Eric J. Chow and Rebecca Gardner, Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, and University of Washington, Seattle, WA; Zoltan Antal, Weill Cornell Medical College, New York Presbyterian Hospital, and Memorial Sloan Kettering Cancer Center, New York; Louis S. Constine, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY; W. Hamish Wallace, Royal Hospital for Sick Children, University of Edinburgh, Edinburgh, United Kingdom; Brent R. Weil and Jennifer M. Yeh, Boston Children's Hospital, Harvard Medical School, Boston, MA; and Elizabeth Fox, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA.
J Clin Oncol. 2018 Jul 20;36(21):2231-2240. doi: 10.1200/JCO.2017.76.4647. Epub 2018 Jun 6.
Incremental improvements in the treatment of children and adolescents with cancer have led to 5-year survival rates reaching nearly 85%. In the past decade, impressive progress has been made in understanding the biology of many pediatric cancers. With that understanding, multiple new agents have become available that offer the promise of more-effective and less-toxic treatment. These include agents that target various cell surface antigens and engage the adaptive immune system, as well as those that interfere with key signaling pathways involved in tumor development and growth. For local control, surgery and radiation techniques also have evolved, becoming less invasive or featuring new techniques and particles that more precisely target the tumor and limit the dose to normal tissue. Nevertheless, targeted agents, like conventional chemotherapy, radiotherapy, and surgery, may have off-target effects and deserve long-term follow-up of their safety and efficacy. These include injury to the endocrine, cardiovascular, and immunologic systems. New radiation and surgical techniques that theoretically reduce morbidity and improve long-term quality of life must also be validated with actual patient outcomes. Finally, with advances in genomics, information on host susceptibility to late effects is beginning to emerge. Such knowledge, coupled with improved metrics that better describe the spectrum of potential late effects across the entire lifespan, can lead to the development of decision models that project the potential long-term health outcomes associated with various treatment and follow-up strategies. These developments will help extend the current focus on precision medicine to precision survivorship, where clinicians, patients, and families will have a better grasp of the potential risks, benefits, and tradeoffs associated with the growing number of cancer treatment options.
儿童和青少年癌症治疗的不断改进，使得 5 年生存率达到近 85%。在过去的十年中，人们在理解许多儿科癌症的生物学特性方面取得了令人瞩目的进展。随着对这些生物学特性的了解，多种新的药物已经问世，为更有效和毒性更小的治疗提供了希望。这些药物包括针对各种细胞表面抗原并参与适应性免疫系统的药物，以及那些干扰肿瘤发生和生长的关键信号通路的药物。为了实现局部控制，手术和放射技术也在不断发展，变得侵入性更小，或者采用新的技术和粒子，更精确地靶向肿瘤，并将剂量限制在正常组织内。然而，靶向药物，如传统的化疗、放疗和手术，可能会产生脱靶效应，需要长期随访其安全性和有效性。这些包括对内分泌、心血管和免疫系统的损伤。新的放疗和手术技术理论上可以降低发病率并提高长期生活质量，也必须通过实际患者的结果来验证。最后，随着基因组学的进步，宿主对迟发性效应易感性的信息开始显现。这种知识，加上能够更好地描述整个生命周期潜在迟发性效应谱的改进指标，可以导致开发决策模型，预测与各种治疗和随访策略相关的潜在长期健康结果。这些发展将有助于将当前对精准医学的关注扩展到精准生存，使临床医生、患者和家属能够更好地理解与不断增加的癌症治疗选择相关的潜在风险、益处和权衡取舍。
