ESTRO 38 Abstract book

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1 Ingham Institute for Applied Medical Research, Collaboration of Cancer Outcomes- Research and Evaluation CCORE and University Of New South Wales, Liverpool BC- NSW, Australia Purpose or Objective Evidence-based modelling estimates show that 52% of all Australian prostate cancer patients would benefit from radiotherapy (RT) at diagnosis 1-3 . It was estimated that the 5-year overall survival (OS) shortfall for prostate cancer due to not receiving EBRT was 1.1% and the 5-year irreplaceable local control (LC) benefit for receiving EBRT was 12.4% 4,5 . Previous study indicated that radiotherapy utilization (RTU) rates decreased with increasing travel distance from patient residence to the nearest RT department (RTD) 6 . The objective of the study was to calculate actual RTU rate, to estimate the shortfall in OS and irreplaceable LC and to identify factors affecting RTU. Material and Methods Data from NSW Central Cancer Registry for patients diagnosed with prostate cancer from 2009-2011 were linked to public and private radiotherapy, admitted patient, clinical cancer registry and death datasets. Patients located near the State border where their closest RT center was outside NSW (cross borders) were excluded from the analysis. To assess the irreplaceable benefit of EBRT, all treatment options where surgery or BT monotherapy were options over EBRT were set to 0% use of EBRT 5 . This method described a scenario where benefits of EBRT were counted only for cases where there was no guideline-recommended alternative treatment 5 . Analysis was performed using SAS, SPSS and ArcGIS software. Results There were 19,816 patients diagnosed with prostate cancer during the study period. The median age was 67 years. Our study showed that 65% of prostate cancer patients had localized disease, 4% had distant disease and 30% had unknown or missing stage. Of patients with localized disease, 18% received EBRT, 37% had radical prostatectomy (RP) and 4% had both RP and EBRT. Twenty- eight percent of all prostate cancer patients had RP alone, 3% had RP & EBRT, 20% had EBRT alone and 49% had neither RP nor EBRT. Overall, 23% of all prostate cancer patients received RT within one year of diagnosis. Of the 5636 patients with complete TNM data available, 68% received RT compared to 6% of patients with no detailed TNM. The annual overall survival person-shortfall was estimated to be 41 and irreplaceable local control person- shortfall was 466. Univariate analysis showed that younger age, patients with loco-regional disease, living in more advantaged areas and outside major cities, and living >100 km of RTD were predictors for RT underutilization. On multivariate logistic regression model, all factors remained significant. Conclusion Prostate cancer was the most diagnosed cancer in NSW and contributed to 18% of the total patients diagnosed with cancer during the study period. Actual RTU rate was half of the estimated optimal rate. Underutilization of RT increases the disease burden on health system due to local failure and overall survival shortfall. The study shows that giving EBRT according to evidence-based guidelines will probably prevent 41 immature death and 466 local failure annually. OC-0159 Long-Term Results of RTOG 0321: HDR Brachytherapy and External Beam Radiotherapy for Prostate Cancer I. Hsu 1 , J. Rodgers 2 , K. Shinohara 3 , J. Purdy 4 , J. Michalski 5 , G. Ibbott 6 , M. Roach 7 , E. Vigneault 8 , R. Ivker 9 , R. Pryzant 6 , M. Kuettel 10 , D. Taussky 11 , G. Gustafson 12 , A. Raben 13 , H. Sandler 14 1 University of California UCSF, Radiation Oncology, San Francisco CA, USA ; 2 NRG, Statistics, Philadelphia, USA ; 3 UCSF, Urology, San Francisco, USA; 4 University of

University Medical Centre, Maastricht, The Netherlands; 2 Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, Zürich, Switzerland Purpose or Objective Although immunotherapy is currently changing cancer treatment practice, primary resistance is still observed partly due to insufficient immunogenic priming. Radiotherapy (RT) induces the release of tumor antigens and thereby increases tumor immunogenicity. Therefore, combination of these therapies has high potential. Here, we investigated the therapeutic outcome of combining a single dose RT with the immunocytokine L19-IL2 and immune checkpoints inhibitors (ICIs) (aCTLA-4, aPD-L1 and aPD-1), aiming to further activate and prolong the RT- elicited anti-tumor immune response. Material and Methods Balb/c or C57BL/6 mice were injected in the right flank with C51 and CT26 colon carcinoma or Lewis lung carcinoma (LLC) cells, respectively. Upon an average volume of 200mm 3 , animals were randomized in different treatment groups: RT + vehicle/L19-IL2 (1 mg/kg) + IgG or RT + vehicle/L19-IL2 + aPD-L1/aPD1/aCTLA-4 (all 10 mg/kg). Tumors were irradiated with 5Gy (C51 and CT26) or 10Gy (LLC), as the latter is less immunogenic. Vehicle/L19-IL2, aCTLA-4 and IgG were given i.v. on day 1, 3 and 5 after RT; aPD-1, aPD-L1 and IgG were given i.p. 1, 3, 5, 7 and 9 days after RT. Tumor response was quantified as time to reach 4 times starting tumor volume (T4xSV). For mechanistic studies, the same treatment schedule was used and mice were sacrificed at day 6 after RT. Results In the CT26 model, RT + L19-IL2 (p<0.001), RT + aCTLA-4 (p<0.01) and RT + aPD-L1 (p<0.05) resulted in longer T4xSV compared to RT. In the C51 model solely RT + L19-IL2 (p<0.001) was better compared to RT. RT + L19-IL2 efficacy was significantly (p<0.001) better compared to RT + ICIs in the C51 model; a similar trend was observed for the CT26 model, albeit not significant. Adding ICIs to RT + L19-IL2 did not result in improved outcome in C51 and CT26 models. Conversely, in the LLC model the triple therapy of RT + L19-IL2 + aPD-L1 yielded a better outcome compared to RT + L19-IL2 (p<0.05) and RT + aPD-L1 (p<0.001). Mechanistically, in LLC tumors we found an increased infiltration of antigen-experienced (CD44+) CD8+ T cells and NK cells after triple therapy as compared to RT (p<0.001), RT +L19-IL2 (p<0.01) and RT + aPD-L1 (p<0.01). Percentage of regulatory T cells (Tregs) was surprisingly higher in tumors treated with RT + aPD-L1 vs RT + L19-IL2 (p<0.05), knowing that IL2 expands Tregs. Interestingly, other immunosuppressive proteins such as PD-1, Tim-3 and CD39 were upregulated on T cells upon PD-L1 blockade. Conclusion Our results show that in the C51 and CT26 models, the therapeutic effect of RT + L19-IL2 is larger than RT + ICIs, while adding ICIs did not improved efficacy of RT + L19- IL2. In the LLC model, RT + L19-IL2 + aPD-L1 improved outcome compared to RT + L19-IL2 or aPD-L1 and was associated with increased infiltration of NK and CD44+ CD8+ T cells; functional co-culture assays are ongoing to prove their role on the anti-tumor response. PD-L1 blockade upregulated other immune-checkpoint proteins on T cells.

Proffered Papers: CL 3: Proffered papers : Prostate and Bladder

OC-0158 Effect of EBRT underutilization in prostate cancer on overall survival and local control,NSW,Australia G. Gabriel 1 , M. Barton 1 , J. Shafiq 1 , G. Delaney 1