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(申请人提供)：宫颈癌是全球癌症死亡的主要原因之一。患者往往很难获得筛查和疫苗接种，并处于晚期，而放化疗是治疗的标准。然而，这种治疗受到高失败率和毒性的限制。虽然加强化疗可以改善肿瘤控制和生存率，但毒性往往高得令人无法接受。因此，在提高化疗疗效的同时降低毒性的策略是必要的。标准的盆腔RT技术包括大量的正常组织。相比之下，图像引导调强放射治疗(IG-IMRT)是一种最大限度地增加目标剂量和最小化正常组织剂量的现代技术。多项研究发现，与标准放疗相比，IG-IMRT可以显著减少器官剂量，减少毒性。这些研究支持这样的假设，即IG-IMRT可以提供更密集的化疗。例如，在随机试验中发现吉西他滨是一种有效的放射增敏剂，可以提高宫颈癌患者的存活率(Dueñas-Gonzalez等人)。然而，当使用标准RT时，毒性是极端的(&gt；80%3-4级毒性)。因此，这种方案并没有单独取代顺铂作为治疗的标准。相反，我们的研究小组发现，使用IG-IMRT时，吉西他滨的最大耐受量增加。一项大型的国际多机构试验也发现，与标准的化疗RT相比，IG-IMRT的毒副作用更低。这些发现支持这样的假设，即IG-IMRT通过减少肠道和骨髓剂量，可以提供更有效的同步化疗。如果得到证实，这将对许多盆腔恶性肿瘤产生重大影响。然而，这一假设尚未在随机试验中得到验证。CVM-1421是NRG肿瘤学合作小组内由NCI资助的一项新的II期随机试验，该试验将测试这样一种假设，即在同时进行顺铂和RT的同时添加核糖核苷酸还原酶抑制剂Triapine可以改善正在接受明确化疗的局部区域晚期宫颈癌患者的预后。这项试验提供了一个独特的机会来研究IG-IMRT对正常组织毒性的影响，因为这将是第一个允许IG-IMRT在这一人群中使用的合作小组试验。这项试验也提供了一个研究如何提高IG-IMRT质量的机会，因为由于IG-IMRT计划的复杂性增加，如何优化设计IG-IMRT计划一直存在相当大的争议。我们研究的目的是研究不同化疗强度下IG-IMRT对毒性、生活质量和治疗结果的影响。我们还将实施一种名为基于知识的计划(KBP)的新技术，以提高计划质量并实现最佳的IG-IMRT剂量分布。这项研究可能有助于建立IG-IMRT作为盆腔恶性肿瘤护理的新标准，并将为未来在临床试验环境中测试新技术的研究奠定基础。