The Blog

By Patricia Kirk

An international roster of distinguished Mesothelioma (MPM) experts came together on Saturday, May 18, in Santa Monica, Calif., to discuss their latest research on lung-sparing therapies for MPM, a rare form of cancer that usually results from exposure to asbestos and commonly affects the pleura, or outer lining of the lungs, and chest wall.

Hosted by the Pacific Heart, Lung and Blood Institute and UCLA, the 3^rd Annual International Symposium on Lung-Sparing Therapies for Malignant Pleural Mesothelioma focused on research aimed at preserving vital lung function in mesothelioma patients. Presentations included the latest surgical techniques for removal of cancerous tumors and adjunct techniques and therapies to kill residual cancer cells following surgery and stop tumor growth.

A long-time advocate for lung-sparing pleurectomy/descortication surgery, Robert B. Cameron, MD, FACS, Director of the UCLA Mesothelioma Comprehensive Research Program and Chief of Thoracic Surgery at the West Los Angeles VA Medical Center, opened the symposium with a presentation on timing of surgical treatment and techniques for safely removing tumors in patients with sarcomatoid-type mesothelioma. He noted that 10% to 15% of MPM cases involve sarcomatoid tumors, which are characteristically a sarcoma and involve a mesothelioma pseudocapsule (PC). “PC makes the surgery possible, but also makes surgery incomplete,” Dr. Camerson said, explaining that unlike epitheliod MPM, which remains localized, this cancer metastasizes quickly to other organs and tissues.

Joseph S. Friedberg, MD, BASc, Associate Professor and thoracic surgeon at the University of Pennsylvania, Hospital of Pennsylvania, Presbyterian Medical Center and Philadelphia VA Medical Center, presented a promising new photodynamic therapy (PDT) that uses light to directly kill residual cancer cells during surgery. “Experiments show that PDT is more effective in stopping tumor growth than chemotherapy,” he noted, suggesting that it may eventually replace chemotherapy follow-up after surgery, but further studies are required to verify its efficacy.

Olga Olevsky, MD, an oncologist at UCLA Medical Center, presented results of clinical trials on the effectiveness of adding the anti-VEGF (vascular endothelial growth factor) antibody to a combination of chemotherapy drugs to provoke immune response to VEGF, which occurs at high levels in mesothelioma patients, as well as a promising new vaccine for mesothelioma. “Mesothelioma resulting from asbestos exposure may have an immune mediated response,” she said, explaining that a phase II clinical trials with Tremelimumab, an anti-CTLA-4 (Cytotoxic T-lymphocyte-associated antigen 4) agent, blocks CTLA-4 activity, which suppresses immune response. “We’re excited about this agent,” said Olevsky, noting that of the 22 patients with advanced disease participating in the study, four achieved stable disease and the rest experienced an immune response that lasted six to nine months.

Raffit Hassan, MD, an oncologist and senior investigator in immunology at the National Cancer Institute, discussed anti-mesothelin agents for mesothelioma therapy.

Italian Radiologist Marco Trovo, MD, discussed a novel IG-IMRT (image-guided intensity-modulated radiotherapy) Helical Tomotherapy technique to effectively kill residual cancer cells post-operatively. A small pilot study involving 28 patients indicated that this approach allows safe delivery of high doses of radiation to the hemithorax of patients with intact lung and led to excellent loco-regional control and survival in MPM patients, he said. “Our data support the idea that this approach represents a concrete alternative to EPP (extrapleural pneumonectomy). EPP involves removal of the diseased lung, part of the pericardium (membrane covering the heart), part of the diaphragm (muscle between the lungs and the abdomen), and part of the parietal pleura (membrane lining the chest)–a procedure that a consensus of MPM experts contend is unnecessary and harms the patient.

Dr. Cameron, who also is Scientific Advisor for the Pacific Meso Center (PMC), delivered a presentation on current thermal therapy research at PMC and the effectiveness of hypothermia for improving, or potentially replacing chemotherapy, to kill residual microscopic disease following surgery. “Mesothelioma is particularly sensitive to cryoablation at temperatures below zero centigrade,” he said, noting that this therapy offers an intraoperative adjuvant therapy with acceptable toxicity.

Marko N. Kostic, PhD, a PMC biomedical engineer who is developing a novel device for treating Mesothelioma patients with hypothermia, discussed the challenges involved in designing a cryo-sprayer that uses liquid nitrogen to freeze cancerous tissue. He has developed three different spray nozzles to help the surgeon safely target the diseased area to a depth of one millimeter, while avoiding sensitive surrounding organs and structures. “It cycles three times to kill more cells, and then we’ll use adjuvant therapies to stimulate the immune system,” Kostic noted.

Raymond Wong, PhD, an immunology researcher at PMC, discussed creation of 3-D mesothelioma spheroid models to investigate altering of the mesothelioma microenvironment with cytokines (immunomodulating agents) to evoke immune response. Noting that research suggests that the immune system has a role in improving patient survival, Wong said, “The provocative idea is to tumor-target cytokine delivery.”

Michael J. Becich, MD, PhD., a pathologist who serves as Chairman of the University of Pittsburgh Department of Bioinformatics and on the National Mesothelioma Virtual Tissue Bank (NMVTB) Steering Committee, provided an update on the NMVTB, which now contains tissue microarrays (TMAs) of 1,200 MTM patients. The TMAs include DNA, blood, plasma and tissue. He explained how to query the system to find and request the appropriate biospecimens, which are available for free to the medical community. Noting that all the academic medical centers currently participating in the specimen bank are located on the East Coast, “ Becich said that NMVTB is planning to expand its reach nationwide and may establish a specimen collection center at PMC/UCLA under Dr. Cameron’s direction

“There were several, incredibly exciting studies coming out of this that far exceeds what we’ve seen before,” said Dr. Cameron. “These scientists translated information about treatment response in humans, which is totally unheard of in mesothelioma patients,” he added, noting that advancements are being made because people are now talking about it at scientific meetings. “All this effort is beginning to pay off finally, with treatments that affect patient care.”

This event, which was held at the Sheraton Delfina Hotel, was attended by physicians, nurses and other medical professionals, who received Continuing Medical Education credits, as well as mesothelioma patients and others with an interest in advances in MPM treatments.