Improved Survival With Prophylactic Cranial Irradiation in Modern Cohort of Limited-Stage Small Cell Lung Cancer Patients With MRI Brain Imaging

Abstract

Clinical trials have shown improved survival in small cell lung cancer (SCLC) patients treated with prophylactic cranial irradiation (PCI). Critiques of the randomized trials have been that MRI brain imaging was not required for patients prior to receiving PCI, therefore many patients likely had asymptomatic brain metastasis thus the survival advantage likely was derived from treating those patients with brain radiation rather than PCI. Therefore, we examined our modern cohort of limited stage small cell lung cancer patients, who were imaged with MRI brain prior to PCI, to determine whether PCI confers a survival advantage. In addition, a variety of dose fractionation schemes are available for patients with SCLC. We compared the outcomes of patients who received treatment twice daily to those who received once daily radiation. A retrospective review was conducted of patients with SCLC treated with chemoradiation at our institution from 1991 to 2012. All patients received concurrent chemoradiation which was followed by restaging scans including a MRI brain, and were offered the choice of PCI (if they exhibited tumor response and had no evidence of brain metastasis). Tumor pathology was examined centrally at our institution. We compared patients who received chemoradiation with PCI versus chemoradiation alone. We compared patients treated with daily radiation (QDAY) versus twice daily radiation (BID). We analyzed the disease-free survival (DFS) and overall survival (OS) by Kaplan-Meier survival curves, and compared groups using log-rank tests of Cox proportional hazard ratios (HR). From 1991 to 2012, 62 patients with SCLC treated with chemoradiation at our institution were identified. Of this cohort, 22 received PCI, 40 did not. Median follow-up was 1 year. Median OS was superior in the PCI group at 2.2 years vs 1.1 years in the chemoradiation alone group. Similarly, 5-yr OS was improved with PCI from 10% to 30% (HR = 2.0, p = 0.043), and 5-yr DFS improved from 7% to 30% (HR = 2.4, p = 0.014). To compare the effect of fractionation schemes, 46 patients were identified who received QDAY radiation, and 16 patients who received BID radiation. There was no statistically significant effect on OS (HR = 1.1, p > 0.8). In a modern cohort of small cell lung cancer patients with MRI brain imaging prior to PCI, PCI still confers a survival advantage over thoracic chemoradiation alone. PCI should be the standard of care, and offered to all small cell lung cancer patients with response to chemotherapy or chemoradiation. Patients treated with daily versus twice-daily radiation appear to have similar outcomes, but this study was not powered to detect a difference.