New Horizons
for Mesothelioma
A rare yet fatal disease is seeing a resurgence in clinical and translational research
By Joseph Friedberg, MD, FACS and Melissa Culligan, RN, MS, PhD candidate, Co-Directors, Temple-Fox Chase Cancer Center Mesothelioma and Pleural Disease Program
Meet Dr. Joseph Friedberg, MD, FACS
Through his surgical experience and ongoing research efforts, Joseph Friedberg, MD, FACS has played a leading role in moving mesothelioma closer to becoming a potentially treatable, chronic disease instead of a rare cancer with no known cure. His clinical interests include mesothelioma and other disorders of the pleura, as well as the treatment of advanced lung cancer and other complex thoracic malignancies.
Dr. Friedberg has published more than 100 peer reviewed articles, more than 30 book chapters, and is the inventor on multiple U.S. patents. He is funded by the National Institute of Health (NIH) and National Science Foundation (NSF) for his mesothelioma and “artificial lung” research. He also serves on the Scientific Advisory Board for the Mesothelioma Applied Research Foundation (MARF), the Board of the International Mesothelioma Interest Group (iMig), and the Mesothelioma Committee for the International Association for the Study of Lung Cancer (IASLC).
Meet Melissa Culligan, RN, MS, PhD candidate
Melissa Culligan has more than 30 years of experience working in the field of thoracic surgery with a special focus and expertise in caring for patients with malignant pleural mesothelioma and advanced stage lung cancer. She is the co-author of multiple peer-reviewed papers on lung cancer and mesothelioma, and has lectured nationally and internationally on the nursing care of patients undergoing thoracic surgery. She has a special interest in clinical trial development and management for thoracic oncology patients and has led multiple surgery-based clinical trials at Temple University Hospital and Fox Chase Cancer Center.
Currently a PhD candidate, Melissa’s doctoral research is focused on the experience of dyspnea for patients undergoing lung-sparing surgery for malignant pleural mesothelioma.
Pleural mesothelioma (PM) is one of the most virulent known cancers, currently considered incurable and with a life expectancy in the one-year range. It is an extremely rare disease, comprising only a few percent of the incidence of lung or breast cancer. Often presenting with shortness of breath, the scarcity of this cancer sometimes results in missed or delayed diagnosis. Some pulmonologists may never see a patient with PM; due to it being an orphan disease, treatment and research are typically focused in centers of excellence.
Temple-Fox Chase Cancer Center offers one of the most comprehensive mesothelioma programs in the United States (the only one of its type in the region), with a number of internationally recognized experts in the field. Here are some of the exciting and innovative treatment and research activities taking place in the field and at the Temple-Fox Chase Cancer Center Mesothelioma and Pleural Disease Program.
Clinical Treatments, Research, and Trials
Systemic therapy is the standard-of-care treatment for PM. For the past two decades, pemetrexed (trade name Alimta) plus either carboplatin or cisplatin has been the standard treatment. Recently, the CheckMate 743 trial in Europe showed improved survival for PM patients treated with immunotherapy—namely, nivolumab plus ipilimumab checkpoint inhibitors—compared with chemotherapy, especially among patients with sarcomatoid and biphasic histologic subtypes.1 Additional combinations are being explored.
Surgery remains an investigational treatment for PM that, in appropriate patients, offers a safe treatment option with potential to extend survival significantly beyond what would be anticipated with systemic therapy alone. Radical pleurectomy that involves either taking or sparing the lung offers surgical options to achieve a macroscopic complete resection. Lung-sparing surgery, although more technically demanding than extrapleural pneumonectomy, is generally accepted as a safer approach. Patients as old as 86 have undergone this operation and returned to their normal activities of daily living. Lung-sparing surgery is an area of expertise for the Temple-Fox Chase Cancer Center Mesothelioma and Pleural Disease Program. A less invasive modification of this operation offered by Temple-Fox Chase has achieved some of the best reported survival results for PM; it will be presented at the 2023 American Association of Thoracic Surgery meeting. Anticipated postoperative quality of life is weighted heavily in determining whether to offer patients surgery, and studying the quality-of-life impact of surgery is a research focus of the Program. The IMPRINT trial, a multi-institution trial combining lung-sparing surgery, systemic therapy, and adjuvant radiation (IMRT) will also be opening shortly. Beyond the multi-institution trials, the Program is preparing for a number of investigator-initiated surgical trials combining immunotherapy and intraoperative adjuvant therapies.
Some unusual clinical trials coming to Temple-Fox Chase include the use of photodynamic therapy (PDT) and radiodynamic therapy (RDT). Both involve the use of a photosensitizing drug, 5-ALA, that accumulates in cancer cells and renders patients light sensitive for less than a day. When activated by light, the drug triggers a series of reactions that are effective at both directly killing cancer cells and also stimulating a tumor-directed immune response. A particularly exciting plan for the Program is to join a preeminent mesothelioma program in Lille, France for the European IMPALA study, in which PDT will be used for the purpose of amplifying and focusing the effect of concomitant immunotherapy. A trial of radiodynamic therapy, available in the Western Hemisphere only at Fox Chase Cancer Center, employs a racetrack microtron. The microtron generates high-energy photons that can trigger a PDT-like reaction but without the limitations of the restricted depth of penetration imposed by conventional PDT, which uses visible light as the stimulating energy.
The ultimate goal of the Temple-Fox Chase program is to have surgical and nonsurgical trials available for patients with every subtype and presentation of pleural mesothelioma.
Translational Research
The Temple-Fox Chase Cancer Center Mesothelioma and Pleural Disease Program is committed not only to delivering the best care available today, but also to pioneering the best treatments for tomorrow. Multiple projects are underway—or being planned—at both Temple and the Fox Chase Cancer Center. Some of these projects include:
- Development of new techniques and modeling systems to study mesothelioma.
- Development of a system to seal pulmonary air leaks, the principal morbidity of lung-sparing surgery.
- Development of new markers to detect and monitor PM treatment response.
One particularly interesting and novel project is the exploration of a nontoxic agent that could be used to prevent the development of mesothelioma in patients exposed to asbestos, and others at high risk. This project will be directed at Fox Chase Cancer Center by Joseph Testa, PhD, FACMG, internationally acclaimed mesothelioma researcher, co-discoverer of the BAP1 tumor predisposition syndrome, and the first investigator to demonstrate that heritable mutations influence the risk of asbestos-induced mesothelioma.
Cause for Optimism
Formation of the Temple-Fox Chase Cancer Center Mesothelioma and Pleural Disease Program establishes a world-class center of excellence for the treatment of mesothelioma. After a period of relative stagnation for many years, new treatments and techniques are now available that are likely not only to prolong life, but also to maintain quality of life. Research is ongoing and accelerating to detect, treat, and prevent this terrible cancer. For the first time in many years, there is just cause to be optimistic.
To refer a patient to the Temple-Fox Chase Cancer Center Mesothelioma and Pleural Disease Program, or to learn about clinical research opportunities, contact:
T.K. Broderic
Director of External Accounts
267-608-8433
thomas.broderic@tuhs.temple.edu
Diane Brown
Manager of Key Accounts, Fox Chase Cancer Center
diane.brown@tuhs.temple.edu
Reference
1 Nowak, A.K., et al. 2022. “Management of Advanced Pleural Mesothelioma—At the Crossroads.” JCO Oncology Practice 18(2): 116-124. DOI: 10.1200/OP.21.00426
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