PREOPERATIVE RT FOR MESOTHELIOMA PATIENTS

Radiation before surgery could boost survival in patients with mesothelioma, according to a report by Canadian researcherspublished 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.

"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, toldMedscape 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.