ESTRO 2023 - Abstract Book

S418

Sunday 14 May 2023

ESTRO 2023

A CNN has been developed and clinically deployed to screen patients in the radiation treatment planning pipeline for ILD. The model has reasonable screening characteristics and prospectively identified five patients with previously unknown radiographic ILD. After external validation, this model could be deployed in radiation treatment planning systems to alert clinicians to ILD patients at high risk of developing complications. OC-0510 Genetically-based Cox-NTCP models for late toxicity after prostate cancer RT T. Rancati 1 , G. Eliana 1 , M. Massi 2 , N.R. Franco 3 , B. Avuzzi 4 , A. Cicchetti 1 , B. Rosenstein 5 , P. Seibold 6 , D. Azria 7 , A. Choudhury 8 , D. De Ruysscher 9 , M. Lambrecht 10 , E. Sperk 11 , C. Talbot 12 , A. Vega 13 , L. Veldeman 14 , A. Webb 15 , P. Zunino 2 , A. Paganoni 3 , F. Ieva 3 , A. Manzoni 3 , S. Gutierrez 16 , S. Kerns 17 , A. Dunning 18 , R. Elliott 19 , C. West 19 , J. Chang-Claude 6 1 Fondazione IRCCS Istituto Nazionale dei Tumori, Prostate Cancer Program, Milan, Italy; 2 Politecnico di Milano, MOX, Milano, Italy; 3 Politecnico di Milano, MOX, Milan, Italy; 4 Fondazione IRCCS Istituto Nazionale dei Tumori, Radiotherapy, Milan, Italy; 5 Icahn School of Medicine at Mount Sinai, Genetics, New York, USA; 6 German Cancer Research Center (DKFZ), Epidemiology, Heidelberg, Germany; 7 Montpellier Cancer Institute, Radiotherapy, Montpellier, France; 8 University of Manchester, Radiotherapy, Manchester, United Kingdom; 9 Maastricht University Medical Center, Radiotherapy, Maastricht, The Netherlands; 10 University Hospitals Leuven, Radiotherapy, Leuven, Belgium; 11 Universitätsmedizin Mannheim, Radiotherapy, Mannheim, Germany; 12 Unversity of Leicester, Genetics, Leicester, United Kingdom; 13 Fundación Pública Galega de Medicina Xenómica, Genetics, Santiago de Compostela, Spain; 14 Ghent University Hospital, Radiotherapy, Gent, Belgium; 15 Univerisity of Leicester, Genetics, Leicester, United Kingdom; 16 Val D'Herbron Istitute of Oncology, Genetics, Barcelona, Spain; 17 University of Rochester Medical Center, Genetics, Rochester, USA; 18 University of Cambridge, Strangeways Research Labs, Genetics, Cambridge, United Kingdom; 19 University of Manchester, Radiobiology, Manchester, United Kingdom Purpose or Objective An international, prospective cohort study recruited prostate cancer patients (pts) in 8 countries (April2014-March2017). It was aimed at multinational validation of clinical/dosimetric/genetic risk factors that predict late toxicity following radiotherapy (RT). We here propose a Cox-NTCP models for late toxicity including genetic information a polygenic risk score, PRS, that incorporates SNP-SNP interactions (PRSi). Materials and Methods 1808 pts were enrolled. RT was prescribed according to local regimens, but centres used standardised data collection. Grade ≥ 1 (G1+) rectal bleeding (G0 at baseline), Grade ≥ 2 (G2+) rectal bleedine, G2+ urinary frequency (GO/G1 at baseline), and G1+ haematuria (G0 at baseline) were considered as separate endpoints. Studied dosimetric descriptors included rectum/whole bladder/bladder neck DVHs and dose-surface-histograms (DSHs). A pool of 43 SNPs associated with late RT toxicity from the literature was tested, and a deep sparse autoencoder method identified the SNPs affecting the toxicity risk at 2 year follow-up (Massi 2020). A new method for accounting for SNP-SNP interactions (PRSi) was developed; the PRSi shows which SNPs and alleles are included, whether they increase or decrease the risk of toxicity and their combined effect s. (Franco 2021, Fig.1 for details). NTCP models were based on Cox regression, allowing inclusion of follow-up time and censoring. Results 1482 pts had long-term follow-up (median 24 mos, 75th perc 60 mos). 75% pts had conventional fractionation (60-81 Gy), 25% received hypofractionation. 70% pts had VMAT, 12% static field IMRT, 18% 3DCRT. 30% had post-prostatectomy RT, 32% pelvic RT and 72% adjuvant/neo-adjuvant hormone therapy. Toxicity crude rates were 18% G1+ rectal bleeding, 5% G2+ bleeding, 5.7% G2+ urinary frequency, 8.5% G1+ haematuria. The previously defined PRSi (at 2 yrs) were still associated to toxicity in the long term (Fig. 2, p<0.001 in all cases). For rectal bleeding the best dosimetric descriptor was the rectal EUD from DVH, for urinary frequency it was the whole bladder EUD from DSH, while for heamaturia the bladder neck EUD from DSHs. All doses were collected for fractionation using the linear quadratic model and alpha/beta ratios derived from maximum likelihood fit. The developed Cox-NTCP models are presented in Fig. 2.