背景:最近的随机III期试验证明了抗程序性细胞死亡1(PD-1)免疫检查点抑制剂(ICIs)在治疗复发性或转移性头颈部鳞状细胞癌(RMHNSCC)患者中的功效。然而,很大一部分此类患者的反应仍然不佳。这项研究旨在确定预测抗PD-1ICI治疗结果的生物标志物。
方法:我们回顾性分析了144例RMHNSCC患者,他们在2017年1月至2022年12月期间在高雄长庚纪念医院接受铂类药物化疗后接受了抗PD-1ICIs。临床病理参数数据,白蛋白水平,钙水平,和其他预处理外周血生物标志物,包括淋巴细胞总数,中性粒细胞与淋巴细胞比率(NLR),血小板与淋巴细胞比率(PLR),淋巴细胞与单核细胞比率(LMR),收集预后营养指数(PNI),并与抗PD-1ICIs的治疗结果相关。
结果:低肿瘤比例评分(TPS),低综合阳性评分(CPS),NLR≥5,PLR≥300,高钙血症,低蛋白血症,PNI<45与ICI反应不良显著相关。钙<10mg/dL和钙≥10mg/dL患者的总有效率分别为25%和3%,分别为(P=0.007)。白蛋白<4g/dL和白蛋白≥4g/dL的患者的总有效率分别为6%和33%。分别(P<0.001)。单因素生存分析显示,低TPS,低CPS,NLR≥5,,高钙血症,低蛋白血症,PNI<45与无进展生存期(PFS)差和总生存期(OS)差显著相关。多因素分析显示,钙≥10mg/dL和白蛋白<4g/dL是PFS较差和OS较差的独立预后指标。钙<10mg/dL和≥10mg/dL患者的两年OS率分别为26%和9%,分别(P<0.001)。白蛋白<4g/dL和≥4g/dL患者的两年OS率分别为10%和33%,分别(P<0.001)。
结论:高钙血症和低白蛋白血症可能预测RMHNSCC患者抗PD-1ICIs的不良治疗结果。血钙和白蛋白水平可能有助于RMHNSCC患者的个体化治疗策略。
BACKGROUND: Recent randomized phase III trials have demonstrated the efficacy of anti-programmed cell death 1 (PD-1) immune checkpoint inhibitors (ICIs) in treating patients with recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC). However, a large proportion of such patients still have poor response. This study aimed to identify biomarkers for predicting anti-PD-1 ICI treatment outcomes .
METHODS: We retrospectively analyzed 144 patients with RMHNSCC who received anti-PD-1 ICIs after progression to platinum-based chemotherapy between January 2017 and December 2022 at Kaohsiung Chang Gung Memorial Hospital. Data on clinicopathological parameters, albumin levels, calcium levels, and other pretreatment peripheral blood biomarkers, including total lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and prognostic nutritional index (PNI) were collected and correlated with the treatment outcome of anti-PD-1 ICIs.
RESULTS: Low tumor proportion score (TPS), low combined positive score (CPS), NLR ≥ 5, PLR ≥ 300, hypercalcemia, hypoalbuminemia, and PNI < 45 were significantly correlated with poor response of ICIs. The overall response rates were 25% and 3% in patients with calcium < 10 mg/dL and calcium ≥ 10 mg/dL, respectively (P = 0.007). The overall response rates were 6% and 33% in patients with albumin < 4 g/dL and albumin ≥ 4 g/dL, respectively (P < 0.001). Univariate survival analysis showed that low TPS, low CPS, NLR ≥ 5,, hypercalcemia, hypoalbuminemia, and PNI < 45 were significantly associated with worse progression-free survival (PFS) and inferior overall survival (OS). Multivariate analysis revealed that calcium ≥ 10 mg/dL and albumin < 4 g/dL were independent poor prognosticators for worse PFS and inferior OS. The two-year OS rates were 26% and 9% in patients with calcium < 10 mg/dL and ≥ 10 mg/dL, respectively (P < 0.001). The two-year OS rates were 10% and 33% in patients with albumin < 4 g/dL and ≥ 4 g/dL, respectively (P < 0.001).
CONCLUSIONS: Hypercalcemia and hypoalbuminemia can potentially predict poor treatment outcomes of anti-PD-1 ICIs in patients with RMHNSCC. Blood calcium and albumin levels may be helpful in individualizing treatment strategies for patients with RMHNSCC.