Mertens Ann C, Yasui Yutaka, Liu Yan, Stovall Marilyn, Hutchinson Ray, Ginsberg Jill, Sklar Charles, Robison Leslie L
Department of Pediatrics, University of Minnesota Medical School and Cancer Center, Minneapolis, Minnesota, USA.
Cancer. 2002 Dec 1;95(11):2431-41. doi: 10.1002/cncr.10978.
The Childhood Cancer Survivor Study is a resource that was designed to investigate long-term effects among 5-year survivors of childhood and adolescent malignancies. Previous studies have shown that exposure to chemotherapy and/or radiation can compromise pulmonary function in these survivors of childhood cancer.
Using information obtained from questionnaires from 12,390 childhood cancer survivors and 3546 randomly selected siblings, the authors evaluated the rate of first occurrence of 15 selected pulmonary conditions in three periods: during therapy, from the end of therapy to 5 years postdiagnosis, and >/= 5 years postdiagnosis. Multivariate analyses were used to determine the relative risks with 95% confidence intervals of reported pulmonary conditions by exposure to the following treatment variables: radiation therapy to the chest, bleomycin, cyclophosphamide, busulfan, lomustine (CCNU), and/or carmustine (BCNU).
Compared with siblings, survivors had a statistically significant increased relative risk (RR) of lung fibrosis, recurrent pneumonia, chronic cough, pleurisy, use of supplemental oxygen, abnormal chest wall, exercise-induced shortness of breath, bronchitis, recurrent sinus infection, and tonsillitis for all three periods. During the period of >or= 5 years postdiagnosis, statistically significant associations were present for lung fibrosis and chest radiation (RR, 4.3; P = 0 001); for supplemental oxygen use and chest radiation (RR, 1.8; P < 0.001), BCNU (RR, 1.4; P = 0.05), bleomycin (RR, 1.7; P = 0.001), busulfan (RR, 3.2; P = 0.002), CCNU (RR, 2.1; P < 0.001), and cyclophosphamide (RR, 1.5; P = 0.01); for recurrent pneumonia and chest radiation (RR, 2.2; P = 0.001) and cyclophosphamide (RR, 1.6; P = 0.04); for chronic cough and chest radiation (RR, 2.0; P < 0.001), bleomycin (RR, 1.9; P < 0.001), and cyclophosphamide (RR, 1.3; P = 0.004); and for pleurisy and chest radiation (RR, 1.4; P = 0.02) and busulfan (RR, 5.1; P = 0.02). Chest radiation was associated with a 3.5% cumulative incidence of lung fibrosis at 20 years after diagnosis.
For self-report of pulmonary conditions, treatment-related factors that continue to manifest > 5 years after diagnosis and treatment are important determinants of risk. Continued follow-up of childhood cancer survivors is needed to evaluate the impact of pulmonary conditions on quality of life.
儿童癌症幸存者研究旨在调查儿童和青少年恶性肿瘤5年幸存者的长期影响。既往研究表明，化疗和/或放疗会损害这些儿童癌症幸存者的肺功能。
作者利用从12390名儿童癌症幸存者和3546名随机选择的同胞的问卷中获得的信息，评估了15种选定肺部疾病在三个时期的首次发生几率：治疗期间、治疗结束至诊断后5年、诊断后≥5年。多变量分析用于确定暴露于以下治疗变量后报告的肺部疾病的相对风险及95%置信区间：胸部放疗、博来霉素、环磷酰胺、白消安、洛莫司汀（CCNU）和/或卡莫司汀（BCNU）。
与同胞相比，幸存者在所有三个时期出现肺纤维化、复发性肺炎、慢性咳嗽、胸膜炎、使用补充氧气、胸壁异常、运动性气短、支气管炎、复发性鼻窦感染和扁桃体炎的相对风险（RR）在统计学上显著增加。在诊断后≥5年期间，肺纤维化与胸部放疗存在统计学显著关联（RR，4.3；P = 0.001）；补充氧气使用与胸部放疗（RR，1.8；P < 0.001）、BCNU（RR，1.4；P = 0.05）、博来霉素（RR，1.7；P = 0.001）、白消安（RR，3.2；P = 0.002）、CCNU（RR，2.1；P < 0.001）和环磷酰胺（RR，1.5；P = 0.01）存在统计学显著关联；复发性肺炎与胸部放疗（RR，2.2；P = 0.001）和环磷酰胺（RR，1.6；P = 0.04）存在统计学显著关联；慢性咳嗽与胸部放疗（RR，2.0；P < 0.001）、博来霉素（RR，1.9；P < 0.001）和环磷酰胺（RR，1.3；P = 0.004）存在统计学显著关联；胸膜炎与胸部放疗（RR，1.4；P = 0.02）和白消安（RR，5.1；P = 0.02）存在统计学显著关联。胸部放疗与诊断后20年肺纤维化的累积发生率3.5%相关。
对于肺部疾病的自我报告，诊断和治疗后>5年仍持续存在的与治疗相关因素是风险的重要决定因素。需要对儿童癌症幸存者进行持续随访，以评估肺部疾病对生活质量的影响。
