Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong SAR, China.
Department of Pathology, Queen Elizabeth Hospital, Hong Kong SAR, China.
JAMA Netw Open. 2023 Jul 3;6(7):e2323890. doi: 10.1001/jamanetworkopen.2023.23890.
Postradiation oral cavity squamous cell carcinoma (OCSCC) is a common secondary malignant neoplasm affecting survivors of head and neck cancer who underwent radiotherapy. The clinical, pathologic, and immune-related features of postradiation OCSCC are poorly characterized, and treatment options are limited because of surgical difficulty and high morbidity associated with reirradiation.
To determine whether postradiation OCSCC has distinctive clinical, pathologic, and immune-related features compared with demographic-matched sporadic OCSCC.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective matched cohort study was conducted at a single tertiary oncology center in Hong Kong. Participants included consecutive patients with OCSCC diagnosed between 2000 and 2020. Patients with postradiation OCSCC were matched with patients with sporadic OCSCC using age, year of diagnosis, sex, and anatomic subsites. Data analysis was performed from July to December 2022.
Head and neck irradiation involving the oral cavity before the diagnosis of OCSCC.
The primary outcomes were relapse pattern, survival, and causes of death. Pathologic features; immunohistochemical staining for programmed death-ligand 1, PD-1, MSH6, PMS2, FOXP3, and Ki67; and mRNA expression of 31 immune-related genes were also analyzed.
A total of 173 patients, 60 with postradiation OCSCC (median [IQR] age, 63.8 [53.0-71.7] years; 43 men [71.7%]) and 113 with sporadic OCSCC (median [IQR] age, 64.4 [52.8-70.6] years; 83 men [73.5%]), were included. Patients with postradiation OCSCC had a higher proportion of N0 disease than those with sporadic OCSCC (50 patients [83.3%] vs 56 patients [49.6%]). With a median (IQR) follow-up of 10.2 (1.2-20.5) years, the 10-year relapse-free survival rates were lower in patients with postradiation OCSCC than sporadic OCSCC (29.6% [95% CI, 17.1%-43.2%] vs 52.4% [95% CI, 41.8%-62.0%]; P = .04), and the same was true for overall survival (30.5% [95% CI, 17.6%-44.4%] vs 52.3% [95% CI, 41.4%-62.1%]; P = .03). All relapses in patients with postradiation OCSCC were locoregional, whereas 35.2% of relapses (12 of 34 patients) in patients with sporadic OCSCC were distant. Despite similar 10-year disease-specific survival rates between the 2 groups (68.8% [95% CI, 55.8%-81.0%] vs 67.1% [95% CI, 57.5%-76.5%]; P = .91), patients with postradiation OCSCC had excess mortality due to pneumonia and cerebrovascular events. Postradiation OCSCC exhibited more adverse pathologic features (perineural invasion, worse pattern of invasion, and tumor budding), higher PD-1 expression, and higher gene expression of CD4 and TGF-β compared with sporadic OCSCC.
This retrospective matched cohort study found distinctive pathologic characteristics and relapse patterns of postradiation OCSCC compared with sporadic OCSCC, which may be attributable to the lack of adjuvant radiotherapy, aggressive biologic phenotype, and different host immune response. Further exploration of the role of immune checkpoint therapy may be justified.
重要性：头颈部癌症患者在接受放疗后发生的口腔腔鳞状细胞癌（OCSCC）是一种常见的继发性恶性肿瘤。与散发型 OCSCC 相比，放疗后 OCSCC 的临床、病理和免疫相关特征描述较差，且由于再放疗相关的手术难度和高发病率，治疗选择有限。
目的：确定放疗后 OCSCC 是否与年龄匹配的散发型 OCSCC 相比具有独特的临床、病理和免疫相关特征。
设计、地点和参与者：这项回顾性匹配队列研究在香港的一家三级肿瘤中心进行。参与者包括 2000 年至 2020 年期间诊断为 OCSCC 的连续患者。放疗后 OCSCC 患者与散发型 OCSCC 患者通过年龄、诊断年份、性别和解剖部位进行匹配。数据分析于 2022 年 7 月至 12 月进行。
暴露：在 OCSCC 诊断之前接受过口腔腔的头颈部放疗。
主要结果和措施：主要结局是复发模式、生存和死亡原因。还分析了病理特征、程序性死亡配体 1、PD-1、MSH6、PMS2、FOXP3 和 Ki67 的免疫组织化学染色以及 31 个免疫相关基因的 mRNA 表达。
结果：共纳入 173 名患者，60 名患有放疗后 OCSCC（中位[IQR]年龄，63.8 [53.0-71.7] 岁；43 名男性[71.7%]）和 113 名散发型 OCSCC（中位[IQR]年龄，64.4 [52.8-70.6] 岁；83 名男性[73.5%]）。与散发型 OCSCC 相比，放疗后 OCSCC 患者的 N0 疾病比例更高（50 例[83.3%] vs 56 例[49.6%]）。中位（IQR）随访 10.2（1.2-20.5）年后，放疗后 OCSCC 患者的 10 年无复发生存率低于散发型 OCSCC（29.6%[95%CI，17.1%-43.2%] vs 52.4%[95%CI，41.8%-62.0%]；P=0.04），总生存情况也是如此（30.5%[95%CI，17.6%-44.4%] vs 52.3%[95%CI，41.4%-62.1%]；P=0.03）。放疗后 OCSCC 患者的所有复发均为局部区域复发，而散发型 OCSCC 患者的复发中有 35.2%（34 例中的 12 例）为远处转移。尽管两组 10 年疾病特异性生存率相似（68.8%[95%CI，55.8%-81.0%] vs 67.1%[95%CI，57.5%-76.5%]；P=0.91），但放疗后 OCSCC 患者的死亡率因肺炎和脑血管事件而增加。与散发型 OCSCC 相比，放疗后 OCSCC 表现出更多不良的病理特征（神经周围侵犯、更差的浸润模式和肿瘤芽生）、更高的 PD-1 表达以及更高的 CD4 和 TGF-β基因表达。
结论：这项回顾性匹配队列研究发现，与散发型 OCSCC 相比，放疗后 OCSCC 具有独特的病理特征和复发模式，这可能归因于缺乏辅助放疗、侵袭性生物学表型以及不同的宿主免疫反应。进一步探索免疫检查点治疗的作用可能是合理的。
