Synapse - 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

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 Journal Article

Authors:	Roth O'Brien, D. A.; Hristidis, V. C.; Chakrani, Z.; McCann, P.; Damato, A.; Williams, V.; Cote, N.; Reyngold, M.; Rosen, R.; Connell, L.; Pappou, E.; Hajj, C.; Paty, P. B.; Horvat, N.; Pernicka, J. S. G.; Fiasconaro, M.; Shia, J.; Lisanti, J.; Wu, A. J.; Gollub, M. J.; Zhang, Z.; Yaeger, R.; Zinovoy, M.; Weiser, M. R.; Saltz, L.; Cuaron, J.; Boe, L.; Cercek, A.; Garcia-Aguilar, J.; Smith, J. J.; Crane, C. H.; Romesser, P. B.
Article Title:	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
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. © 2024 Elsevier Inc.
Keywords:	survival; adult; human tissue; aged; cancer surgery; treatment failure; major clinical study; overall survival; fatigue; neutropenia; cancer recurrence; intensity modulated radiation therapy; salvage therapy; squamous cell carcinoma; cisplatin; fluorouracil; cancer combination chemotherapy; diarrhea; treatment duration; capecitabine; radiation dose; chemotherapy; cancer staging; nuclear magnetic resonance imaging; follow up; cancer grading; progression free survival; computer assisted tomography; anemia; mucosa inflammation; thrombocytopenia; vomiting; radiotherapy; cohort analysis; radiation injury; oncology; retrospective study; distant metastasis; lymphocytopenia; karnofsky performance status; minimal residual disease; granulocyte colony stimulating factor receptor; contrast medium; thorax radiography; disease control; acute toxicity; mitomycin; failure analysis; intensity-modulated radiation therapy; diseases; radiation dermatitis; abdominal radiography; cone beam computed tomography; whole body pet; gross tumor volume; clinical target volume; clinical outcome; pelvis radiography; concurrent chemotherapy; oncological parameters; excisional biopsy; Common Terminology Criteria for Adverse Events; planning target volume; ostomy; methods and materials; human; male; female; article; treatment interruption; anal squamous cell carcinoma; positron emission tomography-computed tomography; late onset disorder; pattern of failures; vagina discharge (disease); anatomical location; anatomical landmark; colostomy-free survival; colostomy free survival; radiation cystitis; radiation proctitis
Journal Title:	International Journal of Radiation Oncology, Biology, Physics
Volume:	121
Issue:	4
ISSN:	0360-3016
Publisher:	Elsevier Inc.
Date Published:	2025-03-15
Start Page:	951
End Page:	962
Language:	English
DOI:	10.1016/j.ijrobp.2024.10.007
PUBMED:	39536799
PROVIDER:	scopus
PMCID:	PMC12067387
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85211020773&doi=10.1016%2fj.ijrobp.2024.10.007&partnerID=40&md5=ac5044cee3b997398937a6cf1eeff499
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Paul B. Romesser -- Source: Scopus