity of an agent to alter its intended target. It therefore seems reasonable to expect an improved rate of success in research on the treatment of brain tumors. Because the special characteristics of these tumors will continue to present problems and challenges, however, the following priorities were identified:
• Facilitate the development of novel therapeutic agents and approaches for adult and pediatric brain tumors. These approaches should include, but not be limited to, chemotherapeutic, immunologic, antiangiogenic, genetic, and viral agents.
• Increase knowledge about the mechanisms of existing therapies for both adult and pediatric brain tumors.
• Improve the therapeutic index of new agents that are specifically relevant to the central nervous system.
• Enhance the therapeutic ratio for radiation therapy for brain tumors. (Overcome radioresistance of primary brain tumors; overcome normal tissue toxicity such as necrosis/edema and functional deficits.)
• Develop novel drug targeting systems that enhance the uptake by brain tumors of small- and large-molecule diagnostic and therapeutic agents.
• Develop clinical consortia for immunotherapy that are similar to those for radiation and chemotherapy.
• Develop therapies that are less toxic than existing therapies to both the mature and the immature nervous system.
Outcomes
Traditional outcome measurements used in brain tumor studies have included overall and recurrence-free patient survival and, in some instances, radiological response to therapy. Such measurements, however, largely ignore crucial issues relating to quality of life and biological endpoints of response. These issues are of particular importance in tumors for which effective therapies may not exist and in pediatric tumors, for which effective tumor control may be associated with significant long-term morbidity. For these reasons, there is an immediate and crucial need for better measurement tools and surrogate markers to assess patient quality of life and tumor response to therapy. Such outcome markers would facilitate the assessment of neurotoxicity, thereby providing an opportunity to discard potentially neurotoxic therapies sooner. They would also facilitate more accurate assessment of therapeutic response, thereby allowing effective therapies to be continued while ineffective therapies are discontinued. The following priorities were therefore identified:
• Improve techniques for measurement of quality of life and include such measurements in all clinical trials of brain tumor.
• Refine the ability to detect response to existing therapies, such as radiation, and to novel treatments, using surrogate markers measured either by imaging or in biological fluids (e.g., serum or cerebrospinal fluid).
• Establish clinical and imaging markers of neurotoxicity from existing therapies, such as radiation, and from novel treatments.
• Extend the use of such markers to preclinical evaluations in animal models.
Living With a Brain Tumor: Dr Peter Black’s Guide to Taking Control of Your Treatment
Peter Black, M.D., Ph.D, F.A.C.S. with Sharon Cloud Hogan
An Owl Book – Henry Holt and Company 2006
New York, New York
ISBN-13: 978-0-8050-7968-5 and ISBN-10:0-8050-7968-8
$17.00 (USA), $23.00 (Canada)
336 Pages
For those patients and carers who are scaling the rock face that is a brain tumor diagnosis, the climb can at times be arduous, fearsome and exhausting. At other times it can be exhilarating, empowering and inspiring. But the main thing is not to panic as you negotiate the steep ledges, precipices and unsure footings along the way.
From the very first page of his new book “Living With a Brain Tumor: Dr Peter Black’s Guide to Taking Control of Your Treatment”, the eminent Harvard Medical School professor of neurosurgery calms the panic that anyone would feel on hearing the words: “You’ve got a brain tumor.”
In straightforward and jargon-free language, Dr Black’s book – aimed primarily at the brain tumor patient, family and caregiver rather than medical professionals – is 336 pages’ worth of invaluable, comprehensive information including numerous aspects of the brain tumor journey.
Dr Black (with Sharon Cloud Hogan, an editor at The New England Journal of Medicine) writes with authority and expertise, but at the same time with great warmth and understanding.
He covers everything from the basics (giving an excellent explanation of the different types of brain tumors and areas of the brain) to various diagnostic tests (how they work, what they feel like, how long they take and how quickly the results are usually available) to treatment options, including a very up-to-date section on newer therapies.
There are more brain tumor treatments in the development pipeline than ever before. New agents and combinations of drugs are being examined in clinical trials. New methods of delivering those therapies are being investigated. Dr Black’s book includes quite a few of these novel approaches. He has usefully divided them into categories so that patients, families and caregivers can get a good overall impression of what areas of research are promising, including drugs that halt cell division, anti-angiogenic therapies, differentiating agents, immunotherapies, gene therapies, targeted molecular therapies and intratumoral therapies.
What’s more, Dr Black actively encourages patients to ask their doctors about emerging and experimental therapies and the possibility of joining a clinical trial. Sometimes patients might feel worried or shy about broaching these subjects. For those who need help with this, he provides a useful list of questions which can be asked of a patient’s specialist.
Information on treatment side effects, drugs for swelling, seizures and other problems is also included in the book.
One of the best features of “Living With a Brain Tumor” is the superb Appendix at the back of the book. Those who want to know more about the prevalence and incidence of brain tumors will find food for thought here. A good reading list, linked to chapter headings, is also included. The resources section of the Appendix contains a listing of over 50 centres in the United States and Canada which treat adults with brain tumors. There are nearly 200 North American centers listed in the book which treat children with brain tumors.
Contact addresses for further information about support groups, radiotherapy and chemotherapies, newer therapies and clinical trials, supportive care, wellness resources and general resources are also included. It must be said that this section is obviously aimed at those brain tumor patients who are living in America and Canada. But on the whole, the book translates very well on an international level and brain tumor patients in other countries will generally find it very relevant to their own situations. Website addresses are included for most of the listings in the Appendix, making virtual visits easy.
Dr Black has been a practicing neurosurgeon for more than 25 years. In addition to his work at Harvard Medical School as the Franc D Ingraham Professor of Neurosurgery, he is also chair of the Department of Neurosurgery at Brigham and Women’s Hospital and at Children’s Hospital in Boston. He is also chief of neurosurgical oncology at the Dana-Farber Cancer Institute. He has treated over 5,000 brain tumor patients and published over 300 professional articles on brain tumors. You might think that a book from someone so long “in the business” might have lost that personal touch and, if you’ll pardon the pun, be written in a very cut and dried manner.
Quite the contrary.
It is a measure of Dr Black’s understanding, not just of the surgical and oncological aspects of a brain tumor diagnosis, but of the emotional and social trauma attached to this disease as well, that he has included a section in his book on “Working on Wellness” and “Reasons for Hope”.
In fact, the word “hope” appears repeatedly throughout Dr Black’s guide – not in the context of false hope, but realistic hope. He admits that brain tumors are a “vicious opponent”. But he also writes: “I want people with brain tumors to know that many kinds of brain tumors are compatible with a long and productive life. If you have a brain tumor, I want you to know you are not alone. I want to get the word out that many people do survive a brain tumor for many, many years, and even with the tumors that remain difficult to treat, we’ve made promising inroads.”
Dr Black acknowledges and describes some tough issues which brain tumor patients face such as their struggle with life decisions. Should they marry? Travel? Continue to work? How much should they tell the children? How is self identity affected? How are relationships altered by a brain tumor diagnosis? One teenager he quotes asks: “After how many dates do I say that I have a brain tumor?” Dr Black writes that he has seen families torn apart by a brain tumor diagnosis but equally he has seen how the challenge has brought out the best in people and become the glue which has held families together. Dr Black devotes an entire chapter to “What a Brain Tumor Means for Me and My Family”. He pulls no punches, but with fatherly wisdom guides one through the perils and pitfalls, challenges and triumphs that people of all ages are faced with on this journey.
He has also included in his book inspirational and moving quotes not only from literary sources, but actual patients, families and caregivers. Brain tumor patient Lucy Grealy (in an excerpt taken from her book “Autobiography of a Face”, Houghton Mifflin Company, 1994) describes her ninth birthday.
“When my whole family came to visit me for my birthday, I sat in a wheelchair and gazed at them, feeling splendid. I could tell they were shocked at the sight of me. I had been an absolutely normal nine-year-old the last time they saw me, some ten days before. My older sister spoke politely to me, as did my twin sister. They’d never been polite to me before, and I knew that a chasm had opened between us. How could I explain that the way I felt now was actually better? How could they ever know where I had just come from? Suddenly, I understood the term visiting. I was in one place, they were in another, and they were only pausing. We made polite conversation about people at school, from the neighbourhood, talked about things entirely inconsequential because it wasn’t the subject that counted but the gesture of conversation itself. You could have parsed each sentence not into nouns and verbs but into signs and symbols, artificial reports from a buffer zone none of us really owned or cared to inhabit.”
As the mother of a brain tumor patient, I am finding this book invaluable in grappling with the day-to-day challenges this illness presents. In the guide’s pages I have found knowledge, reassurance, inspiration and hope. These things don’t come through intravenous drips or in blister packs or pill bottles – but they are certainly a vital part of treatment. For patients, families and caregivers they are powerful tools in dealing with a brain tumor diagnosis.
Knowledge, reassurance, inspiration and hope can be the safety ropes which stop you falling from that daunting rock face you’re climbing.
Kathy Oliver
Secretary, IBTA
London, 28 January 2007
An Owl Book – Henry Holt and Company 2006
New York, New York
ISBN-13: 978-0-8050-7968-5 and ISBN-10:0-8050-7968-8
$17.00 (USA), $23.00 (Canada)
336 Pages
For those patients and carers who are scaling the rock face that is a brain tumor diagnosis, the climb can at times be arduous, fearsome and exhausting. At other times it can be exhilarating, empowering and inspiring. But the main thing is not to panic as you negotiate the steep ledges, precipices and unsure footings along the way.
From the very first page of his new book “Living With a Brain Tumor: Dr Peter Black’s Guide to Taking Control of Your Treatment”, the eminent Harvard Medical School professor of neurosurgery calms the panic that anyone would feel on hearing the words: “You’ve got a brain tumor.”
In straightforward and jargon-free language, Dr Black’s book – aimed primarily at the brain tumor patient, family and caregiver rather than medical professionals – is 336 pages’ worth of invaluable, comprehensive information including numerous aspects of the brain tumor journey.
Dr Black (with Sharon Cloud Hogan, an editor at The New England Journal of Medicine) writes with authority and expertise, but at the same time with great warmth and understanding.
He covers everything from the basics (giving an excellent explanation of the different types of brain tumors and areas of the brain) to various diagnostic tests (how they work, what they feel like, how long they take and how quickly the results are usually available) to treatment options, including a very up-to-date section on newer therapies.
There are more brain tumor treatments in the development pipeline than ever before. New agents and combinations of drugs are being examined in clinical trials. New methods of delivering those therapies are being investigated. Dr Black’s book includes quite a few of these novel approaches. He has usefully divided them into categories so that patients, families and caregivers can get a good overall impression of what areas of research are promising, including drugs that halt cell division, anti-angiogenic therapies, differentiating agents, immunotherapies, gene therapies, targeted molecular therapies and intratumoral therapies.
What’s more, Dr Black actively encourages patients to ask their doctors about emerging and experimental therapies and the possibility of joining a clinical trial. Sometimes patients might feel worried or shy about broaching these subjects. For those who need help with this, he provides a useful list of questions which can be asked of a patient’s specialist.
Information on treatment side effects, drugs for swelling, seizures and other problems is also included in the book.
One of the best features of “Living With a Brain Tumor” is the superb Appendix at the back of the book. Those who want to know more about the prevalence and incidence of brain tumors will find food for thought here. A good reading list, linked to chapter headings, is also included. The resources section of the Appendix contains a listing of over 50 centres in the United States and Canada which treat adults with brain tumors. There are nearly 200 North American centers listed in the book which treat children with brain tumors.
Contact addresses for further information about support groups, radiotherapy and chemotherapies, newer therapies and clinical trials, supportive care, wellness resources and general resources are also included. It must be said that this section is obviously aimed at those brain tumor patients who are living in America and Canada. But on the whole, the book translates very well on an international level and brain tumor patients in other countries will generally find it very relevant to their own situations. Website addresses are included for most of the listings in the Appendix, making virtual visits easy.
Dr Black has been a practicing neurosurgeon for more than 25 years. In addition to his work at Harvard Medical School as the Franc D Ingraham Professor of Neurosurgery, he is also chair of the Department of Neurosurgery at Brigham and Women’s Hospital and at Children’s Hospital in Boston. He is also chief of neurosurgical oncology at the Dana-Farber Cancer Institute. He has treated over 5,000 brain tumor patients and published over 300 professional articles on brain tumors. You might think that a book from someone so long “in the business” might have lost that personal touch and, if you’ll pardon the pun, be written in a very cut and dried manner.
Quite the contrary.
It is a measure of Dr Black’s understanding, not just of the surgical and oncological aspects of a brain tumor diagnosis, but of the emotional and social trauma attached to this disease as well, that he has included a section in his book on “Working on Wellness” and “Reasons for Hope”.
In fact, the word “hope” appears repeatedly throughout Dr Black’s guide – not in the context of false hope, but realistic hope. He admits that brain tumors are a “vicious opponent”. But he also writes: “I want people with brain tumors to know that many kinds of brain tumors are compatible with a long and productive life. If you have a brain tumor, I want you to know you are not alone. I want to get the word out that many people do survive a brain tumor for many, many years, and even with the tumors that remain difficult to treat, we’ve made promising inroads.”
Dr Black acknowledges and describes some tough issues which brain tumor patients face such as their struggle with life decisions. Should they marry? Travel? Continue to work? How much should they tell the children? How is self identity affected? How are relationships altered by a brain tumor diagnosis? One teenager he quotes asks: “After how many dates do I say that I have a brain tumor?” Dr Black writes that he has seen families torn apart by a brain tumor diagnosis but equally he has seen how the challenge has brought out the best in people and become the glue which has held families together. Dr Black devotes an entire chapter to “What a Brain Tumor Means for Me and My Family”. He pulls no punches, but with fatherly wisdom guides one through the perils and pitfalls, challenges and triumphs that people of all ages are faced with on this journey.
He has also included in his book inspirational and moving quotes not only from literary sources, but actual patients, families and caregivers. Brain tumor patient Lucy Grealy (in an excerpt taken from her book “Autobiography of a Face”, Houghton Mifflin Company, 1994) describes her ninth birthday.
“When my whole family came to visit me for my birthday, I sat in a wheelchair and gazed at them, feeling splendid. I could tell they were shocked at the sight of me. I had been an absolutely normal nine-year-old the last time they saw me, some ten days before. My older sister spoke politely to me, as did my twin sister. They’d never been polite to me before, and I knew that a chasm had opened between us. How could I explain that the way I felt now was actually better? How could they ever know where I had just come from? Suddenly, I understood the term visiting. I was in one place, they were in another, and they were only pausing. We made polite conversation about people at school, from the neighbourhood, talked about things entirely inconsequential because it wasn’t the subject that counted but the gesture of conversation itself. You could have parsed each sentence not into nouns and verbs but into signs and symbols, artificial reports from a buffer zone none of us really owned or cared to inhabit.”
As the mother of a brain tumor patient, I am finding this book invaluable in grappling with the day-to-day challenges this illness presents. In the guide’s pages I have found knowledge, reassurance, inspiration and hope. These things don’t come through intravenous drips or in blister packs or pill bottles – but they are certainly a vital part of treatment. For patients, families and caregivers they are powerful tools in dealing with a brain tumor diagnosis.
Knowledge, reassurance, inspiration and hope can be the safety ropes which stop you falling from that daunting rock face you’re climbing.
Kathy Oliver
Secretary, IBTA
London, 28 January 2007
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