Thoracic RT Improves Long-Term Survival in Extensive-Stage SCLC

The addition of thoracic radiotherapy to chemotherapy and prophylactic cranial irradiation significantly improved 2-year survival and other outcomes in patients with extensive-stage small-cell lung cancer (ES-SCLC), according to results of a new phase III randomized trial.

“Survival for ES-SCLC is poor, and has improved little in recent decades,” wrote study authors led by Ben J. Slotman, MD, of VU University Medical Center in Amsterdam. Though previous research has shown prophylactic cranial irradiation can improve outcomes, intrathoracic disease often remains a problem. In this study, the investigators compared 247 patients who received thoracic radiotherapy with 248 patients who did not; all patients underwent prophylactic cranial irradiation. The results were published online ahead of print on September 14 in the Lancet.

The median overall survival at 1 year was no different between the groups, at 33% in the thoracic radiotherapy group and 28% in the control patients, for a hazard ratio (HR) of 0.84 (95% CI, 0.69-1.01; P = .066). But a secondary analysis of 2-year survival did show improvement, at 13% in the radiotherapy group vs 3% in the control patients (P = .004). The number of patients needed to treat to avoid one death was 10.6.

The median survival differed for patients whose diagnosis of extensive-stage disease was on the basis of intrathoracic disease only (11.8 months), distant metastases (7.5 months), or both (8.3 months; P < .0001). Survival did not differ, however, based on presence of intrathoracic disease at randomization, sex, age, response to chemotherapy, WHO performance score, or extent of disease.

Progression was also less likely in the thoracic radiotherapy group, with an HR of 0.73 (95% CI, 0.61-0.87; P = .001). Progression-free survival at 6 months was 24% in the radiotherapy group compared with only 7% in the control group (P = .001).

“Thoracic radiotherapy was well tolerated and we recorded no severe acute or late toxic effects,” the authors wrote. Grade 3 or higher fatigue (11% in radiotherapy group vs 9%) and dyspnea (3% vs 4%) were the most common serious events.

The authors noted that this study lacked patient-reported outcomes. In future studies of potentially higher doses of radiotherapy, patient-reported quality-of-life measures may be important to fully assess the efficacy of the therapy. There may also be merit to testing radiotherapy in sites of extrathoracic disease, which occurs relatively frequently in these patients.

“Our results show that thoracic radiotherapy improves long-term survival,” they concluded. “Therefore, thoracic radiotherapy should be considered for patients with extensive-stage small-cell lung cancer who have responded to chemotherapy.”

In an accompanying editorial, Jan van Meerbeeck and David Ball, of Ghent and Antwerp University and the University of Melbourne, agreed that this therapy should now be considered, but only in certain patients. Those with large volume liver metastases and minimal intrathoracic disease burden, for example, are likely not good candidates. Still, this approach has a lot of promise: “Refreshingly, the radiotherapy in [the study] was not technically complex, and it would be easy to provide at low cost in even the most modestly resourced radiotherapy departments.”

Results of this study were presented earlier this year at the 2014 American Society of Clinical Oncology Annual Meeting.