Radiotherapy re-treatments can be clinically useful but require careful dose and treatment technique selection.

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1 Pelvic re-irradiation 08:30 09:15 The basics of re-irradiation Professor Bleddyn Jones, Oxford Institute of Radiation Radiotherapy re-treatments can be clinically useful but require careful dose and treatment technique selection. Increasing the elapsed time between two treatment courses allows recovery of radiotolerance in the central nervous system (CNS) white matter, such as spinal cord and optic chiasm. The recovery process appears to start at around 90 days after the first treatment is completed. A graphical user interface is now available it contains all available radiobiological data sets and allows estimation of re-treatment dose and fractionation. For the use of protons in re-treatment, careful assessment of linear energy transfer (LET) and relative biological effectiveness (RBE) is also required. Jones B and Grant W. Retreatment of central nervous system tumours. Clin Oncol 2014; 26: Jones B and Hopewell JH. Alternative models for estimating the radiotherapy retreatment dose for the spinal cord. Int J Radiat Biol 2014; 90(9): Woolley TE, Belmonte-Beitia J, Calvo GF, Hopewell JW, Gaffney EA, Jones B. Changes in the retreatment radiation tolerance of the spinal cord with time after the initial treatment. Int J Radiat Biol 2018; 94(6):

2 Pelvic re-irradiation (continues) 09:15 10:00 Re-irradiation in rectal cancer Professor Harm Rutten, Department of Surgery, Catharina Ziekenhuis, Netherlands The role of re-irradiation in the management of locally recurrent rectal cancer. Safety and morbdity of re-irradiation. Combination of re-irradiation with intraoperative radotherapy. The possible advantages of induction chemotherapy before re-irradiation. Interval between re-irradiation and surgery. van Zoggel DMGI, Bosman SJ, Kusters M et al. Preliminary results of a cohort study of induction chemotherapy-based treatment for locally recurrent rectal cancer. Br J Surg 2018; 105(4): Bosman SJ, Holman FA, Nieuwenhuijzen GA et al. Feasibility of reirradiation in the treatment of locally recurrent rectal cancer. Br J Surg 2014; 101(10): Holman FA, Bosman SJ, Haddock MG et al. Results of a pooled analysis of IOERT containing multimodality treatment for locally recurrent rectal cancer: Results of 565 patients of two major treatment centres. Eur J Surg Oncol 2017; 43(1):

3 Pelvic re-irradiation (continues) 11:00 11:55 Re-irradiation using stereotactic ablative radiotherapy (SABR) in the pelvis Dr Louise Murray, Leeds Institute of Cancer and Pathology Pelvic SABR re-irradiation could be a feasible option for previously irradiated patients with pelvic recurrence who otherwise have limited options. There is limited and highly heterogeneous evidence to support pelvic SABR re-irradiation and this suggests initial promise. There is a paucity of evidence regarding the appropriate organ at risk constraints for pelvic SABR re-irradiation. Accounting for anatomical and positional changes between courses of radiotherapy is one of the significant challenges when considering pelvic SABR re-irradiation. Changes in fractionation between courses of radiotherapy should be taken into account when considering pelvic SABR re-irradiation. Abusaris H, Hoogeman M, Nuyttens JJ. Re-irradiation: outcome, cumulative dose and toxicity in patients retreated with stereotactic radiotherapy in the abdominal or pelvic region. Technol Cancer Res Treat 2012; 11(6): Mantel F, Flentje M, Guckenberger M. Stereotactic body radiation therapy in the reirradiation situation a review. Radiat Oncol 2013; 8: 7. Murray LJ, Lilley J, Hawkins MA et al. Pelvic re-irradiation using stereotactic ablative radiotherapy (SABR): A systematic review. Radiother Oncol 2017; 125(2):

4 Pelvic re-irradiation (continued) 15:00 15:15 Using proton therapy for retreatment in the pelvis Dr Stephen Hahn, MD Anderson Cancer Centre, Texas, USA Understand the rationale for proton therapy in the re-irradiation setting. Understand the potential indications of proton therapy in the re-irradiation setting. Understand the current status of studies evaluating re-irradiation with proton therapy. Smith GL, Ganz PA, Bekelman JE et al. Promoting the appropriate use of advanced radiation technologies in oncology: summary of a national cancer policy forum workshop. Int J Radiat Oncol Biol Phys 2017; 97(3): Verma V, Rwigema JM, Malyapa RS et al. Systematic assessment of clinical outcomes and toxicities of proton radiotherapy for reirradiation. Radiother Oncol 2017: 125(1): Boimel PJ, Berman AT, Li J, Apisarnthanarax S et al. Proton beam reirradiation for locally recurrent pancreatic adenocarcinoma. J Gastronintes Oncol 2017; 8(4):

5 Pelvic re-irradiation 15:15 16:10 Re-irradiation with brachytherapy in prostate cancer Dr Roberto Alonzi, Mount Vernon Cancer Centre, Middlesex Re-irradiation of the prostate gland is possible using both high- and low- dose rate brachytherapy with a number of technical challenges that need to be considered. Case selection is very important with patients who have slow prostate specific antigen (PSA) doubling times and long intervals between primary and salvage treatments achieving the best outcomes. Meticulous pre-salvage restaging is critical with detailed re-imaging of the prostate and pelvis with multi-parametric magnetic resonance imaging (MRI), whole-body imaging with choline or PSMA positron emission tomography (PET) or whole-body MRI and a full mapping template biopsy essential before embarking on salvage re-treatment. The incidence and severity of side-effects following prostate re-irradiation seems to be correlated with the volume of the prostate that receives re-treatment with whole gland salvage causing the worst toxicity and small volume focal re-treatment doing the best. Isolated re-irradiation of a seminal vesicle appears to be associated with the least toxicity. Re-irradiation in prostate cancer is an emerging area of research with a number of clinical trials investigating its efficacy and toxicity. Results from several phase II studies are available but as yet there is no phase III evidence or studies that report more than five-year outcomes. H Tharmalingam, M Hamada, Y Tsang, PJ Hoskin and R Alonzi. Salvage high-dose rate (HDR) brachytherapy as a treatment for locally recurrent prostate cancer after primary radiation therapy. Oral presentation RCR18 Liverpool, September Audrey Tetreault-Laflamme and JuanitaCrook. Options for salvage of radiation failures for prostate cancer. Seminars in Radiation Oncology, 2016 Duijzentkunst DA, Peters M, van der Voort van Zyp JR, Moerland MA, van Vulpen M. Focal salvage therapy for local prostate cancer recurrences after primary radiotherapy: a comprehensive review. World J Urol 2016; 34(11):

6 Pelvic re-irradiation 16:40 17:40 Re-irradiation of prostate cancer using stereotactic ablative radiotherapy (SABR) Dr Mauro Loi, Hôpitaux Universitaires Est Parisien, Paris Following radical radiotherapy for prostate cancer, isolated intraprostatic local failure may occur in a significant fraction of patients experiencing biochemical recurrence. Despite initial disappointing results of salvage external beam radiotherapy, re-irradiation using stereotactic body radiotherapy showed promising results in terms of efficacy and tolerability despite technical challenges and risk of severe toxicities. A growing body of literature and emerging morpho-metabolic techniques may provide criteria for selection of patients suitable for salvage treatment and improve the accuracy of focal therapies in previously irradiated patients. Limited level of evidence and methodologic heterogeneity among available studies, underestimation or under-reporting of adverse events, low agreement between experts, and lack of prospective data should be addressed to resolve uncertainties in order to further develop this non-invasive alternative to current salvage options. To better address the utility of re-sbrt, consensus agreement among expert and prospective multicentric collection of data is strongly advised to identify suitable candidates, predictors of efficacy and toxicity, and appropriate dose and target volumes in order to achieve consensus on uniform standardised trial design and develop radiobiological models. Jereczek-Fossa BA, Beltramo G, Fariselli L et al. Robotic image-guided stereotactic radiotherapy, for isolated recurrent primary, lymph node or metastatic prostate cancer. Int J Radiat Oncol Biol Phys 2012; 82(2): Loi M, Di Cataldo V, Simontacchi G et al. Robotic stereotactic retreatment for biochemical control in previously irradiated patients affected by recurrent prostate cancer. Clin Oncol (R Coll Radiol) 2018; 30(2): van den Bos W, Muller BG, de Bruin DM et al. Salvage ablative therapy in prostate cancer: international multidisciplinary consensus on trial design. Urol Oncol 2015; 33(11): 495.e1 7

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