Anal cancer
A tumor control probability model for anal squamous cell carcinoma

https://doi.org/10.1016/j.radonc.2015.07.014Get rights and content

Abstract

Background and purpose

A recent update of the RTOG 9811, reported differing relapse rates for early and late anal squamous cell carcinoma following chemoradiotherapy (CRT). There may be a role for dose-individualization, however the dose–response relationship for anal cancer is not currently known.

Intensity-modulated radiotherapy (IMRT) has been widely adopted with multiple series published. The aim is to fit a tumor control probability (TCP) model to the published IMRT data.

Materials and methods

We performed a systematic review of PubMed and Embase databases to identify thirteen appropriate papers, including 625 patients. Predefined data fields were collected. A standard linear quadratic TCP model, which included repopulation, was fit by least squares minimization.

Results

The fitted TCP curve demonstrated a dose–response relationship with α = 0.196 Gy–1. The curve suggests: in early stage tumours, a dose reduction from 50 Gy to 45 Gy reduces 2 year local control from 98% to 95%; in late stage tumours, a dose escalation from 50 Gy to 55 Gy improves the 2 year local control rate from approximately 50% to 80%.

Conclusions

The published data are broadly consistent with a linear quadratic dose–response model. Dose-individualization in anal cancer should be further investigated in the context of clinical trials.

Section snippets

Materials and methods

We performed a systematic review of PubMed (i.e., MEDLINE and other PubMed resources) and Embase databases in accordance to PRISMA guidelines. The searches were limited to full papers, published in the English language from January 2005 to July 2014 involving the treatment of human patients. Search terms included IMRT, intensity modulated radiotherapy, anal and anus. Four papers were excluded; two as the same series was subsequently updated in a further publication therefore the latter

Results

Thirteen publications incorporating 645 patients were identified, details of individual series are presented in Table 1 [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38].

The resulting 2-year local control predictive models for early and late stage disease are shown in Fig. 1 together with the clinical data from the individual series used for model fitting. Series with a stage mix >60% T1 and T2 are shown as points (●) and series with a stage mix >40% T3+ are shown as

Discussion

We report TCP models for early stage and late stage anal carcinoma and demonstrate a dose–response curve in both. To our knowledge a TCP model in anal cancer has not been previously published. This study highlights the role of individualised radiotherapy dose allowing dose de-escalation in early stage tumours and dose escalation in locally-advanced tumours as a platform for investigation.

Although the IMRT series are more homogeneous than previous conformal series, there remains a degree of

Conflicts of interest statement

None to declare.

Acknowledgments

M.P. is funded by CR UK grant C5255/A15935.

R.M. and M.A.H. are supported by MRC Grant MC_PC_12001/2.

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