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

doi:10.1016/j.ijrobp.2024.10.007

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

Int J Radiat Oncol Biol Phys. 2024 Nov 12:S0360-3016(24)03470-9. doi: 10.1016/j.ijrobp.2024.10.007. Online ahead of print.

Authors

Diana A Roth O'Brien¹, Vasilis C Hristidis¹, Zakaria Chakrani¹, Patrick McCann², Antonio Damato², Vonetta Williams¹, Nicolas Cote², Marsha Reyngold¹, Roni Rosen³, Louise Connell⁴, Emmanouil Pappou³, Carla Hajj¹, Philip B Paty³, Natally Horvat⁵, Jennifer S Golia Pernicka⁵, Megan Fiasconaro⁶, Jinru Shia⁷, Jeanine Lisanti¹, Abraham J Wu¹, Marc J Gollub⁵, Zhigang Zhang⁶, Rona Yaeger⁴, Melissa Zinovoy¹, Martin R Weiser³, Len Saltz⁴, John Cuaron¹, Lillian Boe⁶, Andrea Cercek⁴, Julio Garcia-Aguilar³, J Joshua Smith³, Christopher H Crane¹, Paul B Romesser⁸

Affiliations

¹ Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York, New York.
² Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York.
³ Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York.
⁴ Department of Medicine, Gastrointestinal Service, Memorial Sloan Kettering Cancer Center, New York, New York.
⁵ Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
⁶ Department of Epidemiology and Biostatistics, Biostatistics Service, Memorial Sloan Kettering Cancer Center, New York, New York.
⁷ Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
⁸ Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Early Drug Development Service, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address: [email protected].

PMID: 39536799
DOI: 10.1016/j.ijrobp.2024.10.007

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.