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Oncology Live®
Author(s):
Although malignant pleural mesothelioma (MPM) remains a rare disease, Memorial Sloan Kettering Cancer Center has considerable experience with this malignancy, and our specialists are at the forefront of translating new approaches for the treatment of patients with mesothelioma into the clinic.
Prasad S. Adusumilli, MD
Deputy Chief, Thoracic Service
Memorial Sloan Kettering Cancer Center
Although malignant pleural mesothelioma (MPM) remains a rare disease, Memorial Sloan Kettering Cancer Center has considerable experience with this malignancy, and our specialists are at the forefront of translating new approaches for the treatment of patients with mesothelioma into the clinic.
At Memorial Sloan Kettering, patients with mesothelioma are managed by a working group that consists of specialists from multiple disciplines who use a personalized approach to achieve accurate diagnosis, stage, and treatment stratification. In general, patients with suspected mesothelioma are often misdiagnosed, owing to a lack of pathological expertise and the selection of inappropriate biopsies.
Memorial Sloan Kettering is one of the nation’s largest tertiary referral centers for this disease, and our mesothelioma working group, which meets regularly to discuss all patients with mesothelioma undergoing treatment at our center, has the skills and knowledge to ensure optimal management is consistently achieved.
Our experience with this rare tumor includes the largest study published to date (945 patients) on long-term outcomes among patients with mesothelioma at a single center. The development and maintenance of this vast and meticulous database enables us to design a customized management algorithm for each patient.
For example, to determine the most appropriate surgical resection for each patient, we employ an algorithm that takes into account the potential resectability of the tumor and the individual’s cardiopulmonary reserve—an approach that ensures tolerance of the planned surgical approach and results in better functional outcomes.
A hemithoracic pleural intensity-modulated radiation therapy plan (coronal view) for a right-sided malignant pleural mesothelioma is used for targeted treatments that spare healthy lung tissue
The database has also enabled us to establish patient-management paradigms that have subsequently been adopted by physicians and official medical associations throughout the world.
Through our approach of systematically evaluating each patient with mesothelioma by CT scan, PET scan, and lung function tests, we are able to optimize patients for surgical resection and avoid unnecessary surgery that may delay treatment. Our preoperative assessment skills reflect our extensive research on these imaging modalities.1 With the assistance of Memorial Sloan Kettering radiologists, we are now developing advanced imaging techniques to accurately quantify tumor burden and monitor therapy response.
Working in concert with Memorial Sloan Kettering pathologists, our mesothelioma researchers have identified the key morphological characteristics that drive progression of mesothelioma. These developments have helped inform the efforts of the World Health Organization and other international associations to reclassify mesothelioma.2,3
Mesothelioma patients with early-stage disease are managed by curative-intent surgical resection, using either extrapleural pneumonectomy or pleurectomy and decortication. Our surgeons pioneered these techniques and have trained surgeons across the globe on using them.
In carefully selected patients, extrapleural pneumonectomy— which involves the removal of the involved lung lining, heart lining, nearby lymph nodes, and diaphragm—provides an excellent option. The expertise of our nursing and surgical floor staff is key in successfully managing these patients in the immediate postoperative period.
The majority of mesothelioma patients undergo pleurectomy and decortication—a lung-sparing surgical procedure that aggressively and carefully removes the tumor—so that they can quickly recover and then undergo chemotherapy and/or radiation therapy.
To prevent recurrence of cancer following surgical resection, our radiation oncologists have developed an intensity-modulated radiation technique that precisely targets the tumor while sparing the underlying healthy tissue—namely, the lung (Figure 1).
We continue to lead efforts to elucidate the biological profile of MPM and advance imaging modalities and therapies. Landmark publications from our center have shed light on the biology of this aggressive disease.4-6 We are currently working to translate new imaging modalities developed in clinically relevant mouse models (Figure 2) for use in patients.
An intraoperative fluorescence technique for visualizing pleural mesothelioma, developed for a mouse model, will be evaluated in a clinical trial.
In addition, in an ongoing clinical trial of an oncolytic vaccinia virus (which uses genetically modified smallpox virus to kill cancer cells), we are investigating real-time fluorescent techniques to visualize the microscopic deposits of the tumor in the operating room; this will enable us to accurately assess and remove the entire tumor.
Even more promising, our researchers have identified the beneficial role of antitumor immune responses7 and have discovered candidate cancer antigens to effectively target the tumor.8 We anticipate the initiation of a novel adoptive T-cell immunotherapy clinical trial for mesothelioma patients later this year. In this clinical trial, we will administer the patient’s own immune cells, genetically engineered to target and kill cancer cells, through tunneled pleural catheters that we pioneered for use in mesothelioma patients.9
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