Lung-Sparing RT Technique Safe, Feasible in Malignant Pleural Mesothelioma

The use of hemithoracic pleural IMRT after chemotherapy could become part of a new lung-sparing therapy in patients with malignant pleural mesothelioma.

The use of hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) after chemotherapy in patients with malignant pleural mesothelioma had an acceptable safety profile in a new phase II trial, with relatively low incidence of radiation pneumonitis. The treatment could become part of a new lung-sparing therapy for these patients.

“Safe delivery of cytotoxic radiation to the hemithorax with two intact radiosensitive lungs is challenging,” wrote study authors led by Andreas Rimner, MD, of Memorial Sloan Kettering Cancer Center in New York. “Conventional matched photon-electron radiation techniques are insufficiently able to spare the underlying ipsilateral lung, so the techniques result in excess toxicity.”

The researchers developed a novel intensity-modulated pleural radiation technique, known as IMPRINT, which is designed to target the entire ipsilateral pleura and maximally spare both the ipsilateral and contralateral lungs. A total of 45 patients with malignant pleural mesothelioma were enrolled to test the technique’s efficacy, though only 27 patients began IMPRINT therapy and were evaluable. The results were published in the Journal of Clinical Oncology.

All patients received chemotherapy before the radiation treatment, with pemetrexed plus cisplatin or carboplatin. Eight patients underwent pleurectomy/decortication (P/D) or an extended P/D, and 13 underwent a partial P/D. IMPRINT was delivered with a median dose of 46.8 Gy (of a planned dose of 50.4 Gy in 28 fractions).

The study’s primary endpoint was radiation pneumonitis. Eight patients (30%) developed grade 2 or greater pneumonitis (6 were grade 2, 2 were grade 3); these patients improved with prednisone therapy. There were no grade 4 or 5 cases of radiation pneumonitis, and other common toxicities included fatigue, dermatitis, and several others.

The median progression-free survival for all patients was 12.4 months, and the median overall survival was 23.7 months. Those with resectable disease had better 1- and 2-year overall survival rates compared with those with unresectable disease, and those survival outcomes also differed based on the response to chemotherapy. Most patients (59%) experienced disease failure within the radiation field, most commonly where disease was previously present.

“These results justify our next multicenter trial to explore the safety and feasibility of hemithoracic pleural intensity-modulated radiation therapy” in more medical centers with experience with this malignancy, the authors wrote. They noted that the technique has a significant learning curve, and thus should be exported to other centers slowly and carefully. “This approach represents a new lung-sparing treatment paradigm for locally advanced malignant pleural mesothelioma.”