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- Mesothelin Finding Could Lead to Early Detection of Mesothelioma
- New York Attorney Calls for International Ban on Mesothelioma-Causing Asbestos
- Protein Can be Reliable for Diagnosing Malignant Mesothelioma
- Biomarker Successes Remain Elusive For Mesothelioma and Cancer Researchers
- Avastin May Not be Effective for Breast Cancer, But is Still an Option for Mesothelioma
- Options for Funding Mesothelioma Research
- Golf Outing to Raise Funds for Mesothelioma Research
- 3 Year Mesothelioma Survivor Stays Busy Raising Awareness of the Disease
- MesotheliomaHelp Website Offers Mesothelioma-Related FAQs
- CDMRP System Offers Funding Opportunity to Help Military Mesothelioma Sufferers
Thursday, May 14, 2009
One of the great questions in contemporary mesothelioma treatment is whether pleurectomy/decortication or extrapleural pneumonectomy is the more effective surgical arm for patients with malignant mesothelioma. Different surgeons hold conflicting opinions on this question, but definitive guidance is still not available to recommend one procedure over the other. In light of this situation, physicians in Germany conducted a study to investigate the specific efficacy of pleurectomy/decortication in multimodality therapy and their results compare favorably with prior studies on the efficacy of EPP and multimodal therapy.
The physicians enrolled 35 patients with histologically-confirmed pleural mesothelioma. The staging breakdown was as follow: ten patients with Stage I disease, 6 with Stage II, 17 with Stage III and 2 patients with Stage IV. 25 Patients presented with epithelioid mesothelioma.
The treatment plan of the study stipulated pleurectomy/decortication as the surgical modality, followed by four cycles of pemetrexed and cisplatin. Radiation therapy to the chest wall and mediastinum commenced four to six weeks after surgery. Of the 35 patients who started the study, 33 completed the full treatment plan. One patient died as a result of the surgery and one died as a result of chemotherapy toxicity.
The study results demonstrated overall median survival at 33.2 months. The 1-year survival rate was reported at 75%, the 2-year survival rate at 61% and the 3-year survival was reported as 43%. Due to these excellent results, the physicians concluded that pleurectomy/decortication is effective in multimodal treatments and they call for large, multi-center studies on this treatment.
The physicians presented their findings on May 3, 2009 at the 2009 European Multidisciplinary Conference in Thoracic Oncology (EMCTO).
Labels: mesothelioma, pleuralmesothelioma, surgery, treatments
posted by Joseph DiCastro at 11:35 AM
Thursday, April 30, 2009
One of the primary reasons for the greater effectiveness of contemporary cancer treatments has come from a better understanding of the biological foundations of the tumorgeneic process itself. This research has allowed scientists to develop models that better describe the growth patterns of cancer cells, which has also allowed them to develop therapies that target specific aspects of this process. However, not all forms of cancer have yet benefitted from this type of research. In the case of malignant mesothelioma, for example, much more research is still needed to better understand its developmental biology. Physicians and researchers remain hopeful that more research will lead to more effective therapies, so investigations into its biology are being conducted in labs throughout the world.
One of the active areas of this research involves the analysis of the specific chromosomal structures within mesothelioma cells. Researchers have turned their attention to the unique patterns of translocation and deletion found in these cell types so as to learn more about the genetic changes that lead to their growth. An article on this topic, co-authored by one of the true luminaries in the treatment of mesothelioma— David Sugarbaker of Brigham & Woman’s Hospital in Boston— recently appeared in the journal Interactive Cardiovascular and Thoracic Surgery.
In the article “Chromosomal Deletion in Patients with Malignant Pleural Mesothelioma,” Dr. Sugarbaker and Dr. Siyamek-Miandoab of the New York Medical College describe a study they conducted which looked at the chromosome structures of 40 patients with pleural mesothelioma. Of these patients, 22 demonstrated some evidence of deleted chromosomes, with the most common deletions listed as: 1p, 3p, 6q, 9p and 22q. Prior research has not only identified these areas as the most common among mesothelioma patients, but it has also identified 6q as the location of three separate tumor suppressor genes whose loss has been implicated in mesothelioma genesis. In this study, the authors report that deletions in 6q were the most common (15 of the 22 patients: 68%).
The authors state that greater genomic analysis of mesothelioma cells could identify new avenues of treatment for this tragic disease and they conclude their article with a call for more funding and research on this important topic.
Labels: mesothelioma, pleuralmesothelioma, treatments
posted by Joseph DiCastro at 10:15 AM
Monday, March 2, 2009
Morphotek has announced the beginning of a phase II clinical trial investigating the efficacy of the monoclonal antibody MORAb-009 for the treatment of mesothelioma. The study will evaluate progression-free survival in patients with advanced pleural mesothelioma who are being receiving MORAb-009 in combination with the standard mesothelioma treatment regimen, pemetrexed + cisplatin. The study will also analyze the “safety and anti-tumor activity of MORAb-009 as determined by objective response rate.” Morphotek plans on enrolling more than eighty individuals into the study, which is being conducted at multiple treatment centers around the word.
MORAb-009 is a monoclonal antibody whose mechanism of action inhibits the expression of mesothelin, which is a cell-surface protein highly expressed in mesothelioma, pancreatic cancer and a number of other malignant conditions.
Labels: mesothelioma, pleuralmesothelioma, treatments
posted by Joseph DiCastro at 2:16 PM
Monday, February 16, 2009
Source: NIH News
The development of targeted anti-cancer medications is one of the most important areas of contemporary cancer research. Physicians hope creating agents that are able to select specific cells types over others will lead to treatments that are both more effective and that exhibit less severe side effects. This is especially important for the treatment of mesothelioma, as it remains one of the most difficult of all forms of cancer to treat effectively.
The difficulty for these therapies has always been developing an agent that can effectively differentiate normal from malignant cells. A number of articles investigating a variety of agents and targets have been proposed, but most of these studies have not yet led to the creation of such an agent. However, the results of a recent pre-clinical study conducted by researchers from the National Cancer Institute and the University of Pennsylvania School of Medicine have shown great potential for the creation of such agent.
The treatment involves genetically modifying copies of the body’s T-cells, known as the body’s “killer cells,” to target cells associated with high levels of mesothelin expression. Mesothelin is a protein that is expressed mainly by the various tissues that make up the body’s mesothelium, but it is also highly expressed in certain forms of cancer, such as pleural mesothelioma, peritoneal mesothelioma and the non-small-cell lung cancers. The NCI/UPenn researchers were able to modify T-cells to bind with these mesothelin-expressing cell types and to shrink the tumors associated with them. The study reports that mice bred to develop mesothelioma were injected with the treatment and most saw excellent results from the treatment.
The researchers note that the promising results of their study have led them to plan for human clinical trials investing this agent for the treatment of mesothelioma, and for other cancers as well.
Labels: mesothelioma, pleuralmesothelioma, treatments
posted by Joseph DiCastro at 10:46 AM
Monday, February 2, 2009
Most patients with malignant mesothelioma are only diagnosed with the disease in its later stages, when treatment options are generally limited to systemic chemotherapy. For these patients, combination therapy with pemetrexed and cisplatin is the current standard of care. This treatment has proven effective at extending survival times longer than prior mesothelioma treatments were able to, but it is still not considered a curative solution. At some point during treatment, the therapy’s efficacy breaks down and the disease eventually begins to progress again.
Physicians and researchers have experimented with a number of treatments after pemetrexed ceases being effective, but a standard “second-line therapy” has not yet been discovered. A class of chemotherapy drugs known as histone deacetylase (HDAC) inhibitors are among the latest agents to be tested for this purpose. Histones are proteins that DNA binds with in the formation of chromosomes and are important elements in the regulation of gene expression. Researchers discovered that the inhibition of histone deacetylation can lead to the expression of genes associated with tumor suppression and cell cycle arrest and this spurred the creation of HDAC inhibitors for use in chemotherapy. The FDA has already approved one agent, Vorinostat, for this purpose and another, Belinostat, is being studied as well. Lab studies on HDAC inhibition indicated it may have some anticancer benefits to people with mesothelioma so a group of researchers conducted a phase II study on the use of Belinostat for second-line therapy in patients with pleural mesothelioma. Their results recently appeared in the Journal of Thoracic Oncology, in an article entitled “Phase II Study of Belinostat (PXD101), a Histone Deacetylase Inhibitor, for Second Line Therapy of Advanced Malignant Pleural Mesothelioma.”
Belinostat and Pleural Mesothelioma – Results
The researchers enrolled 13 patients into their study of Belinostat as second-line therapy for patients with pleural mesothelioma. The primary endpoint of the study was to identify an objective response rate among this cohort of patients. The researchers identified the following as secondary endpoints: safety profile, median progression-free survival and overall survival.
None of the patients demonstrated objective tumor response to the treatment, so the researchers closed the study for lack of efficacy. They noted that Belinostat was well-tolerated in all patients and that two patients demonstrated stable disease for a period.
In the conclusion to their article the researchers noted that studies completed during their trial began to note that HDAC inhibition as single-agent therapy was not showing much overall efficacy, but that results in combination regimens were showing greater clinical benefit. Because of this, they state that even though their study did not show benefits for the use of Belinostat as single agent second-line therapy, they recommend further studies investigating the efficacy of HDAC inhibitors and other chemotherapy agents in patients with malignant mesothelioma.
Labels: chemotherapy, mesothelioma, pleuralmesothelioma, treatments
posted by Joseph DiCastro at 11:47 AM
Tuesday, January 27, 2009
Article: Surgery for Malignant Pleural Mesothelioma
Malignant mesothelioma is one of the most difficult diseases in all of medicine to manage effectively. Median survival time typically averages only 12-14 months. For patients lucky enough to receive a diagnosis in the disease’s earliest stages, median survival can sometimes be extended two or three years, but a complete cure remains impossible and the vast majority of people who are diagnosed with pleural mesothelioma or peritoneal mesothelioma will eventually die from the disease. Because of this disappointing situation, physicians and scientists all over the world are searching for more effective treatments. In some cases, this research may focus on the investigation of a novel therapeutic strategy; in other cases, it may focus on improving a current treatment modality or on comparing the effectiveness of competing modalities when a standard-of-care has not yet been established.
One of the most controversial questions in contemporary mesothelioma treatment research concerns the choice of pleurectomy/decortication (P/D) vs. extrapleural pneumonectomy (EPP) for the surgical management of pleural mesothelioma. Both of these treatments are highly invasive procedures and both are properly considered radical surgery, but there is not yet clear guidance on which surgery should be performed for what patient. EPP is considered the more invasive of the two procedures, so some physicians will perform P/D on early-stage patients and EPP on late-stage patients, but a standard does not exist which actually specifies this. In many cases, the question of procedure will be based on a physician’s personal history in treating the disease. A number of retrospective studies have been performed, but direct comparison of their results is impossible due to differences in study design, staging guidelines, reporting and a host of other factors. However, these studies are still helpful for the working physician and many doctors will look at these studies in an attempt to draw some conclusions from their findings.
In an article recently published in the Annals of Diagnostic Pathology, David Rice, MB, BCh, FRCSI, of the MD Anderson Cancer Center, summarized much of the available literature on the treatment of pleural mesothelioma and addressed the controversy of P/D vs. EPP as well. He stated that the goal of any curative surgery should be the removal of all macroscopic evidence of disease, but that the available evidence does not indicate which procedure should be the one deployed for this purpose, because neither shows any greater long-term survival when compared to the other. EPP has demonstrated better rates of local disease control than P/D has and it more readily allows the use of radiation than does pleurectomy/decortication, which are important factors in its favor. However, EPP is also associated with a greater risk of serious side effects and of treatment-related death than is pleurectomy/decortication. It is also associated with a greater likelihood of metastatic spread of the disease. Because of this situation, the choice regarding which procedure is more effective is still an open question. Dr. Rice does say, however, that should physicians be able to stop the metastasic spread of the disease, then EPP would likely lead to longer survival in patients who are able to tolerate it.
Labels: epp, mesothelioma, pd, pleuralmesothelioma, treatments
posted by Belluck & Fox at 5:39 PM
Friday, January 23, 2009
Source: Honolulu Advertiser
Dr. Haining Yang, MD, PhD, a scientist and mesothelioma specialist affiliated with the Thoracic Oncology Program at the Cancer Research Center of Hawaii, was recently awarded two research grants to study the manner in which mesothelioma develops in people. Dr. Yang received a $100,000 grant from the Mesothelioma Applied Research Foundation to study the biological events triggered by asbestos exposure that lead to the development of pleural mesothelioma and peritoneal mesothelioma. Her second grant was awarded by the Hawai’i Community Foundation’s Leahi Fund. Part of this money will be applied to a study devoted to the early detection of mesothelioma that Dr. Yang is conducting in Turkey. For reasons not yet understood, there are villages in Turkey that demonstrate mesothelioma rates far, far above national and international averages of disease genesis and Dr. Yang will be investigating some of these villages.
To learn more about Dr. Yang and the important work she is conducting on mesothelioma, please read the profile of her in the Honolulu Advertiser, “Young cancer scientist receives prestigious grant awards of $200,000.”
Labels: mesothelioma, pleuralmesothelioma
posted by Joseph DiCastro at 4:31 PM
Thursday, January 8, 2009
Combination therapy with pemetrexed and cisplatin has been the standard of care for the treatment of mesothelioma since its approval in 2004 by the US FDA. The treatment’s approval was driven by the results of a large Phase III study that demonstrated greater treatment efficacy for patients with malignant mesothelioma than any other chemotherapy treatment had previously demonstrated. The currently approved treatment regimen involves 500 mg/m2 of pemetrexed and 75 mg/m2 of cisplatin in 21-day cycles, along with folic acid and vitamin B12 supplementation to reduce the potentially toxic side effects of the main agents. The latter supplements were added to this regimen after pemetrexed and cisplatin dosing levels were finalized and because they’ve been successful in reducing side effects, a number of physicians have wondered if an increase in pemetrexed levels would still be tolerable, as well as more effective, for individual patients. Some studies have looked at higher doses of single agent pemetrexed treatment, but few have looked at increasing pemetrexed levels when still used in combination with cisplatin and vitamin supplements.
To learn more about the tolerability of increased pemetrexed levels in this context, Eli Lilly—makers of Alimta, pemetrexed’s trade name—worked with a group of researchers to discover the maximum tolerated dose (MTD) of pemetrexed, as well as the highest recommended dose of the drug. The paper describing the results of this research, “Phase I and Pharmacokinetic Study of Pemetrexed plus Cisplatin in Chemonaive Patients with Locally Advanced or Metastatic Malignant Pleural Mesothelioma or Non-Small Cell Lung Cancer,” was recently published in the journal Clinical Cancer Research.
Introduction to the Study
To discover the maximum tolerated dose and highest recommended dose of pemetrexed in combination with cisplatin and vitamin supplementation, the researchers enrolled 21 chemonaive patients with locally-advanced or metastatic cases of pleural mesothelioma or non-small cell lung cancer. 12 of these patients had non-small cell lung cancer and 9 were diagnosed with pleural mesothelioma. These 21 patients were then split into 5 different pemetrexed dosing groups: 3 patients received a dose of 500 mg/m2, 3 received 600 mg/m2 and 3 more received 700 mg/m2 doses, while 6 patients received 800 mg/m2 and the final 6 received 900 mg/m2 doses. All patients received the standard cisplatin level of 75 mg/m2.
The patients were primarily evaluated on tolerability, but part of the study also included a pharmacokinetic (PK) analysis of the body’s reaction to the drug agent. PK analysis evaluates the manner in which the drug combination is broken down by the body and then absorbed, distributed and excreted from it. Results from this type of analysis can be useful in predicting the possible effects of dose escalation on treatment efficacy.
Results & Conclusion
The study found that 900 mg/m2 was the maximum tolerated dose, but was associated with a number of grade 3 toxicities and one patient experienced a grade 4 neutropenia and later died from sepsis (this is considered a Grade 5 toxicity). None of the patients who received the 800 mg/m2 dose administration experienced any dose limiting toxicities, so the researchers concluded that—in terms of tolerability—800 mg/m2 was the highest recommended dose.
However, the authors also note that the results of their own PK analysis, as well as the results of previous PK analyses and of studies that evaluated higher doses of pemetrexed in single-agent therapy, have not shown a likelihood of increased therapeutic efficacy from a larger dosing regimen. These studies have shown that the manner in which pemetrexed is metabolized by the body shows a very similar response curve over a wide range of dosing levels, so an increase from 500 mg/m2 to 800 mg/m2 would be unlikely to be show clinical benefit to the patient. Because of these findings, the authors recommend keeping the standard dosing level of pemetrexed at 500 mg/m2 for patients with pleural mesothelioma or non-small cell lung cancer.
Labels: chemotherapy, mesothelioma, pleuralmesothelioma
posted by Joseph DiCastro at 3:18 PM
Tuesday, December 23, 2008
Source: Telegraph.co.uk
UK paper The Telegraph is a running a story on a woman named Debbie Brewer, who was diagnosed with pleural mesothelioma in November of 2006 and is being treated with a form of chemotherapy called chemoembolisation, which features a direct application of chemotherapy agents into the malignant areas. Whereas traditional chemotherapy is a systemic treatment where the drugs are injected into the blood stream and circulate throughout the body, with chemoembolisation, the drugs are delivered to the actual tumor cells through a catheter.
Chemoembolisation is more often used for cancers that feature individual tumors with distinct boundaries, as opposed to mesothelioma which is most often characterized by a diffuse spread of malignant cells throughout a surface area. However, for Debbie Brewer, the treatment has been totally effective: the oncologists at the University Clinic in Frankfurt, Germany, the center where she has been treated, have declared her in remission. Because of the success in treating her disease, Debbie is spending Christmas with her family.
Original Title: “Pioneering treatment enables cancer sufferer to spend Christmas with family”
Labels: chemotherapy, mesothelioma, pleuralmesothelioma, treatments
posted by Joseph DiCastro at 10:16 AM
Monday, December 22, 2008
Source: Journal of Occupational Medicine and Toxicology
Difficulties in the long term management of malignant mesothelioma are one of the most common topics covered on this site. Even as recent years have seen improvements in our ability to treat patients with pleural mesothelioma and peritoneal mesothelioma, the disease remains without a cure and median survival times are still much too short. This situation has spurred physicians and researchers throughout the world to investigate novel therapeutic options using a number of different agents and modalities. Some of these studies have identified possibly new avenues of treatment, while others have confirmed a similar lack of efficacy as to the standard therapies. In all cases, however, research into creating more effective mesothelioma treatment options continues all over the world.
A paper describing the results of a new chemotherapy regimen was recently published in the Journal of Occupational Medicine and Toxicology. The study under discussion was conducted by researchers from Germany who were investigating the efficacy of chemotherapy involving oxaliplatin monotherapy or oxaliplatin in combination with gemcitabine in patients with pleural mesothelioma who had previously been treated with pemetrexed and a platinum agent.
The study enrolled 29 patients between February 2005 and September 2007 and analyzed their performance along a number of axes, including: response rate, disease control rate, overall survival, time to progression, progression-free survival, time to treatment failure and toxicity.
The authors report survival median survival from the start of treatment at just over 24 weeks (24.3), with overall survival for the patients from original diagnosis at almost 72 weeks (71.7). They also report median time to progression at 9.3 weeks. The article reports that 13 of 29 patients experienced a partial response or stable disease, for a disease control rate of 44.8%, while 55.2% of patients (16 of 29) experienced progressive disease. Toxicity was well managed, with no Grade 4 toxicities noted in the patient cohort.
With a disease control rate of nearly 45% and no grade high level toxicities reported, the authors conclude that until more data on alternative treatments is available oxaliplatin in combination with gemcitabine should be considered an option for patients with relapsed pleural mesothelioma.
Labels: chemotherapy, mesothelioma, pleuralmesothelioma, treatments
posted by Joseph DiCastro at 4:40 PM
Friday, December 12, 2008
Radiological imaging techniques, such as CT (computed tomography) and MRI (magnetic resonance imaging), are some of the most important technologies used in the diagnosis of most forms of cancer, including malignant mesothelioma, because they allow the visualization of the underlying malignancy without the need for invasive biopsy techniques. However, mesothelioma’s unique morphological presentation can complicate these technologies’ ability to accurately determine the existence and extent of the disease’s infiltration of a person’s organs and tissue structures. Most forms of cancers present as individually identifiable tumors with clear borders and boundaries, so their presence within human tissue can often be identified by means of images alone. Mesothelioma’s typical presentation is quite different. Instead of a single tumor with clear boundaries, pleural mesothelioma and peritoneal mesothelioma are most often characterized by the diffuse spread of malignant tissue along the surfaces of large tissue areas, making a precise demarcation between malignant and non-malignant areas quite difficult. As is so often the case with this tragic disease, the accurate interpretation of these scans usually requires a specialist-in this case, a radiologist-with previous experience diagnosing the disease.
As indicated above, there are a number of different imaging technologies that can be deployed for a mesothelioma diagnosis. The different technologies have their own strengths and weaknesses and some are indicated for mainly diagnostic purposes and others are most commonly used to determine disease stage.
The most commonly used imaging technology in all of medicine is the x-ray, which is also the oldest of the technologies. The x-ray was developed for medical use in 1895, by the German physics professor Wilhelm Conrad Röntgen. X-rays have a number of important diagnostic functions, but they are rarely effective in the determination of mesothelioma. The principle reason for this ineffectiveness lies in x-ray’s poor visualization of soft tissue: the technology simply does not have the necessary resolution to accurately identify the manner in which mesothelioma invades tissue structures. An x-ray may indicate the presence of a pleural abnormality, but it will not be able to identify this abnormality as mesothelioma.
CT (computed tomography) is generally considered the “gold-standard” in the diagnosis of the disease, and is the most commonly prescribed imaging technology for this purpose, because of its ability to visualize the structure of the malignancy. Should an x-ray show some kind of abnormal shadowing, or should a physician suspect mesothelioma due to a patient’s symptoms and/or known exposures to asbestos, the patient will likely undergo a computed tomography scan of the suspected area. If the physician suspects pleural mesothelioma, this will likely be a chest CT; if the physician suspects peritoneal mesothelioma, this will be an abdominal scan. In many cases though, the physician may suspect an altogether different disorder and will be presented with a set of images indicative of mesothelioma.
CT, however, presents its own diagnostic limitations in the determination of mesothelioma. CT is often enough to visualize the presence of the disease, but the technology has known problems in soft tissue contrast, so the full extent of tissue infiltration can be difficult to determine. In these cases, MRI (magnetic resonance imaging) will be deployed, which features a much more accurate determination of tissue infiltration. For most diagnostic cases, CT will be fine, but MRI is especially useful when planning for surgery because it allows the surgeon more accurate images when planning his or her resection strategy.
Another common imaging technology used in mesothelioma treatment is positron emission tomography, known as PET, which is an altogether different technology than CT or MRI. Whereas those technologies are used for their ability to visualize local tissue structures, PET is most commonly used in the staging of the disease to determine if the disease has spread beyond local areas and metastasized to distant areas of the body. If PET determines the presence of distant tumors, the patient will be immediately upstaged and considered to have Stage IV disease, which means he or she will not be eligible for radical surgeries and aggressive treatment modalities. This is an important determination because the mesothelioma treatments that are most associated with enhanced survival are radical and invasive procedures and patients with late stage disease should be treated palliatively and spared the burdens of these aggressive techniques.
CT, MRI and PET are the most common imaging technologies used in the diagnosis and treatment of all forms of malignant mesothelioma. Much research is being conducted on combined modality PET/CT, which is a technology that precisely aligns the two imaging technologies and keeps their results synchronized, but it has not yet been made a standard technology in the diagnosis of the disease.
Labels: diagnosis, mesothelioma, peritonealmesothelioma, pleuralmesothelioma
posted by Joseph DiCastro at 10:41 PM
Thursday, December 4, 2008
Source: Internal Medicine
Malignant mesothelioma typically presents with a unique morphological pattern that complicates the use of radiological imaging in the definitive determination of a diagnosis or the evaluation of treatment response. Unlike most solid tumors that present as (generally) spherical masses with clear boundaries between malignant and non-malignant tissue, mesothelioma’s natural growth behavior is characterized by the diffuse spread of cancerous cells along the surfaces of tissue structures, where the malignancy co-mingles and invades adjacent structures in a way that makes determining the boundaries between non-cancerous and cancerous tissues more difficult than it is for other forms of cancer. CT is still the imaging “gold standard” among mesothelioma physicians, but more accurate and efficient procedures and technologies are regularly being evaluated for this purpose.
One such technology, FDG-PET (fluorodeoxyglucose positron emission tomography) has shown promise for similar purposes among other forms of cancer, but its specific use in the evaluation of treatment response for pleural mesothelioma has not received wide study. PET has a common use in mesothelioma treatment and diagnosis for staging purposes and to examine the body for distant metastases, but its value as an evaluative technology is still in question.
An article on the use of FDG-PET for this purpose has recently been published in the journal Internal Medicine. The authors of the article provide a case report of a man with pleural mesothelioma who they enrolled in study that examined FDG-PET’s ability to evaluate treatment response.
Case Report
In the article “Monitoring of Chemotherapy Response in Malignant Pleural Mesothelioma Using Fluorodeoxyglucose Positron Emission Tomography,” the researchers, all from Japan, describe the presentation of a 56 year-old man with a massive pleural effusion on his right side, who, apart from the dyspnea produced by the effusion, otherwise appeared relatively healthy. After a number of tests, his physicians diagnosed pleural mesothelioma, biphasic subtype, from a biopsy of tissue from his chest well. The physicians started him on a chemotherapy regimen of cisplatin and irinotecan, but after he developed severe diarrhea due to the later agent, he was switched to a regimen involving cisplatin and docetaxel. The man completed this second course of therapy.
He demonstrated a 90 day period of progression-free disease and survived for 320 days, post-chemotherapy.
Overview of Study
When the man presented, the Osaka City University Hospital was involved in a small scale study evaluating the functional use of FDG-PET for patients with pleural mesothelioma. Patients who were enrolled received CT and FDG-PET scans before the start of chemotherapy, between the first and second courses, and then after the second course. The researchers compared the findings of the CT scan, which provided the baseline evaluation of tumor location and extent, with the findings of the PET scan to determine if they could correlate the metabolic response measured by PET to the objective changes in the tumor reflected in the CT scan.
For the man in the case report, they were able to correlate the findings between CT and PET in response to his chemotherapy. The scans were able to relate tumor volume (CT) and metabolic response (PET) from the initial evaluation and to show a related reduction in both findings after the first round of chemo was able to slow the progression of the cancer, as well as a subsequent increase in both after the second course of chemotherapy failed to contain it.
Conclusion
The authors conclude their article with a review of the relevant literature on PET-FDG’s functional efficacy. They note that not enough study has been conducted with large enough study populations to fully determine FDG-PET’s value as an evaluative technology and they note a number of problems and other contra-indications of its use. However, they do note that their findings suggest a possible role for its use in response evaluation for patients with pleural mesothelioma.
Labels: chemotherapy, CT, imaging, mesothelioma, PET, pleuralmesothelioma
posted by Belluck & Fox at 4:55 PM
Wednesday, December 3, 2008
Source: American Journal of Clinical Pathology
Preoperative histologic assessment of mesothelioma tissue is one of the primary means by which mesothelioma specialists develop individualized treatment plans. It is commonly known that patients who present with epithelioid mesothelioma typically demonstrate better treatment response and longer survival times than do patients who present with sarcomatoid mesothelioma, so histological analysis is used to determine which patients will be treated with aggressive therapies and which patients will be treated more palliatively. However, a number of recent studies have noted that post-operative assessment of resected tissue is increasingly reclassifying the pre-op histological diagnosis so the value of determining mesothelioma treatment plans based on this preoperative prognosis is increasingly being called into question.
A group of researchers from the MD Anderson Cancer Center at the University of Texas have recently published the results of a small-scale study that looked at the value of preoperative histological assessment and its relationship to a final histological determination made after surgery. While their findings reinforced the notion that sarcomatoid mesothelioma is associated with a worse treatment response, they also showed a very high number of histological reclassifications and called for more study into this question.
Overview of the Study
The researches analyzed the results of 56 patients with confirmed pleural mesothelioma who underwent extrapleural pneumonectomy. The median age of this cohort was 61 years old. There were 50 males and 6 females. Preoperative staging identified 1 case of Stage I disease, 6 cases of Stage II disease, 33 cases of Stage III disease and 14 Stage IV cases. Preoperative histological analysis identified 37 cases of epithelioid mesothelioma, 9 sarcomatoid cases, 6 cases of biphasic mesothelioma and 4 cases where the type was not specified.
When the researchers compared the results of the preoperative histological diagnoses with those of the post-operative analyses they found significant differences between the two. Post-op analysis showed 21 cases of epithelioid mesothelioma, down from 37; 6 cases of sarcomatoid mesothelioma, down from 9; and the biggest change: 28 cases of biphasic mesothelioma, up from just 6 in the preoperative classification. These results showed that preoperative determinations of histological subtype cannot be used in a categorical manner to determine a treatment plan.
The researchers analyzed these results in a number of other ways as well. They showed that patients with sarcomatoid mesothelioma were associated with a 3.1x greater risk of dying from disease-specific symptoms than were patients with epithelioid mesothelioma. They also showed that patients who received some form of post-operative therapy, such as radiation therapy, demonstrated a greater than 70% decreased risk of disease-specific death or recurrence than patients who did not receive post-operative therapy.
Conclusion
Due to the high number of reclassifications, the authors conclude their article by questioning the prognostic value of preoperative histological analysis. They feel that the limited scope of the tissues made available during biopsy do not provide enough sample area to determine treatment strategies, especially because so little is known about the behavior of biphasic tumors. Because of this, they call for more research into the biphasic subtype of malignant pleural mesothelioma.
Labels: diagnosis, epp, mesothelioma, pleuralmesothelioma
posted by Joseph DiCastro at 5:39 PM
Tuesday, October 21, 2008
Source: Journal of Thoracic Oncology
The development of truly curative therapeutic approaches for the treatment of mesothelioma is the “Holy Grail” of contemporary research into malignant mesothelioma. Even as improvements to the available treatments have led to extended patient survival time, the disease is still without cure. The most effective current treatments call for a multimodal therapeutic approach where eligible patients receive surgery, chemotherapy and radiotherapy. Patients treated with these therapies consistently demonstrate the longest median survival times of all pleural mesothelioma patients, but the five-year survival figures are still disappointing. Most patients, however, are not even eligible for these new therapies because the disease is most often diagnosed in its latest stages when surgery is no longer appropriate. For the majority of mesothelioma patients chemotherapy using pemetrexed and cisplatin (Alimta therapy) is the standard of care, but median survival for this patient class is only 10-15 months—an improvement over the historical efficacy in treating mesothelioma, but one that does not approach the tremendous advances that recent years have seen in the treatment of other forms of cancer.
Because of this, many researchers believe that the key to revolutionizing mesothelioma treatment will come from the development of novel therapeutic agents whose mechanisms of action target specific aspects of the disease’s underlying biological behavior. One such agent that is being examined for mesothelioma treatment is an inhibitor of Hsp90 (heat shock protein 90), a “molecular chaperone” protein whose primary function is the mediation and regulation of a large number of other proteins. Hsp90 has been implicated in the development of a number of cancers, so the development of therapeutic agents that inhibit its activity may be an important step in the battle against mesothelioma. Researchers from a number of internationally-renown mesothelioma treatment centers have recently published an article where they report on a study they conducted into the efficacy of Hsp90 inhibition for the treatment of malignant pleural mesothelioma.
Overview of the Study
Heat shock proteins are a family of “chaperone proteins” involved in the maintenance and stability of other proteins. Hsp90 is a particular member of this family whose primary importance is the regulation of proteins involved with signal transduction, the process by which a signal from outside of a cell is converted to a message that can be acted upon inside of the cell. Aberrant activity among signaling pathways is a major factor in the development of cancer and Hsp90 has been implicated as an important factor in this signaling chain.
Two important proteins related to the genesis of mesothelioma are AKT and survivin, both of which are mediated by Hsp90. The signaling pathways associated with them have been implicated in the development of cancer in general, and, in particular, their activity and overexpression can lead to anti-apoptotic effects among constituent cancer cells. Survivin levels, especially, have been implicated in relation to mesothelioma and high levels of it function as an indicator of poor prognosis for patients with the disease.
Prior studies into Hsp90 have shown that its inhibition has a positive effect on direct cancer treatment and on the sensitizing of cancer cells for traditional chemotherapy. The major agent used in these studies is 17-AAG (17-allylamino-17-demethoxygeldanamycin), a small molecule inhibitor of Hsp90. 17-AAG is being studied in phase I and phase II trials for a number of solid tumors and has shown inhibitory effects on the growth of Hodgkin lymphoma cell lines as well, but has received only limited attention in relation to mesothelioma treatment.
To investigate the efficacy of Hsp90 inhibition as a viable treatment option for malignant mesothelioma, the authors treated a series of mesothelioma cell lines with 17-AAG and then analyzed the resulting lines for evidence of cell cycle arrest and suppression of cell growth. They found strong evidence of both.
Their analysis of the treated cell lines showed cell cycle arrest during multiple cycle phases, including the G1 and G2/M phases, which led to the overall suppression of new mesothelioma cells. They also found that the 17-AAG treated cell lines induced apoptosis among mesothelioma cells, likely due to the decreased levels of AKT and survivin that they also discovered among the treated cell lines. These are exciting results for a disease that is universally fatal becuase they point to a new avenue of treatment for researchers to explore.
The authors conclude their article by noting that Hsp90 is a promising target for future treatment agents. Much more research is necessary to better understand the complex biology of mesothelioma and the specific effects that 17-AAG has on these cells, but the identification of a new treatment target is an important development nonetheless.
Labels: mesothelioma, pleuralmesothelioma, treatments
posted by Belluck & Fox at 4:55 PM
Friday, October 17, 2008
Source: European Journal of Cardio-Thoracic Surgery
Full Title: Preoperative Staging of Mesothelioma by 18F-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography/Computed Tomography Fused Imaging and Mediastinoscopy Compared to Pathological Findings After Extrapleural Pneumonectomy
Disease staging is one of the fundamental steps in the development of a treatment plan for patients with mesothelioma. Effective measurement of tumor spread and the identification of distant metastases are important indications of long-term prognosis and, therefore, are determinate conditions in deciding which patients are eligible for radical surgery and which patients will be treated less invasively. Generally speaking, patients who are considered Stage I-III for pleural mesothelioma may be acceptable for “curative” surgeries such as extrapleural pneumonectomy, while patients with Stage IV disease are excluded from these procedures and will be treated palliatively. Staging is designed to separate out patients so those in the disease’s later stages do not undergo operations that are associated with significant surgical complications and extended recovery time when their long-term prognosis is not hopeful.
Historically, however, there have been difficulties in the accurate determination of stage because of mesothelioma’s unique behavior and morphological form. Unlike most other cancers which present as an individualized tumor with clear boundaries (even if there are multiple tumors, they generally fit this same individualized pattern), pleural mesothelioma presents as a diffuse malignancy that grows along tissue surfaces, with little distinction between malignant and non-malignant areas. This can make determining the full extent of tumor infiltration difficult to properly image. CT is the standard technology in diagnostic imaging for mesothelioma and MRI can be used to supplement its results, but these technologies have known limitations in determining a number of important tumor states, including tumor involvement of the chest wall and diaphragm, as well as a fundamental inability to identify distant metastatic events or to determine lymph node status. PET can be used to identify distant metastases, but it has poor spatial resolution, so precise localization is difficult. Mediastinoscopy is used to determine the status of the mediastinal lymph nodes, but it is an invasive procedure and is limited in its ability to target all of the important lymph nodes.
Because of these difficulties, some of which are common to all cancers and some of which are specific to pleural mesothelioma, researchers have developed a number of new technologies to aid physicians in their ability to accurately diagnose and stage malignant events. One of these new systems is integrated PET/CT, which combines PET’s ability to identify distant metastases with CT’s high resolution imaging of internal anatomic structures. A number of studies on this technology’s use for mesothelioma have been published and the results have been quite promising. Continuing this researching, researchers in Denmark have recently published an article on their use of PET/CT in the preoperative staging of patients with pleural mesothelioma. In their article, “Preoperative Staging of Mesothelioma by 18F-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography/Computed Tomography Fused Imaging and Mediastinoscopy Compared to Pathological Findings After Extrapleural Pneumonectomy,” the authors demonstrate PET/CT’s advancements over CT for pre-operative staging and they recommend its greater use in the staging of mesothelioma, but they also show that it cannot replace mediastinoscopy for the analysis of nodal status.
Overview of the Study
42 patients were enrolled in the study between October 2003 and October 2006. All patients had histologically-confirmed mesothelioma, epitheloid subtype. All patients received neoadjuvant chemotherapy prior to their staging assessments, which were conducted by CT and PET/CT. The results of the scans were interpreted separately and blinded from the other. Patients whose PET/CT results indicated any non-resectable tumor infiltration of the chest wall or of structures in the mediastinum, or any evidence of distant metastases, were not given surgery, although patients whose results indicated possible N2 or N3 metastases were still referred for mediastinoscopy for histological determination of stage. If these results also showed positive N2 or N3 metastatic status, the patients did not undergo surgery.
All other patients were referred for extrapleural pneumonectomy.
The study was interested in two major topics:
- The ability of PET/CT compared to CT to detect inoperative stages of mesothelioma; and,
- The validity of PET/CT’s results for staging, when compared against mediastinoscopy and final staging determined at EPP
Results
CT vs. PET/CT for Preoperative Staging
The results of the CT vs. PET/CT analysis showed a clear benefit to PET/CT. Of the 42 patients who were screened, PET/CT discovered: T4 disease in 7 patients, while CT did not show any; 14 patients with N2 or N3 disease, while CT only showed 7 patients; and 7 cases of distant metastases, while CT, again, did not show any. These findings resulted in an “upstage migration” of 8 cases: CT disclosed only one case as Stage IV disease, while PET/CT identified nine Stage IV cases (including the one identified by CT). In total, PET/CT excluded 12 of the 42 cases as non-resectable due to T4/M1 status, while CT did not exclude any.
PET/CT vs. Mediastinoscopy
PET/CT identified 30 patients with potentially-resectable disease. Of these patients, 14 indicated possible N2/N3 status, but they were not excluded from surgical consideration without histological confirmation of the findings. All 30 patients were then referred for mediastinoscopy. 6 patients demonstrated histologically-confirmed N2 metastases, which reduced the number of patients eligible for extrapleural pneumonectomy to 24.
All of these patients then received an EPP.
PET/CT vs. Final EPP Staging Results
Of the 24 patients who underwent EPP, 2 had undiagnosed T4 disease that PET/CT missed. T-stage was lower in 1 patient, equal in 13 and higher in 10. These results led to the following stage migration: percentage of patients identified as Stage I was reduced from 63% to 21%, while Stage IV patients increased from 4% to 12%. When compared to both mediastinoscopy and EPP staging, PET/CT correctly identified a number of N-stage cases, but it was also less accurate then both: it under-staged 3 patients when compared to mediastinoscopy and 7 when compared to final staging completed during EPP.
Conclusion
Mesothelioma remains a very difficult disease to treat effectively, and only a subset of patients are eligible for the invasive procedures that are necessary to possibly extend survival times for the disease. The need for accurate staging technologies is not unique to the treatment of pleural mesothelioma, but the difficulties of the disease complicate it. CT has been used, but it has well-known limitations for mesothelioma staging. PET/CT has showed great promise in other studies and the authors of the article describing the present study conclude that PET/CT is an important advancement in the surgical staging of pleural mesothelioma, but that it doesn’t alleviate the need for invasive, yet more accurate, diagnostic techniques such as mediastinoscopy. PET/CT can improve the selection of patients for EPP, especially when compared with CT, but the authors state that more work needs to be done to develop more accurate, non-invasive techniques.
Labels: mesothelioma, pleuralmesothelioma, staging
posted by Belluck & Fox at 3:23 PM
Wednesday, October 15, 2008
Source: The Journal of Thoracic and Cardiovascular Surgery
Full Title: The Impact of Lymph Node Station on Survival in 348 Patients with Surgically Resected Malignant Pleural Mesothelioma: Implications for Revision of the American Joint Committee on Cancer Staging System
The current system for staging cases of pleural mesothelioma is based on a TNM model, where the determination of disease stage is based on the relationship between tumor status (T stage), lymph node status (N stage) and the presence or absence of distant metastases (M stage). This system was proposed in 1995, validated through a number of reports and subsequently accepted as the standard mesothelioma staging system by the American Joint Committee on Cancer Staging System, as well as by the Union Internationale Contre le Cancer.
However, a number of questions regarding its underlying classification structure have existed since it was initially proposed. Writing in the journal The Journal of Thoracic and Cardiovascular Surgery, physicians from the Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City state that the current staging system was designed to be adjusted as more and better data regarding the classification of nodal status was developed. The authors of the article note that the staging system uses the lymph node map developed for lung cancer staging, but that pleural mesothelioma may require a different pattern map because lymphatic drainage from the pleura may differ from that of the lung.
To answer these questions, as well as others regarding the nodal classification system in mesothelioma patients, the physicians from MSKCC conducted a study on patients with pleural mesothelioma who were treated at their institution and they have recently published their results in an article entitled “The Impact of Lymph Node Station on Survival in 348 Patients with Surgically Resected Malignant Pleural Mesothelioma: Implications for Revision of the American Joint Committee on Cancer Staging System.”
Overview of the Study
The staging system is only applicable to surgical patients, so the retrospective study that the physicians conducted was limited to those patients who underwent either extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D). 348 patients were finally selected for analysis. The sample population, as is common with all forms of mesothelioma, was heavily male gender with the epitheloid histological subtype. 222 patients received EPP, while 126 underwent P/D. Most patients were Stage III at time of surgery.
These patient records were analyzed on a number of fronts, including nodal status (both individual and concurrent metastases), common nodal station involvement, surgical procedures and time to survival.
Results
Overall median survival for the entire patient cohort was 15 months, with significant variations in survival when patients were analyzed for differences in nodal status, as well as histological subtype and overall stage. Patients with N0 or N1 status demonstrated a 19-month median survival time, while patients positive for N2, N2/N1 or internal thoracic node metastases demonstrated a 10-month median survival. Patients with only N2 status did not differ significantly from patients who were positive for both N2 and N1, but multiple N2 nodal stations were indicative of more restricted median survival time.
Other variations in survival were also reported: epitheloid vs. non-epitheloid histology, with non-epitheloid disease associated with worse survival; male gender vs. female gender, with men demonstrating a worse prognosis then women; Stage III/IV patients were associated with shorter survival than were Stage I/II patients.
Conclusion
In the discussion section of the article, the authors considered the importance of their findings in relation to the current staging system. Their results show that pleural mesothelioma is most likely to metastasize to N2 nodes, rather than to N1 nodes. The authors also note that because patients positive for only N1 nodes were associated with longer median survival than were patients positive any form of N2 metastases, the staging system should likely be changed to incorporate this distinction.
These results also confirmed an earlier study these physicians conducted which found that nodal metastasis is common in patients with pleural mesothelioma—nearly 50% of the patient cohort demonstrated some lymph node involvement.
Along with the differences in survival between N1 and N2 status, the results also demonstrated that metastases in multiple N2 nodal stations correlates with a worse prognosis than does N2 status in only one station. Because of this, the authors also state that the staging system could possibly be adjusted to show that multiple N2 stations reflect a higher stage than does a single N2 station.
The authors close the article with a call for larger study on the impact of nodal status on mesothelioma prognosis. Their research indicates grounds for revision of the staging system, but a larger, multicenter study would be needed to confirm these findings.
Labels: mesothelioma, pleuralmesothelioma, staging
posted by Joseph DiCastro at 3:44 PM
Friday, October 10, 2008
Source: Journal of Clinical Laboratory Analysis
Advances in our ability to diagnose mesothelioma in its earlier stages are among the most important developments in the recent fight against the disease. Along with the development of more effective treatment agents, these diagnostic advances have allowed physicians to begin treatment earlier than they have previously been able to—which is a key factor in their ability to extend patient survival and to improve issues related to a patient’s quality-of-life.
These advances in these diagnostic and treatment techniques have been the result of innovative research into the disease’s underlying biological activity. As scientists and physicians have learned more about mesothelioma, they have also been able to identify prognostic indicators that have enabled them to better identify the patient classes that will respond best to aggressive treatments and those whose disease requires a more palliative therapeutic protocol. This distinction is important because aggressive treatment protocols require highly invasive surgical techniques and a significant recovery time, so patients who present with specific disease characteristics that indicate poor treatability should not be burdened with such regimens.
The quest to identify more precise prognostic indicators for mesothelioma patients has taken many forms and the variety of research that is being conducted shows the interest that international researchers are now taking in studies of pleural mesothelioma and peritoneal mesothelioma. The latest example of this research is a paper that that has been published from researchers in Turkey. In an articled entitled “Pleural Fluid Findings as Prognostic Factors for Malignant Pleural Mesothelioma,” published in the Journal of Clinical Laboratory Analysis, they report the results of a retrospective study they conducted that analyzed the characteristics of pleural fluid in patients with pleural mesothleioma for any prognostic indicators it may contain regarding overall patient survival.
Overview of the Study
The researchers report that only one previous study had analyzed pleural fluid for its prognostic benefits, but only 26 patients had been enrolled in that study. In this study, they examined 71 patient records. There were 33 males and 38 females in the study population, with a mean age of 59 years. 23 people were smokers. Even though smoking has not been shown to have any causative affect on mesothelioma genesis, it is known to be a causative factor for a number of other cardiovascular diseases.
The patients were diagnosed by cytological or histological analysis, usually with a immunohistochemical panel that tested for combinations of calretinin, epithelial membrane antigen (EMA), thrombomodulin, HBME-1, CD15, B72.3 or carcinoembryonic antigen (CEA). Pleural fluid was analyzed for a number of specific characteristics, including pleural fluid glucose levels, lactate dehydrogenase (LDH), albumin, protein-to-serum levels and pleural fluid leukocyte counts. For their reported survival figures, the authors defined survival from date of thoracentesis to time of death.
Results
When the authors analyzed the results of the entire patient cohort, they found two independent prognostic factors that were indicative of survival: the ratio of pleural fluid to serum LDH > 1.0 and total leukocyte count in the fluid. They found a mean leukocyte count of 648+-860/mm3 for the entire cohort, but a significant increase in survival for those patients with a count of >700/mm3. When patients who used diuretics were excluded from these results, they found that fluid glucose levels also achieved statistical significance as a predictor of survival.
Conclusion
This study has indicated another set of prognostic tests that physicians can use in their determination of survival and overall prognosis for patients with pleural mesothelioma. These results will need to be independently verified before their scientific and medical value can be fully validated, but this study provides valuable information about specific biological factors involved with mesothelioma. The authors also note that the low leukocyte mean suggests a “weak inflammatory reaction against the tumor” and they suggest the “stimulation of antitumor response” is a possible treatment avenue for mesothelioma patients.
Labels: diagnosis, mesothelioma, pleuralmesothelioma
posted by Belluck & Fox at 2:51 PM
Wednesday, September 17, 2008
Full Title: Prevention of Malignant Seeding at Drain Sites after Invasive Procedures (Surgery and/or Thoracoscopy) by Hypofractionated Radiotherapy in Patients with Pleural Mesothelioma
Source: Acta Oncologica
Radiotherapy is not a general modality in the treatment of mesothelioma because the diffuse nature of the disease’s invasion pattern rarely presents a localized malignancy for the radiation to be applied to. Due to mesothelioma’s widespread appearance, the radiation would have to be delivered over a very wide area at very high doses to be effective, but this would put vital organs such as the lungs, heart and kidneys at serious risk for radiation overexposure and sickness. There is, however, a very specific use of radiotherapy that has shown some efficacy in the treatment of pleural mesothelioma and peritoneal mesothelioma: localized application of radiation to drain sites and other instrumentation sites after treatment, or other medical intervention.
Metastases to areas of surgical intervention are a common problem in the treatment of a number of different cancers, but the problem seems especially acute with mesothelioma treatments. Different studies have reported different figures on the likelihood of this occurring, but most estimates report a 20-50% of chance of surgical site metastases following treatment. Prior studies have reported on the benefits of radiotherapy to prevent tumor seeding, but the treatment is still not deployed in many cases and research into this question continues on a number of fronts.
An article has recently been published in the journal Acta Oncologica that describes the results of a study conducted by Italian physicians on their use of radiation to prevent drain site metastases. That article will be summarized in the following sections.
Overview of the Study
To investigate the efficacy of radiation therapy for the prevention of tract site metastases in patients treated for pleural mesothelioma, the authors enrolled 32 patients with histologically-confirmed mesothelioma into their study. There were 24 men and 8 women, with the average age at diagnosis listed at 64 years-old. 25 patients presented with epithelial mesothelioma, 6 with sarcomatoid mesothelioma and there was 1 case of the biphasic subtype. When the patient cohort was analyzed by stage at time of diagnosis, the authors found that 2 patients were considered Stage IA, 3 patients were considered Stage IB, 20 patients were listed as Stage II, 4 presented as Stage III and 3 others as Stage IV.
The patients underwent a variety of procedures in their diagnosis and treatment: some were palliative in their intent, while others were curative, but all involved some type of surgical intervention, from the insertion of drainage tubes to radical pleurectomy to other procedures as well. After their wounds healed from the original operations, all of the patients then received radiation therapy to each area that was treated by the procedure. 21Gy were delivered in three daily fractions to each patient. After the completion of treatment, 20 patients received some form of chemotherapy.
Patients received clinical examinations every 3-4 months during the first two years of treatment and then at 6-8 months following the initial two-year period.
Results
The authors were quite pleased with the results of their study. They report that “after a mean follow-up of 13.6 months…from the end of radiation therapy, no patient developed subcutaneous nodules in the treated area.” They also report that the therapy was well tolerated, with 11 patients developing a temporary grade I erythema, which is a reddening and swelling of the skin, but seemingly nothing more serious and no late treatment effects were seen.
The one year survival for the patient cohort was reported as 68.9% and the two-year rate was reported as 30.3%—both of which are excellent results for pleural mesothelioma patients. 17 patients (52%) died of mesothelioma due to local progression after a mean survival of 12.6 months. The authors note that 13 patients (41%) are still alive after a 13.9 month mean follow-up and two others are alive “without evidence of disease after a mean follow-up of 16.5 months.”
Conclusion
Because of the results of their study, the authors conclude that radiotherapy following therapeutic treatment of pleural mesothelioma is an effective methodology to prevent tumor seeding in areas of surgical intervention. They note that although this procedure has not yet been incorporated into standard treatment protocols, their results, as well as the results of a number of other studies, demonstrate radiation therapy’s benefits for the treatment of mesothelioma and they propose that it be deployed as a standard therapy.
Labels: mesothelioma, pleuralmesothelioma, radiation, treatments
posted by Belluck & Fox at 4:40 PM
Wednesday, September 3, 2008
Source: MolMed.com
Italian biotechnology company MolMed has recently announced that ARENEGYR, its experimental anti-cancer drug that is being investigated for the treatment of mesothelioma and a number of other cancers, has been granted orphan drug status from the US FDA. This announcement follows on a similar designation given by the EU’s pharmaceutical regulatory agency in June. Orphan drug status is available to investigational treatment agents that focus on uncommon and/or rare diseases, specifically defined as pathologies that affect less than 5 in 10,000 people, and it confers a number of benefits to the manufacturer to reward their research.
Malignant pleural mesothelioma remains a very difficult disease to treat effectively. Even though contemporary multimodal treatment protocols have increased median survival time, the disease is still not curable, so research into more effective therapeutics continues on a number of fronts. ARENEGYR represents one of the most promising avenues of contemporary research. It is a vascular targeting agent that selectively targets and binds with a tumor’s blood vessels. Its mechanism of action is governed by two major elements: NGR, a “tumor homing peptide” that allows this binding to occur, and TNF, a cytokine known for its ability to trigger apoptosis, which is the principal mechanism for ARENEGYR’s antitumor activity.
Along with its proposed use for mesothelioma treatment, ARENEGYR is being investigated in single agent therapy for the treatment of colorectal cancer, hepatocellular carcinoma and small-cell lung cancer. Molmed is also exploring ARENEGYR in combination with cisplatin for mesothelioma treatment and with Xelox for colorectal cancer.
Labels: chemotherapy, mesothelioma, pleuralmesothelioma, treatments
posted by Belluck & Fox at 10:52 AM
Friday, July 25, 2008
Source: Cancer
Even as improvements in the therapies available for mesothelioma patients have been made in recent years, the disease remains without cure. Most patients are ineligible for curative surgeries, so investigations into improving the efficacy of chemotherapy are among the most common research programs in contemporary mesothelioma treatment studies. Combination chemotherapy using pemetrexed and cisplatin (Alimta therapy) is considered first-line chemotherapy because it has demonstrated the most effective improvement in median time of survival when compared to every other chemotherapy regimen that has been tried. However, at some point during treatment, the disease always takes the upper hand and the chemo’s attempt to control the mesothelioma becomes more and more ineffective, until the drugs are no longer able to restrict the disease at all. When this happens in other cancers, one of the standard responses is for an oncologist to attempt another course of chemotherapy using different agents. This type of treatment regimen is known as second-line chemotherapy. Unfortunately, research has not yet identified an effective second-line chemotherapy regimen for pleural mesothelioma. Even as research into it continues, most results have been disappointing.
A group of renowned mesothelioma specialists has recently released the results of a study they conducted in hopes of identifying an effective second-line chemotherapy for pleural mesothelioma. Their study investigated the use of erlotinib plus bevacizumab for this purpose and their results have recently appeared in the journal Cancer.
This article is a summary of their findings.
Overview of the Study
A number of different agents and treatment regimens have been studied for the second-line use of chemotherapy in pleural mesothelioma patients. No standard has been identified though, so research into this question continues in hospitals around the world. Much of this research is being conducted based on our growing understanding of the biological foundations of the disease.
Some studies have demonstrated that vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) are important co-factors in the growth and spread of mesothelioma, so the authors of the present study investigated whether agents that inhibit these growth factors would be effective for treatment of the disease. Erlotinib is an inhibitor of EGFR, while bevacizumab inhibits VEGF. Combination therapy using these agents has been shown to have clinical efficacy as second-line treatment for non-small cell lung cancer and the physicians were hopeful that it would demonstrate similar efficacy for pleural mesothelioma.
The treatment plan under study called for the daily administration of 150 mg of erlotinib and for the administration of 15 mg/kg of bevacizumab on Day 1 of a 21-day cycle. Patients would be assessed for individual reactions to the treatment at each administration, while tumor assessment would be conducted through CT every two cycles.
Results
A total of 24 patients were included in the final study. As in most mesothelioma-related studies, the majority of those studied were older Caucasian men. There were 15 men and 9 women, with an average age of 62.5 years. 23 of the patients were white and one was Hispanic. 8 of the patients began the study with a performance status of 0 and 16 began it with PS of 1. The authors report on a number of other breakdowns and classifications as well.
The overall results of the treatment were disappointing. This chemotherapy regimen was not nearly nearly as effective for mesothelioma patients as it was for patients with non-small cell lung cancer. There were no complete or partial responses, but temporary stable disease was achieved in 12 patients. The other 12 patients had had progressive disease throughout the study. Of the 12 patients who demonstrated stable disease, 7 (of 
were from the group with the best performance status (0) and 10 (of 16) presented with epithelial mesothelioma, the form of the disease with the best prognosis.
The patient cohort demonstrated a median time-to-progression of 2.2. months and a median survival time of 5.8 months. When studied at 6- month and 12- month intervals, the time-to-progression percentages were 29% and 6%, respectively, and the survival rate percentages were 46% and 24%, respectively.
Conclusion
Because of mesothelioma’s unique behavior pattern, chemotherapy remains the most commonly deployed treatment modality and this situation is unlikely to change in the near future. Advancements in the available therapies have already led to increased survival time, but more research is needed before medicine truly turns the corner on its ability to effectively treatment pleural mesothelioma. Even though this study did not demonstrate any clinical efficacy, other studies have identified alternative agents as possible treatment candidates and results from those investigations are eagerly awaited by doctors and patients alike.
Labels: chemotherapy, mesothelioma, pleuralmesothelioma, treatments
posted by Belluck & Fox at 10:14 AM
Friday, July 11, 2008
Source: Environmental Health Perspectives
Researchers have identified a number of factors in a patient’s presentation with mesothelioma that serve as important indicators of the disease’s treatability and overall prognosis. Two of the most significant indicators are the gender of the patient and the histological subtype of the disease. In terms of gender, studies have shown time and time again that men are more likely to be given a limited prognosis than are women. Regarding histology, other studies have shown that patients who are diagnosed with epitheloid mesothelioma have a better prognosis—in some cases, a much better prognosis—than do patients who are diagnosed with either biphasic mesothelioma or sarcomatoid mesothelioma, which are the other subtypes of the disease. This information is important to mesothelioma physicians as they develop individualized treatment plans because the particular forms these indicators take will dictate one particular therapy over another.
Even as researchers have confirmed the importance of these factors in numerous trials, they have also investigated if other presentational features can function in a similar manner. A feature of particular interest to physicians involves the relationship—if any—between overall asbestos burden and treatment outcomes. Researchers have known for almost one hundred years that asbestos is the only cause of mesothelioma and that longer exposures to its dust and particulate matter, especially in occupational settings, often correlate with a greater likelihood of developing the disease, but few quantitative studies have been completed that specifically addressed the relationship between asbestos burden and treatment outcome.
In response to this, a group of researchers from some of the finest hospitals and mesothelioma research programs in the United States conducted a study that addressed this question and have recently published their findings in the journal Environmental Health Perspectives.
This article is a summary of their findings.
Overview of the Study
To address the question of the relationship between asbestos burden and mesothelioma prognosis, the study looked at a population of 128 pleural mesothelioma patients that were treated in the International Mesothelioma Program at Brigham and Women’s hospital in Boston, MA. To analyze asbestos burden, the researchers used two sets of data: self-reported data from individual patients, or data given during interviews with a trained industrial hygienist, on their occupational histories and known asbestos exposures, as well as an analysis of actual lung and tumor tissue that was removed from the patients during surgery. Reported data was available for all 128 patients, while the tissue samples were available for 83 patients.
The researchers looked at a number of factors in relation to this data, including overall asbestos exposures, actual body burden of asbestos fibers, tumor characteristics and patient demographics. Each piece of information was analyzed singularly and in combination with the other factors.
Results
In the cohort of 128 patients, there were 98 males and 38 females, with a mean age of 62 years. There were 91 cases of epitheloid mesothelioma, 33 cases of biphasic mesothelioma and 4 sarcomatoid cases. When the researchers compared the relationships between histology and gender with survival time, they again confirmed the efficacy of these two factors as important indicators of survivability: epitheloid types were associated with significantly better survival times than the other histological types, and longer survival times were demonstrated, on average, by more women than men.
To compare asbestos burden levels between individuals, the researchers used the patient’s reported data as well as data from an analysis of actual tissues (when such tissues were available). They analyzed multiple samples from resected lung tissues to determine the number of asbestos bodies per gram of tissue (ABs/g lung). The median level for the entire cohort was 158 ABs/g lung. Three individuals demonstrated a radically higher ABs/g lung figure than all other patients, so their information was not included in any of the reported statistics. The researchers also created a three-tiered structure that identified different levels of exposure and categorized those levels using the following: low burden (0-99 ABs/g lung), moderate burden (100-1099 ABs/g lung) and high burden (> 1099 ABs/g lung).
The researchers did not find an overall relationship between self-reported asbestos exposures and survival times, but they did find a relationship between older age at diagnosis of mesothelioma and self-reported exposures. An analysis of asbestos body burden levels between genders showed that men had significantly-higher median fiber levels than did women (219 vs 20 ABs/g lung), which is not surprising given the greater number of men who worked in occupations with products containing asbestos.
When the researchers compared actual tissue burden levels to survival times, they were quite surprised to learn that burden level and survivability did not progress in a linear fashion. Instead, they found that those with moderate levels of exposure survived longer, on average, than those with low or high burdens. The researchers were not able to determine the reason why the low burden group demonstrated a greater risk of shorter survival than did the moderate burden group, but they suggest that if certain individuals have a natural susceptibility to the disease then they may be susceptible to a more aggressive form of it as well.
The researchers did find, however, a significant correlation between the high asbestos burden category and shorter survival times compared to the other two levels.
Conclusion
The researchers conclude that asbestos burden could be an important factor in mesothelioma prognosis, but they state that more research studies involving larger sample populations are necessary before a final determination can be established. Mesothelioma, especially its most common form of pleural mesothelioma,is a difficult disease to manage effectively and still remains an enigma in many ways. It is through the innovative research of dedicated physicians and scientists that we’ve learned all that we currently know about this terrible disease and it is through the continual renewal of this research that we’ll learn even more.
Labels: mesothelioma, pleuralmesothelioma
posted by Belluck & Fox at 3:45 PM