ESTRO 2025 - Abstract Book

S819

Clinical - Gynaecology

ESTRO 2025

2072

Digital Poster Evaluation of molecular signature predictive power for response to neoadjuvant chemoradiotherapy in patients with locally advanced cervical cancer ROSA AUTORINO 1 , LUIGI PEDONE ANCHORA 2 , MARIANNA BUTTARELLI 3 , CAMILLA CERTELLI 4 , VIVIANA ROMANO 5 , ENRICA MARTINELLI 5 , FRANCESCA TITONE 6 , STEFANO RESTAINO 7 , ALESSIA SURGO 8 , FRANCESCO LEGGE 9 , FRANCESCO COSENTINO 10 , GIANFRANCO ZANNONI 11 , GIOVANNI SCAMBIA 4 , MARIA ANTONIETTA GAMBACORTA 12 , MARIA GABRIELLA FERRANDINA 4 , GABRIELLA MACCHIA 13 1 Department of Radiological, Radiotherapeutic, and Hematological Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Radiotherapy Unit,, Rome, Italy. 2 Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Gynecologic Oncology Unit, Rome, Italy. 3 Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Unit of Translational Medicine for Woman and Child Health, Rome, Italy. 4 Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Gynecologic Oncology Unit, ROME, Italy. 5 Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Unit of Translational Medicine for Woman and Child Health, ROME, Italy. 6 Santa Maria Della Misericordia Hospital, Azienda Sanitaria Friuli Centrale, Radiation Oncology Unit, UDINE, Italy. 7 Department of Medical Area (DMED), Clinic of Obstetrics and Gynecology Unit, Santa Maria Della Misericordia Hospital, Azienda Sanitaria Friuli Centrale, UDINE, Italy. 8 Regional General Hospital 'F. Miulli, Radiation Oncology Unit, Acquaviva (Bari), Italy. 9 Regional General Hospital 'F. Miulli, Unit of Obstetrics and Gynecology, Acquaviva (Bari), Italy. 10 Department of Gynecologic Oncology, Responsible Research Hospital, CAMPOBASSO, Italy. 11 Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Gynecopathology and Breast Pathology Unit, ROME, Italy. 12 Department of Radiological, Radiotherapeutic, and Hematological Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS,, Radiotherapy Unit, Institute of Radiology, ROME, Italy. 13 Responsible Research Hospital, Radiation Oncology Unit, CAMPOBASSO, Italy Purpose/Objective: Pathologic response is the most significant prognostic factor for patients with locally advanced cervical cancer (LACC) undergoing neoadjuvant chemoradiotherapy (CRT) followed by radical surgery (RS). Three genes -ANXA2, NDRG1, and STAT1- have been identified associated with treatment response: ANXA2 and NDRG1 are overexpressed in resistant cells, while STAT1 is overexpressed in sensitive cells. The aim of this study is to validate the predictive accuracy of this three-gene molecular signature for the treatment response. Material/Methods: This research is part of the prospective multicenter LARA 4.0 study, which enrolled LACC patients who received CRT followed by RS from 2021 to 2023. Only patients with complete response (sensitive) and macroscopic disease or progressive disease (resistant) were included. RNA expression levels of the three genes were assessed from pretreatment biopsies using RT-qPCR. Clinical data and HPV status were also recorded and incorporated into the predictive model. Results: A total of 57 patients, 27 sensitive and 30 resistant, were included for training and testing the predictive model. The integration of clinical variables (age, BMI, histology, grade, tumor volume, parametrial invasion, lymph node metastasis, pretreatment blood tests) and molecular variables (HPV status and levels of ANXA2, NDRG1 and STAT1) yielded an area under the curve (AUC) of 0.81. Figure 1 shows the association of each variable with the response to CRT. ANXA2 and NDRG1 reaffirmed their roles in radioresistance, while STAT1 appeared to lose its predictive value. Conclusion: Our findings indicate that integrating clinical and molecular data can effectively predict the response to neoadjuvant CRT in LACC patients. This project represents the first significant effort to incorporate biological information into clinical practice for cervical cancer.