Effect of overall treatment time on outcomes after concurrent chemoradiation for locally advanced non–small-cell lung carcinoma: Analysis of the Radiation Therapy Oncology Group (RTOG) experience

Abstract

To determine whether overall treatment time affects outcomes after definitive concurrent chemoradiotherapy for locally advanced non-small-cell lung carcinoma (NSCLC). Data were analyzed from 3 prospective Radiation Therapy Oncology Group trials (RTOG 91-06, 92-04, and 94-10) in which immediate concurrent chemoradiation (cisplatin-based) was the primary therapy for good-performance status Stage III (and selected inoperable Stage II) NSCLC. "Short" overall treatment time (per protocol) was defined as completing treatment within 5 days of plan; other patients were considered to have had "prolonged" treatment time (protocol violation); treatment time was also analyzed as a continuous variable in a multivariate model. Actuarial analysis was performed for overall survival, progression-free survival, freedom from local-regional progression, and toxicity. A total of 474 patients were analyzed. Median follow-up for surviving patients was 6.1 years. Treatment time was delivered per protocol in 387 (82%), whereas 87 patients (18%) had a prolonged treatment time. Long treatment time was significantly associated with severe acute esophagitis. Median survival was slightly better in patients completing treatment on time (19.5 months vs. 14.8 months), but this did not reach statistical significance (p = 0.15) in the univariate analysis. However, in the multivariate analysis of treatment time as a continuous variable, prolonged treatment time was significantly associated with poorer survival (p = 0.02), indicating a 2% increase in the risk of death for each day of prolongation in therapy. Histology (squamous fared worse) and performance status were also significant in the multivariate model. This retrospective analysis demonstrates a correlation between prolonged overall radiotherapy treatment time and survival in patients with locally advanced NSCLC, even when concurrent chemotherapy is used. Further study of novel radiation-chemotherapy dose/fractionation regimens is warranted.