Rotz Seth J, Stratton Kayla, Leisenring Wendy M, Smith Susan A, Howell Rebecca M, Bates James E, Pappo Alberto S, Neglia Joseph P, Armstrong Gregory T, Turcotte Lucie M
Department of Pediatric Hematology, Oncology, and Bone Marrow Transplantation, Cleveland Clinic Children's Hospital, Cleveland, OH.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
J Clin Oncol. 2025 Apr;43(10):1219-1228. doi: 10.1200/JCO-24-01519. Epub 2025 Jan 8.
Melanoma as a subsequent malignant neoplasm has been described among childhood cancer survivors; however, the risk factors and long-term survival are not well understood.
We assessed incidence, risk factors, and outcomes for melanoma among participants in the Childhood Cancer Survivor Study cohort. Cumulative incidence and standardized incidence ratios (SIRs) were calculated, and multivariable Cox models were used to determine hazard ratios (HRs) and associated 95% CI for melanoma risk factors. Radiation exposure to seven body regions and melanoma status for each of eight regions per survivor were integrated into the Cox model.
Among 25,716 participants, 177 melanomas developed in 160 survivors (110 invasive, 62 in situ cutaneous, five ocular). The 40-year melanoma cumulative incidence was 1.1% (95% CI, 0.9 to 1.4) for all participants and 1.5% (95% CI, 1.0 to 2.1) among those receiving a cumulative radiation dose of ≥40 Gy. Compared with the general population, the SIR for invasive skin or ocular melanoma was 2.0 (95% CI, 1.6 to 2.4). A cumulative radiation dose of ≥40 Gy to the corresponding body region(s) of the melanoma (HR, 2.0 [95% CI, 1.1 to 3.7]), a cumulative cyclophosphamide equivalent dose of ≥20,000 mg/m (HR, 1.9 [95% CI, 1.1 to 3.6]), and bleomycin exposure (HR, 2.2 [95% CI, 1.2 to 4.1]) were associated with increased cutaneous melanoma. Invasive melanoma at any site was associated with an increased risk of death (HR, 2.4 [95% CI, 1.7 to 3.3]).
Childhood cancer survivors have more than a two-fold increased risk of melanoma compared with the general population, and those with an invasive melanoma have more than a two-fold risk of death. High-dose radiation and alkylating agent exposure, and bleomycin are important risk factors for melanoma and should be considered in future patient guidance and screening.
儿童癌症幸存者中已发现黑色素瘤作为继发恶性肿瘤;然而,其危险因素和长期生存率尚未完全明确。
我们评估了儿童癌症幸存者研究队列参与者中黑色素瘤的发病率、危险因素和转归。计算累积发病率和标准化发病率比(SIR),并使用多变量Cox模型确定黑色素瘤危险因素的风险比(HR)及相关95%置信区间。将七个身体部位的辐射暴露以及每位幸存者八个区域中每个区域的黑色素瘤状态纳入Cox模型。
在25716名参与者中,160名幸存者发生了177例黑色素瘤(110例侵袭性、62例原位皮肤癌、5例眼部黑色素瘤)。所有参与者40年黑色素瘤累积发病率为1.1%(95%置信区间,0.9至1.4),接受累积辐射剂量≥40 Gy者为1.5%(95%置信区间,1.0至2.1)。与一般人群相比,侵袭性皮肤或眼部黑色素瘤的SIR为2.0(95%置信区间,1.6至2.4)。黑色素瘤相应身体部位累积辐射剂量≥40 Gy(HR,2.0 [95%置信区间,1.1至3.7])、累积环磷酰胺等效剂量≥20000 mg/m(HR,1.9 [95%置信区间,1.1至3.6])以及博来霉素暴露(HR,2.2 [95%置信区间,1.2至4.1])与皮肤黑色素瘤风险增加相关。任何部位的侵袭性黑色素瘤与死亡风险增加相关(HR,2.4 [95%置信区间,1.7至3.3])。
与一般人群相比,儿童癌症幸存者患黑色素瘤的风险增加了两倍多,侵袭性黑色素瘤患者的死亡风险增加了两倍多。高剂量辐射、烷化剂暴露和博来霉素是黑色素瘤的重要危险因素,在未来的患者指导和筛查中应予以考虑。