Mesothelioma: Radiation Before Surgery Feasible, Boosts Survival

Megan Brooks

January 23, 2014

Radiation before surgery could boost survival in patients with mesothelioma, according to a report by Canadian researchers published online January 17 in the Journal of Thoracic Oncology.

The study of 25 patients with resectable malignant pleural mesothelioma (MPM) showed that using hemithoracic intensity-modulated radiation therapy (IMRT) before extrapleural pneumonectomy (EPP) is feasible and could prolong survival, the researchers report.

However, an expert not involved in the study noted that these results should be interpreted as showing that this approach is feasible, rather than suggesting a new standard of care.

Dr. John Cho

"There is still much controversy over the best management of MPM, and there is no generally accepted standard of care, per se," first author John Cho, MD, PhD, told Medscape Medical News. He is a radiation oncologist at the University Health Network's Princess Margaret Cancer Centre and assistant professor in the Department of Radiation Oncology at the University of Toronto.

The "SMART" Approach

Dr. Cho and colleagues pioneered the SMART approach — Surgery for Mesothelioma After Radiation Therapy — in which patients receive a short accelerated course of high-dose hemithoracic IMRT before EPP. One of the reasons for using IMRT before surgery is "to induce a tumorostatic and tumoricidal effect" to prevent inadvertent spillage of tumor cells during EPP, which is a possible mechanism of distant failure, the researchers explain.

"This SMART approach has more than doubled our 3-year survival in epithelial mesothelioma, from 32% to 72%," said coauthor Marc de Perrot, MD, head of the mesothelioma research program and associate professor of surgery at the University of Toronto.

Dr. de Perrot said in a statement that the SMART approach offers "real hope to mesothelioma patients who have too often been told...that they may have only 6 months to live."

The team has used the SMART approach to successfully treat 20 patients in addition to the 25 study patients.

The IMRT regimen consists of 25 Gy delivered to the entire ipsilateral hemithorax in 5 daily fractions over 1 week, with a concomitant 5 Gy boost to at-risk areas. This is followed by EPP within 1 week. For patients with ypN2 lymph node status on final pathology, adjuvant chemotherapy is offered.

All 25 study patients who completed the SMART protocol had resectable clinical T1-3N0M0 MPM.

IMRT was "extremely" well tolerated, with no grade 3 or higher toxicities, and all patients proceeded to EPP in the predefined time frame (1 week) with no perioperative mortality, the researchers report.

Thirteen patients (52%) developed grade 3 or higher surgical complications, mainly atrial fibrillation. "Despite the preoperative radiation, no patient developed bronchopleural fistula immediately after surgery or during follow-up," they note.

On final pathology, all but 1 patient had stage III or IV disease. Five of the 13 ypN2 patients received adjuvant chemotherapy.

"Remarkably" good outcomes were achieved in patients with epithelial histologic subtypes, the researchers say. In fact, after a median follow-up of 23 months, 3-year survival was better in that subtype than in biphasic subtypes (84% vs 13%; P = .0002).

"At the last follow-up, only 1 of 9 patients with epithelial N2-negative disease had developed recurrence, despite the fact that all tumors were pathologic staged ypT3 and ypT4. Although longer follow-up and a larger number of patients is required to make definitive conclusions on the long-term impact of this treatment protocol, these initial results are extremely encouraging for patients with epithelial MPM," they write.

More Study Needed

These are "good results in a small group of patients in a feasibility study," said Prasad Adusumilli, MD, an associate attending in thoracic surgery at the Memorial Sloan-Kettering Cancer Center and associate professor of cardiothoracic surgery at Weill Cornell Medical Center, both in New York City.

As the researchers themselves acknowledge, "feasibility-wise, it's tough to do this kind of radiation to the patient and go for surgery within a week," Dr. Adusumilli told Medscape Medical News.

"It is exciting that it's a new approach," he added, "and it's nice to see that they are able to manage this high-risk approach — radiation and extrapleural pneumonectomy." However, "the conclusion is that it's just a feasibility study and I don't think we can jump to say that it's a standard of care."

Dr. Cho described the next 2 steps: "First, consider mounting a multicenter phase 3 clinical trial, and second, further optimize the approach (such as adding targeted agents)."

In addition, Dr. Cho said that this study "provides some evidence that EPP, at least in the context of this approach, is an important component of treatment (compared with extended pleurectomy/decortication [EDP]). Ideally, a randomized phase 3 trial comparing SMART with EPD plus adjuvant radiotherapy would help establish which surgery is better for MPM."

Early Diagnosis Is Critical

One of the biggest challenges in mesothelioma is diagnosing the disease at an earlier stage. "Individuals with known exposure to asbestos who experience shortness of breath, weight loss, and fatigue for more than 3 weeks need to see a doctor," Dr. de Perrot emphasized.

"A basic chest x-ray will show a pleural effusion, which appears as half the lung in white shadow. That is the trigger to seek specialist care quickly. We need to shorten the diagnostic and treatment cycle in mesothelioma because we now have an approach that makes it possible to control the disease and improve quality of life for several years," he explained.

Dr. Cho agrees. "Delayed diagnosis can be an issue. Often, patients suffer delay in diagnosis in periphery due to rarity, challenges in pathologic assessment, and the nonspecific nature of presenting symptoms (dyspnea, pleural effusion). For patients with pleural effusion and a history of exposure to asbestos, direct referral to a specialized mesothelioma center" would speed the time to treatment.

This research was funded by The Princess Margaret Cancer Foundation and The Toronto General and Western Hospital Foundation. The study authors and Dr. Adusumilli have disclosed no relevant financial relationships.

J Thorac Oncol. Published online January 17, 2014. Abstract

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