Magnetic Resonance-based Response Assessment and Dose Adaptation in Human Papilloma Virus Positive Tumors of the Oropharynx treated with Radiotherapy (MR-ADAPTOR): An R-IDEAL stage 2a-2b/Bayesian phase II trial.
Magnetic Resonance-based Response Assessment and Dose Adaptation in Human Papilloma Virus Positive Tumors of the Oropharynx treated with Radiotherapy (MR-ADAPTOR): An R-IDEAL stage 2a-2b/Bayesian phase II trial.
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DOI：
10.1016/j.ctro.2018.08.003
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发表时间：
2018-11
影响因子：
3.1
通讯作者：
Fuller CD
中科院分区：
文献类型：
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作者：
Bahig H;Yuan Y;Mohamed ASR;Brock KK;Ng SP;Wang J;Ding Y;Hutcheson K;McCulloch M;Balter PA;Lai SY;Al-Mamgani A;Sonke JJ;van der Heide UA;Nutting C;Li XA;Robbins J;Awan M;Karam I;Newbold K;Harrington K;Oelfke U;Bhide S;Philippens MEP;Terhaard CHJ;McPartlin AJ;Blanchard P;Garden AS;Rosenthal DI;Gunn GB;Phan J;Cazoulat G;Aristophanous M;McSpadden KK;Garcia JA;van den Berg CAT;Raaijmakers CPJ;Kerkmeijer L;Doornaert P;Blinde S;Frank SJ;Fuller CD
HPV+口咽癌的治疗降级是一个活跃的研究领域。提出了一项mr引导放射治疗剂量适应的贝叶斯II期试验。根据肿瘤的反应，每周的MRI将调整高剂量。将评估剂量适应与标准IMRT相比的非劣效性。目前口咽癌（OPC）的标准放疗与严重毒性的高发率相关，对患者的生活质量产生不利影响。鉴于人乳头瘤病毒（HPV）相关的OPC的良好预后和这些典型的年轻患者的长期生存，旨在提高生存率同时保持良好的疾病控制的去强化治疗现在是一个中心问题。最近实施的磁共振图像引导放射治疗（MRgRT）系统允许在治疗期间进行个体肿瘤反应评估，并提供个性化剂量减少的可能性。在这项两阶段的贝叶斯II期研究中，我们建议检查基于磁共振成像（MRI）评估肿瘤反应的每周放疗剂量适应。个体患者的计划将被设计为优化风险器官的剂量减少，并根据rt期间的序列MRI最小化局部区域失败概率。我们的主要目的是评估低风险hpv相关OPC患者的MRgRT剂量适应与历史对照组相比的非劣效性，通过局部区域控制的贝叶斯后验概率（LRC）来衡量。T1-2 N0-2b（根据AJCC第7版）hpv阳性OPC，淋巴结<3 cm，吸烟史<10包年的患者计划单独进行33份剂量为70 Gy的治愈性放疗，将符合条件。所有患者将接受治疗前MRI检查和至少每周治疗期间MRI检查。接受MRgRT的患者将根据总体肿瘤体积反应每周调整高剂量计划靶体积。该研究的第一阶段将招募15名患者进行MRgRT剂量适应。如果根据贝叶斯模型，6 个月的LRC与MRgRT剂量适应被发现足够安全，方案的第二阶段将扩大入组到额外的60名患者，随机分配到MRgRT或标准IMRT。目前正在研究hpv阳性OPC患者安全治疗降级的多种方法。通过利用先进的MRI技术在整个治疗过程中可视化肿瘤和软组织的能力，该方案提出了一种安全的个性化放射剂量降低工作流程，用于放射敏感肿瘤的良好应答者，同时确保对更多放射耐药肿瘤的杀瘤剂量。MRgRT剂量适应可以转化为降低长期辐射毒性和改善生存，同时在有利的OPC中保持良好的LRC结果。ClinicalTrials.gov ID: NCT03224000；报名日期：2017年7月21日。
Treatment de-escalation in HPV+ oropharynx cancer is an active area of research. A Bayesian phase II trial of MR-guided radiotherapy dose adaptation is proposed. High dose volume will be adapted on weekly MRI based on tumor response. The non-inferiority of dose adaptation compared to standard IMRT will be assessed. Current standard radiotherapy for oropharynx cancer (OPC) is associated with high rates of severe toxicities, shown to adversely impact patients’ quality of life. Given excellent outcomes of human papilloma virus (HPV)-associated OPC and long-term survival of these typically young patients, treatment de-intensification aimed at improving survivorship while maintaining excellent disease control is now a central concern. The recent implementation of magnetic resonance image – guided radiotherapy (MRgRT) systems allows for individual tumor response assessment during treatment and offers possibility of personalized dose-reduction. In this 2-stage Bayesian phase II study, we propose to examine weekly radiotherapy dose-adaptation based on magnetic resonance imaging (MRI) evaluated tumor response. Individual patient’s plan will be designed to optimize dose reduction to organs at risk and minimize locoregional failure probability based on serial MRI during RT. Our primary aim is to assess the non-inferiority of MRgRT dose adaptation for patients with low risk HPV-associated OPC compared to historical control, as measured by Bayesian posterior probability of locoregional control (LRC). Patients with T1-2 N0-2b (as per AJCC 7th Edition) HPV-positive OPC, with lymph node <3 cm and <10 pack-year smoking history planned for curative radiotherapy alone to a dose of 70 Gy in 33 fractions will be eligible. All patients will undergo pre-treatment MRI and at least weekly intra-treatment MRI. Patients undergoing MRgRT will have weekly adaptation of high dose planning target volume based on gross tumor volume response. The stage 1 of this study will enroll 15 patients to MRgRT dose adaptation. If LRC at 6 months with MRgRT dose adaptation is found sufficiently safe as per the Bayesian model, stage 2 of the protocol will expand enrollment to an additional 60 patients, randomized to either MRgRT or standard IMRT. Multiple methods for safe treatment de-escalation in patients with HPV-positive OPC are currently being studied. By leveraging the ability of advanced MRI techniques to visualize tumor and soft tissues through the course of treatment, this protocol proposes a workflow for safe personalized radiation dose-reduction in good responders with radiosensitive tumors, while ensuring tumoricidal dose to more radioresistant tumors. MRgRT dose adaptation could translate in reduced long term radiation toxicities and improved survivorship while maintaining excellent LRC outcomes in favorable OPC. ClinicalTrials.gov ID: NCT03224000; Registration date: 07/21/2017.