Role of Prophylactic Whole Brain Radiotherapy for Small-Cell Lung Cancer

Abstract & Commentary

By Adília Hormigo, MD, PhD, Assistant Professor of Neurology, Weill Medical College, Cornell University; Dr. Hormigo reports no financial relationships relevant to this field of study.

Synopsis: In this study of patients with extensive small-cell lung cancer, prophylactic brain irradiation decreased the incidence of symptomatic brain metastases and prolonged disease-free survival and overall survival without significant impact on global health status.

Source: Slotman B, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 2007;357:664-672.

It is well established that prophylactic whole brain radiotherapy plays a role in decreasing the incidence of brain metastases in patients with limited small-cell lung cancer.1 A multicenter study was conducted in Europe to evaluate the role of prophylactic cranial radiation in patients ages 18-75 who responded to chemotherapy for extensive small-cell lung cancer, which was defined as disease beyond the hemithorax and supraclavicular nodes or presence of a malignant pleural effusion. After a response was obtained to 4-6 cycles of chemotherapy, patients who had no evidence of brain or leptomeningeal disease by contrast head CT scan or MRI were randomized to receive prophylactic 25-39 Gy of cranial irradiation or no further treatment. The primary end-point was development of symptomatic brain metastases, defined by a symptom suggestive of CNS disease and a positive contrast head CT scan or MRI. Each group accrued 143 patients. The risk for symptomatic metastases was significantly lower in the group that received irradiation (hazard ratio, 0.27; p<0.001). The cumulative risk of brain metastases within one-year was 14.6% in the irradiated group versus 40.4% in the control group. A significant increase in median disease-free survival from 12 to 14.7 weeks (p=0.02) and median overall survival from 5.4 to 6.7 months (p=0.003) after randomization was seen for the irradiated group vs. the control group. The one-year survival rate was 27.1% in the irradiated group versus 13.3% in the control group.

The authors concluded that in patients with extensive small-cell lung cancer, prophylactic brain irradiation decreased the incidence of symptomatic brain metastases and prolonged disease-free survival and overall survival without significant impact on global health status.

Commentary

This multi-center trial conducted in Europe compared prophylactic cranial radiotherapy to no further treatment in patients with extensive small-cell lung cancer and found a significant benefit for the patients who received cranial irradiation. The treatment was well tolerated and there were no significant side effects. The allowed use of head CT scan instead of MRI for follow-up in some patients is a limitation of the study. The optimal schedule of radiotherapy remains to be determined as several schedules were used. Nevertheless, the study clearly concluded that prophylactic radiotherapy should be used for patients with extensive small-cell lung cancer after chemotherapy is completed and a response is obtained to the initial chemotherapy treatment. While global health was not different between the two groups, the late neurocognitive consequences of prophylactic whole brain radiation were not assessed and remain a potential concern as better treatments improve the length of survival. However, prophylactic radiotherapy should be extended to include these patients in addition to the standard recommendation for patients with limited small-cell lung cancer who have a complete response after chemotherapy.

Reference

1. Aupérin A, et al. N Engl J Med 1999;341:476-484.