PROTON RADIATION THERAPY RESEARCH

质子放射治疗研究

• 批准号: 6736937
• 负责人: JAY Steven LOEFFLER
• 金额: $ 268.6万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-31 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6736937
• 关键词: clinical research; neoplasm /cancer radiation therapy; proton beam

DESCRIPTION (Applicant's Description) It is estimated that between 20-80 percent of patients treated for locally advanced epithelial or mesenchymal tumors will die secondary to the failure of photon therapy and/or surgery to achieve local control. Furthermore, these aggressive local therapies are themselves often associated with significant acute and late morbidity. There are other tumors, particularly pediatric tumors, for which local control is often satisfactory but treatment-related late effects are high. It is the primary aim of this Program Project to exploit the superior dose distributions of proton beams to improve clinical outcomes for patients with a variety of solid tumors both in terms of cancer control and treatment-related morbidity. We have treated over 5,000 cancer patients with proton therapy at the Harvard Cyclotron Laboratory since 1974. We have achieved significant gains in clinical outcomes for a number of disease sites including chondrosarcomas and chordomas of the skull base and cervical spine (95 percent and 50 percent local control, respectively), paranasal sinus tumors (87 percent local control), and ocular melanomas (97 percent local control). We propose to carry out clinical trials using proton beams in additional tumor sites where photon therapy has provided suboptimal treatment outcomes. The two basic hypotheses for this Program Project are that, using the superior dose distributions of proton beams, we can (in subproject 5) escalate tumor dose and improve local control without increasing damage to non-target normal tissues and (in subproject 6) maintain high rates of local control while decreasing treatment related morbidity. We will assess clinical gains in terms of five endpoints: 1) local control, 2) distant metastasis-free survival, 3) overall survival, 4) treatment-related morbidity, and 5) quality-of-life (QOL) We also hypothesize that proton irradiation will decrease the comorbidity between radiation therapy and chemotherapy thus improving compliance and intensity of treatment. We will use well-designed prospective phase I/II/III trials to test these hypotheses. The proposed research program consists of three closely related projects. In subproject 5 we will carry out phase I/II/III dose escalation studies for prostate, lung, paranasal sinus, nasopharynx and hepatocellular cancers. The goals of these trials are to improve local control and survival. In subproject 6 we will carry out phase II/III studies designed to reduce treatment-related morbidity for pediatric cancers including medulloblastoma, retinoblastoma, and soft tissue sarcomas, and adult tumors including rectal carcinoma and choroidal melanoma. In the prostate clinical trial we will collaborate with the Loma Linda University Medical Center in protocol design and patient accrual. In subproject 4 we will develop treatment delivery and planning systems, and design and carry out dosimetry and quality assurance programs to support the proposed clinical trials. The Northeast Proton Therapy Center (NPTC), jointly funded by the NCI and the MGH, has been built on the MGH campus. The NPTC will provide the increased capacity and new technologies needed to conduct the clinical trials proposed in this application. With our experience in conducting proton clinical trials, and the resources offered by the NPTC, we have unique capabilities to carry out the proposed research. It is our expectation that these clinical trials will show improved cancer control rates, reduced treatment morbidity and improved QOL.

描述（申请人的描述） 据估计，接受局部治疗的患者中有20％至80％ 晚期上皮或间质肿瘤将死于继发于失败 光子疗法和/或手术以实现局部控制。此外，这些 积极的当地疗法本身通常与重要 急性和晚期发病。还有其他肿瘤，尤其是小儿 肿瘤，局部控制通常令人满意，但与治疗有关 晚效果很高。这是该计划项目的主要目的 利用质子束的上剂量分布以改善临床 在癌症方面，患有多种实体瘤的患者的结果 控制和治疗相关的发病率。 我们已经在哈佛治疗了5,000多名质子治疗的癌症患者 自1974年以来的回旋实验室。我们在 许多疾病部位的临床结局，包括软骨肉瘤和 颅底和颈椎的丘陵（95％和50％ 局部控制分别），旁鼻窦肿瘤（局部87％ 控制）和眼部黑色素瘤（局部控制97％）。我们建议 在其他肿瘤部位使用质子梁进行临床试验 光子疗法提供了次优的治疗结果。 该计划项目的两个基本假设是，使用上级 质子束的剂量分布，我们可以（在第5个下）升级肿瘤剂量 并改善本地控制而不增加对非目标正常的损害 组织和（在subproject 6中）保持局部控制率很高，而 降低治疗相关的发病率。我们将根据术语评估临床收益 五个终点：1）局部控制，2）遥远的无转移生存，3） 总体生存，4）与治疗相关的发病率和5）生活质量（QOL） 我们还假设质子辐照将降低合并症 在放射疗法和化学疗法之间，从而提高了依从性和 治疗强度。我们将使用精心设计的前瞻性I/II/III 试验以检验这些假设。 拟议的研究计划由三个密切相关的项目组成。在 第5次，我们将进行I/II/II/III期剂量升级研究 前列腺，肺，副窦，鼻咽和肝细胞癌。这 这些试验的目标是改善当地的控制和生存。在第6次 我们将进行II/III期研究，旨在减少与治疗相关的研究 小儿癌的发病率，包括髓母细胞瘤，视网膜细胞瘤和 软组织肉瘤和成年肿瘤，包括直肠癌和 脉络膜黑色素瘤。在前列腺临床试验中，我们将与 洛马·琳达大学协议设计和患者的医学中心 应计。在第4台下，我们将开发治疗交付和计划系统， 设计并执行剂量和质量保证计划，以支持 拟议的临床试验。 东北质子治疗中心（NPTC），由NCI和 MGH，建于MGH校园。 NPTC将提供增加 进行临床试验所需的能力和新技术 在此应用程序中。凭借我们进行质子临床试验的经验， 以及NPTC提供的资源，我们具有独特的能力来携带 提出了拟议的研究。我们期望这些临床试验 将显示癌症控制率提高，治疗发病率降低和 改进的QOL。