Cancer and Radiation Team, Center for Research in Epidemiology and Population Health, INSERM U1018, Villejuif, France.
Pediatric Hematology Oncology Department, CHU Angers, Angers, France.
J Clin Oncol. 2020 Jun 1;38(16):1785-1796. doi: 10.1200/JCO.19.02361. Epub 2020 Mar 20.
Between 10% and 20% of childhood cancer survivors (CCS) experience impaired growth, leading to small adult height (SAH). Our study aimed to quantify risk factors for SAH or growth hormone deficiency among CCS.
The French CCS Study holds data on 7,670 cancer survivors treated before 2001. We analyzed self-administered questionnaire data from 2,965 CCS with clinical, chemo/radiotherapy data from medical records. SAH was defined as an adult height ≤ 2 standard deviation scores of control values obtained from a French population health study.
After exclusion of 189 CCS treated with growth hormone, 9.2% (254 of 2,776) had a SAH. Being young at the time of cancer treatment (relative risk [RR], 0.91 [95% CI, 0.88 to 0.95] by year of age), small height at diagnosis (≤ 2 standard deviation scores; RR, 6.74 [95% CI, 4.61 to 9.86]), pituitary irradiation (5-20 Gy: RR, 4.24 [95% CI, 1.98 to 9.06]; 20-40 Gy: RR, 10.16 [95% CI, 5.18 to 19.94]; and ≥ 40 Gy: RR, 19.48 [95% CI, 8.73 to 43.48]), having received busulfan (RR, 4.53 [95% CI, 2.10 to 9.77]), or > 300 mg/m of lomustine (300-600 mg/m: RR, 4.21 [95% CI, 1.61 to 11.01] and ≥ 600 mg/m: RR, 9.12 [95% CI, 2.75 to 30.24]) were all independent risk factors for SAH. Irradiation of ≥ 7 vertebrae (≥ 15 Gy on ≥ 90% of their volume) without pituitary irradiation increased the RR of SAH by 4.62 (95% CI, 2.77 to 7.72). If patients had also received pituitary irradiation, this increased the RR by an additional factor of 1.3 to 2.4.
CCS are at a high risk of SAH. CCS treated with radiotherapy, busulfan, or lomustine should be closely monitored for growth, puberty onset, and potential pituitary deficiency.
10%至 20%的儿童癌症幸存者(CCS)存在生长受损,导致成年身高矮小(SAH)。本研究旨在量化 CCS 中 SAH 或生长激素缺乏的风险因素。
法国 CCS 研究包含了 2001 年前接受治疗的 7670 名癌症幸存者的数据。我们分析了来自 2965 名 CCS 的自我管理问卷数据,这些 CCS 有临床和化疗/放疗数据来自病历。SAH 定义为成年身高≤法国人群健康研究中获得的对照值的 2 个标准差分数。
排除 189 名接受生长激素治疗的 CCS 后,9.2%(254/2776)存在 SAH。治疗时年龄较小(相对风险 [RR],0.91 [95%CI,0.88 至 0.95],每岁)、诊断时身高较小(≤2 个标准差分数;RR,6.74 [95%CI,4.61 至 9.86])、垂体放疗(5-20 Gy:RR,4.24 [95%CI,1.98 至 9.06];20-40 Gy:RR,10.16 [95%CI,5.18 至 19.94];≥40 Gy:RR,19.48 [95%CI,8.73 至 43.48])、接受白消安(RR,4.53 [95%CI,2.10 至 9.77])或洛莫司汀>300mg/m(300-600 mg/m:RR,4.21 [95%CI,1.61 至 11.01]和≥600 mg/m:RR,9.12 [95%CI,2.75 至 30.24])均为 SAH 的独立危险因素。如果≥7 个椎体(≥15 Gy,≥90%的体积)未进行垂体放疗,SAH 的 RR 增加 4.62(95%CI,2.77 至 7.72)。如果患者还接受了垂体放疗,RR 会额外增加 1.3 至 2.4 倍。
CCS 发生 SAH 的风险很高。接受放疗、白消安或洛莫司汀治疗的 CCS 应密切监测生长、青春期开始和潜在的垂体功能减退。