RADIATION/HYPERTHERMIA THERAPY FOR CHORIDAL MELANOMA

脉络膜黑色素瘤的放射/热疗

• 批准号: 3265102
• 负责人: PETER E LIGGETT
• 金额: $ 20.08万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3265102
• 关键词: combination cancer therapy; cytotoxicity; disease /disorder model; dosage; electroretinography; eye disorder diagnosis; eye neoplasms; fluorescein angiography; histopathology; human therapy evaluation; laboratory rabbit; neoplasm /cancer radiation therapy; neoplasm /cancer thermotherapy; radiation immunosuppression; radiation therapy dosage; radiobiology; radiotracer; xenotransplantation

Malignant choroidal melanoma is the most common primary intraocular neoplasm in adults. For over 100 years, enucleation was the accepted treatment for this disease. The ideal treatment, however, would eradicate the tumor while preserving ocular function. Recent suggestions that enucleation may, in fact, promote the development of distant metastases has led to the use of limited surgical techniques which preserve the eye. Radiation therapy has replaced enucleation as the most common treatment, and is now the subject of a nation-wide clinical trial (Collaborative Ocular Melanoma Study). Unfortunately, the potential advantages of radiation therapy can be negated by the development of chronic radiation- induced complications, particularly in the treatment of tumors grater than 8mm height. The secondary complications eventually impair ocular function and may result in loss of the eye. The use of hyperthermia (42o to 45o C) in combination with radiation has been demonstrated to enhance the effectiveness of radiation therapy in the treatment of human cutaneous melanomas by a factor of two. In an animal model of Greene choroidal melanoma, the combination of these modalities has been demonstrated to allow a reduction of radiation dose while maintaining tumor control. We expect that reducing the radiation dose will lead to fewer secondary complications, thereby preserving useful vision. We have established a new xenograft model of human choroidal melanoma in immuno-suppressed rabbit eyes which we expect to behave more like human choroidal melanoma in situ than the older Greene model. In addition, we have developed a new clinical technique for combining hyperthermia produced by 500 KHz radiofrequency current with I125 irradiation using a gold episcleral plaque. A Phase-1 clinical evaluation of this technique is currently in progress at our institution. We have developed quantitative I125 dosimetry for our plaque delivery system, and preliminary hyperthermia dosimetry in normal rabbit eyes. We have demonstrated that the normal rabbit eye can tolerate temperatures up to 45oC, measured at the plaque- sclera interface, with tolerable acute toxicity. We proposed to: 1) develop quantitative hyperthermia dosimetry for our heating technique in rabbit eyes containing the human uveal melanoma xenograft; 2) determine the dose-response relationship for our xenograft model to I125 irradiation alone; 3) determine the "dose" temperature response for the xenograft model to hyperthermia alone; 4) determine the dose-response of the xenograft model to the combined modalities, and 5) assess acute chronic toxicity following treatment with irradiation, hyperthermia, or the combined modalities and doses associated with tumor control. Due to the lack of a fovea in the rabbit eye, we further propose to evaluate acute toxicity (from the combined modalities) in a limited number of primate eyes if results using the rabbit model disclose a potential therapeutic gain.

恶性脉络膜黑色素瘤是最常见的原发眼内肿瘤 成人中的肿瘤。在100多年的时间里，眼球摘除被接受 治疗这种疾病的方法。然而，理想的治疗方法将根除 在保留眼功能的同时切除肿瘤。最近的建议是 事实上，摘除可能会促进远处转移癌的发展。 导致了有限的保护眼睛的外科技术的使用。 放射治疗已经取代眼球摘除成为最常见的治疗方法， 现在是一项全国性临床试验的主题(Collaborative 眼部黑色素瘤研究)。不幸的是，它的潜在优势 放射治疗可能会因慢性放射的发展而被否定- 引起的并发症，尤其是在治疗大于 8 mm高。继发性并发症最终会损害眼功能。 并可能导致失明。 热疗(42摄氏度至45摄氏度)与放射的结合使用有 已证实能提高放射治疗的有效性 治疗人类皮肤黑色素瘤的两个因素。在动物身上 格林脉络膜黑色素瘤模型，这些模式的组合有 已被证明可以在保持辐射剂量的同时减少辐射剂量 肿瘤控制。我们预计，减少辐射剂量将导致 减少继发并发症，从而保留有用的视力。 我们建立了一种新的人脉络膜黑色素瘤移植模型。 免疫抑制的兔眼，我们希望它的行为更像人类 脉络膜原位黑色素瘤比较老的格林模型。此外，我们 已经开发出一种新的临床技术来结合产生的热疗 用500 kHz射频电流和I125照射使用金 巩膜上斑块。这项技术的第一阶段临床评估是 目前正在我们的机构进行。我们已经开发了定量的 我们的斑块输送系统的I125剂量测定和初步热疗 正常兔眼的剂量学研究。我们已经证明了正常的 兔眼可以耐受高达45摄氏度的温度，在斑块上测得- 巩膜界面，急性毒性可耐受。 我们建议：1)发展定量热疗剂量学，为我们的 含人葡萄膜黑色素瘤兔眼的加热技术 异种移植；2)确定异种移植的剂量-反应关系 I125单独照射模型；3)确定“剂量”温度 异种移植模型对单纯热疗的反应；4)确定 异种移植模型对组合方式的剂量-反应；5) 评估放射治疗后的急性慢性毒性， 热疗，或与肿瘤相关的组合方式和剂量 控制力。由于兔眼缺少中心凹，我们进一步建议 在有限的情况下评估急性毒性(来自联合方式) 如果使用兔模型的结果显示灵长类动物的眼睛数量 潜在的治疗收益。