Wong Philip, Houghton Peter, Kirsch David G, Finkelstein Steven E, Monjazeb Arta M, Xu-Welliver Meng, Dicker Adam P, Ahmed Mansoor, Vikram Bhadrasain, Teicher Beverly A, Coleman C Norman, Machtay Mitchell, Curran Walter J, Wang Dian
Department of Radiation Oncology, Centre Hospitalier de L'Université de Montréal, Montréal, Québec, Canada (PW); Research Institute at Nationwide Children's Hospital, Columbus, OH (PH); Departments of Radiation Oncology and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC (DGK); 21st Century Oncology Translational Research Consortium (TRC) Headquarters, Scottsdale, AZ (SEF); Department of Radiation Oncology, University of California Davis Comprehensive Cancer Center, Sacramento, CA (AMM); Department of Radiation Oncology, the Ohio State University, Columbus, OH (MXW); Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA (APD); Radiotherapy Development Branch & Molecular Radiation Therapeutics Branch, Radiation Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD (MA, CNC); Clinical Radiation Oncology Branch, National Cancer Institute, Bethesda, MD (BV); Molecular Pharmacology Branch, National Cancer Institute, Bethesda, MD (BAT); Department of Radiation Oncology, University Hospitals Case Medical Center, Cleveland, OH (MM); Winship Cancer Institute, Woodruff Health Science Center, Emory University, Atlanta, GA (WJC); Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (DW).
J Natl Cancer Inst. 2014 Oct 18;106(11). doi: 10.1093/jnci/dju329. Print 2014 Nov.
Improved understanding of soft-tissue sarcoma (STS) biology has led to better distinction and subtyping of these diseases with the hope of exploiting the molecular characteristics of each subtype to develop appropriately targeted treatment regimens. In the care of patients with extremity STS, adjunctive radiation therapy (RT) is used to facilitate limb and function, preserving surgeries while maintaining five-year local control above 85%. In contrast, for STS originating from nonextremity anatomical sites, the rate of local recurrence is much higher (five-year local control is approximately 50%) and a major cause of death and morbidity in these patients. Incorporating novel technological advancements to administer accurate RT in combination with novel radiosensitizing agents could potentially improve local control and overall survival. RT efficacy in STS can be increased by modulating biological pathways such as angiogenesis, cell cycle regulation, cell survival signaling, and cancer-host immune interactions. Previous experiences, advancements, ongoing research, and current clinical trials combining RT with agents modulating one or more of the above pathways are reviewed. The standard clinical management of patients with STS with pretreatment biopsy, neoadjuvant treatment, and primary surgery provides an opportune disease model for interrogating translational hypotheses. The purpose of this review is to outline a strategic vision for clinical translation of preclinical findings and to identify appropriate targeted agents to combine with radiotherapy in the treatment of STS from different sites and/or different histology subtypes.
对软组织肉瘤（STS）生物学认识的提高，使得对这些疾病有了更好的区分和亚型分类，有望利用各亚型的分子特征来制定合适的靶向治疗方案。在肢体STS患者的治疗中，辅助放疗（RT）用于促进肢体功能恢复，保留手术机会，同时将五年局部控制率维持在85%以上。相比之下，对于起源于非肢体解剖部位的STS，局部复发率要高得多（五年局部控制率约为50%），这是这些患者死亡和发病的主要原因。结合新技术进展来精准实施放疗，并联合新型放射增敏剂，可能会提高局部控制率和总生存率。通过调节血管生成、细胞周期调控、细胞存活信号传导以及癌症与宿主免疫相互作用等生物学途径，可以提高STS的放疗疗效。本文综述了以往的经验、进展、正在进行的研究以及目前将放疗与调节上述一种或多种途径的药物联合应用的临床试验。对STS患者进行预处理活检、新辅助治疗和初次手术的标准临床管理，为验证转化性假设提供了一个合适的疾病模型。本综述的目的是概述临床转化临床前研究结果的战略构想，并确定在治疗不同部位和/或不同组织学亚型的STS时，与放疗联合使用的合适靶向药物。
