Predictors of pulmonary toxicity in limited-stage (LS) small cell lung cancer (SCLC) patients treated with concurrent chemotherapy (CTX) and high-dose (70 Gy) daily radiotherapy (RT): a pooled analysis of three CALGB studies

Abstract

BACKGROUND: Predictors of post CTX-RT pulmonary toxicity in LS-SCLC patients are not well defined. Current guidelines are derived from NSCLC regimens, not accounting for the unique biology of SCLC. We analyzed patients on 3 consecutive CALGB LS-SCLC trials to determine factors predicting for post-treatment pulmonary toxicity. METHODS: Patients treated on CALGB protocols 39808, 30002, 30206, investigating 2 cycles of newer CTX agents (39808: topotecan, paclitaxel; 30002: paclitaxel, oral etopside, oral topotecan; 30206: cisplatin, irinotecan) followed by concurrent carboplatin/etopside and 70 Gy daily RT were pooled. Patient, tumor, and treatment related factors were evaluated to determine predictors of grade 3-5 pulmonary toxicities following CTX-RT. PFT data were not routinely collected and not included in this analysis. RESULTS: 211 patients were treated, 100 patients (39808 n=9, 30002 n=34, 30206 n=57) were evaluable with RT dose-volume parameters and adverse event data. Patient characteristics were balanced between except for those in 30206 with significantly improved baseline PS. Median overall and progression free survival was 22.6 months (95% CI: 18.5-29.4) and 13.9 months (95% CI: 12.6-16.7), respectively. Three patients experienced post-treatment pulmonary toxicity. No patients experienced grade 4-5 pulmonary toxicity. Patients with post-treatment grade 3 pulmonary toxicity were likely to be older (p=0.09) and have a smaller total lung volume (p=0.05). Furthermore, exposure of larger volumes of lung to lower (median V5=70%, p=0.09, median V10=63%, p=0.07), intermediate (median V20=50%, p=0.04) and high (median V60=25%, p=0.01) doses of RT were all associated with grade 3 pulmonary toxicity, as was larger mean lung RT dose (median 31 Gy p=0.02). CONCLUSIONS: Post-treatment pulmonary toxicity following completion of 2 cycles CTX followed by CTX-RT was uncommon. Few events limtied statistical power to draw firm conclusions. Data available suggest that care should be taken to minimize mean lung RT exposure, as well as volumes of low, intermediate and high doses of RT.