Abstract Book

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ESTRO 37

17 Università degli Studi di Milano, Department of Oncology and Haemato-oncology, Milan, Italy 18 San Raffaele Scientific Institute, Medical Physics, Milan, Italy Purpose or Objective To fit the Normal Tissue Complication Probability (NTCP) models for predicting late severe urinary symptoms after radical radiation therapy (RT) for prostate cancer (PCa). Material and Methods Patients were enrolled in a prospective, multicentre, observational trial in 2010-2014 and treated with conventional (74-80 Gy at 1.8-2 Gy/fr) or moderately hypofractionated IMRT (65-75.2 Gy at 2.2-2.7 Gy/fr) in 5 fr/week. Bladder dose-surface histograms were corrected to 2 Gy/fr equivalent doses (EQD2) and reduced to Equivalent Uniform Doses (EUD), computed at varying α/β and n (volume parameter summarizing the organ architecture). Four severe radiation-induced toxicities were considered: urethral stricture requiring urethrotomy and bleeding, assessed by the physicians, and late obstructive symptoms and incontinence, patient-reported through the ICIQ and IPSS questionnaires. They were evaluated before RT and at its completion, thereafter every 6 months until 5 years of follow-up. Incidence of late obstructive symptoms was defined as an increase of ≥10 points with respect to baseline in the IPSS score, occurring at least once between 6 and 36 months after RT. Incidence of incontinence was defined as a sum of the ICIQ3 and ICIQ4 questions >5, with the same timing, in patients without symptoms before RT (ICIQ3+ICIQ4=0). Primary endpoint was the incidence of at least one out of the four symptoms above. Maximum likelihood estimation (MLE) was employed for calculating the best-fit NTCP parameters of all symptoms: EUD50 (EUD at 50% of toxicity risk) and k (NTCP steepness). Results 319 patients were followed for ≥36 months and had at least 3 follow-up evaluations. Overall, 72/319 (23%) patients exhibited a severe late urinary symptom: 24/155 (15.5%) in the conventional cohort and 48/164 (25%) in the hypofractionated one. Importantly, the rate of late symptoms were 27/172 (16%) and 45/147 (31%) for patients treated at prescribed EQD2≤78Gy or >78 Gy (with α/β=1 Gy). For each symptom, the highest likelihood was obtained for very low n, while low α/β was found for all the endpoints except for urethral stricture. Figure shows the best-fit NTCP parameters obtained with MLE at fixed α/β=1 Gy and n=0.01 for all symptoms and at α/β=10 Gy and n=0.01 for urethral stricture. Incontinence and bleeding showed steep increase in incidence with rising EUD: 5.5-7.7% every 5Gy in EUD in the range 75-90Gy.

(Median R 2 : 0.94 (range: 0.80-1.00); Figure left). The Identified COMT DVHs (EQD2 (%Vol)) for these symptoms emphasized dose-response relationships both within the low-intermediate, and within the high-dose region (DU: 30(55), 62(25); DI: (28(72), 54(42)); FI: 21(76), 56(32), P: 32(67), 63(24); RB 44(46), 62(32), 70(10)). For BT, DVH thresholds were primarily identified for GI toxicity (N thresholds GI/GU/SD: 14/4/2), but quantitative synthesis was only possible for RB (R 2 : 0.93; COMT DVH : 103(5); Figure right).

Conclusion Overall Rectal bleeding remains the most studied symptom after prostate cancer EBRT and BT, but novel tolerance doses since the Emami paper/QUANTEC reports were found for 17 additional distinct GI, GU, and SD symptoms. Quantitative synthesis was possible for Defecation urgency, Diarrhea, Fecal incontinence, Proctitis, and Rectal bleeding, and suggested coherence between identified DVH thresholds in both the low- intermediate (EQD2: ≤41Gy) and the high-dose region (EQD2: ≥54Gy). Continuous collection of dose-response data for all investigated symptoms is still needed to fully acknowledge the causality of both treatment- and patient-related characteristics on a certain symptom. To accelerate this process, researchers are encouraged to harmonize reporting of tolerance doses and to participate in data sharing initiatives. PV-0320 NTCP models of late severe urinary symptoms after radical IMRT for prostate cancer F. Palorini 1 , A. Cicchetti 1 , T. Rancati 1 , C. Cozzarini 2 , B. Avuzzi 3 , A. Botti 4 , D. Cante 5 , V. Casanova Borca 6 , C. Degli Esposti 7 , E. Garibaldi 8 , G. Girelli 9 , C. Iotti 10 , A. Maggio 11 , F. Munoz 12 , M. Palombarini 13 , A. Pierelli 14 , E. Pignoli 15 , V. Vavassori 16 , R. Valdagni 17 , C. Fiorino 18 1 Fondazione IRCCS Istituto Nazionale dei Tumori, Prostate Cancer Program, Milan, Italy 2 San Raffaele Scientific Institute, Radiotherapy, Milan, Italy 3 Fondazione IRCCS Istituto Nazionale dei Tumori, Radiotherapy 1, Milan, Italy 4 Azienda Unità Sanitaria Locale di Reggio Emilia – IRCCS, Medical Physics, Reggio Emilia, Italy 5 Ospedale ASL TO4, Radiotherapy, Ivrea, Italy 6 Ospedale ASL TO4, Medical Physics, Ivrea, Italy 7 Ospedale Bellaria, Radiotherapy, Bologna, Italy 8 Istituto di Candiolo- Fondazione del Piemonte per l'Oncologia IRCCS, Radiotherapy, Candiolo, Italy 9 Azienda Sanitaria Locale di Biella, Radiotherapy, Biella, Italy 10 Azienda Unità Sanitaria Locale di Reggio Emilia – IRCCS, Radiotherapy, Reggio Emilia, Italy 11 Istituto di Candiolo- Fondazione del Piemonte per l'Oncologia IRCCS, Medical Physics, Candiolo, Italy 12 Ospedale Regionale U.Parini-AUSL Valle d’Aosta, Radiotherapy, Aosta, Italy 13 Ospedale Bellaria, Medical Physics, Bologna, Italy 14 Cliniche Gavazzeni-Humanitas, Medical Physics, Bergamo, Italy 15 Fondazione IRCCS Istituto Nazionale dei Tumori, Medical Physics, Milan, Italy 16 Cliniche Gavazzeni-Humanitas, Radiotherapy, Bergamo, Italy