Curtis R E, Boice J D, Stovall M, Bernstein L, Holowaty E, Karjalainen S, Langmark F, Nasca P C, Schwartz A G, Schymura M J
Radiation Epidemiology Branch, National Cancer Institute, Bethesda, Md.
J Natl Cancer Inst. 1994 Sep 7;86(17):1315-24. doi: 10.1093/jnci/86.17.1315.
Radiotherapy has been linked infrequently to secondary leukemia despite extensive exposure of the active bone marrow to ionizing radiation. Few studies include substantial numbers of elderly patients.
We evaluated women with cancer of the uterine corpus, the majority of whom were treated at older ages, to gain additional information on cancer risk following partial-body radiotherapy and to examine differences in risk between external-beam therapy and brachytherapy.
A cohort of 110,000 women with invasive cancer of the uterine corpus who survived at least 1 year following their initial cancer was assembled from nine population-based cancer registries. Cancer diagnoses occurred from 1935 through 1985, and most patients were diagnosed during the 1960s and 1970s. Radiation doses were computed to 17 sections of the active bone marrow for 218 women who developed leukemia and for 775 matched control subjects.
Radiotherapy did not increase the risk of chronic lymphocytic leukemia (CLL) (relative risk [RR] = 0.90; 95% confidence interval [CI] = 0.4-1.9). However, for all leukemias except CLL, a significant risk was identified (RR = 1.92; 95% CI = 1.3-2.9). Overall, the pattern of risk in relation to dose was erratic and was most consistent with a constant increased risk across the entire dose range. The risk following continuous exposures from brachytherapy at comparatively low doses and low dose rates (RR = 1.80; 95% CI = 1.1-2.8; mean dose = 1.72 Gy) was similar to that after fractionated exposures at much higher doses and higher dose rates from external-beam treatment (RR = 2.29; 95% CI = 1.4-3.7; mean dose = 9.88 Gy), indicating a large difference in the estimated risk per unit dose. Risk did not vary by age at first exposure; increased risks were apparent for irradiated patients aged 65 years or older (RR = 1.77; 95% CI = 0.9-3.5).
The leukemia risk associated with partial-body radiotherapy for uterine corpus cancer was small; about 14 excess leukemia cases were due to radiation per 10,000 women followed for 10 years. Women aged 65 years or older had a radiation risk comparable with that found in younger women. The relationship of leukemia risk to radiation dose was found to be complex due to the competing processes of cell killing, transformation, and repair. At very high doses delivered at high rates, destruction of cells likely dominates, and the risk per unit dose is low. In the low dose range, where dose was protracted and delivered at relatively low dose rates, the leukemia risk appears lower than that projected from risk estimates derived from the instantaneous whole-body exposures of atomic bomb survivors.
尽管活跃骨髓广泛暴露于电离辐射，但放疗与继发性白血病的关联并不常见。很少有研究纳入大量老年患者。
我们评估了子宫体癌女性患者，她们大多数在老年时接受治疗，以获取关于局部放疗后癌症风险的更多信息，并研究外照射治疗和近距离放疗之间的风险差异。
从9个基于人群的癌症登记处收集了110,000例子宫体浸润癌女性患者队列，这些患者在初次患癌后至少存活1年。癌症诊断时间为1935年至1985年，大多数患者在20世纪60年代和70年代被诊断。计算了218例患白血病女性患者和775例匹配对照对象的17个活跃骨髓部位的辐射剂量。
放疗未增加慢性淋巴细胞白血病（CLL）的风险（相对风险[RR]=0.90；95%置信区间[CI]=0.4 - 1.9）。然而，对于除CLL之外的所有白血病，均发现有显著风险（RR = 1.92；95% CI = 1.3 - 2.9）。总体而言，风险与剂量的关系不稳定，最符合在整个剂量范围内风险持续增加的情况。低剂量和低剂量率的近距离放疗连续照射后的风险（RR = 1.80；95% CI = 1.1 - 2.8；平均剂量 = 1.72 Gy）与高剂量和高剂量率的外照射分次照射后的风险相似（RR = 2.29；95% CI = 1.4 - 3.7；平均剂量 = 9.88 Gy），表明每单位剂量的估计风险存在很大差异。风险在首次暴露时的年龄方面没有变化；65岁及以上接受照射的患者风险增加明显（RR = 1.77；95% CI = 0.9 - 3.5）。
子宫体癌局部放疗相关的白血病风险较小；每10,000名随访10年的女性中约有14例额外的白血病病例归因于放疗。65岁及以上的女性辐射风险与年轻女性相当。由于细胞杀伤、转化和修复等相互竞争的过程，发现白血病风险与辐射剂量的关系很复杂。在高剂量率下给予的非常高剂量时，细胞破坏可能占主导，每单位剂量的风险较低。在低剂量范围内，剂量持续时间长且以相对低剂量率给予，白血病风险似乎低于原子弹幸存者全身瞬间暴露的风险估计所预测的风险。
