Hyperthermia and Perfusion Effects in Cancer Therapy

描述(由申请者提供)：该计划拨款的长期目标是优化热疗(HT)与放射治疗(RT)和/或化疗(CTX)的使用，以改善局部肿瘤控制、无病和总存活率，这些患者患有局部晚期癌症，但未经最佳传统疗法有效治疗。该计划先前的优势在于热剂量学、羟色胺与肿瘤生理学之间的相互关系以及使用羟色胺来增强脂质体的药物输送。新的临床试验仍在继续，并扩大了主题：(1)开发非侵入性体温测量，(2)结合脂质体药物，尤其是新型不耐热脂质体，在达到其相变温度后几秒钟内释放内容物，(3)进行III期试验，比较最佳传统疗法Q-HT，(4)研究治疗前和治疗期间获得的病理生理学和/或基因表达模式是否可预测治疗结果。 多学科方法包括辐射和医学肿瘤学、生物统计学、放射学、病理学、外科、癌症生物学、生理学、遗传学、热疗物理学以及工程和材料科学方面的专家，以接近这四个主题。项目1将使用完全集成的磁共振兼容射频加热设备，在四肢、乳房和骨盆/腹部肿瘤中开发基于磁共振的非侵入性测温。项目2将开发模型，以便于在高温期间使用非侵入性测温作为反馈进行实时功率控制。项目3将使用新型MR可成像的耐热阿霉素脂质体来比较不同药物剂量“涂抹”方案的抗肿瘤效果，并测试顺铂耐热脂质体克服顺铂耐药性和/或与RT正相互作用的潜力。项目4将研究热剂量分割、肿瘤生理变化和采用分割RT治疗自发性软组织肉瘤的狗的治疗结果之间的关系。项目5有五项旨在进行的临床试验：(1)用于软组织肉瘤和肢体黑色素瘤的无创测温，(2)用于局部晚期宫颈癌患者的CTX+RT+/-羟色胺的多机构III期试验；(3)用于局部晚期乳腺癌的、测试HT+非热敏性和不耐热的阿霉素脂质体的L/11期试验。(4)考虑到方案中肿瘤生理和基因表达模式在控制治疗结果线索中的作用。四个核心(管理、生物统计、组织、成像/工程)支持该计划。

DESCRIPTION (provided by applicant): The long-term goal of this program grant is to optimize the use of hyperthermia (HT) with radiotherapy (RT) and/or chemotherapy (CTx) to improve local tumor control, disease free and overall survival for patients with locally advanced cancers that are not effectively treated with best conventional therapy. Prior strengths of the program have been the emphases on thermal dosimetry, interrelationships between HT and tumor physiology and use of HT to augment liposomal drug delivery. New clinical trials continue and expand the themes to: (1) develop non-invasive thermometry, (2) examine HT combined with liposomal drugs, particularly with novel thermolabile liposomes that release contents within seconds of reaching their phase transition temperature, (3) conduct phase III trials comparing best conventional therapy q HT, (4) examine whether pathophysiology and/or gene expression patterns obtained prior to and during therapy predict for treatment outcome. A multidisciplinary approach includes experts in radiation and medical oncology, biostatistics, radiology, pathology, surgery, cancer biology, physiology, genetics, hyperthermia physics and engineering and materials science to approach the four themes. Project 1 will develop MR-based non-invasive thermometry in tumors of extremities, breast and pelvis/abdomen using fully integrated MR compatible RF heating devices. Project 2 will develop models to facilitate real-time power control during HT using non-invasive thermometry as feedback. Project 3 will use novel MR-imageable thermolabile doxorubicin containing liposomes to compare anti-tumor effects of different drug dose "painting" protocols and test the potential of a cisplatin thermolabile liposome to overcome cisplatin resistance and/or interact positively with RT. Project 4 will examine the relationship between thermal dose fractionation, tumor physiologic change and treatment outcome in dogs with spontaneous soft tissue sarcomas treated with fractionated RT. Project 5 has five clinical trials aimed toward conducting: (1) non-invasive thermometry in soft tissue sarcomas and extremity melanomas treated with infusional chemotherapy, (2) a multi-institutional phase III trial testing CTx+RT+/- HT in patients with locally advanced cervix cancer, (3) phase l/ll trials testing HT + non-thermally sensitive and thermolabile doxorubicin containing liposomes for locally advanced breast cancer. (4) The role of tumor physiology and gene expression patterns in controlling treatment outcome threads thoughout the program. Four cores (Administrative, Biostatistics, Tissue, Imaging / Engineering) support the program.