Cioffi Gino, Ascha Mustafa S, Waite Kristin A, Dmukauskas Mantas, Wang Xiaoliang, Royce Trevor J, Calip Gregory S, Waxweiler Timothy, Rusthoven Chad G, Kavanagh Brian D, Barnholtz-Sloan Jill S
Trans Divisional Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892,USA.
Flatiron Health, Inc., New York, NY 10013, USA.
Cancers (Basel). 2024 May 3;16(9):1771. doi: 10.3390/cancers16091771.
Sex differences in cancer are well-established. However, less is known about sex differences in diagnosis of brain metastasis and outcomes among patients with advanced melanoma. Using a United States nationwide electronic health record-derived de-identified database, we evaluated patients diagnosed with advanced melanoma from 1 January 2011-30 July 2022 who received an oncologist-defined rule-based first line of therapy ( = 7969, 33% female according to EHR, 35% w/documentation of brain metastases). The odds of documented brain metastasis diagnosis were calculated using multivariable logistic regression adjusted for age, practice type, diagnosis period (pre/post-2017), ECOG performance status, anatomic site of melanoma, group stage, documentation of non-brain metastases prior to first-line of treatment, and BRAF positive status. Real-world overall survival (rwOS) and progression-free survival (rwPFS) starting from first-line initiation were assessed by sex, accounting for brain metastasis diagnosis as a time-varying covariate using the Cox proportional hazards model, with the same adjustments as the logistic model, excluding group stage, while also adjusting for race, socioeconomic status, and insurance status. Adjusted analysis revealed males with advanced melanoma were 22% more likely to receive a brain metastasis diagnosis compared to females (adjusted odds ratio [aOR]: 1.22, 95% confidence interval [CI]: 1.09, 1.36). Males with brain metastases had worse rwOS (aHR: 1.15, 95% CI: 1.04, 1.28) but not worse rwPFS (adjusted hazard ratio [aHR]: 1.04, 95% CI: 0.95, 1.14) following first-line treatment initiation. Among patients with advanced melanoma who were not diagnosed with brain metastases, survival was not different by sex (rwOS aHR: 1.06 [95% CI: 0.97, 1.16], rwPFS aHR: 1.02 [95% CI: 0.94, 1.1]). This study showed that males had greater odds of brain metastasis and, among those with brain metastasis, poorer rwOS compared to females, while there were no sex differences in clinical outcomes for those with advanced melanoma without brain metastasis.
癌症中的性别差异已得到充分证实。然而，对于晚期黑色素瘤患者脑转移的诊断及预后方面的性别差异，我们了解得较少。利用美国全国性电子健康记录衍生的去识别数据库，我们评估了2011年1月1日至2022年7月30日期间被诊断为晚期黑色素瘤且接受了肿瘤学家定义的基于规则的一线治疗的患者（n = 7969，根据电子健康记录33%为女性，35%有脑转移记录）。使用多变量逻辑回归计算记录脑转移诊断的几率，并对年龄、执业类型、诊断时期（2017年前/后）、东部肿瘤协作组（ECOG）体能状态、黑色素瘤的解剖部位、分组分期、一线治疗前非脑转移的记录以及BRAF阳性状态进行了调整。从一线治疗开始评估实际总生存期（rwOS）和无进展生存期（rwPFS），按性别进行分析，将脑转移诊断作为一个随时间变化的协变量，使用Cox比例风险模型，调整与逻辑模型相同，不包括分组分期，同时还对种族、社会经济地位和保险状况进行了调整。调整分析显示，与女性相比，晚期黑色素瘤男性接受脑转移诊断的可能性高22%（调整后的优势比[aOR]：1.22，95%置信区间[CI]：1.09，1.36）。一线治疗开始后，有脑转移的男性rwOS较差（aHR：1.15，95%CI：1.04，1.28），但rwPFS没有更差（调整后的风险比[aHR]：1.04，95%CI：0.95，1.14）。在未被诊断为脑转移的晚期黑色素瘤患者中，生存情况不存在性别差异（rwOS的aHR：1.06[9:5%CI：0.97，1.16]，rwPFS的aHR：1.02[95%CI：0.94，1.1]）。这项研究表明，与女性相比，男性发生脑转移的几率更高，且在有脑转移的患者中，rwOS更差，而在没有脑转移的晚期黑色素瘤患者的临床结局方面不存在性别差异。
