Bentzen Søren M, Trotti Andrea
University of Wisconsin School of Medicine and Public Health, Department of Human Oncology, Madison, WI, USA.
J Clin Oncol. 2007 Sep 10;25(26):4096-103. doi: 10.1200/JCO.2007.13.3983.
Combined chemoradiotherapy is increasingly becoming a standard of care for the nonoperative management of a variety of solid malignancies. A string of randomized controlled phase III trials have shown statistically significant and clinically relevant improvements in outcome, ostensibly without any apparent increase in late toxicity. However, the reliability and the sensitivity of toxicity reporting in most trials are questionable. Audits and phase IV studies suggest that the chemoradiotherapy success comes at a price in terms of late toxicity. This review presents some of the challenges in recording, analyzing, and reporting toxicity data. METHODS for summarizing toxicity are reviewed, and a new investigational metric, the TAME reporting system, is discussed. The need for special vigilance in the era of molecular-targeted agents is emphasized because of the possibility that unexpected serious adverse events with a low incidence may occur. Finally, we discuss how progress in molecular pathology and radiation biology may provide novel opportunities for stratifying patients according to risk of adverse effects, interventional targets for reducing or treating adverse effects, and surrogate markers of normal-tissue injury.
放化疗联合治疗正日益成为多种实体恶性肿瘤非手术治疗的标准治疗方法。一系列随机对照III期试验表明，在疗效方面有统计学意义且临床相关的改善，表面上晚期毒性没有任何明显增加。然而，大多数试验中毒性报告的可靠性和敏感性值得怀疑。审核和IV期研究表明，放化疗的成功是以晚期毒性为代价的。本综述介绍了毒性数据记录、分析和报告方面的一些挑战。对总结毒性的方法进行了综述，并讨论了一种新的研究指标——TAME报告系统。强调在分子靶向药物时代需要特别警惕，因为可能会出现低发生率的意外严重不良事件。最后，我们讨论分子病理学和放射生物学的进展如何为根据不良反应风险对患者进行分层、减少或治疗不良反应的干预靶点以及正常组织损伤的替代标志物提供新的机会。
