A Strategy to Reduce Acute Toxicity from Twice Daily Chemoradiation Therapy for Limited-Stage Small-Cell Lung Cancer

Abstract

The standard of care for limited stage small cell lung cancer (LS-SCLC), as outlined in the Intergroup 0096 trial, involves twice daily radiation therapy delivered to two out of four fields at a time. This results in high rates of clinically significant acute toxicities, especially esophagitis. This study examines acute esophagitis and treatment breaks in patients treated with radiation therapy as outlined by Intergroup 0096 versus those treated with all four fields treated with each fraction, a minor modification of the Intergroup 0096 technique that we hypothesize will reduce acute esophagitis rates and treatment breaks. We identified SCLC patients who received 45 Gy in 1.5 Gy twice-daily fractions from an institutional database. Treatment break was defined as an interruption of ≥3 total days. Associations were assessed via Chi-squared test. 74 LS-SCLC patients were treated with 3D-conformal radiation therapy from 2004 - 2010. 18 patients did not satisfy criteria described in the Methods and were excluded. 28 patients were treated per Intergroup 0096 with AP/PA fields twice daily for 1 week followed by AP/PA fields in the AM and 2 oblique fields in the PM for 2 weeks. 28 patients were treated with the same approach except all four fields were treated with each fraction. Patient characteristics were well distributed with no differences observed in median age, race, gender, performance status, T and N stage, lung lobe, laterality, Charlson score, and type and timing of chemotherapy (p >0.20 for all). 35% of patients had CTCAE grade 3 esophagitis with the Intergroup 0096 approach vs. 13% in patients treated with an integrated 4-field approach (p = 0.04). Across groups, 32% of grade 3 esophagitis patients had breaks vs. 8% with grade ≤2 esophagitis (p = 0.02). There was no difference in survival (p = 0.37), with 39% survival in both arms at three years. Grade 3 esophagitis and treatment breaks were reduced in patients receiving integrated 4-field treatment. Future investigation is required to determine whether the observed reduction in treatment breaks could translate to a local control or survival benefit if applied to a larger patient sample, or whether IMRT could further benefit this population of patients.