Impact of Overall Treatment Time on Survival and Local Control in Patients With Anal Cancer: A Pooled Data Analysis of Radiation Therapy Oncology Group Trials 87-04 and 98-11

Abstract

A B S T R A C T PurposeTo determine whether increased duration of radiation therapy (RT) and overall treatment (RX) time has a detrimental effect in anal cancer. Patients and MethodsData from Radiation Therapy Oncology Group (RTOG) 87-04 and RTOG 98-11 trials were combined to form three treatment groups: RT/fluorouracil (FU)/mitomycin (n ϭ 472), RT/FU/ cisplatin (n ϭ 320), and RT/FU (n ϭ 145). Cox proportional hazards models were used with the following variables: RT duration, RT intensity, RX duration, treatment group, age, sex, Karnofsky performance score (KPS), T stage, N stage, and RT dose. ResultsIn the univariate analysis, there was a significant association between RX duration and colostomy failure (CF; hazard ratio [HR] ϭ 1.51; 95% CI, 1.07 to 2.14; P ϭ .02), local failure (HR ϭ 1.52; 95% CI, 1.14 to 2.03; P ϭ .005), locoregional failure (HR ϭ 1.51; 95% CI, 1.15 to 1.98; P ϭ .003), and time to failure (HR ϭ 1.40; 95% CI, 1.10 to 1.79; P ϭ .007). The significance of RX duration was maintained after adjusting for treatment group. In multivariate modeling there was a trend toward an association between RX duration and CF (HR ϭ 1.57; 95% CI, 0.98 to 2.50; P ϭ .06) and a statistically significant association with local failure (HR ϭ 1.96; 95% CI, 1.34 to 2.87; P ϭ .0006). Age, sex, KPS, T stage, N stage, and RT dose, but not RT duration, RT intensity, or RX duration, were found to be statistically significant predictors of OS and colostomyfree survival. ConclusionTotal treatment time, but not duration of radiation therapy, seems to have a detrimental effect on local failure and colostomy rate in anal cancer. Induction chemotherapy may contribute to local failure by increasing total treatment time.

Effect of chemotherapy delays and dose reductions on progression free and overall survival in the treatment of epithelial ovarian cancer

“…Time to completion of therapy has been shown to have an impact on survival in patients undergoing radiation therapy, yet this relationship is less well-defined in patients receiving chemotherapy (13,14). Though no studies have been performed in patients with EOC, decreased survival has been documented in breast cancer patients who experience delays and dose reductions in chemotherapeutic regimens [15-18].…”

The Impact of the Duration of Adjuvant Chemotherapy on Survival in Patients with Epithelial Ovarian Cancer – A Retrospective Study

“…In cervical and anal cancer the duration of chemotherapy was reported to have a decisive effect on the patients’ survival [7, 8]. In EOC data on the association between duration of chemotherapy and survival outcome are partially inconsistent.…”

Outcomes of anal cancer treated with definitive IMRT-based chemoradiation

“…All eventually had a complete clinical response and currently have no evidence of disease. Some studies have not shown an association between treatment breaks with worse clinical outcomes, including a pooled data analysis of RTOG 87-04 and 98-11 [30,31]. Although the effect of a treatment break is unclear, an uninterrupted treatment course should be delivered if possible.…”