Early morbidity and dose–volume effects in definitive radiochemotherapy for locally advanced cervical cancer: a prospective cohort study covering modern treatment techniques

Abstract

Predicting morbidity for patients with locally advanced cervix cancer after external beam radiotherapy (EBRT) based on dose–volume parameters remains an unresolved issue in definitive radiochemotherapy. The aim of this prospective study was to correlate patient characteristics and dose–volume parameters to various early morbidity endpoints for different EBRT techniques, including volumetric modulated arc therapy (VMAT) and adaptive radiotherapy (ART). The study population consisted of 48 patients diagnosed with locally advanced cervix cancer, treated with definitive radiochemotherapy including image-guided adaptive brachytherapy (IGABT). Multiple questionnaires (CTCAE 4.03, QLQ-C30 and EORTC QLQ-CX24) were assessed prospectively for patients treated with different EBRT techniques, including online adaptive VMAT. Contouring and treatment planning was based on the EMBRACE protocols. Acute toxicity, classified as general, gastrointestinal (GI) or genitourinary (GU) and their corresponding dose–volume histograms (DVHs) were first correlated by applying least absolute shrinkage and selection operator (LASSO) and subsequently evaluated by multiple logistic binomial regression. The treated EBRT volumes varied for the different techniques with ~2500\u202fcm3 for 3D conformal radiotherapy (3D-CRT), ~2000\u202fcm3 for EMBRACE‑I VMAT, and ~1800\u202fcm3 for EMBRACE-II VMAT and ART. In general, a worsening of symptoms during the first 5 treatment weeks and recovery afterwards was observed. Dose–volume parameters significantly correlating with stool urgency, rectal and urinary incontinence were as follows: bowel V40Gy\u202f<\u2009250\u202fcm3, rectum V40Gy\u202f<\u200980% and bladder V40Gy\u202f<\u200980–90%. This prospective study demonstrated the impact of EBRT treatment techniques in combination with chemotherapy on early morbidity. Dose–volume effects for dysuria, urinary incontinence, stool urgency, diarrhea, rectal bleeding, rectal incontinence and weight loss were found.