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Prognostic factors for recurrence and survival in anal cancer
Generating hypotheses from the mature outcomes of the first United Kingdom Coordinating Committee on Cancer Research Anal Cancer Trial (ACT I)
Version of Record online: 25 SEP 2012
Copyright © 2012 American Cancer Society
Volume 119, Issue 4, pages 748–755, 15 February 2013
How to Cite
Glynne-Jones, R., Sebag-Montefiore, D., Adams, R., Gollins, S., Harrison, M., Meadows, H. M., Jitlal, M. and for the United Kingdom Coordinating Committee on Cancer Research Anal Cancer Trial Working Party (2013), Prognostic factors for recurrence and survival in anal cancer. Cancer, 119: 748–755. doi: 10.1002/cncr.27825
- Issue online: 4 FEB 2013
- Version of Record online: 25 SEP 2012
- Manuscript Accepted: 7 AUG 2012
- Manuscript Revised: 31 JUL 2012
- Manuscript Received: 26 JUN 2012
- anal cancer;
- squamous cell carcinoma;
- locoregional failure;
- prognostic factors
Only 2 prospective studies have previously reported prognostic factors for anal cancer, European Organization for Research and Treatment of Cancer trial 22861 (EORTC 22861) and Radiation Therapy Oncology Group trial 98-11 (RTOG 98-11). Both of those trials reported that clinically positive lymph nodes and male sex predicted poorer overall survival (OS). The EORTC 22861 trial indicated that the same factors were prognostic for locoregional control. In the current report, the authors investigated potential prognostic factors from the first United Kingdom Coordinating Committee on Cancer Research Anal Cancer Trial (ACT I), in which patients were randomized to receive either radiotherapy alone or chemoradiation (CRT) with concurrent 5-fluorouracil/mitomycin C.
In the ACT I trial, associations between several baseline characteristics and 3 endpoints were investigated: locoregional failure (LRF), anal cancer death (ACD), and OS. The analyses were restricted to 292 patients who received CRT, which subsequently became standard treatment. A score was derived using multivariable Cox regression to identify the set of factors that, together, had the best prognostic performance. This score was then validated with a large, independent prospective trial (the ACT II trial).
Palpable, clinically positive lymph nodes were associated with LRF (P = .012), a greater risk of ACD (P = .031), and decreased OS (P = .006) in multivariable analyses. Men had worse outcomes than women for LRF (P = .036), ACD (P = .039), and OS (P = .008). On average, a lower hemoglobin level had an adverse effect on ACD (P = .008), and a higher white blood cell count had an adverse effect on OS (P = .001). However, external validation of the score was poor for LRF (area under the curve [AUC] = 54%) but was better for ACD (AUC = 67%) and OS (AUC = 63%).
The results from this analysis of the ACT I trial supported evidence for palpable lymph nodes and male sex as prognostic factors for LRF and OS, and lower hemoglobin levels and a higher white blood cell count were identified as prognostic factors for ACD and OS, respectively. Cancer 2013. © 2012 American Cancer Society.