Hanrahan Grace B, Giobbie-Hurder Anita, Allais Blair, Vogelzang Jayne, Fay Christopher, Tsibris Hillary C
Center for Melanoma Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
University of Massachusetts T.H. Chan School of Medicine, Worcester.
JAMA Dermatol. 2025 Feb 1;161(2):198-202. doi: 10.1001/jamadermatol.2024.4819.
UV-induced mutagenesis leads to a higher tumor mutational burden (TMB) in cutaneous melanoma relative to other cancer types. TMB is an important prognostic marker in advanced melanoma; higher TMB is associated with greater clinical response to immune checkpoint inhibition and improved survival.
To evaluate the association between cutaneous melanoma TMB and indoor tanning exposure, as well as other demographic, dermatologic, and tumor characteristics.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study took place at Dana-Farber Cancer Institute, a tertiary-care cancer treatment center in Boston, Massachusetts, between 2013 and 2022. Patients with a diagnosis of cutaneous melanoma for whom next-generation sequencing data and tanning bed exposure history were available were included.
Indoor tanning exposure history, tumor characteristics, demographics, and dermatologic history were collected via retrospective medical record review.
The association of tanning bed use with TMB was modeled using inverse probability of treatment weighted, multivariable modeling.
Among 617 patients (median [IQR] age at diagnosis, 61 [50-71] years; 337 [62.9%] male), there was no association between indoor tanning exposure and TMB after adjustment for demographic, tumor, and dermatologic characteristics (yes vs no: log2 TMB [SE], 4.07 [0.44] vs 3.97 [0.45]; P = .39). However, there was a statistically significant association between higher TMB and older age at diagnosis, history of nonmelanoma skin cancer, and head and neck tumors relative to other primary sites. Average TMB was statistically significantly lower in patients with a history of abnormal nevi (yes vs no: log2 TMB [SE], 3.89 [0.44] vs 4.15 [0.44]; P = .01).
This cohort study suggests that indoor tanning exposure, while known to increase risk of melanoma, may not be meaningfully associated with melanoma TMB. Additional characteristics were associated with higher TMB and, thus, potentially improved immune checkpoint inhibitor response.
与其他癌症类型相比，紫外线诱导的诱变导致皮肤黑色素瘤的肿瘤突变负担（TMB）更高。TMB是晚期黑色素瘤的重要预后标志物；更高的TMB与对免疫检查点抑制的更大临床反应和更好的生存率相关。
评估皮肤黑色素瘤TMB与室内晒黑暴露之间的关联，以及其他人口统计学、皮肤病学和肿瘤特征。
设计、地点和参与者：这项回顾性队列研究于2013年至2022年在马萨诸塞州波士顿的三级癌症治疗中心达纳-法伯癌症研究所进行。纳入了诊断为皮肤黑色素瘤且有二代测序数据和晒黑床暴露史的患者。
通过回顾性病历审查收集室内晒黑暴露史、肿瘤特征、人口统计学和皮肤病史。
使用治疗加权逆概率多变量模型对晒黑床使用与TMB之间的关联进行建模。
在617例患者中（诊断时的中位[四分位间距]年龄为61[50-71]岁；337例[62.9%]为男性），在调整人口统计学、肿瘤和皮肤病学特征后，室内晒黑暴露与TMB之间无关联（是与否：log2 TMB[标准误]，4.07[0.44]对3.97[0.45]；P = 0.39）。然而，与其他原发部位相比，更高的TMB与诊断时年龄较大、非黑色素瘤皮肤癌病史以及头颈部肿瘤之间存在统计学显著关联。有异常痣病史的患者的平均TMB在统计学上显著较低（是与否：log2 TMB[标准误]，3.89[0.44]对4.15[0.44]；P = 0.01）。
这项队列研究表明，室内晒黑暴露虽然已知会增加黑色素瘤风险，但可能与黑色素瘤TMB无显著关联。其他特征与更高的TMB相关，因此可能改善免疫检查点抑制剂反应。
