DOSE-RESPONSE RELATIONSHIP FOR RADIATION-THERAPY OF SUBCLINICAL DISEASE
DOSE-RESPONSE RELATIONSHIP FOR RADIATION-THERAPY OF SUBCLINICAL DISEASE
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DOI：
10.1016/0360-3016(94)00354-n
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发表时间：
1995-01-15
影响因子：
7
通讯作者：
TAYLOR, JMG
中科院分区：
文献类型：
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作者：
WITHERS, HR;PETERS, LJ;TAYLOR, JMG
目的：确定亚临床转移灶选择性治疗的剂量-反应关系，验证转移瘤细胞负荷模型。方法与材料：比较头颈部、乳腺癌、子宫颈癌、卵巢癌、肺癌、睾丸癌、黑色素瘤和骨肉瘤选择性照射后转移灶的显性转移发生率，并与未接受选择性照射的患者进行比较。结果：控制亚临床转移的剂量-反应曲线是线性的、浅的，并且外推到剂量截距没有明显不同于零。一个小的阈值可能反映了初次放射治疗和选择性放射治疗之间残留微转移的生长情况。浅的线性剂量响应反映了转移性肿瘤细胞负荷的患者间的异质性，范围从1到M个细胞，其中M是临床不可检测的上限。虽然要使转移的发生率总体上降低90%，剂量为50Gy2次/次是必要的，但部分患者的转移细胞负担可以通过低剂量来消除。因此，当“耐受性”低于最佳剂量时，仍然可以实现有价值的控制率，剂量-反应曲线的线性和缺乏显著的阈值证明了这一点。这是与治疗肉眼疾病的一个重要区别。选择性治疗的生物有效性直接通过失败率下降的百分比来衡量。虽然它取决于对数细胞苏格兰裙，但它只与患有亚临床疾病的患者的比例有关，因此不能很好地用总患者群体治愈率的增加来描述。降低失败率的线性剂量-反应关系与亚临床转移的“自然”(未治疗)发生率无关，因此也与肿瘤的部位、组织学、生长速度、分期或其他特征无关。相反，选择性治疗的临床效果是通过肿瘤控制率的增加来衡量的，并取决于转移的“自然”发生率：它越高，从恒定的生物学效应(对数细胞杀伤)中绝对增加的治愈率就越大。结论：(A)要想获得高的亚临床转移控制率，需要接受约50Gy2次的剂量，但如果需要降低耐受性，则可以通过较低的剂量获得好处；(B)亚临床转移的选择治疗应在接近原发灶的治疗时间进行；(C)选择性放疗(或化疗)的生物有效性应以转移减少的百分比来衡量，而不是通过控制率的提高来衡量；和(D)在辅助治疗的临床试验中证明成功的可能性更大，未经治疗的对照组的转移发生率越高。
Purpose: To determine the dose-response relationship for elective treatment of subclinical metastatic deposits and validate a model for metastatic tumor cell burden.Methods and Materials: The incidence of overt metastases in electively irradiated potential sites of spread from carcinomas of the head and neck, breast, cervix, ovary, lung, and testis, and from melanomas and osteosarcomas, was compared with the incidence in patients not receiving elective irradiation. The reduction in incidence of metastases was analyzed as a function of radiation dose.Results: The dose-response curve for control of subclinical metastases is linear and shallow and extrapolates to a dose intercept not demonstrably different from zero. A small threshold may reflect growth of residual micrometastases between treatment for the primary and elective irradiation. The shallow linear dose response reflects interpatient heterogeneity in metastatic tumor cell burden, ranging from 1 to M cells, where M is the upper limit of clinical undetectability. While a dose of 50 Gy in 2 Gy fractions is necessary to achieve an overall 90% reduction in the incidence of metastases, the metastatic cell burden in a proportion of patients can be eliminated by low doses. Thus, worthwhile rates of control can still be achieved when ''tolerance'' dictates lower than optimal doses, evidenced by the linearity and lack of significant threshold in the dose-response curve. This is an important difference from treatment of gross disease. The biological effectiveness of elective treatment is measured directly by the percent reduction in failure rate. Although it depends upon the log cell kilt, it relates only to that proportion of patients harboring subclinical disease, and, therefore, is not well described by the increase in the cure rate for the total patient population. The linear dose-response relationship for reduction in failure rate is independent of the ''natural'' (untreated) incidence of subclinical metastasis, and, therefore, of site, histology, growth rate, stage, or other characteristics of the tumor. Conversely, the clinical effectiveness of elective treatment is measured by increase in tumor control rate and depends upon the ''natural'' incidence of metastasis: the higher it is, the greater the absolute increase in cure rate from a constant biological effect (log cell kill).Conclusions: (a) High control rates for subclinical metastases require doses of about 50 Gy in 2 Gy fractions, but worthwhile benefits can be achieved by lower doses if necessitated by reduced tolerance; (b) elective treatment of subclinical metastases should be instituted close to the time of treatment of the primary; (c) the biological effectiveness of elective radiation (or chemotherapy) should be measured by the percentage decrease in metastasis, not by improvements in the rate of control; and (d) demonstration of success in clinical trials of adjuvant therapy is more likely the higher the incidence of metastases in untreated controls.