ESTRO 36 Abstract Book

S98 ESTRO 36 _______________________________________________________________________________________________

Material and Methods Between March 2007 and December 2014, 250 patients with localized prostate cancer underwent PPB, of which 32 patients had MLH identified radiologically on the MRI scan. These patients were divided into three MLH groups, mild(<5mm), moderate(5-10mm), severe(>10mm), by measuring the distance of MLH (dMLH); between the posterior transitional zone and the prostatic tissue protruding into the bladder. We retrospectively analyzed seed migration, DVH, operation time, genitourinary (GU) toxicity, and DFS. Results Median follow-up is 53.5 months (range; 9-104months) and median age is 68.5 years old(range; 57-75yo). MLH group were respectively classified mild in 12, moderate in 12, severe in 8. D’Amico risk classification were low risk in 21, intermediate risk in 11.Median prostate volume was such as 34.4cc/32.8cc/28.6cc (severe/moderate/mild). The median D90 was 145Gy. All patients still have achieved relapse-free survival. Implant migration and low-dose level of median lobe tended to increase in severe MLH.There was no relapse and PSA failure. The IPSS (International Prostate Symptom Score) for most patients worsened during the immediate post-implant period, but most of these patients were resolved by their second follow-up at 6 months. The median IPSS one month or six months after post-implant were respectively 21.5 or 13.We observed Grade 2 acute toxicity. The late toxicity such as Grade 2 was observed in 25%, such as erectile dysfunction, urinary hemorrhage and urethralgia. Hemorrhage in Grade 3 was observed in just one case, who had taken an aspirin for cerebral infarction. There was no Grade 4 complication and the all complication was In our study, MLH does not appear to be a strong contraindication to PPB because there were no significant differences in DFS and GU toxicity. However, we experienced that seed migration and cold spot degree tended to increase in severe MLH cases, we have to pay attention to treat severe MLH. Traditional approaches to head and neck cancer (HNC) have used either surgery +/- adjuvant radiotherapy, or radiotherapy +/- chemotherapy. Thus treatment was practiced with a paradigm that head and neck cancer (HNC) is one disease requiring the same treatment, modulated according to anatomic constraints influencing whether function might be preserved, largely governed by psychosocial attitudes directed at avoidance of surgical ablation with resulting loss of function and esthetic appearance. In fact, while avoiding surgery, a philosophy evolved that greater intensity of non-surgical management is optimal. However, current evidence suggests the contrary and strong evidence that treatment- related death (e.g. pharyngeal disabilities or other problems) is claiming 10-20% of contemporary HNC survivors (Forastiere et al JCO 2013) For the recently emerged HPV-related oropharyngeal cancer (OPC), approaches are even more complex since the traditional cause of death (local or regional recurrence) is now rare and most patients who die of disease succumb to distant metastases (DM). Stage-for-Stage HPV-related OPC has extremely favorable outcomes in terms of locoregional control, overall survival, and outcome of salvage acceptable. Conclusion Award Lecture: Honorary Members’ Award Lectures SP-0191 Optimizing the Treatment of HPV-related Oropharyngeal Cancer: the difficult journey back B. O'Sullivan 1 1 Princess Margaret Cancer Centre University Health Network, Toronto, Canada

treatments compared to traditional HNCs and the evolution to current treatment intensity did not consider HPV-related disease. The profiles of patients with HPV- related OPC at risk of DM are now being better understood. There is opportunity to modify approaches so that intensive local treatment can be minimized while patients at risk of DM are still selected for systemic treatments. These strategies are being carefully explored in clinical trials using risk-stratified approaches directed by relevant end-points intended to safely return to less intensive treatments analogous to those used in a previous era. SP-0192 Potential of radiation therapy to convert the tumor into an in situ vaccine S. Formenti 1 1 Weill Cornell Medical Center of Cornell University, New York- NY, USA Radiation therapy contributes both immunogenic and immunosuppressive signals to the tumor microenvironment. Preclinical strategies to enhance the formers and/or mitigate the latter have demonstrated the concrete possibility to shift this balancing act toward a therapeutic success (J Natl Cancer Inst. 2013;105(4):256- 265). Preclinical experiments in several syngeneic mouse models that mimic the setting of advanced cancer have demonstrated promise of combining radiation and immunotherapy. The preclinical data has consistently found clinical confirmation. Particularly when combined with immune checkpoint blockade, radiotherapy has demonstrated to be a powerful adjuvant to immunotherapy (Clin Cancer Res. 2005;11:728-734). Clinical examples of synergy between radiation and immune checkpoint inhibitors have been reported (N Engl J Med. 2012;366(10):925-931; Transl Oncol. 2012;5(6):404-407; Int J Radiat Oncol Biol Phys. 2013;85(2):293-295; Cancer Immunol Res 2013;1(6):365- 372) and and interim results in our prospective clinical trial confirm this finding (presented in room 1, May 17 session 051). Currently, multiple clinical trials are exploring optimal combinations and scheduling of radiotherapy and immunotherapy. Early evidence from these trials confirms the hypothesis that radiation can enhances responses to immune checkpoint inhibitors but in the majority of patients tumors remain unresponsive, warranting research to identify markers that predict response. A recent study testing radiation with ipilimumab in melanoma suggested that tumor expression of PDL-1 may predict lack of response to radiation and ipilimumab. However, in lung cancer patients treated with radiation and ipilimumab we found high PDL-1 expression among patients achieving durable complete and partial responses, without addition of PD-1 pathway inhibitors (ASTRO Proceedings 2015, abstract #149). In fact, higher expression of immune checkpoints has been hypothesized as a marker of more immunogenic tumors (Science, 2015,October 9: 207-211). In addition, pre-treatment mutational load has been found to be associated with responses to immune checkpoint inhibitors (Science, 2015 Apr 3: 124-8). It will be important to determine if radiation can compensate tumors with a low mutational load, by inducing induce de novo T cell priming to multiple tumor antigens (12) and could, therefore, achieve responses in the absence of pre-existing neoantigens (Science 2015;348(6230):69-74). The overall degree of immune impairment of the patients may also be a critical predictor of response to radiation + immunotherapy. For instance, we found the pretreatment neutrophil / lymphocyte ratio might enable a priori selection of individuals with a propensity to develop abscopal responses to the combination of radiation and GM-CSF (Lancet Oncol. 2015 Jul;16(7):795-803). Strategies at reducing radiation-induced lymphopenia are warranted to assure adequate availability of naïve T cells when