ESTRO 36 Abstract Book

S111 ESTRO 36 _______________________________________________________________________________________________

Gy. Biomarkers of DNA double-strand breaks (DSB) recognition and repair were assessed from 10 minutes to 24 hours after irradiation, including the relocalization of phosphorylated ATM Protein (pATM) as nuclear foci. These biological results were plotted against the CTCAE grades. A ROC curve analysis was then performed on patients after they were merged in two groups: radioresistant (grade <2) and radiosensitive (grade ≥2). Results This study showed that a delay in the nucleoshuttling of the ATM protein, which is involved in the recognition of the DSB, was a common feature to patients with overreaction (OR). The maximal number of pATM foci between 10 min and 1h post irradiation (pATMmax) was found to be the parameter with the best correlation with each OR severity grade, independently of tumor localization and of the early or late nature of reactions. When taken as a binary predictive assay with the optimal cut-off value of 35 pATM foci, pATMmax foci showed promising predictive performances, with an AUC of 0.97, a PPV of 99%, a specificity of 92% and a sensitivity of 100%. Conclusion The results of these experiments allowed us to identify pATMmax as a high performance predictive parameter of post-radiotherapy OR. Additional studies are in progress to confirm that this radiosensitivity assay reaches the same performances in any radiotherapy condition to change our daily clinical practice. OC-0222 GnRH receptor blockade reduces radiation- induced bladder toxicity: first evidence in a rat model. G. Fallara 1 , F. Benigni 1 , C. Cozzarini 2 , B. Noris Chiorda 2 , C. Sini 3 , L. Perani 4 , A. Spinelli 4 , M. Venturini 4 , A. Salonia 1 , A. Briganti 1 , F. Montorsi 1 , N. Di Muzio 2 , C. Fiorino 3 1 Ospedale San Raffaele- Vita-Salute University, URI/Urology, Milan, Italy 2 Ospedale San Raffaele, Radiotherapy, Milan, Italy 3 Ospedale San Raffaele, Medical Physics, Milan, Italy 4 Ospedale San Raffaele, Experimental Imaging Center, Milan, Italy Purpose or Objective Genitourinary toxicity represents a major side effect in patients treated with primary, adjuvant or salvage radiotherapy for prostate cancer (PCa). Many clinical trials aimed at finding predictive factors of radiation-induced toxicity analyzed the impact of androgen deprivation therapy (ADT) with controversial results. However, recent data on large groups of patients support the hypothesis that short-term ADT is protective towards radiation cystitis. Our pilot study is aimed at supporting the putative beneficial role of a GnRHR antagonist (degarelix) by means of an animal model that recapitulates many features of Male rats were surgically catheterized and randomly divided into three groups: radio-treated only (RT, n=4), radio-treated+degarelix (RT+DGX, n=4) and control (CTRL, n=2). Rats from RT and RT+DGX group were irradiated with a single fraction of 20 Gy to the bladder. The RT+DGX group received the drug (150 µg/kg, sub-cute) once a week for 3 weeks, starting 1 week prior to irradiation. Each rat underwent pelvic ultrasound, before and after (day 6) irradiation, to evaluate bladder wall thickness. At day 21, cystometry was performed to evaluate bladder function. Then the animals were sacrificed and their bladder analysed in H&E and Azan-Mallory trichrome staining (day 21). One-way ANOVA with Tukey post test and t-Student were used to assess the statistical differences. Results Our data show that, in RT group, compared to pre- irradiation baseline, bladder wall thickness increased 1.8- fold after radiations (0.5±0.2 vs 0.9±0.4 mm, p<0.05), the human pathology. Material and Methods

while no significant differences were found in RT+DGX group (0.6±0.2 mm). Bladder basal (BP), threshold (TP), flow (FP), and maximal (MP) pressures as well as AUC/MI increased significantly in RT group compared to RT+DGX (BP: 21±6 vs 9.8±0.5; TP: 41±16 vs 15±4; FP: 53±19 vs 24±4; MP: 83±25 vs 41±3; AUC/MI: 30±10 vs 13±2, cmH2O, all p<0.01). Also, both micturition volume (MV) and intervals (MI) were reduced in RT animals and improved after DGX (MV: 0.4±0.1 vs 1.1±0.3 mL; MI: 174±45 vs 349±116 sec, all p<0.01). The non-voiding bladder contractions in each micturition cycle were significantly higher in RT than RT+DGX group (5.5±2 vs 0.6±0.5, p<0,05). Compared to CTRL, histopathological analysis confirmed in RT group an increased mucosal layer (81±25 vs 40±16 µm, p<0.05), which was instead less pronounced in RT+DGX (63±23 µm). Finally, the bladder muscle/collagen ratio decreased in RT rats (0.8±0.1, p<0.01) compared to CTRL (1.3±0.2) and almost normalized by DGX (1.1±0.2). Conclusion In irradiated rats, DGX prevented the urinary functional impairment and histological subversion of bladder wall. The differences in terms of both mucosa thickness and reduced collagen deposition suggest a possible effect by DGX on inflammation-mediated tissue remodeling. The presence of GnRH receptors in the bladder urothelium advocates a local effect with potential applications as radioprotectors, firstly in high-dose RT for PCa. Childhood head and neck rhabdomyosarcomas are often large tumors at diagnosis. These tumors are usually located in areas with many vital structures. Radiotherapy to these tumors will have a high probability for serious late sequelae because of the sensitivity of normal tissue for radiation at young age. For these reasons the AMORE concept was developed in the nineties of last century for local treatment after the standard chemotherapy courses. AMORE is the acronym for Ablative surgery, MOld brachytherapy, and REconstruction. After a macroscopic radical excision, pulsed-dose rate brachytherapy (32-36 x 1.25 Gy at 2.1hour interval) is applied with a mold technique. The dose is prescribed on 5 mm from the mold surface. After brachytherapy the mold is surgically removed and the defect reconstructed with a free vascularized flap or a transpositional muscle flap. The Amsterdam cohort, with AMORE treated patients, was compared to a similar group of patients from London treated with only external beam radiotherapy (EBRT) as the radiation modality. Failure-free survival and overall survival were 58% and 76%, respectively and not statistically significant different between the two groups. Both groups were identically analyzed in a Late Effects Outpatient Clinic and all possible late effects scored according to the Common Terminology Criteria for Adverse Events version 4. The most seen late effect was musculoskeletal deformities; 60% any grade. The EBRT- based cohort therapy resulted in more adverse effects than the AMORE-based cohort. Also grade 3-4 adverse events were significantly more pronounced in the EBRT- based cohort. The largest difference in late effects was found for growth hormone deficiency. The odds ratio was 2.1 for EBRT-based therapy compared to AMORE-based therapy. In conclusion AMORE, with brachytherapy as radiation modality, is proven to be equivalent to EBRT with less late effects. Symposium: Paediatric brachytherapy SP-0223 The AMORE concept and late effects outcome for paediatric brachytherapy B. Pieters 1 1 Academic Medical Center P.O. Box, Radiation Oncology, Amsterdam, The Netherlands