Tumor bed implant for simultaneous heat and radiation of resectable brain tumors

用于同时加热和辐射可切除脑肿瘤的肿瘤床植入物

• 批准号: 9907105
• 负责人: Paul Rath Stauffer
• 金额: $ 30万
• 依托单位: MAE CONSULTING GROUP LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9907105
• 关键词: Address; Agreement; Animals; Beds; Brachytherapy; Brain; Brain Neoplasms; Breast; Caliber; Chemotherapy and/or radiation; Client satisfaction; Clinical; Clinical Trials; Computers; Coupling; Development; Devices; Dose; Effectiveness; Ensure; Excision; External Beam Radiation Therapy; Family suidae; Glioblastoma; Goals; Head and neck structure; Heating; Human; Implant; Inferior; Investigation; Laboratories; Laboratory Study; Life; Liver; Magnetic nanoparticles; Measures; Metastatic malignant neoplasm to brain; Mission; Modality; Modeling; Muscle; Neurologic Deficit; Neurosurgeon; Normal tissue morphology; Oncologist; Operative Surgical Procedures; Outcome; Pathway interactions; Patient-Focused Outcomes; Patients; Pattern; Performance; Perfusion; Peripheral; Phase; Phase II Clinical Trials; Preparation; Procedures; Protocols documentation; Psyche structure; Public Health; Radiation; Radiation Dose Unit; Radiation Toxicity; Radiation-Sensitizing Agents; Radiometry; Radiosurgery; Randomized Clinical Trials; Recurrence; Regulatory Pathway; Research; Resectable; Resected; Risk; Route; Safety; Saline; Seeds; Site; Source; Structure; Surgically-Created Resection Cavity; Survival Rate; System; Technology; Temperature; Testing; Thigh structure; Time; Tissue Model; Tissues; Toxic effect; Treatment Protocols; Tumor Cell Migration; Universities; Work; alternative treatment; animal tissue; base; brain surgery; brain tissue; brain tumor resection; cost; design; dosimetry; follow-up; healing; improved; in vivo; innovation; irradiation; lung sarcoma; magnetic field; nanoparticle; neoplastic cell; neural implant; new technology; novel; outcome forecast; prototype; radiation response; response; sensor; success; synergism; treatment comparison; treatment planning; tumor; white matter; Address; Agreement; Animals; Beds; Brachytherapy; Brain; Brain Neoplasms; Breast; Caliber; Chemotherapy and/or radiation; Client satisfaction; Clinical; Clinical Trials; Computers; Coupling; Development; Devices; Dose; Effectiveness; Ensure; Excision; External Beam Radiation Therapy; Family suidae; Glioblastoma; Goals; Head and neck structure; Heating; Human; Implant; Inferior; Investigation; Laboratories; Laboratory Study; Life; Liver; Magnetic nanoparticles; Measures; Metastatic malignant neoplasm to brain; Mission; Modality; Modeling; Muscle; Neurologic Deficit; Neurosurgeon; Normal tissue morphology; Oncologist; Operative Surgical Procedures; Outcome; Pathway interactions; Patient-Focused Outcomes; Patients; Pattern; Performance; Perfusion; Peripheral; Phase; Phase II Clinical Trials; Preparation; Procedures; Protocols documentation; Psyche structure; Public Health; Radiation; Radiation Dose Unit; Radiation Toxicity; Radiation-Sensitizing Agents; Radiometry; Radiosurgery; Randomized Clinical Trials; Recurrence; Regulatory Pathway; Research; Resectable; Resected; Risk; Route; Safety; Saline; Seeds; Site; Source; Structure; Surgically-Created Resection Cavity; Survival Rate; System; Technology; Temperature; Testing; Thigh structure; Time; Tissue Model; Tissues; Toxic effect; Treatment Protocols; Tumor Cell Migration; Universities; Work; alternative treatment; animal tissue; base; brain surgery; brain tissue; brain tumor resection; cost; design; dosimetry; follow-up; healing; improved; in vivo; innovation; irradiation; lung sarcoma; magnetic field; nanoparticle; neoplastic cell; neural implant; new technology; novel; outcome forecast; prototype; radiation response; response; sensor; success; synergism; treatment comparison; treatment planning; tumor; white matter

Abstract / Summary Glioblastoma multiforme (GBM) is an aggressive brain tumor that generally recurs locally and has a median survival <18 months. Treatment typically involves surgery followed by radiation and chemotherapy but the challenge remains to provide sufficient radiation dose to sterilize tumor bed without unacceptable toxicity in surrounding normal brain. A randomized clinical trial studying brachytherapy radiation boost to tumor bed with and without sequentially applied local heat showed a doubling of two-year survival in GBM compared to brachytherapy alone. Although that 31% two-year survival rate is higher than current state of the art treatment approaches for GBM, previous thermobrachytherapy studies used University prototype heating systems that were never commercialized, and thus the approach was discontinued. With alternative treatments still failing to match prior results, the time has come to optimize thermobrachytherapy. Ensuing in vivo studies have shown that synergy between heat (HT) and radiation (RT) is maximized when the two therapies are applied simultaneously. To meet the urgent need for improved survival following brain tumor surgery, we propose a dual-modality thermobrachytherapy (TBT) balloon implant to fill the resection cavity and further increase the survival benefit seen in prior studies by: i) delivering HT and RT more uniformly to tumor bed; ii) providing potent thermal enhancement of RT response up to 5X in tumor bed by combining HT and RT simultaneously; iii) beginning RT of tumor bed immediately after surgery before tumor cell migration; and iv) improving patient satisfaction and reducing cost by decreasing treatment time from 3-6 weeks of daily external beam RT to <5 days total therapy. Our premise is that by applying local heat and brachytherapy simultaneously for maximum synergy and uniformly to the resection cavity wall for effective localization of effect before tumor cells migrate, we can significantly enhance local response and survival while minimizing peripheral toxicity and thereby improve clinical outcomes. Our Phase I development has three specific aims: i) to fabricate a dual-therapy balloon device; ii) to evaluate the device for compatibility of HT and RT components and characterize thermal and radiation dosimetry in laboratory studies; and iii) demonstrate appropriate heat distributions that coincide with computer treatment plans in in vivo animal perfused tissue studies. After demonstrating safety and effectiveness in followup clinical trials in Phase II, we anticipate neurosurgeons and oncologists associated with ~250 brain surgery centers already owning HDR afterloaders will embrace this new technology due to obvious need for improved therapy in >52,000 resected brain tumors annually in the US, impressive clinical precedent in GBM with inferior thermobrachytherapy approaches, and established regulatory pathway for component technologies. While this development is focused towards brain tumor therapy, the TBT balloon procedure is expected to find application in other tumor resection sites including head and neck, breast, lung, and sarcoma (with potentially ~600,000 patients annually in US) following successful launch in brain tumors.

摘要 /摘要 胶质母细胞瘤多形（GBM）是一种侵略性的脑肿瘤，通常在局部复发，并具有中位数 生存<18个月。治疗通常涉及手术，然后进行放疗和化学疗法，但 挑战仍然是提供足够的辐射剂量以对肿瘤床进行消毒，而无需不可接受的毒性 围绕正常大脑。研究近距离放射治疗放射的随机临床试验，以 并且没有依次施加的局部热量，与GBM相比，GBM的两年生存率增加了一倍 单独的近距离放射治疗。尽管该31％的两年生存率高于当前治疗的现状 GBM的方法，先前的热肉手疗法研究使用了大学原型加热系统 从未商业化，因此该方法被停止了。替代治疗仍然无法 匹配先前的结果，已经到了优化热透射疗法的时间了。随后的体内研究表明 当应用两种疗法时，最大化热量（HT）和辐射（RT）之间的协同作用 同时地。为了满足脑肿瘤手术后迫切需要改善生存的需求，我们建议 双模式热润滑疗法（TBT）气球植入物以填充切除腔并进一步增加 在先前的研究中看到的生存益处：i）更均匀地将HT和RT递送到肿瘤床； ii）提供 通过同时组合HT和RT，在肿瘤床中的RT响应的有效热增强最高为5倍； iii）在肿瘤细胞迁移前手术后立即开始肿瘤床的RT；和iv）改善患者 通过从3-6周的每日外束RT减少治疗时间到<5来减少满意度和降低成本 天总治疗。我们的前提是，通过同时施用局部热量和近距离放射治疗以最大程度地 协同效应并统一地与切除腔壁有效地定位肿瘤细胞迁移， 我们可以显着提高局部反应和生存，同时最大程度地减少外围毒性，从而 改善临床结果。我们的I阶段开发具有三个特定的目的：i）制造双治疗 气球装置； ii）评估设备的HT和RT组件的兼容性并表征热量 和实验室研究中的辐射剂量法； iii）展示了合成的适当热量分布 随着计算机治疗计划，体内动物灌注的组织研究。证明安全性和 在第二阶段的后续临床试验中有效性，我们预计神经外科医生和肿瘤学家相关 由于〜250个脑外科手术中心已经拥有HDR后负载器，因此将接受这项新技术 在美国，明显需要改善> 52,000个切除的脑肿瘤的治疗，令人印象深刻的临床 具有劣质放射治疗方法的GBM的先例，并建立了调节途径 组件技术。虽然这种发育专注于脑瘤疗法，但TBT气球 预计过程将在其他肿瘤切除部位找到应用，包括头部和颈部，乳房，肺， 在脑肿瘤中成功发射后，肉瘤（每年有约60万名患者）。