Hyperthermia and Perfusion Effects in Cancer Therapy

描述（由申请人提供）： 该计划赠款的长期目标是优化热疗（HT）与放疗（RT）和/或化疗（CTx）的使用，以改善局部肿瘤控制，无病生存率和局部晚期癌症患者的总生存率，这些患者不能有效地接受最佳常规治疗。该计划的优势是强调热剂量测定，HT和肿瘤生理学之间的相互关系以及使用HT来增强脂质体药物递送。新的临床试验继续进行，并将主题扩展到：（1）开发非侵入性测温法，（2）检查HT与脂质体药物的组合，特别是与在达到其相变温度的数秒内释放内容物的新型热不稳定脂质体的组合，（3）进行比较最佳常规疗法的III期试验qHT，（4）检查在治疗之前和治疗期间获得的病理生理学和/或基因表达模式是否预测治疗结果。 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、外科学、癌症生物学、生理学、遗传学、热疗物理学和工程学以及材料科学方面的专家，以探讨这四个主题。项目1将使用完全集成的MR兼容射频加热器械开发四肢、乳腺和骨盆/腹部肿瘤的MR无创测温。项目2将开发模型，以促进在HT期间使用非侵入式测温作为反馈的实时功率控制。项目3将使用新的MR可成像的热不稳定阿霉素脂质体，比较不同药物剂量“涂敷”方案的抗肿瘤效果，并测试顺铂热不稳定脂质体克服顺铂耐药性和/或与RT积极相互作用的潜力。项目4将研究热剂量分级，肿瘤生理学变化和用分割RT治疗的自发性软组织肉瘤的狗的治疗结果。项目5有五个临床试验，旨在进行：（1）在用输注化疗治疗的软组织肉瘤和肢体黑色素瘤中的非侵入性测温，（2）在患有局部晚期宫颈癌的患者中测试CTx+RT+/- HT的多机构III期试验，（3）I/II期试验，其测试含有HT +非热敏性和热不稳定性多柔比星的脂质体用于局部晚期乳腺癌。(4)肿瘤生理学和基因表达模式在控制治疗结果中的作用贯穿整个项目。四个核心（行政、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.