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"Mind the gap" - The impact of variations in the duration of the treatment gap and overall treatment time in the first UK anal cancer trial (ACT I)

Glynne-Jones, Rob, Sebag-Montefiore, David, Adams, Richard, McDonald, Alec, Gollins, Simon, James, Roger, Northover, John M. A., Meadows, Helen M. and Jitlal, Mark 2011. "Mind the gap" - The impact of variations in the duration of the treatment gap and overall treatment time in the first UK anal cancer trial (ACT I). International Journal of Radiation Oncology*Biology*Physics 81 (5) , pp. 1488-1494. 10.1016/j.ijrobp.2010.07.1995

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Purpose: The United Kingdom Coordinating Committee on Cancer Research anal cancer trial demonstrated the benefit of combined modality treatment (CMT) using radiotherapy (RT), infusional 5-fluorouracil, and mitomycin C over RT alone. The present study retrospectively examines the impact of the recommended 6-week treatment gap and local RT boost on long-term outcome. Methods and Materials: A total of 577 patients were randomly assigned RT alone or CMT. After a 6-week gap responders received a boost using either additional external beam radiotherapy (EBRT) (15 Gy) or iridium-192 implant (25 Gy). The effect of boost, the gap between initial treatment (RT alone or CMT) and boost (Tgap), and overall treatment time (OTT) were examined for their impact on outcome. Results: Among the 490 good responders, 436 (89%) patients received a boost after initial treatment. For boosted patients, the risk of anal cancer death decreased by 38% (hazard ratio [HR]: 0.62, 99% CI 0.35–1.12; p = 0.04), but there was no evidence this was mediated via a reduction in locoregional failure (LRF) (HR: 0.90, 99% CI 0.48–1.68; p = 0.66). The difference in Tgap was only 1.4 days longer for EBRT boost, compared with implant (p = 0.51). OTT was longer by 6.1 days for EBRT (p = 0.006). Tgap and OTT were not associated with LRF. Radionecrosis was reported in 8% of boosted, compared with 0% in unboosted patients (p = 0.03). Conclusions: These results question the benefit of a radiotherapy boost after a 6-week gap. The higher doses of a boost may contribute more to an increased risk of late morbidity, rather than local control.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Centre for Trials Research (CNTRR)
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: Squamous cell carcinoma of the anus; Chemoradiation; Treatment gaps; Overall treatment time; Locoregional control
Additional Information: Partly supported by the UCL/H Comprehensive Biomedical Research Centre
Publisher: Elsevier
ISSN: 0360-3016
Funders: Cancer Research UK
Last Modified: 07 Jun 2021 13:06

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