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

Abstract

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.

Impact of compliance to chemoradiation on long-term outcomes in squamous cell carcinoma of the anus: results of a post hoc analysis from the randomised phase III ACT II trial

“…A more recent National Cancer Data Base (NCDB) analysis of CRT (2004e2014), also showed prolonging radiotherapy was independently associated with reduced OSdwith most effect when RT was delayed !2 days. 25 Additional proactive strategies could further improve compliance. First, meticulous hydration in the first cycle of chemotherapy might minimise toxicity in patients with baseline GFR < 60.…”

“…Second, the association between absolute nadir and the V10/V20 of pelvic and lumbosacral bone marrow could be addressed by bone marrow sparing, optimising constraints and plan evaluation. 25 Data on chemotherapy compliance in SCCA is sparse (supplementary Table S8, available at Annals of Oncology online). In the ACCORD 03 trial, 78/82 (95%) (Arm C) and 71/75 (95%) (Arm D) received the second cycle of concurrent chemotherapy in the 157 patients who received chemoradiation without induction chemotherapy.…”

MRI-Based Radiomics Input for Prediction of 2-Year Disease Recurrence in Anal Squamous Cell Carcinoma

“…Thirdly, this model takes into account the length of CRT (removing it resulted in poorer performances), which de facto prevents from using this model in intensification trials including adjuvant chemotherapy or dose escalation. However, it highlights an important message that avoiding as much treatment interruptions as possible and reducing their duration seem to improve the patients’ outcome, pauses being increasingly questioned [ 29 ]. As a matter of fact, in a recent pooled analysis, shorter overall treatment time was associated with longer PFS [ 30 ].…”

Volumetric Modulated Arc Therapy Improves Outcomes in Definitive Radiochemotherapy for Anal Cancer Whilst Reducing Acute Toxicities and Increasing Treatment Compliance

“…Remarkably, we observed this effect in spite of the more aggressive tumors (G3 tumors, 29.0% vs. 13.8%) seen in the VMAT group [ 47 ]. During the last few decades, several studies have highlighted the negative prognostic impact of decreased treatment compliance on patient survival in anal cancer [ 4 , 10 , 44 ]. Thus, the better prognosis in VMAT-treated patients might be a consequence of the reduction in acute toxicities and the improvement of treatment compliance.…”

“…Long-term morbidity leads to a significant impairment of patients’ quality of life [ 8 , 9 ]. As a consequence of CRT-related toxicities, treatment interruptions or delays are necessary for a relevant proportion of patients [ 4 , 10 ]. These events can negatively affect oncologic outcomes [ 4 , 10 ].…”