Abstract
BackgroundDefinitive chemoradiotherapy is standard of care in locally advanced cervical cancer (LACC). Both toxicity and local relapse remain major concerns in this treatment. We hypothesize that a magnetic resonance imaging (MRI) based redefining of the radiotherapeutic target volume will lead to a reduction of acute and late toxicity. In our center, chemoradiotherapy followed by hysterectomy was implemented successfully in the past. This enables us to assess the safety of reducing the target volume but also to explore the biological effects of chemoradiation on the resected hysterectomy specimen.MethodsThe EXIT-trial is a phase II, single arm study aimed at LACC patients. This study evaluates whether a MRI-based exclusion of the non-tumor-bearing parts of the uterus out of the target volume results in absence of tumor in the non-high doses irradiated part of the uterus in the hysterectomy specimen. Secondary endpoints include a dosimetric comparison of dose on normal tissue when comparing study treatment plans compared to treatment of the whole uterus at high doses; acute and chronic toxicity, overall survival, local relapse- and progression-free survival. In the translational part of the study, we will evaluate the hypothesis that the baseline apparent diffusion coefficient (ADC) values of diffusion weighted MRI and its evolution 2 weeks after start of CRT, for the whole tumor as well as for intra-tumoral regions, is prognostic for residual tumor on the hysterectomy specimen.DiscussionAlthough MRI is already used to guide target delineation in brachytherapy, the EXIT-trial is the first to use this information to guide target delineation in external beam radiotherapy. Early therapy resistance prediction using DW-MRI opens a window for early treatment adaptation or further dose-escalation on tumors/intratumoral regions at risk for treatment failure.Trial registrationBelgian Registration: B670201526181 (prospectively registered, 26/11/2015); ClinicalTrials.gov Identifier: NCT03542942 (retrospectively registered, 17/5/2018).
Highlights
Definitive chemoradiotherapy is standard of care in locally advanced cervical cancer (LACC)
There is no unequivocal evidence supporting the dogma that the whole uterus should be included in the Clinical target volume (CTV) [12]
As the understanding of radiation and radiation techniques improved, intensity modulated RT (IMRT) and arc techniques have become more prevalent and the standard-of-care to deliver external beam radiotherapy (EBRT) in cervical cancer based on reduced gastro-intestinal (GI), genito-urinary (GU) and hematological toxicity [7, 17, 21,22,23,24]
Summary
Definitive chemoradiotherapy is standard of care in locally advanced cervical cancer (LACC) Both toxicity and local relapse remain major concerns in this treatment. In exchange for an improved overall survival (OS), adding chemotherapy to conventional EBRT has doubled the risk of severe acute hematological and gastro-intestinal toxicity and tripled platelet toxicity [4] Triggered off by both the high local recurrence and the toxicity rates we challenged the gold standard by introducing intensity-modulated arc therapy (IMAT) followed by C1 radical hysterectomy (HRT) [5]. This HRT allows removing CRT-resistant tumor foci [6, 7]. Further research aiming at decreasing toxicity and increasing disease control is needed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
