Constine Louis S, Tarbell Nancy, Hudson Melissa M, Schwartz Cindy, Fisher Susan G, Muhs Ann G, Basu Swati K, Kun Larry E, Ng Andrea, Mauch Peter, Sandhu Ajay, Culakova Eva, Lyman Gary, Mendenhall Nancy
Department of Radiation Oncology, University of Rochester, Rochester, NY 14642, USA.
Int J Radiat Oncol Biol Phys. 2008 Sep 1;72(1):24-33. doi: 10.1016/j.ijrobp.2008.04.067.
Subsequent malignant neoplasms (SMNs) are a dominant cause of morbidity and mortality in children treated for Hodgkin's disease (HD). We evaluated select demographic and therapeutic factors associated with SMNs, specifically gender and radiation dose.
A total of 930 children treated for HD at five institutions between 1960 and 1990 were studied. Mean age at diagnosis was 13.6 years, and mean follow-up was 16.8 years (maximum, 39.4 years). Treatment included radiation alone (43%), chemotherapy alone (9%), or both (48%).
We found that SMNs occurred in 102 (11%) patients, with a 25-year actuarial rate of 19%. With 15,154 patient years of follow-up, only 7.18 cancers were expected (standardized incidence ratio [SIR] = 14.2; absolute excess risk [AER] = 63 cases/10,000 years). The SIR for female subjects, 19.93, was significantly greater than for males, 8.41 (p < 0.0001). After excluding breast cancer, the SIR for female patients was 15.4, still significantly greater than for male patients (p = 0.0012). Increasing radiation dose was associated with an increasing SIR (p = 0.0085). On univariate analysis, an increased risk was associated with female gender, increasing radiation dose, and age at treatment (12-16 years). Using logistic regression, mantle radiation dose increased risk, and this was 2.5-fold for female patients treated with more than 35 Gy primarily because of breast cancer.
Survivors of childhood HD are at risk for SMNs, and this risk is greater for female individuals even after accounting for breast cancer. Although SMNs occur in the absence of radiation therapy, the risk increases with RT dose.
继发性恶性肿瘤（SMNs）是接受霍奇金病（HD）治疗的儿童发病和死亡的主要原因。我们评估了与SMNs相关的特定人口统计学和治疗因素，特别是性别和放射剂量。
对1960年至1990年间在五家机构接受HD治疗的930名儿童进行了研究。诊断时的平均年龄为13.6岁，平均随访时间为16.8年（最长39.4年）。治疗包括单纯放疗（43%）、单纯化疗（9%）或两者联合（48%）。
我们发现102例（11%）患者发生了SMNs，25年精算发生率为19%。经过15154患者年的随访，预期仅7.18例癌症发生（标准化发病率比[SIR]=14.2；绝对超额风险[AER]=63例/10000年）。女性受试者的SIR为19.93，显著高于男性的8.41（p<0.0001）。排除乳腺癌后，女性患者的SIR为15.4，仍显著高于男性患者（p=0.0012）。放射剂量增加与SIR升高相关（p=0.0085）。单因素分析显示，风险增加与女性性别、放射剂量增加以及治疗时年龄（12 - 16岁）有关。使用逻辑回归分析，斗篷野放射剂量增加了风险，对于接受超过35 Gy放疗的女性患者，风险增加了2.5倍，主要是因为乳腺癌。
儿童HD幸存者有发生SMNs的风险，即使在考虑乳腺癌后，女性个体的这种风险更高。虽然在没有放疗的情况下也会发生SMNs，但风险随放疗剂量增加而增加。
