Clinical outcomes of extensive stage small cell lung cancer patients treated with intensive modified radiotherapy

Objective: To determine the effect and the patterns of failure in extensive small cell lung cancer (SCLC) patients treated with thoracic intensive modified radiotherapy (IMRT). Methods: A retrospective review was conducted on 130 extensive stage SCLC patients received thoracic IMRT from January 2007 to December 2012. Most patients received initial chemotherapy with carboplatin plus etoposide or chemotherapy with cisplatin plus etoposide and 35 patients received PCI. The median thoracic radiation dose was 56 Gy (32-67 Gy) with 1.8-2.3 Gy per fractions. The Kaplan-Meirer and log-rank test, Cox regression were used for survival analysis and to identify prognostic factors. Results: The median follow-up duration was 37 months (range, 4-66) in all patients and follow-up rate was 96.1%(5 patients lost). The acute toxicity was relatively mild. Hematological toxicity of ≥ grade 2 occurred in 22.3% and acute esophagitis of ≥ Grade 2 occurred in 12.2% of the patients. 7.7% of patients developed ≥ Grade 2 radiation pneumonitis after radiation. The rates of CR, PR, SD, PD after thoracic radiation were 4.6%, 72.3%, 6.2%, 13.1%, respectively, response information of 5 patients lost and objective response rate was 76.9%. The median survival time was 18 months (range, 4-66) and 1-year, 2-year overall survival rate were 72.3%, 38.3% Respectively. Eighty-three patients had distant metastatic and 30 patients had local-regional failure (LRF). There were 26 patients experienced LRF with electronically archived treatment plans available for analysis, 22 patients only experienced in-filed failures, 2 patients only developed out-filed failures and 2 patients developed simultaneous in-field and out-filed failures. By univariate analysis, age, LDH level, thoracic radiation dose and PCI were statistically significant prognostic factor for OS (P = 0.014, 0.049, 0.043, 0.003). Thoracic radiation dose and PCI show statistically significant difference in multivariate analysis (P = 0.021, 0.007). PCI reduces cumulative brain metastases rates (18.4% vs. 37.2%, P = 0.038) and prolongs overall survival (HR = 2.318, 95% CI = 1.388-3.871, F = 0.003) Patients received thoracic radiation EQD₂ ≥ 54 Gy improved overall survival (HR = 1.615, 95% CI = 1.016-2.567, 0.043) and tended to improved progression free survival (HR = 1.49, 95% CI = 0.965-2.299, P = 0.072). Conclusions: Definitive thoracic radiation by IMRT in ED-SCLC responsive to chemotherapy may improve local-regional control and overall survival. Relatively high BED radiation seems to be favorable. Prophylactic cranial irradiation can notably prolong survival and reduce brain metastases. (authors)