ESTRO 36 Abstract Book

S250 ESTRO 36 _______________________________________________________________________________________________

The role of radiotherapy in pancreatic ductal adenocarcinoma (PDAC) remains controversial. In contrast to the notion that all patients with PDAC die of metastatic disease, at least a 20% suffer and die from local recurrence. The latter provides a strong rationale for improving local control using radiotherapy, including dose escalation with SBRT. The advent of modern RT and imaging technology can reduce toxicity without compromising efficacy. International consensus on the definition of R1-resection in primarily and borderline resectable PDAC is needed to better define radiotherapy indications. SBRT and chemoradiotherapy (CRT) have to be tested in the context of more efficient chemotherapy regimens, such as FOLFIRINOX and Gemcitabine/Nab- paclitaxel if it is to unmask the importance of improved local control. The development of molecular signatures to differentiate patients with high risk of developing only local recurrence from those likely to die of distant metastases is urgently needed. Preclinical and patient data indicate testing the efficacy of immunotherapeutics in combination with (C)RT in future clinical trials. SP-0471 Standard treatment in anal cancer: where do we stand and where should we go? R. Muirhead 1 1 CRUK/MRC Oxford Institute for Radiation Oncology, Oncology, Oxford, United Kingdom Introduction - Anal cancer is a rare disease but the incidence is increasing rapidly. Despite its rarity there is significant research, development and interest in this topic with large phase III trials involving hundreds of patients’ completed, and literature on anal cancer regularly on the “most read” list of radiotherapy journals. The initial phase III trials investigated the use of concurrent chemotherapy with radiotherapy, confirming the benefit of concurrent chemoradiotherapy using Mitomycin and Fluorouracil. These trials changed the standard treatment in anal cancer from APR with permanent stoma to CRT. Subsequent phase III trials have investigated diverse concurrent chemotherapy regimens and the different settings of systemic therapy; namely the role of neo-adjuvant and adjuvant chemotherapy and different concurrent regimens. However these strategies failed to demonstrate significant impact on outcome, and the optimal concurrent regimen remains Mitomycin and Fluorouracil. The ESMO-ESSO-ESTRO and NCCN guidelines support the use of capecitabine as an alternative to fluorouracil, however phase III evidence supporting this recommendation is not available. The phase I and II studies, multicentre and single centre data supporting this regimen, highlight the different toxicity profiles. Due to a failure to demonstrate improved outcomes in recent phase III trials investigating different systemic strategies, moving forward we will need to consider how improving the radiotherapy component of our treatment can improve both cancer outcomes and the late toxicity of this toxic but effective treatment. Radiotherapy Technique - The RTOG 0529, a phase II study investigating the acute toxicity of IMRT in comparison to the historical RTOG 9811, raised some important questions regarding the challenges of implementation of IMRT in anal cancer. The central review of volumes revealed a large numbers of revisions required in contouring. In addition there is a correlation between plans that fail to meet the recommended dose constraints and G3 toxicity. In implementing IMRT, thought has to be given to volumes to be included, doses and fractionations, margins used and organ at risk constraints; each of these issues alongside the relevant literature will be discussed in the context of designing the UK IMRT guidance. Late toxicity and Quality of Life – Until recently there was minimal literature on the late toxicity of this treatment despite cure rates of >70%. With the requirement to

quantify late toxicity in order to design studies to improve morbidity and increasing awareness of cancer survivorship; there is renewed interest in this topic. A number of recent series have reported the late toxicity following IMRT using a combination of physician recorded and patient reported outcome measures. While there is recovery of the majority of acute side effects and quality of life 3 months after completing treatment, diarrhoea, urinary incontinence and dyspareunia persisted beyond 1 year. These adverse effects were reported following "modern" CRT techniques therefore it is arguable that to see an improvement in these outcomes, we will need to explore individualising treatment dose to minimise late effects. RT stratification according to stage – Although there has always been much interest in increasing doses with external beam or brachytherapy boosts in all stages of anal cancer until recently there was no dose response data available. The RTOG 0529 study set a precedence for stratifying dose delivered according to tumour stage. This lecture will discuss the dose response model which reports while there was a dose response in both early and locally advanced stages of tumour, the improved local control rates achieved by dose escalating in locally advanced tumours far exceeds what can be achieved by dose escalating in early tumours. Future international trials - The UK led PLATO study trial (ISRCTN88455282) is funded by Cancer Research UK and incorporates many of the themes of the teaching lecture. PLATO is a unique “umbrella” trial addressing a number of radiotherapy questions in the loco-regional management of anal cancer. It incorporates 3 individual trials: ACT3 - for T1N0 anal margin tumours, evaluating a strategy of selective reduced dose chemoradiotherapy after local excision, within a single arm phase II trial; ACT4 – for T1- 2 N0 (≤4cm) tumours, evaluating reduced dose chemoradiotherapy to the primary tumour, in a randomised 2:1 phase II study, with the aim of reducing toxicity and maintaining efficacy; ACT5 – for T2 N1-3, T3/4 Nany, evaluating dose escalation within a seamless randomised trial design moving from pilot to phase II to phase III, with the aim of reducing locoregional failure. The primary endpoint for all 3 trials is 3 year local regional failure, key secondary outcomes will focus on patient reported outcome measures. SP-0472 The pros, cons, process and challenges for achieving better radiotherapy through data -an introduction L.C. Holloway 1,2,3,4 1 Ingham Institute and Liverpool and Macarthur Cancer Therapy Centres, Medical Physics, Sydney, Australia 2 University of Wollongong, Centre for Medical Radiation Physics, Wollongong, Australia 3 University of Sydney, Institute of Medical Physics, Sydney, Australia 4 University of New South Wales, South West Sydney Clinical School, Sydney, Australia The magnitude and use of data is expanding in many areas including medicine. The opportunities for using data to improve our knowledge and understanding are many and varied including demographic, disease and outcome investigations. Within current radiotherapy practice data may be collected in a very rigorous approach within for instance a clinical trial framework and data is also collected in an ongoing fashion during standard clinical practice. It is possible for us to gain knowledge from both rigorously collected data and clinical practice data. The gold standard of randomised clinical trial (RCT) Joint Symposium: ESTRO-RANZCR: Big data to better radiotherapy