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 (n= 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.
癌症的性别差异已得到广泛确认。然而，关于晚期黑色素瘤患者脑转移诊断及预后的性别差异研究尚不充分。本研究利用美国全国性电子健康记录生成的去标识化数据库，对2011年1月1日至2022年7月30日期间确诊晚期黑色素瘤并接受肿瘤专家制定的规则性一线治疗的患者进行分析（n=7969，电子健康记录显示女性占33%，35%有脑转移记录）。通过多变量逻辑回归计算脑转移诊断概率，校正因素包括年龄、诊疗机构类型、诊断时期（2017年前后）、ECOG体能状态、黑色素瘤解剖部位、分组分期、一线治疗前非脑转移记录及BRAF阳性状态。采用Cox比例风险模型评估一线治疗开始后的真实世界总生存期（rwOS）和无进展生存期（rwPFS），将脑转移诊断作为时变协变量，除分组分期外采用与逻辑模型相同的校正因素，并额外校正种族、社会经济状况和保险状态。校正分析显示，与女性相比，男性晚期黑色素瘤患者被诊断为脑转移的概率高出22%（校正比值比[aOR]：1.22，95%置信区间[CI]：1.09-1.36）。在脑转移患者中，男性一线治疗后的rwOS更差（校正风险比[aHR]：1.15，95% CI：1.04-1.28），但rwPFS无显著差异（aHR：1.04，95% CI：0.95-1.14）。在未发生脑转移的晚期黑色素瘤患者中，生存期无性别差异（rwOS aHR：1.06 [95% CI：0.97-1.16]，rwPFS aHR：1.02 [95% CI：0.94-1.1]）。本研究表明，男性患者发生脑转移的概率更高，且脑转移患者的rwOS较女性更差，而在无脑转移的晚期黑色素瘤患者中，临床结局未见性别差异。
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