Hyperthermia and Perfusion Effects in Cancer Therapy

描述（由申请人提供）：本项目资助的长期目标是优化热疗（HT）联合放疗（RT）和/或化疗（CTx）的使用，以改善局部肿瘤控制、无病和局部晚期癌症患者的总生存期，这些患者无法通过最佳常规疗法得到有效治疗。该计划先前的优势是强调热剂量学，HT与肿瘤生理学之间的相互关系以及使用HT增加脂质体药物递送。新的临床试验继续并将主题扩展到：(1)发展无创测温，(2)检查HT与脂质体药物联合使用，特别是在达到其相变温度后几秒内释放内容的新型耐热性脂质体，(3)进行比较最佳常规疗法与HT的III期试验，(4)检查治疗前和治疗期间获得的病理生理和/或基因表达模式是否预测治疗结果。

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.