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. 2025 Mar 15;121(4):951-962.
doi: 10.1016/j.ijrobp.2024.10.007. Epub 2024 Nov 12.

Clinical Outcomes, Patterns of Failure, and Salvage Therapies of a Large Modern Cohort of Patients With Anal Squamous Cell Carcinoma Treated With Definitive-Intent Intensity-Modulated Radiation Therapy

Diana A Roth O'Brien  1 , Vasilis C Hristidis  1 , Zakaria Chakrani  1 , Patrick McCann  2 , Antonio Damato  2 , Vonetta Williams  1 , Nicolas Cote  2 , Marsha Reyngold  1 , Roni Rosen  3 , Louise Connell  4 , Emmanouil Pappou  3 , Carla Hajj  1 , Philip B Paty  3 , Natally Horvat  5 , Jennifer S Golia Pernicka  5 , Megan Fiasconaro  6 , Jinru Shia  7 , Jeanine Lisanti  1 , Abraham J Wu  1 , Marc J Gollub  5 , Zhigang Zhang  6 , Rona Yaeger  4 , Melissa Zinovoy  1 , Martin R Weiser  3 , Len Saltz  4 , John Cuaron  1 , Lillian Boe  6 , Andrea Cercek  4 , Julio Garcia-Aguilar  3 , J Joshua Smith  3 , Christopher H Crane  1 , Paul B Romesser  8
Affiliations

Clinical Outcomes, Patterns of Failure, and Salvage Therapies of a Large Modern Cohort of Patients With Anal Squamous Cell Carcinoma Treated With Definitive-Intent Intensity-Modulated Radiation Therapy

Diana A Roth O'Brien et al. Int J Radiat Oncol Biol Phys. .

Abstract

Purpose: Patterns of failure and salvage therapy options for patients with anal squamous cell carcinoma (ASCC) who recur after definitive-intent intensity-modulated radiation therapy (IMRT) with concurrent chemotherapy are not well described.

Methods and materials: We identified consecutive patients with ASCC treated with definitive-intent IMRT between July 2005 and December 2019. Relevant patient and tumor parameters, disease outcomes (locoregional failure [LRF], distant failure, progression-free survival, colostomy-free survival, and overall survival [OS]), patterns of failure, and salvage therapies were collected. Failures were analyzed using competing risk methods, whereas survival endpoints were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed. Landmark analyses were conducted by considering whether patients had LRF within 12 months of completing IMRT.

Results: A total of 375 patients were identified with a median follow-up of 6 years. Stage breakdown was 15%, 23%, and 62% for the American Joint Committee on Cancer stages 0 to I, II, and III, respectively. Six-year rates of LRF, distant failure, progression-free survival, colostomy-free survival, and OS were 12%, 13%, 73%, 76%, and 80%, respectively. Disease recurred in 74 patients. Among the 45 patients with LRF, 39 (87%) failed within the anorectum, with 25 anal canal, 6 anal margin, and 8 rectal recurrences. Only 4 (9%) patients had isolated nodal failure. Patients experiencing LRF had worse 6-year OS than patients without LRF (44% vs 86%, P < .0001). Approximately 30% of patients who underwent salvage therapy were alive to 10 years after recurrence, compared with none of the patients who were managed with chemotherapy alone or the best supportive care.

Conclusions: This large ASCC cohort managed with definitive-intent IMRT demonstrated excellent rates of locoregional control and survival. Isolated regional nodal failures were uncommon, whereas the majority of LRFs occurred within the anorectum, despite dose escalation by tumor stage. We observed poor outcomes for patients experiencing locoregional disease recurrence, even after aggressive salvage treatment.

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Conflict of interest statement

P.B.R received research funding (2019) and serves as a consultant for EMD Serono (2018-present), receives research funding from XRAD Therapeutics (2022-present), is a consultant for Faeth Therapeutics (2022-present), is a consultant for Natera (2022-present), and is a volunteer on the advisory board for the HPV Alliance and Anal Cancer Foundation non-profit organizations.

J.J.S. received travel support for fellow education from Intuitive Surgical (August 2015). He also served as a clinical advisor for Guardant Health (March 2019), a clinical advisor for Foundation Medicine (April 2022), and a consultant and speaker for Johnson and Johnson (May 2022); he serves as a clinical advisor and consultant for GSK (2023-24).

J.G.A. owns stock in Intuitive Surgical. He also receives as Honoraria from Johnson & Johnson and Intuitive Surgical, and is a consultant for Medtronic, Intuitive Surgical, and Johnson & Johnson.

M.R.W. serves as a consultant for Precisca and as a section editor for UpToDate.

A.C. receives research funding from Seagen, Rgenix, and GlaxoSmithKline. She also serves as a consultant for Bayer, GlaxoSmithKline, Incyte, Merck, Janssen, Seagen, and G1 Therapeutics.

L.S. serves as a consultant for Genor BioPharma.

M.J.G. serves as a consultant for GlaxoSmithKline.

N.H. receives honoraria from Bayer and serves as a consultant for Guerbet.

A.D. receives research funding from Alpha Tau Medical and partial support for conference travel. He also has 3 patents pending of which 2 are related to brachytherapy and 1 is related to workflow management for RT planning. He was also the Chait of the AAPM working group on brachytherapy application and is a member of the AAPM brachytherapy SC.

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