3410 - Modest Dose Escalation for Early-Stage Anal Cancer: Cancer Control and Toxicity Outcomes
Presenter(s)
S. A. Copling1, M. K. Rooney2, P. Das3, E. J. Koay3, E. B. Ludmir3, B. D. Minsky4, S. S. Noticewala2, G. L. Smith4, and E. Holliday4; 1McGovern Medical School, Houston, TX, 2Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 3Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 4The University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s): The optimal dose for patients with early-stage squamous cell carcinoma of the anus (SCCA) is unknown. We aimed to evaluate the impact of modest dose escalation (54-55 Gray (Gy)) compared with standard dose (50 Gray) on local failure-free survival (LFFS) and toxicity outcomes for patients with T1-2N0 SCCA.
Materials/Methods: Patients with T1-T2N0 SCCA treated with definitive, intensity-modulated radiation therapy-based radiation from 1/1/2003 until 6/31/2022 were included in this retrospective analysis. A regression discontinuity analysis was performed to evaluate for a potential causal effect of dose escalation on LFFS. During this time period, patients with T1 tumors were typically treated with 50 Gy in 25 fractions, and patients with T2 tumors were treated with 54 Gy in 27 fractions. Thus, a tumor size of 2 cm was used as the cutoff for predicting modest dose escalation (defined as 54 Gy). Cox proportional hazards model was generated to estimate the effect of modest dose escalation on LFFS, restricting the dataset to individuals with tumors measuring 1.5-2.5cm. An additional global multivariable Cox proportional hazards model was generated to estimate the effect of dose escalation on LFFS, including all T1-T2N0 patients in this dataset. Ordinal logistic regression was used to identify factors associated with several graded toxicity outcomes including acute and late gastrointestinal (GI), genitourinary (GU), dermatologic, and acute pain toxicities. All toxicities were measured using the Common Terminology Criteria for Adverse Events version 4 (CTCAEv4) on a scale of 0 to 5, with increasing scores reflecting worse toxicity.
Results: Two hundred thirty-four patients with T1N0 (N=85, 36%) or T2N0 (N=149, 64%) SCCA were included in the analysis. Most patients were women (N=183, 78.2%), white (N=221, 94.4%) and HIV-negative (N=228, 97.4%). Eighty-four (35.9%) received 50 Gy, 147 (62.8%) received 54Gy and 3 (1.3%) received 54-55 Gy. The median [IQR] time from the end of radiation to last follow up was 78 [44-119] months. Two- and 5-year LFFS were 90.7% and 88.6%. There was no significant association between modest dose escalation and LFFS (HR 0.6, 95% CI 0.2-1.9, P =0.4) in the analysis restricted to patients with tumors 1.5-2.5 cm. In the global multivariable Cox regression model including all 234 patients, only positive HIV status (HR 5.2 [1.2-21.5], P = 0.02) persisted as a significant predictor of worse LFFS on multivariate analysis. Modest dose escalation (P=0.3) and tumor size (P=0.6) did not predict LFFS. Regarding toxicity, modest dose escalation was associated with worse acute GU toxicity (OR 3.28, 95% CI 1.40-8.59, p = .010) and worse acute pain toxicity (OR 3.63, 95% CI 2.03- 6.65, p < .0001).
Conclusion: Modest dose escalation was not associated with improved LFFS among patients with T1-2N0 SCCA; however, it was associated with worse acute GU and pain toxicity. Future efforts should focus on biomarkers to identify patients who may potentially benefit from treatment escalation.