ESTRO 2023 - Abstract Book

S416

Sunday 14 May 2023

ESTRO 2023

N. Horeweg 1 , R.A. Nout 2 , J.J. Jobsen 3 , J.C. Lutgens 4 , I.M. Jürgenliemk-Schulz 5 , D.M. Haverkort 6 , J.W.M. Mens 7 , M.A. de Jong 8 , B.G. Wortman 1 , S.M. de Boer 1 , H. Putter 9 , E. Stelloo 10 , V.T. Smit 10 , T. Bosse 10 , C.L. Creutzberg 1 1 Leiden University Medical Center, Radiation Oncology, Leiden, The Netherlands; 2 Leiden University Medical Center (currently working at Erasmus MC Cancer Center), Radiation Oncology, Leiden (currently Rotterdam), The Netherlands; 3 Medisch Spectrum Twente, Radiotherapy, Enschede, The Netherlands; 4 Maastricht Radiation Oncology Clinic, Radiation Oncology, Maastricht, The Netherlands; 5 University Medical Center Utrecht, Radiation Oncology, Utrecht, The Netherlands; 6 Radiotherapiegroep, Radiotherapy, Arnhem, The Netherlands; 7 Erasmus MC Cancer Institute, Radiation Oncology, Rotterdam, The Netherlands; 8 Radiotherapeutic Institute Friesland, Radiotherapy, Leeuwarden, The Netherlands; 9 Leiden University Medical Center, Biomedical data sciences, Leiden, The Netherlands; 10 Leiden University Medical Center, Pathology, Leiden, The Netherlands Purpose or Objective The molecular classification of endometrial cancer (EC) has proven prognostic value and was found to be predictive for response to chemotherapy in the PORTEC-3 trial. The predictive value of the molecular classification for response to adjuvant radiotherapy has not yet been determined. Therefore, we investigated whether benefit of adjuvant radiotherapy differs across the four molecular classes. Materials and Methods We evaluated the combined cohort of participants from the randomized PORTEC-1 (n=714) and -2 clinical trials (n=427). The PORTEC-1 and -2 trials respectively included women with intermediate and high-intermediate risk stage I endometrioid EC. In PORTEC-1 pelvic external beam radiotherapy (EBRT) was compared to no adjuvant treatment, and in PORTEC-2 vaginal brachytherapy (VBT) to EBRT. All cases that were molecularly profiled according to the WHO 2020 classification were included for analyses (n=484 of PORTEC-1 and n=396 of PORTEC-2). Locoregional recurrence-free survival (LRFS) was estimated using Kaplan-Meier’s methodology by adjuvant treatment with stratification for molecular class, and compared using log-rank tests. Results A total of 880 women with a median follow-up of 11.3 years were included (Table 1). Most women had stage I disease (96%) and tumors with an endometrioid histotype (98%). EC were classified as POLE-mutant (POLEmut, 8%) mismatch-repair deficient (MMRd, 28%), p53-abnormal (p53abn, 8%) and non-specific molecular profile (NSMP, 57%). In POLEmut EC, no recurrences were observed, even among those who had received no adjuvant therapy (Figure 1A). In MMRd EC, a small non significant benefit of VBT and EBRT (5-year LRFS respectively 94% and 95%) over no adjuvant treatment was observed (89%, p=0.20, Figure 1B). In p53abn EC, EBRT (97%) but not VBT (64%) significantly improved LRFS compared to no adjuvant treatment (72%, p=0.042, figure 1C). In NSMP EC, both EBRT (98%) and VBT (96%) significantly improved LRFS (no adjuvant treatment 88%, p=0<0.0001, figure 1D).

Table 1. Overview of the included patients from the PORTEC-1 and -2 trials

Figure 1. Locoregional recurrence-free survival by adjuvant therapy across the four molecular groups of endometrial cancer