Background:Sex difference in the immune response may influence patients’ response to immune checkpoint inhibitors (ICIs). We conducted a prospective observation study to determine the correlation between pretreatment sex hormone levels and response to ICIs in metastatic non-small cell lung cancer (NSCLC).Method:Pretreatment plasma samples from 61 patients with newly diagnosed NSCLC prior to ICI therapy were collected. Six sex hormone levels [pyrazole triol, 17 β-estradiol, 5-androstenediol, 3β-androstenediol, dehydroepiandrosterone (DHEA), and S-equol] were measured using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Overall survival (OS) and progression-free survival (PFS) were compared between the high- and low-level groups in the whole cohort.Result:Among the six sex hormones measured, DHEA levels were significantly higher among patients without clinical benefits in the discovery cohort; the remaining sex hormones did not differ significantly. In the whole cohort, median PFS was 22 months for patients with low DHEA levels vs. 3.8 months for those with high DHEA [hazard ratio, 14.23 (95% CI, 4.7–43);p< 0.001]. A significant association was also observed for OS [hazard ratio, 8.2 (95% CI, 2.89–23.35);p< 0.0001].Conclusions:High pretreatment plasma DHEA levels were associated with poor clinical outcomes for patients with metastatic NSCLC treated with ICIs.
背景：免疫应答的性别差异可能影响患者对免疫检查点抑制剂（ICIs）的治疗反应。本研究通过前瞻性观察，旨在探讨转移性非小细胞肺癌（NSCLC）患者接受ICIs治疗前性激素水平与治疗反应的相关性。 方法：收集61例初诊NSCLC患者在ICIs治疗前的血浆样本，采用液相色谱-高分辨质谱联用技术（LC-HRMS）检测六种性激素水平[吡唑三醇、17β-雌二醇、5-雄烯二醇、3β-雄烯二醇、脱氢表雄酮（DHEA）及S-雌马酚]。在整个队列中，比较高水平组与低水平组患者的总生存期（OS）和无进展生存期（PFS）。 结果：在检测的六种性激素中，发现队列中未获得临床获益患者的DHEA水平显著更高，其余性激素未见显著差异。在整个队列中，低DHEA水平患者的中位PFS为22个月，而高DHEA水平患者为3.8个月[风险比14.23（95% CI 4.7–43）；p<0.001]。OS也呈现显著相关性[风险比8.2（95% CI 2.89–23.35）；p<0.0001]。 结论：接受ICIs治疗的转移性NSCLC患者，治疗前血浆高DHEA水平与不良临床结局相关。
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