Impact of radiotherapy duration on overall survival in squamous cell carcinoma of the anus

Background: Prolongation of radiotherapy (RT) in the treatment of numerous types of cancer has been shown to reduce overall survival (OS). Treatment delays are common in squamous cell carcinoma of the anus (SCCA) due to the toxicity of definitive chemoradiation (CRT). The effect of these delays on outcomes has not been well evaluated. This study investigated the effects of RT prolongation on OS in patients receiving CRT for SCCA. Methods: The National Cancer Database was queried for adult patients diagnosed with SCCA and treated with CRT from 2004–2014. Cox proportional hazard regression models examined the effect of duration of RT, measured as fractions delivered per week, on OS. Negative binomial regression assessed the effects of demographic and prognostic factors on the duration of RT. Results: A total of 8,948 patients were included in the analysis of factors impacting treatment duration, and 6,429 patients in the OS analysis. Multivariable analysis (MVA) showed female gender, non-private insurance, treatment at a low or intermediate volume facility, Charlson/Deyo score ≥2, and advanced disease were associated with longer RT duration. Treatment with IMRT, with single agent chemotherapy, at an academic center, and in later years were associated with shorter RT duration. A decrease in fractions delivered per week was independently associated with reduced OS with a cutoff of 4.72 fractions per week (about 2 missed fractions over a 30 fraction treatment) delineating the largest differences in OS. Conclusions: Efforts should be made to avoid RT interruptions of any length in SCCA patients and to compensate for treatment breaks to reduce the total duration of RT.