Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins Medical Institutions, Baltimore, Maryland.
JAMA Otolaryngol Head Neck Surg. 2022 Jun 1;148(6):540-546. doi: 10.1001/jamaoto.2022.0640.
Tumor histological factors that predict immunotherapy response in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are not well defined.
To investigate the association between tumor grade and immunotherapy response in patients with recurrent or metastatic mucosal HNSCC.
DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study, the medical records of 60 patients with recurrent or metastatic mucosal HNSCC treated with immune checkpoint inhibitors at Johns Hopkins Hospital between July 1, 2015, and January 22, 2020, were reviewed.
High-grade tumors (HGTs) vs low-grade tumors (LGTs) in recurrent or metastatic HNSCC.
Patients were divided into 2 groups: those with LGTs (well differentiated and moderately differentiated) and those with HGTs (poorly differentiated). The main outcome was a clinically beneficial immunotherapy response, defined as complete response or partial response. Univariable and multivariable logistic regressions were conducted to calculate odds ratios for each variable's association with immunotherapy response. Survival differences were evaluated using Kaplan-Meier survival curves with multivariable Cox proportional hazards regression models.
The 60 patients (35 with HGTs and 25 with LGTs) had a mean (SD) age of 64.6 (8.88) years; 51 were male (85%); and 38 were current or former smokers (63%). The oropharynx was the most common primary tumor site both in patients with HGTs (22 of 35; 63%) and those with LGTs (12 of 25; 48%). Bivariate analysis showed the proportion of patients having a beneficial response to immunotherapy was greater for patients with HGTs (12 of 35; 34.3%) than those with LGTs (2 of 25, 8.0%) (difference, 26.3%; 95% CI, 7.3%-45.3%). Upon multivariable analysis, patients with HGTs had 5.35-fold increased odds (95% CI, 1.04-27.37) of having a clinically beneficial response to immunotherapy. Among patients with available tumor genomic profiling data, the mean tumor mutational burden was greater for patients with HGTs (mean [SD], 8.6 [5.4] mut/Mb; n = 8) than patients with LGTs (mean [SD], 3.6 [1.1] mut/Mb; n = 4) (difference = 5.0 mut/Mb; 95% CI -1.4 to 11.4 mut/Mb; Cohen d = 1.2).
In this cohort study, tumor grade was independently associated with immunotherapy response in patients with recurrent or metastatic mucosal HNSCC. These findings highlight the potential role of tumor grade in predicting immunotherapy response in mucosal HNSCC.
预测复发性或转移性头颈部鳞状细胞癌（HNSCC）患者免疫治疗反应的肿瘤组织学因素尚未明确。
研究复发性或转移性黏膜 HNSCC 患者肿瘤分级与免疫治疗反应之间的关系。
设计、地点和参与者：在这项回顾性队列研究中，对 2015 年 7 月 1 日至 2020 年 1 月 22 日在约翰霍普金斯医院接受免疫检查点抑制剂治疗的 60 例复发性或转移性黏膜 HNSCC 患者的病历进行了回顾。
复发性或转移性 HNSCC 中的高级别肿瘤（HGT）与低级别肿瘤（LGT）。
患者被分为 2 组：LGT 组（高分化和中分化）和 HGT 组（低分化）。主要结果是临床获益的免疫治疗反应，定义为完全缓解或部分缓解。进行单变量和多变量逻辑回归，以计算每个变量与免疫治疗反应相关的优势比。使用 Kaplan-Meier 生存曲线和多变量 Cox 比例风险回归模型评估生存差异。
60 例患者（35 例 HGT 和 25 例 LGT）的平均（SD）年龄为 64.6（8.88）岁；51 例为男性（85%）；38 例为现吸烟者或曾吸烟者（63%）。HGT 患者（35 例中的 22 例，63%）和 LGT 患者（25 例中的 12 例，48%）中最常见的原发肿瘤部位均为口咽。双变量分析显示，HGT 患者（12/35，34.3%）对免疫治疗有获益反应的比例高于 LGT 患者（2/25，8.0%）（差异，26.3%；95%CI，7.3%-45.3%）。多变量分析显示，HGT 患者对免疫治疗有临床获益反应的可能性是 LGT 患者的 5.35 倍（95%CI，1.04-27.37）。在有肿瘤基因组分析数据的患者中，HGT 患者的肿瘤突变负荷中位数（均数[SD]，8.6[5.4]mut/Mb；n=8）高于 LGT 患者（均数[SD]，3.6[1.1]mut/Mb；n=4）（差异=5.0mut/Mb；95%CI，1.4 至 11.4mut/Mb；Cohen d=1.2）。
在这项队列研究中，肿瘤分级与复发性或转移性黏膜 HNSCC 患者的免疫治疗反应独立相关。这些发现突出了肿瘤分级在预测黏膜 HNSCC 免疫治疗反应中的潜在作用。
