Shen Yinchen, Li Jiaqi, Qiang Huiping, Lei Yuqiong, Chang Qing, Zhong Runbo, Stella Giulia Maria, Gelsomino Francesco, Kim Yeon Wook, Abed Afaf, Qian Jialin, Chu Tianqing
Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy.
Transl Lung Cancer Res. 2022 Aug;11(8):1619-1630. doi: 10.21037/tlcr-22-493.
Diabetes mellitus (DM) is common and recognized as a risk factor for developing non-small cell lung cancer (NSCLC) while the prognostic evaluation is still controversial. As immunotherapy is widely used in clinical practice, its efficacy and survival should be investigated in patients with DM.
We retrospectively recruited 266 locally advanced and metastatic NSCLC patients who received pembrolizumab alone or in combination with chemotherapy. Patients' clinicopathological data, including age, history of DM, hemoglobin A1c (HbA1c), genetic tumor profiling, and survival data were collected. Associations between clinical characteristics and survival were evaluated by univariate and multivariate analyses.
In this cohort, 15.04% (40/266) of the patients had a history of DM. Fifty-nine (22.2%) patients had a HbA1c level ≥6.5%. A total of 169 (63.5%) patients received 1st-line therapy, and 97 (36.5%) received 2nd- or subsequent-line therapy. Patients with high (≥6.5%) HbA1c and lower (<35 g/L) albumin levels at baseline had worse survivals, and epidermal growth factor receptor () mutants significantly associated with worse outcomes at normal HbA1c (<6.5%) levels (all P<0.05). Among the 1st-line therapy patients, a higher HbA1c level (≥6.5%) at baseline indicated a worse overall survival (OS) (2-year survival rate: 31.25% 27.03%, P=0.045), tumor protein p53 () alternations and high programmed death-ligand 1 (PD-L1) expression (≥50%) were significantly associated with better outcomes (P<0.05). For 2nd- or subsequent-line patients, mutants and non-squamous carcinomas (non-SCs) indicated worse survivals, and the normal peripheral blood markers of the carcinoembryonic antigen (CEA), C-reactive protein (CRP), albumin levels were favorable prognostic factors for survivals. In non-SCs, Kirsten rat sarcoma viral oncogene homolog () mutations, high PD-L1 expression, and normal alkaline phosphatase (ALP) levels favored better progression-free survival (PFS), while mutants indicated poor PFS (P<0.05).
Among patients treated with 1st-line immunotherapy, a higher HbA1c level (≥6.5%) indicated dismal OS, while history of DM, baseline blood glucose levels, and glucose changes during the treatment process were not significantly associated with any of the outcomes.
糖尿病（DM）很常见，被认为是发生非小细胞肺癌（NSCLC）的一个危险因素，而其预后评估仍存在争议。由于免疫疗法在临床实践中广泛应用，因此应在糖尿病患者中研究其疗效和生存期。
我们回顾性招募了266例接受帕博利珠单抗单药治疗或联合化疗的局部晚期和转移性NSCLC患者。收集患者的临床病理数据，包括年龄、糖尿病史、糖化血红蛋白（HbA1c）、肿瘤基因图谱分析以及生存数据。通过单因素和多因素分析评估临床特征与生存之间的关联。
在该队列中，15.04%（40/266）的患者有糖尿病史。59例（22.2%）患者的HbA1c水平≥6.5%。共有169例（63.5%）患者接受一线治疗，97例（36.5%）接受二线或后续治疗。基线时HbA1c水平高（≥6.5%）且白蛋白水平低（<35 g/L）的患者生存期较差，表皮生长因子受体（）突变在正常HbA1c（<6.5%）水平时与较差预后显著相关（所有P<0.05）。在一线治疗患者中，基线时较高的HbA1c水平（≥6.5%）表明总生存期（OS）较差（2年生存率：31.25% 27.03%，P=0.045），肿瘤蛋白p53（）改变和高程序性死亡配体1（PD-L1）表达（≥50%）与较好预后显著相关（P<0.05）。对于二线或后续治疗患者， 突变和非鳞癌（non-SCs）表明生存期较差，癌胚抗原（CEA）、C反应蛋白（CRP）、白蛋白水平正常的外周血标志物是生存期的有利预后因素。在非鳞癌中， Kirsten大鼠肉瘤病毒癌基因同源物（）突变、高PD-L1表达和正常碱性磷酸酶（ALP）水平有利于更好的无进展生存期（PFS），而 突变表明PFS较差（P<0.05）。
在接受一线免疫治疗的患者中，较高的HbA1c水平（≥6.5%）表明OS不佳，而糖尿病史、基线血糖水平以及治疗过程中的血糖变化与任何预后均无显著关联。
