Bowel Obstructions in Patients with Peritoneal Mesothelioma

Mary Hesdorffer, NPPatients with peritoneal mesothelioma appear to be at an increased risk of bowel obstructions either due to disease or perhaps as a consequence of their treatment. They can be caused by adhesions (scar tissue) and/or tumors among other predisposing conditions. Signs of a bowel obstruction include abdominal pain, cessation of bowel movement, absence of bowel sounds and inability to digest food.  Patients might also vomit fecal material.

Bowel obstructions are considered to be a medical emergency and require immediate attention. However, not all obstructions require surgery. Patients are often admitted to the hospital where they receive IV hydration. A nasal gastric tube is placed to remove stomach contents thus permitting the bowel to rest and inflammation to resolve on its own. Symptoms usually resolve 3-5 days following this intervention. In some cases it may be necessary to perform a surgical procedure to remove the mass or adhesion thus freeing the bowel to receive the necessary blood supply to remain healthy and functional. Patients with symptoms consistent with a bowel obstruction should contact their medical team immediately.

If a bowel obstruction is suspected, the patient will undergo a series of abdominal X-rays which can help diagnose an obstruction and determine if it is located in the large or small intestine.

Some symptoms of obstruction may lead to the diagnosis of an ileus, which is a functional obstruction caused by the absence of peristalsis, without a true blockage. It can be the result of narcotics or side-effect of some chemotherapeutic drugs or other administered medications. Sometimes medication to increase gastric motility can help in reversing this condition and surgery is usually not indicated in this situation. Patients are often discharged from the hospital with instructions to continue with regimens that will help to produce increased bowel evacuation.

For questions about treatment options, clinical trials, side-effect, or general support, patients are encouraged to contact Mary Hesdorffer, Nurse Practitioner. Ms. Hesdorffer is the executive director of the Mesothelioma Applied Research Foundation. She received her undergraduate degree at the College of New Rochelle in NY and went on to receive her Masters of Science at the same institution. She is fully credentialed as a nurse practitioner and has spent 16 years actively treating patients with mesothelioma.

Mary has an expertise in the development and implementation of clinical trials. She is published in peer-reviewed journals and has lectured nationally on topics pertaining to mesothelioma with particular emphasis on clinical trials as well as symptom and disease management.

Mary is a strong voice in urging increased transparency to the medical and legal issues surrounding mesothelioma with a strong emphasis on ethics.

She is passionate in her commitment to the treatment and management of this disease and hopes to increase awareness of the need to advance the science that will lead to a cure. She is available via phone or email to assist patients and caregivers as they regain control after being thrust into the chaos of this disease.

The Journey of a Mesothelioma Research Study

When patients and their families need help following a diagnosis or throughout treatment, the Meso Foundation is there for them – day or night.

Researcher

But getting patients and their families through the immediate treatment is only one side of tackling this disease. At the Meso Foundation, we believe that research into new treatments is fundamental to eradicating mesothelioma and the suffering caused by it. In fact, our mission statement emphasizes that the Foundation must “fund the highest quality and most promising meso research projects from around the world through rigorous peer review.”

Yesterday, the Meso Foundation released the important news that, this year, researchers from across the world submitted 48 proposals for funding (22 applications were from international applicants). In the next week, we will divide the number of submitted proposals among our Science Advisory Board (SAB) members and assign approximately 7 to 10 proposals to each reviewer, and 2 to 3 reviewers to each proposal.

Our SAB is made up of scientists and doctors from around the world, who have devoted their lifework to researching mesothelioma, making them the peers of our applicants, thus making our review a peer review.

We placed the adjective “rigorous” into the sentence describing our peer review, because it truly is.  The review process consists of scoring and critiquing each and every application submitted. Below are a few examples of the detailed questions each reviewer is asked when reviewing a proposal.

  • Does the project address an important problem or a critical barrier to progress in the field?
  • How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
  • Are the PD/PIs, collaborators, and other researchers well suited to the project?
  • Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions?
  • Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project?
  • Will the scientific environment in which the work will be done contribute to the probability of success?

The reviewers must then score each proposal according to these questions, on a scale of 9 to 1, with 1 being the highest possible score. In September, these scores will be collected and the proposals ranked accordingly. Only the top half of the total number of proposals will pass this stage and move to the next, where they will be scrutinized further in depth.

At this point, we select SAB members who are experts in the fields of those applicants whose projects have advanced. This ensures that the proposals are evaluated by someone who can speak to the plausibility and soundness of the hypothesis submitted, which, in turn, ensures that our funding be awarded to the most promising projects.

Following the second round, the proposals are once again scored and ranked. Based on this line-up, each remaining application is opened for discussion by the entire SAB. We hold a conference-call in November to facilitate this discussion and we come away with a solid list of top 10 projects. This list is presented in January to the Board of Directors, which selects proposals for funding. This decision is based on the critiques and ranking received from the SAB, and the financial capability of the Foundation.

At the end of this process, an approved application will have moved through three review cycles, be assessed by no less than 6 SAB members, be scrutinized by at least one expert within its specific field, and approved by the two governing bodies of the organization.

This is, no doubt, a relatively long and labor-intensive process, but it is a necessary one to make sure that the limited funds available for research are spent responsibly only on the most promising and the highest quality studies. As a nonprofit organization, we have an obligation to our patients, constituents and donors to make the most of their donations and support, and with this review model, we believe to fulfill and exceed all expectations.

EPHB2 as a New Treatment Target for Mesothelioma

MesoSym-0150_smallLast week, the Journal of Thoracic Oncology published the results of a study looking into the overexpression of the ephrin B2 receptor (EPHB2) in patients with mesothelioma. The researchers at the New York University Langone Medical Center observed that EPHB2 is overexpressed in all malignant mesothelioma cell lines, but not in benign mesothelial cells. In addition, they found that silencing this receptor resulted in a significant increase in certain processes responsible for naturally ridding the body of old and defective cells (including cancerous ones).

The team of researchers who worked on this study includes Dr. Harvey Pass, one of the founders and a former board member of the Mesothelioma Applied Research Foundation. Dr. Pass has been a leader in the field of mesothelioma and a vocal advocate for mesothelioma patients.

“The mesothelioma community is looking for novel targets for therapy, and the data on the ephrins may provide an opportunity for this,” said Dr. Pass. “Certainly we also must expand our findings to elucidate the prognostic and predictive characteristics of this important pathway,” he added.

Support future research efforts. Donate to the Mesothelioma Applied Research Foundation today.

Personalized Medicine and Mesothelioma – Are We There Yet?

personalized_medicine_mesothelioma

Personalized medicine is the ability to select a biologic target and direct therapy against this target.  It is associated with improved outcomes in a number of tumor types. The most startling was the development of Gleevec which targets CKit in gastrointestinal stromal tumors. The field has since grown by leaps and bounds. We are making progress in mesothelioma, too.

An example of what I’m talking about is displayed in the presentation made by one of our grant recipients, Liang-Chuan (Steve) Wang, Ph.D., at our International Symposium on Malignant Mesothelioma.

In his presentation of his Foundation-funded grant, Dr. Wang and his colleagues at UPenn identified a gene that may be responsible for chemotherapy resistance in mesothelioma patients to Pemetrexed (Alimta) and cisplatin. As per Dr. Wang, this may identify a group of patients who may need higher doses or longer duration of therapy or perhaps should be encouraged to try new drugs. This is step one and Dr. Wang has assured us that he will continue to work on the concept and in the future hopes that it will lead to a clinical trial.

Another example is the work currently underway to exploit mesothelin as a target and way into the malignant cell. Many of you have met patients at our symposium who have benefited from some of these trials and I remain excited and committed to stewarding patients through the clinical trials system to ensure that they know of all opportunities to participate in cutting edge research. Please take a moment to visit the research section on our website to see how the Meso Foundation has funded grants that have laid the groundwork upon which much of what you read about in mesothelioma news has been built upon.

To further advance our ability to get to the point of personalized medicine the Foundation will continue to foster communication among clinician, basic scientists, pathologists and members of biotech and pharmaceutical companies to disseminate information, as well as fund the work that will take us to the next level. Early on, we partnered with Dr. Mike Becich to ensure that the Mesothelioma Virtual Tissue Bank became a reality and we are proud to say that our efforts have paid off. Mesothelioma researchers now have access to mesothelioma tissue to conduct their experiments and further their scientific endeavors.

Update from The American Society of Clinical Oncology (ASCO) Annual Meeting

By Lee Krug, MD, Memorial Sloan-Kettering Cancer Center

ASCO-2013_1The American Society of Clinical Oncology meeting was held from June 1-4 in Chicago. This is the largest oncology meeting each year with around 30,000 attendees from all over the globe who congregate to discuss the latest research in all cancer types. I thought I would summarize a few of the presentations that were made regarding mesothelioma.

Accelerated hypofractionated hemithoracic intensity modulated radiation therapy followed by extrapleural pneumonectomy for malignant pleural mesothelioma (IMRT)

This study was presented by Dr. Marc de Perrot from Toronto, a member of our Science Advisory Board. In this approach, patients with early stage mesothelioma are treated first with high dose radiation over one week, and then, after one week of rest, patients then undergo an extrapleural pneumonectomy (EPP). If patients were found to have mediastinal lymph nodes at the time of surgery, they were planned to get chemotherapy afterward. This was a select group of patients who participated since only 18% of the patients with mesothelioma seen at the center over 4 years were enrolled on this study. Amazingly, the complications after the surgery were not more than expected, though one patient did die of an infection. Furthermore, the survival rates were quite promising; for patients with epithelioid subtype, 85% were predicted to be alive after 3 years. This is a high risk, aggressive treatment modality appropriate for only a select group of patients, and more follow up is needed. However, the excellent survival results are notable.

Randomized phase II study adding axitinib to pemetrexed-cisplatin in patients with malignant pleural mesothelioma

This was a trial conducted at a single institution in the Netherlands.  The researchers were aiming to find a drug that would improve the results of standard Pemetrexed (Alimta) and cisplatin chemotherapy. In this study, another drug called axitinib was added to that chemotherapy combination. Axitinib is an oral drug that blocks the vascular endothelial growth factor receptor (VEGFR) which is responsible for the formation of new blood supply to feed the tumor, which contributes to tumor growth. Patients were placed in two groups, one-third receiving treatment with pemetrexed and cisplatin alone, and two-thirds receiving the same chemotherapy plus axitinib. Patients received three cycle of therapy, and then underwent a pleurectomy (PD). The rate of tumor shrinkage and survival times were no different with the addition of axitinib, but the trial was quite small with only 31 patients in total, so it is difficult to draw definitive conclusions.

Phase I study of cediranib in combination with cisplatin and pemetrexed in chemonaive patients with malignant pleural mesothelioma

Dr. Anne Tsao from MD Anderson (another member of our Science Advisory Board) presented the results of this study on behalf of the Southwest Oncology Group. This study had a similar goal, to find a drug that could be added to standard chemotherapy. Like axitinib, cederinib is a pill that blocks the VEGF receptor, but it also blocks another growth factor called platelet derived growth factor receptor (PDGFR).  This study was designed to determine the side effects of that treatment and find the best dose. Twenty patients received the combination, and two doses of cederinib were tested. Patients received 6 rounds of chemotherapy plus cederinib, and then stayed on cederinib as a maintenance therapy after that. At the higher dose, two patients had severe diarrhea, two had debilitating fatigue, and one had confusion, so the lower dose was chosen for further study. Although the number of patients with tumor shrinkage was not impressive, the time before the cancer grew again was much longer than usual. A larger study is now ongoing in which patients are randomized, some receiving chemotherapy alone and some with chemotherapy plus cederinib.

Sensitivity of malignant mesothelioma lacking Merlin to the FAK inhibitor VS-6063: Evaluation of merlin/NF2 status in clinical samples

One of the genes that is commonly mutated in mesothelioma tumors is NF2 “(neurofibromin 2) This gene makes a protein called Merlin. Merlin sends growth signals inside the cancer cell and one of the proteins it interacts with is focal adhesion kinase (FAK). This abstract reported on experiments in the laboratory. The researchers treated mesothelioma cancer cells and also tumors in mice with a drug that blocks FAK called VS-6063. The treatment worked best in tumor cells that had NF2 mutations supporting their hypothesis. They have used this information to plan a large randomized trial with VS-6063 that is set to start this summer. Patients who have completed initial treatment with chemotherapy will be randomized to receive VS-6063 or placebo, to see if this drug delays the time before the cancer will start to grow again.