Abstract
BackgroundOrgan-preserving chemo-radiotherapy (CRT) is the standard of care for non-metastatic anal squamous cell carcinoma (SCC). The optimal dosing schedules are yet to be determined. To improve local control rates, dose escalation has been investigated but found to not increase efficacy at the expense of increased toxicity for an unselected patient population.Diffusion weighted imaging (DWI) and dynamic contrast enhanced (DCE) Magnetic Resonance Imaging (MRI) performed during CRT have early data suggesting it to be an effective tool in predicting later tumour response for SCC in related body sites.By performing multi-parametric MRI (mpmMRI) incorporating standard morphological, DWI and DCE sequences, we aim to determine whether the early changes in multi-parametric parameters during CRT can predict for later response in anal SCC. This may create opportunities to investigate treatment adaptation, either intensification or de-escalation, during CRT.Methods/DesignThis protocol describes a prospective non-interventional multi-centre single-arm clinical trial. Twenty eligible patients with histologically confirmed non-metastatic anal SCC will receive standard definitive CRT and undergo multi-parametric MRI’s at the following 4 time points; prior to treatment, during the second and fourth weeks of treatment and 6-8 weeks following treatment.Complete response will be defined by the absence of tumour persistence or recurrence as determined by clinical examination at 6 months.Images will be retrospectively analysed to determine the apparent diffusion coefficient and tumour perfusion coefficients (Ktrans and Kep) at each time point. The Mann-Whitney-Wilcoxon Test will be utilised to compare the change in these parameters for responder’s verses non-responders.DiscussionIf validated, mpmMRI, along with other risk factors, can be used to stratify patients and guide radiation dosing in a prospective trial. Informed individualisation of treatment intensity should help us achieve our goals of improved efficacy and reduced toxicity.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12614001219673 (19/11/2014).
Highlights
Organ-preserving chemo-radiotherapy (CRT) is the standard of care for non-metastatic anal squamous cell carcinoma (SCC)
If validated, multi-parametric Magnetic Resonance Imaging (MRI) (mpmMRI), along with other risk factors, can be used to stratify patients and guide radiation dosing in a prospective trial
As cervical and some head and neck SCCs share a common aetiology with anal SCC via Human Papilloma Virus (HPV), there are grounds to hypothesize that similar tumour response patterns may occur across these various malignancies when treated with organ preserving CRT
Summary
There is no consensus on the optimal radiation dose for the treatment of patients with AC. Improved prognostication may be achieved with further information such as HPV status and mpmMRI tumour response. If this exploratory phase 2 study finds compelling evidence for an imaging biomarker being independently predictive of later tumour response, a subsequent study would aim to validate this by intensifying radiotherapy dose for tumours with unfavourable biology, and deescalating radiotherapy dose for favorable tumours. JM conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors participated in the design of the study.
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