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carcinoma was conducted. Patients were randomized to receive SBRT either prior to the first cycle (arm A) or prior to the third cycle (arm B) of pembrolizumab. SBRT was delivered in 3 fractions of 8 Gy to the largest lesion that could be irradiated safely. Secondary outcomes include overall objective response rate according to RECIST v1.1 and immune related response criteria (irRC), overall survival, progression-free survival and systemic immune response as assessed via liquid biopsies throughout the trial. Results 18 patients were enrolled and received trial treatment. Treatment-related adverse events grade 1-2 occurred in 6 out of 9 patients in arm A and in 9 out of 9 patients in arm B. No grade 3-5 treatment-related adverse events and no dose-limiting toxicities occurred. Treatment- related adverse events included pruritus (n=7), thyroid function test abnormalities (n=8), lymphopenia (n=5), maculopapular rash (n=3), fatigue (n=3), diarrhea (n=3), radiodermatitis (n=1), arthralgia (n=1) and edema (n=1). In arm A all patients experienced progressive disease as best overall response as per RECIST v1.1 and irRC. In arm B an objective response rate of 44,4% was noted, with 3 partial responses and 1 complete response as per RECIST v1.1 and irRC; all other patients experienced progressive disease. Median progression-free survival was 11,9 and 11,1 weeks in arm A and B respectively. Median overall survival was 17,9 weeks in arm A and not reached in arm B. Conclusion We conclude that the combination of pembrolizumab with SBRT is feasible and safe in patients with metastatic urothelial carcinoma. To further explore the benefit of this combination, future phase II and III clinical trials should administer SBRT prior to the third cycle of pembrolizumab. SP-0683 Stereotactic radiosurgery for patients with 10 or more brain metastases M. Yamamoto 1 1 Yamamoto Masaaki, Department of Neurosurgery, Hitachi-naka, Japan Abstract text The JLGK0901 study showed the non-inferiority of stereotactic radiosurgery (SRS) alone as initial treatment for 5-10 as compared to 2-4 brain metastases (BMs) in terms of overall survival and most secondary endpoints (Lancet Oncol 2014;15:387-95). A trend for patients with 5-10 tumors to undergo SRS alone has since became apparent. The next step is to reappraise whether SRS alone treatment results for tumor numbers ≥10 differ from those for 2-9. During the past two decades, several retrospective studies have demonstrated the SRS alone treatment strategy to have certain benefits for carefully- selected patients with ≥10 BMs, i.e., sufficiently long survival period, with lower incidences of neurological death, neurological deterioration, local recurrence and SRS-related complications. Herein, we introduce our Mito experiences with SRS for ≥10 BMs, employing a case- matched study on 934 patients, 467 each in the groups with 2-9 BMs and ≥10 BMs. Post-SRS treatment results, i.e., median survival time and cumulative incidences of neurological death, neurological deterioration, local recurrence, repeat SRS for new lesions and SRS-related complications, were not inferior for patients with ≥10 BMs as compared to those with 2-9 BMs. We conclude that Debate: This house believes that stereotactic radiosurgery will replace whole brain radiotherapy in patients with ten brain metastases

patients with ≥10 tumors are not unfavorable candidates for SRS alone. SP-0684 Against the motion J.F. Daisne 1 1 CHU-UCL-Namur- site Sainte-Elisabeth, Radiation Oncology, NAMUR, Belgium Abstract text Brain metastases from solid tumours are constantly increasing in incidence because people live longer thanks to improved systemic treatments [1]. As a consequence, there is an increase in radiotherapy needs. In the meantime, most centres tend to abandon whole brain radiotherapy (WBRT) in favour of stereotactic radiosurgery (SRS) for patients presenting up to ten lesions, even in the postoperative setting. This heavy trend is “justified” by randomized studies showing that, in up to 3 intact lesions, SRS is equivalent to SRS + WBRT for overall survival while maintaining a better cognitive outcome on the mid-term [2,3]. The same conclusions were drawn from a randomized study comparing SRS to WBRT in the postoperative setting [4]. A meta-analysis on three of the four published randomized trials [2,3,5,6] found an advantage in overall survival to omitting WBRT in patients younger than 50 years [7]. In the same time, the QUARTZ study did not find any advantage of WBRT in terms of QALY, overall survival or corticoids dependence compared to best supportive care (BSC) for patients presenting with brain metastases from non small cell lung cancer [8]. The JLKG (non randomized) prospective study showed that patients treated with SRS for five to ten metastases had the same outcome in terms of overall survival and needs of salvage treatments compared to patients with four or less intact lesions [9]. Anyway, does it mean that no indication persists in 2018 and that WBRT should be abandoned? The criticical analysis of these articles puts this deduction in doubt. In the QUARTZ study, most patients presented a bad prognosis (RPA 3 in 38% and DS-GPA < 2 in 80%) and eleven percent randomized to WBRT did not receive the planned dose. Altogether, these are potential biases favouring the BSC arm. Moreover, the forest plot analysis shows that some patients still benefit from WBRT, i.e. those younger than 60, presenting a good Karnofsky performance status (≥ 70) or a DS-GPA ≥ 2.5 and a controlled primary [8]. In the four studies of SRS versus SRS + WBRT in up to 3 or 4 lesions, all showed a significant decrease in local and distant brain control, necessitating more follow-up with regular magnetic resonance imaging (MRI) and salvage treatments [2,3,5,6]. Beyond the necessity to buy dedicated (and more expensive) machines for SRS deliverance, it induces also an increase in MRI prescriptions, a more expensive imaging technique with long waiting lists in most countries. Though statistically significant, the gain in neurocognitive functions is small enough that its clinical significance is questionable. The identification of the hippocampus as a key structure for neurocognition and the development of techniques to minimize its irradiation open the way to a rebirth of the WBRT. A prospective phase II trial demonstrated that the risk of peri-hippocampic relapse was 8% and that the neurocognitive functions were maintained in long survivors (> 6 months) [10]. The ongoing NRGCC-001 and 003 randomized trials should define more clearly the place of hippocampal avoidance (HA) WBRT. If these trials confirm the benefit of HA strategies, new randomized studies should be set up to challenge SRS to HA-WBRT with dose escalation on metastases by SRS or simultaneous integrated boost [11]. REFERENCES [1] Tabouret E. Anticancer Res 2012;32:4655–62. [2] Chang EL. Lancet Oncol 2009. [3] Brown PD. Jama 2016;316:401–9. [4] Brown PD,. Lancet Oncol 2017;0:1049–60.