Pre-operative chemoradiotherapy (CRT) for MRI-defined, locally advanced rectal cancer is primarily intended to reduce local recurrence rates by downstaging tumours, enabling an improved likelihood of curative resection. However, in a subset of patients complete tumour regression occurs implying that no viable tumour is present within the surgical specimen. This raises the possibility that surgery may have been avoided. It is also recognised that response to CRT is a key determinant of prognosis. Recent radiological advances enable this response to be assessed pre-operatively using the MRI tumour regression grade (mrTRG). Potentially, this allows modification of the baseline MRI-derived treatment strategy. Hence, in a ‘good’ mrTRG responder, with little or no evidence of tumour, surgery may be deferred. Conversely, a ‘poor response’ identifies an adverse prognostic group which may benefit from additional pre-operative therapy. TRIGGER is a multicentre, open, interventional, randomised control feasibility study with an embedded phase III design. Patients with MRI-defined, locally advanced rectal adenocarcinoma deemed to require CRT will be eligible for recruitment. During CRT, patients will be randomised (1:2) between conventional management, according to baseline MRI, versus mrTRG-directed management. The primary endpoint of the feasibility phase is to assess the rate of patient recruitment and randomisation. Secondary endpoints include the rate of unit recruitment, acute drug toxicity, reproducibility of mrTRG reporting, surgical morbidity, pathological circumferential resection margin involvement, pathology regression grade, residual tumour cell density and surgical/specimen quality rates. The phase III trial will focus on long-term safety, regrowth rates, oncological survival analysis, quality of life and health economics analysis. The TRIGGER trial aims to determine whether patients with locally advanced rectal cancer can be recruited and subsequently randomised into a control trial that offers MRI-directed patient management according to radiological response to CRT (mrTRG). The feasibility study will inform a phase III trial design investigating stratified treatment of good and poor responders according to 3-year disease-free survival, colostomy-free survival as well as an increase in cases managed without a major resection. ClinicalTrials.gov, ID: NCT02704520 . Registered on 5 February 2016.

Purpose of Review Pathological complete response is seen in approximately one fifth of rectal cancer patients following neoadjuvant chemoradiation. Since these patients have excellent oncological outcomes, there has been a rapidly growing interest in organ preservation for those who develop a clinical complete response. We review the watch-and-wait strategy and focus on all aspects of this hot topic, including who should be considered for this approach, how should we identify treatment response and what are the expected outcomes. Recent Findings The major challenges in interpreting the data on watch-and-wait are the significant heterogeneity of patients selected for this approach and of methods employed to identify them. The evidence available comes mostly from retrospective cohort studies, but has shown good oncological outcomes, including the rate of successful salvage surgery, locoregional control and overall survival. Summary There is currently not enough and not robust enough evidence to support watch-and-wait as a standard approach, outside a clinical trial, for patients achieving clinical complete response following neoadjuvant chemoradiation. Furthermore, there is a lack of data on long-term outcomes. However, the results we have so far are promising, and there is therefore an urgent need for randomised control studies such as the TRIGGER trial to confirm the safety of this strategy.

Intensity-modulated radiotherapy (IMRT) for anal canal carcinoma (ACC) is associated with favourable toxicity outcomes. Side effects include sexual dysfunction, skin desquamation, pain and fibrosis to perineum and genitalia region. The genitalia are situated anterior to the primary ACC between two inguinal regions providing a challenging structure to avoid. Techniques improving outcomes require robust, consistent genitalia contouring to ensure standardization and production of fully optimized IMRT plans. Official recommendations for genitalia contouring are lacking. We describe a potential genitalia contouring atlas for ACC radiotherapy. Following a review of genitalia CT anatomy, a contouring atlas was generated for male and female patients positioned prone and supine. Particular attention was paid to the reproducibility of the genitalia contour in all planes. Male and female genitalia positioned prone and supine are described and represented visually through a contouring atlas. Contoured areas in males include penis and scrotum, and in females include clitoris, labia majora and minora. The muscles, bone, prostate, vagina, cervix and uterus should be excluded. The genitalia contour extends laterally to inguinal creases and includes areas of fat and skin anterior to the symphysis pubis for both genders. This atlas provides descriptive and visual guidance enabling more consistent genitalia delineation for both genders when prone and supine. The atlas can be used for other sites requiring radiotherapy planning. This atlas presents visual contouring guidance for genitalia in ACC radiotherapy for the first time. Contouring methods provide reproducible genitalia contours that allow the provision of accurate dose toxicity data in future studies.

Objective: Literature regarding image-guidance and interfractional motion of the anal canal (AC) during anal cancer radiotherapy is sparse. This study investigates interfractional AC motion during anal cancer radiotherapy. Methods: Bone matched cone beam CT (CBCT) images were acquired for 20 patients receiving anal cancer radiotherapy allowing population systematic and random error calculations. 12 were selected to investigate interfractional AC motion. Primary anal gross tumour volume and clinical target volume (CTVa) were contoured on each CBCT. CBCT CTVa volumes were compared to planning CTVa. CBCT CTVa volumes were combined into a CBCT-CTVa envelope for each patient. Maximum distortion between each orthogonal border of the planning CTVa and CBCT-CTVa envelope was measured. Frequency, volume and location of CBCT-CTVa envelope beyond the planning target volume (PTVa) was analysed. Results: Population systematic and random errors were 1 and 3 mm respectively. 112 CBCTs were analysed in the interfractional motion study. CTVa varied between each imaging session particularly T location patients of anorectal origin. CTVa border expansions ≥ 1 cm were seen inferiorly, anteriorly, posteriorly and left direction. The CBCT-CTVa envelope fell beyond the PTVa ≥ 50% imaging sessions (n = 5). Of these CBCT CTVa distortions beyond PTVa, 44% and 32% were in the upper and lower thirds of PTVa respectively. Conclusion: The AC is susceptible to volume changes and shape deformations. Care must be taken when calculating or considering reducing the PTV margin to the anus. Advances in knowledge: Within a limited field of research, this study provides further knowledge of how the AC deforms during anal cancer radiotherapy.