A population-based analysis of the impact of 1 vs. 2 doses of mitomycin on patterns of failure of anal cancer patients treated with concurrent chemoradiotherapy

Kurian Joseph; Zainab Al Habsi; Aswin Abraham; Arun Elangovan; Sunita Ghosh; TruongMinh Pham; Devika Shreekumar; Zeyana Ramji; Kim Paulson; Keith Tankel; Nawaid Usmani; Diane Severin; Dan Schiller; Clarence Wong; Karen Mulder; Hatim Karachiwala; Corinne Doll; Karen King; Tirath Nijjar

doi:10.1016/j.radonc.2024.110219

A population-based analysis of the impact of 1 vs. 2 doses of mitomycin on patterns of failure of anal cancer patients treated with concurrent chemoradiotherapy

Radiother Oncol. 2024 Mar 12:196:110219. doi: 10.1016/j.radonc.2024.110219. Online ahead of print.

Authors

Kurian Joseph¹, Zainab Al Habsi², Aswin Abraham³, Arun Elangovan², Sunita Ghosh⁴, TruongMinh Pham⁵, Devika Shreekumar⁶, Zeyana Ramji⁶, Kim Paulson², Keith Tankel², Nawaid Usmani², Diane Severin², Dan Schiller⁷, Clarence Wong⁸, Karen Mulder⁹, Hatim Karachiwala¹⁰, Corinne Doll¹⁰, Karen King⁹, Tirath Nijjar²

Affiliations

¹ Division of Radiation Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, 11560 University Ave, Edmonton AB T6G 1Z2, Alberta, Canada. Electronic address: kurian.joseph@albertahealthservices.ca.
² Division of Radiation Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, 11560 University Ave, Edmonton AB T6G 1Z2, Alberta, Canada.
³ Division of Radiation Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, 11560 University Ave, Edmonton AB T6G 1Z2, Alberta, Canada. Electronic address: Aswin.Abraham@albertahealthservices.ca.
⁴ Division of Medical Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, Alberta, Canada. Electronic address: sunita.ghosh@albertahealthservices.ca.
⁵ Cancer Research & Analytics, Alberta health services, Edmonton, Alberta, Canada.
⁶ Univerisity of Alberta, Canada.
⁷ Department of Surgical Oncology, Royal Alexandra Hospital, University of Alberta, Edmonton, Alberta, Canada.
⁸ Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Canada.
⁹ Division of Medical Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, Alberta, Canada.
¹⁰ Division of Radiation Oncology, Department of Oncology, University of Calgary & Tom Baker Cancer Centre, Calgary, Alberta, Canada.

PMID: 38479443
DOI: 10.1016/j.radonc.2024.110219

Abstract

Purpose: We report the impact of 1 vs. 2 doses of mitomycin-C (MMC) based chemoradiation (CRT) on patterns of treatment failure and long-term patient outcomes in anal squamous cell carcinoma (ASCC) and the predictors for locoregional failure (LRF) and distant metastasis (DM).

Methods: In this population-based study, we identified all patients with anal cancer in our province treated radically with radiation and concurrent 5-Fluorouracil (5FU) and 1 vs. 2 doses of MMC between the years 2000-2019. The primary outcomes analyzed were locoregional recurrence (LRR), disease free survival (DFS), ASCC cancer-specific survival (ASCC-CSS) and overall survival (OS).

Results: 451 patients were identified. 272 (60%) patients received 1 cycle of MMC (MMC1) and 179 (40%) received 2 cycles (MMC2) as part of the CRT regimen. The median follow-up was 57 (36-252) and 97 (38-239) months for MMC1 and MMC2, respectively. Cox Regression analysis showed stage IIIb and IIIc were associated with worse locoregional recurrence free survival (RFS) (HR=2.851, p=<0.001) and distant RFS (HR=3.391, p=<0.001). Similarly, stage IIIb and IIIc patients had poorer DFS (HR 3.439, p=<0.001), ASCC-SS (HR 3.729, p=<0.001) and OS (2.230, p=<0.001). The use of MMC2 showed a positive impact on improved ASCC-SS (HR 0.569, p=0.029) and distant RFS (HR 0.555, p=0.040) in patients with stage IIIb and IIIc.

Conclusions: Our analysis showed that 1 vs. 2 cycles of MMC along with 5FU and radiation is associated with comparable treatment outcomes in general. However, in patients with stage IIIb and IIIc cancer, 2 doses of MMC were associated with improved ASCC-SS and distant DFS.

Keywords: Anal Cancer; Chemoradiotherapy; Mitomycin-C.