Letters COMMENT & RESPONSE

Survival and Outcomes After Noncompletion of Treatment for Anal Cancer To the Editor We read with great interest the Original Investigation from Raphael et al1 on factors associated with chemoradiation interruptions and noncompletion among patients with squamous cell anal carcinoma. In this Canadian populationbased, retrospective cohort study, 1125 patients with stage I to III anal cancer were treated with curative-intent radiotherapy. This number is larger than any of the published randomized clinical trials with chemoradiation in squamous cell anal carcinoma. There are 2 important findings from this study. First, patients who did not complete chemoradiation had a higher risk of salvage abdominoperineal resection, overall death, cancer-specific death, and colostomy or death. Second, treatment interruptions occurred in 262 patients (23%); radiotherapy and chemoradiation noncompletion occurred in 199 patients (18%) and 280 patients (25%), respectively. In fact, treatment interruptions longer than 7 days were not associated with increased risk of death. The definition of completion of radiotherapy was at least 45 Gy and 25 fractions per National Comprehensive Cancer Network guidelines.2 The authors note the lack of information regarding the radiotherapy volumes and technique, in particular the use of intensity-modulated radiotherapy, available in the data set.3 This may influence the ability of patients to complete the prescribed course. It would be interesting to know the rate of completion and outcome of patients who received higher doses of radiation (54-59 Gy). In this observational cohort, 934 of 1125 patients (83%) received fluorouracil with mitomycin as the concurrent chemotherapy protocol. The authors should report the grade 4 hematologic and nonhematologic and fatal toxic effects with this protocol. The Anal Cancer Trial Working Party of the United Kingdom Coordination Committee on Cancer Research trial4 reported 6 deaths in the chemoradiation arm. The toxicity data from this observation cohort have both clinical and research implications. The authors should also explore if the outcomes varied with the caseload of participating centers. There were 3 cen-

ters that treated 15 or fewer patients over a span of 8 years compared with 6 centers that treated more than 50 patients over the same period. It is also interesting to see that in this cohort of patients, none of the patients received a capecitabine combination with mitomycin C or cisplatin. The rate of complete response and locoregional control with the use of concurrent capecitabine range from 77% to 89% and 79% and 94%, respectively, in phase 1/2 studies, and other retrospective series are comparable to prior pivotal studies.5 Ankit Jain, MBBS, MD, DM, DNB, M.CLAM Desmond Yip, MBBS Amy Shorthouse, BMed(hons) Author Affiliations: Department of Medical Oncology, The Canberra Hospital, ANU Medical School, Australian National University, Canberra, Australian Capital Territory, Australia (Jain, Yip); Department of Radiation Oncology, The Canberra Hospital, ANU Medical School, Australian National University, Canberra, Australian Capital Territory, Australia (Shorthouse). Corresponding Author: Ankit Jain, MBBS, MD, DM, DNB, M.CLAM, Department of Medical Oncology, The Canberra Hospital, Australia ANU Medical School, Australian National University, Canberra, Garran 2606, ACT, Australia ([email protected]). Published Online: October 1, 2020. doi:10.1001/jamaoncol.2020.3952 Conflict of Interest Disclosures: None reported. 1. Raphael MJ, Ko G, Booth CM, et al. Factors associated with chemoradiation therapy interruption and noncompletion among patients with squamous cell anal carcinoma. JAMA Oncol. 2020;6(6):881-887. doi:10.1001/jamaoncol.2020. 0809 2. Benson AB III, Venook AP, Al-Hawary MM, et al. Anal carcinoma, version 2.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2018;16(7):852-871. doi:10.6004/jnccn.2018.0060 3. Kachnic LA, Winter K, Myerson RJ, et al. RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal. Int J Radiat Oncol Biol Phys. 2013;86(1):27-33. doi:10.1016/j.ijrobp.2012.09.023 4. UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research. Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. Lancet. 1996;348(9034):1049-1054. doi:10.1016/S0140-6736(96)03409-5 5. Chong LC, Healey T, Michele T, Price TJ. Capecitabine in locally advanced anal cancer, do we need randomised evidence? Expert Rev Anticancer Ther. 2017;17 (5):411-416. doi:10.1080/14737140.2017.1302333

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Letters COMMENT & RESPONSE Survival and Outcomes After Noncompletion of Treatment for Anal Cancer To the Editor We read with great interest the Origi...
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