Radiation Oncology, Ghent University Hospital, C. Heymanslaan 10, 9000, Ghent, Belgium.
Gynaecologic Oncology, Ghent University Hospital, C. Heymanslaan 10, 9000, Ghent, Belgium.
BMC Cancer. 2018 Sep 17;18(1):898. doi: 10.1186/s12885-018-4800-0.
Definitive 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.
The 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.
Although 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.
Belgian Registration: B670201526181 (prospectively registered, 26/11/2015); ClinicalTrials.gov Identifier: NCT03542942 (retrospectively registered, 17/5/2018).
根治性放化疗是局部晚期宫颈癌（LACC）的标准治疗方法。在这种治疗中，毒性和局部复发仍然是主要关注点。我们假设基于磁共振成像（MRI）对放射治疗靶区进行重新定义将降低急性和迟发性毒性。在我们中心，放化疗后行子宫切除术已成功实施。这使我们能够评估缩小靶区的安全性，同时探索放化疗对切除的子宫标本的生物学效应。
EXIT 试验是一项针对 LACC 患者的 II 期单臂研究。该研究评估了基于 MRI 将子宫非肿瘤部位排除在靶区之外，是否会导致子宫非高剂量照射部分在子宫切除标本中无肿瘤。次要终点包括当比较研究治疗计划与高剂量全子宫治疗时，对正常组织剂量的比较；急性和慢性毒性、总生存率、局部复发和无进展生存率。在研究的转化部分，我们将评估假设，即在 CRT 开始后 2 周，扩散加权 MRI 的基线表观扩散系数（ADC）值及其演变，对于整个肿瘤以及肿瘤内区域，对于子宫切除标本中的残留肿瘤是否具有预后价值。
尽管 MRI 已经用于指导近距离放射治疗的靶区勾画，但 EXIT 试验是第一个将此信息用于指导外照射放疗的靶区勾画的试验。使用 DW-MRI 进行早期治疗耐药性预测为有治疗失败风险的肿瘤/肿瘤内区域提供了早期治疗适应或进一步剂量递增的机会。
比利时注册：B670201526181（前瞻性注册，2015 年 11 月 26 日）；ClinicalTrials.gov 标识符：NCT03542942（回顾性注册，2018 年 5 月 17 日）。
