Lukens J N
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Cancer. 1994 Nov 1;74(9 Suppl):2710-8. doi: 10.1002/1097-0142(19941101)74:9+<2710::aid-cncr2820741821>3.0.co;2-g.
Solid tumors account for approximately 70% of malignant neoplasms in children younger than 15 years of age. The 5-year survival of children with solid tumors increased from 27% to 70% between 1960 and 1990. The slope of the curve that describes the change in survival over this period is remarkably constant, reflecting the nature of progress made through clinical trials. In addition to providing data important for the refinement of treatment for specific tumors, clinical trials have made numerous important, global contributions for the practice of oncology. The development of uniform response criteria, for example, was necessitated by clinical trials. The identification of histologic subtypes and the recognition of prognostic variables have permitted refinements in diagnosis and staging. By exploring novel strategies for the integration of different therapeutic modalities, clinical trials have identified indications for the use of presurgical chemotherapy, preradiation chemotherapy, and second-look and delayed primary surgeries. Refinements in the utilization of chemotherapy have been made possible by the evaluation of new agents, the study of dose intensity, and the use of the "window of opportunity" to identify active agents for tumors for which there is no effective treatment. Clinical trials have been instrumental in defining the late effects of treatment, investigating the causes of childhood cancer through epidemiologic studies, and supporting cancer biology research. The close collaboration of basic and clinical investigators offers the best opportunity for realizing the rewards of transitional research.
实体瘤约占15岁以下儿童恶性肿瘤的70%。1960年至1990年间,实体瘤患儿的5年生存率从27%提高到了70%。描述这一时期生存率变化的曲线斜率非常稳定,反映了通过临床试验取得进展的性质。除了提供对特定肿瘤治疗优化至关重要的数据外,临床试验还为肿瘤学实践做出了许多重要的全球性贡献。例如,统一反应标准的制定是临床试验所必需的。组织学亚型的鉴定和预后变量的识别使得诊断和分期得以完善。通过探索整合不同治疗方式的新策略,临床试验确定了术前化疗、放疗前化疗以及二次探查和延迟初次手术的应用指征。对新药的评估、剂量强度的研究以及利用“机会窗”来识别对尚无有效治疗方法的肿瘤有活性的药物,使得化疗的应用得以优化。临床试验在确定治疗的晚期效应、通过流行病学研究调查儿童癌症的病因以及支持癌症生物学研究方面发挥了重要作用。基础研究人员和临床研究人员的密切合作提供了实现转化研究成果的最佳机会。