ESTRO 2020 Abstract book

S297 ESTRO 2020

tumors or distant metastasis. Herein, the role of aberrant cancer metabolism emerges as a potential therapeutic target in radiation oncology. Oncogene-driven aberrant cell metabolism and scavenging of nutrients from the microenvironment are common characteristics of cancer cells and help them to meet the high demands in energy, building blocks and antioxidant capacity to fuel abnormal growth and proliferation. High consumption of glucose is exploited for diagnostic imaging and target volume definition in radiotherapy. However, by limiting oxygen and nutrients such as glucose and amino acids, and by secreting metabolites such as lactate in high concentrations into the tumor environment an aberrant cancer metabolism also impacts the composition, the phenotype, and the activation state of stromal cells in the tumor microenvironment with relevance to the outcome of radiotherapy and combinatorial treatments. Herein, the pronounced plasticity of cell metabolism allows cells to dynamically reprogramm their metabolism under fluctuating nutrient and oxygen availability in the tumor microenvironment and to meet altered bioenergetic and redox demands upon exposure to radiotherapy. Of note, stress-induced metabolic adaptation can create novel metabolic vulnerabilities amenable to pharmacologic inhibition to improve radiotherapy outcome. The presentation will introduce metabolic pathways and adaptive metabolic processes in the adverse tumor microenvironment with relevance to efficacy and toxicity of radiotherapy and combinatorial treatments. The presentation will also discuss metabolic characteristics of the cellular radiation response in view of the reported links between cell metabolism and DNA repair, and of metabolic inhibitors that might be suited for increasing cancer cell radiosensitivity. Finally, the presentation will highlight some limitations and requirements for a future clinical use of cancer metabolism as therapeutic target in radiation oncology. SP-0490 The treatment of anal cancer D. Sebag-Montefiore 1 1 university Of Leeds And Leeds Cancer Centre, Leeds Cancer Centre, Leeds, United Kingdom Abstract text Introduction - Anal cancer is a rare disease but its incidence is rising rapidly. The majority of tumours are squamous cell carcinoma or its histological variants. A high proportion of these cancers are associated with HPV viral exposure. Despite its rarity phase, III clinical trials have been successfully performed. Three phase III trials determined the standard of care for the curative treatment of anal cancer as concurrent chemoradiotherapy using Mitomycin C and 5 fluorouracil. A further three phase III trials that explored the use of neoadjuvant, concurrent or maintenance cisplatin based chemotherapy did not change the standard of care. The ESMO-ESSO-ESTRO and NCCCN guidelines provide evidence based recommendations for the management of anal cancer and aspects of the guidelines will be reviewed during this teaching lecture. Staging – Although pelvic MR is not mandated in the guidelines it provides superior anatomical images of the primary tumour. CT-PET is also not mandated but is shown to upstage a minority of patients from a “N0” category to Teaching Lecture: The treatment of anal cancer

“N+.” Recent evidence that improved imaging may result in stage migration will be discussed. Radiotherapy dose – despite evidence of a clear dose response relationship and differing complete response rates for the regional stage of the disease, there is very limited data to inform the optimal radiation dose. There is wide international variation in the dose prescription used and limited high quality data sets that report patient focused late toxicity outcomes. The EORTC ANL27 questionnaire is a welcome development to assess late toxicity Radiotherapy technique and target volume definition - The use of IMRT has significantly increased in the treatment of anal cancer and its use is supported by the RTOG 0529 phase II trial, UK guidelines and other guidance. Although IMRT is preferred and will reduce acute genital toxicity, careful target volume definition and delineation of organs at risk and high quality QA are required to ensure accurate treatment delivery. Response assessment - Clinical and radiological assessment is required to both identify early local treatment failures and to establish whether complete response had been achieved. The ACT 2 clinical trial data will be used to discuss the best time to assess complete response.Treatment of metastatic disease - Approximately 10-20% of patients will develop metastatic disease. Recent clinical trial data will be discussed regarding first and second line treatment including the InterAAcT tria, an international randomized phase II study comparing cisplatin 5FU with Carboplatin and Paclitaxel Research - Clinical trials are essential to provide more information on outcome and late toxicity with the use of IMRT. The UK led PLATO trial consortium are conducting a “platform” type trial with the ACT3,4 and 5 trials addressing specific research questions to optimize radiotherapy dose with associated translational research. Other key ongoing trials will also be discussed SP-0491 Latest updates on non-metastatic nasopharyngeal carcinoma in 2020: screening, workup, and treatment paradigms M.L.K. Chua 1 1 National Cancer Center Singapore, Radiation Oncology, Singapore, Singapore Abstract text The treatment landscape of nasopharyngeal carcinoma (NPC) has evolved substantially in recent years, and thus deserves a timely update. In the 90s, improvement in survival rates of locally advanced (stage 3 and 4) NPC were driven by both advances in radiotherapy and the combination of radiotherapy with systemic chemotherapy. This has led to a change in the natural history of the disease, with distant metastasis dominating as the primary pattern of failure. This clinical phenomenon has provided the scientific rationale for the design of more contemporary studies testing the clinical efficacy of different timings, sequencing, and intensities of chemotherapy in combination with radiotherapy. We now have new data from several randomised clinical trials supporting the recommendation of induction chemotherapy with chemo-radiotherapy as an option for first-line standard of care in these high-risk patients. Teaching Lecture: Latest updates on non-metastatic nasopharyngeal carcinoma in 2020: screening, workup, and treatment paradigms