PO-0735: Patient-reported nocturia 1 to 14 years after radiation therapy for prostate cancer

S34 Early GI side effects ≥ grade 2 were detected in 26 % (115/447) and in 41 % (53/128) of patients receiving local or pelvic irradiation, respectively (p=0.0006). Late GI adverse events ≥ grade 2 were detected in 14 % (63/447) of patients receiving local, and in 14% (18/128) of patients receiving pelvic irradiation (p=0.77). The corresponding 5-year actuarial incidence rates were 14 % for both irradiation techniques; in contrast, the prevalence rates at 5 years were 2 % and 0 %. Early GU side effects ≥ grade 2 were detected in 15 % (69/447) and 16 % (20/128) of patients with local or pelvic irradiation, respectively (p=0.96). Late GU morbidity ≥ grade 2 was detected in 18 % (80/447) of patients receiving local irradiation compared to 24 % (31/128) for pelvic irradiation (p=0.001). The corresponding 5-year actuarial incidence rates were 16% and 35% respectively, while the prevalence after 5 years was 6 % and 0 %. Conclusions: Despite a generally low prevalence of GI/GU side effects, four-field-box pelvic nodal irradiation in the postoperative treatment of prostate cancer results in a significant increase in the actuarial incidence rates of both early and late side effects. Therefore, optimized pelvic node irradiation techniques should be administered in order to reduce the dose to pelvic organs at risk and thus minimize the incidence of adverse events. PO-0733 Cross-sectional study about prevalence of MetS and osteoporosis in PC treated with ADT and their impact on QL Y. Rios Kavadoy1, J.L. Munoz Garcia1, P. Samper Ots2, M.L. Couselo Paniagua3, E. Villafranca Iturre4, M. Rodríguez Liñán5, A.M. Pérez Casas6, R. Muelas Soria7, B. Ludeña Martínez8, J. López Torrecilla9 1 Hospital Infanta Cristina, Radiation Oncology, Badajoz, Spain 2 Rey Juan Carlos Hospital, Radiation Oncology, Badajoz, Spain 3 Gómez Ulla Hospital, Radiation Oncology, Badajoz, Spain 4 Navarra Hospital, Radiation Oncology, Badajoz, Spain 5 Reina Sofia Hospital, Radiation Oncology, Badajoz, Spain 6 Jimenez Diaz Hospital, Radiation Oncology, Badajoz, Spain 7 Provincial Hospital of Castellon, Radiation Oncology, Badajoz, Spain 8 Fuenlabrada Hospital, Radiation Oncology, Badajoz, Spain 9 General University Hospital of Valencia, Radiation Oncology, Badajoz, Spain Purpose/Objective: Around 20-25% of the adult population of the world has metabolic syndrome (MetS). Patients (pts) with prostate cancer (PC) treated with androgen deprivation therapy (ADT) have been reported to have a higher prevalence of MetS (50%) and osteoporosis (35.4%-49.2%) and increased risk of fracture. The primary aim of our study was to assess the prevalence of MetS and osteoporosis in pts with PC who have received or will receive radiation therapy (RT) withr radical intention and ADT and its impact on Quality of life secondarily (QL). Materials and Methods: Multicenter cross-sectional study of 270 pts with PC who have received or will receive RT with radical intention and ADT (6, 12-18, ≥24 months, and a control group without ADT). The presence of MetS was defined according to the updated NCEP: ATP III by the presence of 3 or more of the following risk factors: (1) waist circumference ≥102cm (European Cardiovascular Societies), (2) fasting glucose ≥100 mg/dL or previously diagnosed type 2 diabetes,(3) serum triglyceride level ≥150 mg/dL or pharmacological treatment for it, (4) systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥85 mm Hg or previously diagnosed hypertension, and (5) high-density lipoprotein (cHDL) cholesterol <40mg/dL. Osteoporosis was diagnosed by dual energy X-ray absorptiometry (DEXA) and QL by EPIC. The study was approved by the Clinical Research Ethics Committee and the patients signed the informed consent form. Results: From November 2011 to October 2012, 259 out of 270 pts included in the study were assessable for MetS (46 pts hormone-naive, 58 pts had undergone ADT for 6 moths, 97 ptes for 12-18 months, and 58 pts for 24 months or longer) and according to the above criteria, 122 pts (47%) had MetS, 19% in hormone-naive patients, 21% 6 months of ADT, 36% after 12-18 months, and 24% after 24 or more months. The majority of pts had no family history of diabetes mellitus, hypertension or dyslipidemia. 168 out of 270 (62%) pts had DEXA and osteoporosis was present in 11 pts (6.5%). 2 (18%) pts hormone-naive, 1 (9%) pts ≥ 6months of ADT, 6 (55%) in the group of 12-18 months and 2 (18%) in pts receiving ≥ 24 months of ADT. The median (range) urinary,intestinal, sexual and hormonal EPIC were 91.67 (28-100), 100(0-100), 16.67 (0-100) and 82.50 (8-100) respectively. Conclusions: Patients with prostate cancer treated with androgen deprivation therapy between 12-18 months showed a higher prevalence of metabolic syndrome than patients treated during ≤6 months or ≥24 months.Patients hormone-naïve had a MetS prevalence similar to the ADT ≤6 months or ≥ 24 months. For the total sample the MetS prevalence

ESTRO 33, 2014 observed was higher than published in the general population (45%).The prevalence of osteoporosis was low but higher again in the group of patients treated with ADT for 12-18 months. Sexual function was the parameter more affected in QL questionnaire. PO-0734 Assessing response to radiotherapy with diffusion weighted MRI (DWMRI) in muscle invasive bladder cancer (MIBC) S. Hafeez1, M. Koh1, A. Sohaib2, R. Huddart1 1 Institute of Cancer Research & The Royal Marsden NHS Foundation Trust, Radiotherapy and Imaging, Sutton Surrey, United Kingdom 2 Royal Marsden NHS foundation Trust, Imaging, Sutton Surrey, United Kingdom Purpose/Objective: Chemo-radiotherapy for muscle invasive bladder cancer in selected patients allows organ preservation with comparable survival to contemporary surgical series. Conventionally response assessment is with cystoscopy. We report on the use of DW-MRI as a potential non-invasive alternative means of assessment and as a predictor of radiotherapy (RT) sensitivity. Materials and Methods: 28 patients with confirmed MIBC suitable for radical RT were recruited prospectively to an ethics approved protocol. 17 patients received neo-adjuvant chemotherapy, 19 patients received RT with concurrent chemotherapy. DW-MRI was performed on a 1.5T system using b-values 0,50,100,250,500 and 750s/mm2 following transuretheral resection but prior to any other treatment and on completion of RT. Tumour was drawn on the 750s/mm2 images and transferred onto the corresponding ADC map to record mean values. Following final DWMRI patients proceeded to cystoscopy + biopsy. Association between RT sensitivity, pre-treatment ADC, post- RT ADC and change of ADC (ΔADC) was analysed. Results: Following RT 17 patients achieved pathological complete response, 3 achieved partial response and 3 demonstrated poor response with residual pT2a disease at biopsy. 5 patients did not complete post treatment assessments. Baseline tumour median ADC was 1.31x103 mm2/s (range 0.98-1.76x10-3mm2/s). Pathological complete response was associated with a significant increase in median ADC from 1.37x10-3mm2/s (range 0.98-2.26x103 mm2/s) to 2.01x10-3mm2/s (range 1.43-3.96x10-3mm2/s) (p<0.001). Change in mean ΔADC was significantly greater in complete responders compared to poor responders; complete responders median ΔADC 0.65 x10-3 mm2/s (range 0.18-1.97x10-3 mm2/s), poor responders median ΔADC 0.07x10-3 mm2/s (range 0.04-0.18x10-3 mm2/s) (p=0.025). Pre-treatment ADC was not predictive

Conclusions: DW-MRI is useful in assessing response in MIBC. It may be a potential biomarker for predicting RT sensitivity and guide selection for bladder sparing approaches but further work is needed. PO-0735 Patient-reported nocturia 1 to 14 years after radiation therapy for prostate cancer N. Pettersson1, C. Olsson2, D. Alsadius2, G. Steineck2 1 Sahlgrenska University Hospital, Department of Physics and Biomedical Engineering, Göteborg, Sweden 2 Institute of Clinical Sciences the Sahlgrenska Academy at the University of Gothenburg, Division of Clinical Cancer Epidemiology Department of Oncology, Göteborg, Sweden Purpose/Objective: Nocturia, or waking one or several times per night due to the need to urinate, is a symptom that emotionally ranges from annoying to highly bothersome. We analysed treatment- and age-related factors that affect the prevalence of patient-reported nocturia following prostate cancer radiation therapy. Materials and Methods: Men with prostate cancer treated with radiation therapy from 1993 to 2006 (n=985) were in 2008 approached with a study-specific questionnaire addressing symptoms after treatment, including nocturia. The men had received primary or salvage externalbeam radiation therapy (EBRT) or EBRT in combination with high-dose-

ESTRO 33, 2014 rate brachytherapy (EBRT+BT). In this work, we studied men treated to 70 Gy delivered as either 35x2.0 Gy EBRT or 25x2.0+2x10.0 Gy EBRT+BT. Urinary bladder mean absorbed doses for EBRT were assessed from treatment records. We also recruited 350 non-pelvic-irradiated population-based reference men (without prostate cancer diagnosis) matched for age and residency for symptom comparison. We stratified the prostate cancer survivors according to treatment modality and used logistic regression to analyse the influence of age and mean dose on the occurrence of nocturia (defined as urinating at least twice each night). Prevalence ratios (cf. relative risks) and their 95% confidence intervals (CIs) were used to compare symptom rates between survivors and reference men. Results: Overall, the number of men treated to 70 Gy and answering the question on nocturia was 745. Of these, 248 (33%) were symptomatic compared to 52/237 (22%) of the reference men. According to logistic regression, age at follow-up was a significant predictor of nocturia (p<0.05 in all groups), Figure 1. Men treated with salvage EBRT had similar prevalence as reference men while nocturia was more common among men treated with primary EBRT or EBRT+BT. In the age interval 65-75 years, the prevalence ratio was 1.6 (95% CI: 1.1-2.3;p=0.02) for men treated with primary EBRT compared to reference men. Corresponding numbers for men treated with EBRT+BT were 1.5 (95% CI: 1.0-2.1; p=0.03). Including urinary bladder mean dose in logistic regression models together with age did not result in a significantly improved model fit for any treatment group.

Conclusions: Age was a significant predictor of nocturia in all three treatment groups as well as among the reference men. This may lead to an overestimation of treatment-induced nocturia when patients are followed up over long time periods. Men treated with primary EBRT or EBRT+BT had higher prevalence of nocturia compared with nonirradiated reference men indicating a possible treatment-related effect. The relationship between the urinary bladder dose distribution and nocturia therefore needs to be investigated in more detail for these two treatment groups. PO-0736 Pattern of failure after sentinel node based individualization of pelvic IMRT for high risk prostate cancer A.C. Müller1, F. Eckert1, F. Paulsen1, M. Bamberg1, A. Stenzl2, D. Schilling2, M. Alber3, R. Bares4, C. Belka5, U. Ganswindt5 1 Eberhard Karls University of Tübingen, Department of Radiation Oncology, Tübingen, Germany 2 Eberhard Karls University of Tübingen, Department of Urology, Tübingen, Germany 3 Aarhus University, Department of Oncology, Aarhus, Denmark 4 Eberhard Karls University of Tübingen, Department of Radiology Institute of Nuclear Medicine, Tübingen, Germany 5 Ludwig-Maximilians-University of Munich, Department of Radiation Oncology, Munich, Germany Purpose/Objective: In high risk, node-negative prostate cancer patients, approximately 30% of sentinel nodes (SN) are detected outside of the standard pelvic target volume. We individualized pelvic radiation treatment by inclusion of individual SN into the standard pelvic target volume and report patterns of failure after long-term follow-up. Materials and Methods: From 2003 to 2007, 61 high risk prostate cancer patients with an estimated risk of nodal involvement of >15% according to the Roach formula (mean 33.5%) and/or high risk according to NCCN criteria were treated by intensity-modulated radiation therapy (IMRT) and neo-/adjuvant long-term androgen deprivation therapy. SNvisualization was performed by a SPECT (single photon emission

S35 computed tomography)-derived technique after intraprostatic injection of 99mTc-Nanocoll. The pelvis including individual SNs/prostate was treated with a simultaneous-integrated boost with single doses of 1.8/2.0 Gy 5x/week to 50.4/56.0Gy. A boost of 2.0Gy 5x/week was given to the prostate to a total dose of 70.0Gy. IMRT treatment plans were optimized by an equivalent uniform dose (EUD)-based algorithm and calculated using the Monte Carlo dose algorithm. Results: Fifteen recurrences according to the Phoenix definition occurred after a median follow-up of 60 months. In 8/15 patients we observed only a PSA-relapse without evidence of any macroscopic disease. Bone metastases (n=3), local recurrence (n=1) and combinations of both (n=3) were detected in the remaining seven patients. Pelvic nodal recurrences did not occur. Estimated biochemical control reached 73.8% after 5 years according to the Phoenix definition. Higher Gleason score (8-10) was associated with a higher risk of relapse with an estimated 5-year-PSA-control of 62.2% vs. 80.5% (trend with p=0.057). Estimated five-year overall and cancer-specific survival reached 84.4% and 96.3%, respectively. Conclusions: The pattern of relapse indicates that the individualized SNbased target volume concept correctly covers individual pelvic nodes, which is substantiated by the absence of any nodal pelvic recurrence despite a risk according to the Roach formula of mean 33.5% for all patients. Outcome parameters were at least comparable to available data of the same treatment period. Thus, this SN-based approach justifies further evaluation including current dose-escalation strategies to prostate in addition to pelvic node irradiation in a larger prospective series. PO-0737 Effects of Radium-223 Dichloride on Health-Related QOL in CRPC Pts with Bone Mets from the Ph 3 ALSYMPCA Trial J. O'Sullivan1, C. Parker2, D. Heinrich3, D. Bottomley4, P. Hoskin5, L. Franzén6, A. Solberg7, P. Cislo8, A. Aksnes9, S. Nilsson10 1 Centre for Cancer Research and Cell Biology Queen's University, Radiation Oncology, Belfast, Ireland Republic of 2 The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Urologic Oncology, Sutton, United Kingdom 3 Akershus University Hospital, Oncology, Lørenskog, Norway 4 St James Hospital, Oncology, Leeds, United Kingdom 5 Mount Vernon Hospital Cancer Centre, Oncology, Middlesex, United Kingdom 6 Länssjukhuset Sundsvall-Härnösand County Hospital Sundsvall and Umeå University Hospital, Oncology, Umeå, Sweden 7 St Olavs Hospital, Oncology and Radiotherapy, Trondheim, Norway 8 Bayer HealthCare, Research, Whippany NJ, USA 9 Algeta ASA, Clinical, Oslo, Norway 10 Karolinska University Hospital, Oncology, Stockholm, Sweden Purpose/Objective: Ra-223, a first-in-class alpha-emitter, significantly improved overall survival (OS) by 3.6 months versus placebo (HR = 0.70; 95% CI, 0.58-0.83; P < 0.001) and was well tolerated in CRPC patients with symptomatic bone metastases from ALSYMPCA. Ra-223 also had a positive impact on pain, significantly delaying time to external beam radiation therapy and reducing opioid use (Nilsson et al, ASCO GU 2013). Reported here are results from a post hoc analysis of Ra-223 effects on overall QOL and pain-related QOL over the entire treatment and followup phases. Materials and Methods: QOL was assessed at baseline and during treatment (weeks 16, 24) and scheduled follow-up visit 2 (week 44) using the Functional Assessment of Cancer Therapy—Prostate (FACT-P) questionnaire. Based on minimal important difference estimates for FACT-P total scores between 6 and 10 points, the time to deterioration in QOL analysis defined deterioration as a ≥ 10-point reduction in FACT-P total score (Cella et al, Value Health, 2009). Mixed-effect linear regression models were used to assess the effect of treatment on mean change from baseline in the FACT-P total score, five FACT-P subscales, and trial outcome index (TOI). Pain-related QOL was analyzed as the sum of scores for four pain-related questions in the FACT-P prostate cancer subscale. Results: Placebo patients experienced deterioration in QOL more quickly than did Ra-223 patients (HR = 1.34; 95% CI, 1.06-1.69; P =0.015). Patients in the placebo group had a significantly greater decrease from baseline in FACT-P total score and TOI than patients in the Ra-223 group (P = 0.004 and 0.01, respectively). Four of five FACT-P subscales showed a similar effect; placebo patients, compared with Ra-223 patients, had significantly greater declines in QOL scores for physical well-being (WB), emotional WB, functional WB, and prostate cancer subscales, but not for social/family WB. Ra-223 was also associated with less pain (higher painrelated QOL score) versus placebo (8.4 vs 7.6; P = 0.006); these changes