Effectiveness of IG-IMRT for Locally Advanced Cervix Cancer on NRG Trial CVM-1421

NRG 试验 CVM-1421 中 IG-IMRT 对局部晚期宫颈癌的有效性

• 批准号: 9104120
• 负责人: Loren K. Mell
• 金额: $ 25.36万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-02 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9104120
• 关键词: American; Anterior; Bone Marrow; Boxing; Cancer Etiology; Cancer Patient; Cessation of life; Cisplatin; Clinical Trials; DNA Synthesis Inhibitors; Data; Diagnosis; Disease; Dose; Effectiveness; Failure; Funding; Future; Genitourinary system; Goals; Gynecologic; Health; Intensity-Modulated Radiotherapy; International; Intestines; Lateral; Machine Learning; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Maximum Tolerated Dose; Modeling; Normal tissue morphology; Organ; Patients; Pelvis; Population; Progression-Free Survivals; Protocols documentation; Quality of life; Radiation; Radiation therapy; Radiation-Sensitizing Agents; Randomized; Regimen; Research; Research Personnel; Ribonucleotide Reductase Inhibitor; Secondary to; Shapes; Staging; Techniques; Testing; Therapeutic; Tissues; Toxic effect; Treatment outcome; Triapine; Vaccination; chemoradiation; chemotherapy; comparative effectiveness; contrast imaging; design; gastrointestinal; gemcitabine; image guided; improved; improved outcome; interest; knowledge base; new technology; novel; oncology; phase I trial; phase II trial; radiation effect; randomized trial; screening; standard of care; tool; treatment planning; tumor

 DESCRIPTION (provided by applicant): Cervical cancer is among the leading causes of cancer death worldwide. Patients often have poor access to screening and vaccination, and present in advanced stages, for which chemoradiotherapy (chemoRT) is the standard of care. This treatment is limited, however, by high rates of failure and toxicity. Although intensifying chemotherapy can improve tumor control and survival, toxicity is often unacceptably high. Strategies to reduce toxicity while increasing efficacy of chemoRT are therefore needed. Standard pelvic RT techniques encompass large volumes of normal tissue. In contrast, image-guided intensity-modulated RT (IG-IMRT) is a modern technique that maximizes target dose and minimizes normal tissue dose. Multiple studies have found that IG-IMRT can significantly reduce organ dose and reduce toxicity compared to standard RT. These studies support the hypothesis that IG-IMRT can permit delivery of more intensive chemotherapy. For example, gemcitabine, a potent radiosensitizer, has been found to improve survival for cervical cancer patients in randomized trials (Dueñas-Gonzalez et al.). However, the toxicity when delivered with standard RT is extreme (>80% grade 3-4 toxicity). Therefore, this regimen has not replaced cisplatin alone as the standard of care. In contrast, our research group has found that the maximum tolerated dose of gemcitabine was increased when given with IG-IMRT. A large international multi-institutional trial has also found lower rates of toxicity with IG-IMRT compare to standard chemoRT. These findings support the hypothesis that IG-IMRT, by reducing bowel and bone marrow dose, could permit delivery of more effective concurrent chemotherapy. If confirmed, this would have significant implications for many pelvic malignancies. However, this hypothesis has not been tested in a randomized trial. CVM-1421 is an emerging NCI-funded randomized phase II trial within the NRG Oncology Cooperative Group that will test the hypothesis that adding concurrent triapine, a ribonucleotide reductase inhibitor, to concurrent cisplatin and RT can improve outcomes in patients with locoregionally advanced cervix cancer undergoing definitive chemoradiation. This trial presents a unique opportunity to study the effects of IG- IMRT on normal tissue toxicity, as it will be the first cooperative group trial to permit IG-IMRT in this population. This trial also presents an opportunity to study ways to improve IG-IMRT quality, as there has been considerable controversy in how to optimally design IG-IMRT plans, due to their increased complexity. The goal of our research is to study the effect of IG-IMRT on toxicity, quality of life, and treatment outcomes, under varying intensities of chemotherapy. We will also implement a novel technique called knowledge-based planning (KBP) in order to improve plan quality and achieve optimal IG-IMRT dose distributions. This research could help establish IG-IMRT as a new standard of care for pelvic malignancies, and will lay groundwork for future studies testing novel technologies in clinical trial settings.

 描述（由适用提供）：宫颈癌是全球癌症死亡的主要原因之一。患者通常无法获得筛查和疫苗接种，并且是在晚期阶段出现的，而化学疗法（化学）是护理标准。尽管加强化疗可以改善肿瘤的控制和存活，但毒性通常不可接受。因此，需要降低毒性同时提高化学效率的策略。标准骨盆RT技术包含大量正常组织。相反，图像引导强度调节的RT（IG-IMRT）是一种现代技术，可最大化目标剂量并最大程度地减少正常组织剂量。多项研究发现，与标准RT相比，Ig-IMRT可以显着降低器官剂量并降低毒性。这些研究支持以下假设：Ig-IMRT可以允许提供更深入的化学疗法。例如，在随机试验中，吉西他滨是一种有效的放射敏化剂，可改善宫颈癌患者的存活率（Dueñas-Gonzalez等人）。但是，用标准RT递送时的毒性极高（> 80％3-4级毒性）。因此，该方案尚未单独替代顺铂作为护理标准。相比之下，我们的研究小组发现，用Ig-IMRT给出时，吉西他滨的最大耐受剂量会增加。一项大型国际多机构试验还发现，与标准化学相比，IG-IMRT的毒性率较低。这些发现支持以下假设：通过减少肠子和骨髓剂量，Ig-IMRT可以允许提供更有效的并发化疗。如果得到证实，这将对许多骨盆恶性肿瘤产生重大影响。但是，该假设尚未在一项随机试验中进行检验。 CVM-1421是NRG肿瘤学合作组中新兴的NCI资助的随机II期试验，它将检验以下假设：添加并发的三合一（一种降低的抑制剂）同时替代型cyplatin和RT可以改善局部性癌症的疾病癌症癌症的疾病，以改善Cisplatin和rt的同时cisplatin和RT。该试验为研究Ig-IMRT对正常组织毒性的影响提供了独特的机会，因为这将是第一个允许该人群IG-IMRT的教练组试验。该试验还为研究改善IG-IMRT质量的方法提供了机会，因为由于其复杂性的增加，因此如何最佳设计IG-IMRT计划引起了极大的争议。我们研究的目的是研究Ig-IMRT对化学疗法强度不同的毒性，生活质量和治疗结果的影响。我们还将实施一种称为基于知识的计划（KBP）的新型技术，以提高计划质量并实现最佳的IG-IMRT剂量分布。这项研究可以帮助建立Ig-IMRT作为骨盆恶性肿瘤的新护理标准，并将为未来的研究为在临床试验环境中测试新技术的研究奠定基础。