Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA.
Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Oral Oncol. 2024 Apr;151:106761. doi: 10.1016/j.oraloncology.2024.106761. Epub 2024 Mar 20.
The adaptive immune response is physiologically regulated by the circadian rhythm. Data in lung and melanoma malignancies suggests immunotherapy infusions earlier in the day may be associated with improved response; however, the optimal time of administration for patients with head and neck squamous cell carcinoma (HNSCC) is not known. We aimed to evaluate the association of immunotherapy infusion time with overall survival (OS) and progression free survival (PFS) in patients with HNSCC in an Institutional Review Board-approved, retrospective cohort study. 113 patients met study inclusion criteria and 98 patients were included in a propensity score-matched cohort. In the full unmatched cohort (N = 113), each additional 20 % of infusions received after 1500 h conferred an OS hazard ratio (HR) of 1.35 (95 % C.I.1.2-1.6; p-value = 0.0003) and a PFS HR of 1.34 (95 % C.I.1.2-1.6; p-value < 0.0001). A propensity score-matched analysis of patients who did or did not receive ≥20 % of infusions after 1500 h showed that those who were administered ≥20 % of infusions after 1500 h trended towards a shorter OS (HR = 1.35; p-value = 0.26) and a shorter PFS (HR = 1.57, 95 % C.I. 1.02-2.42, p-value = 0.04). Each additional 20 % of infusions received after 1500 h remained robust in the matched cohort multivariable analysis and was associated with shorter OS (adjusted HR = 1.4 (95 % C.I.1.2-1.8), p-value < 0.001). Patients with advanced HNSCC who received more of their infusions in the afternoon were associated with shorter OS and PFS and scheduling immunotherapy infusions earlier in the day may be warranted.
适应性免疫反应在生理上受到昼夜节律的调节。肺部和黑色素瘤恶性肿瘤的数据表明，在一天中较早的时候进行免疫治疗输注可能与改善反应相关；然而，目前尚不清楚头颈部鳞状细胞癌（HNSCC）患者的最佳给药时间。我们旨在评估免疫治疗输注时间与接受 HNSCC 治疗的患者的总生存（OS）和无进展生存（PFS）之间的关联，这是一项经过机构审查委员会批准的回顾性队列研究。113 名符合研究纳入标准的患者中，有 98 名患者被纳入倾向评分匹配队列。在未匹配的全队列（N=113）中，每增加 20%的输注量在 1500 小时后，OS 风险比（HR）为 1.35（95%CI 1.2-1.6；p 值=0.0003），PFS HR 为 1.34（95%CI 1.2-1.6；p 值<0.0001）。对接受或未接受 1500 小时后接受≥20%输注量的患者进行倾向评分匹配分析显示，在 1500 小时后接受≥20%输注量的患者 OS 较短（HR=1.35；p 值=0.26）和较短的 PFS（HR=1.57，95%CI 1.02-2.42，p 值=0.04）。在匹配队列的多变量分析中，1500 小时后每增加 20%的输注量仍然稳健，与 OS 较短相关（调整后的 HR=1.4（95%CI 1.2-1.8），p 值<0.001）。接受更多下午免疫治疗输注的晚期 HNSCC 患者与较短的 OS 和 PFS 相关，因此有必要尽早安排免疫治疗输注。
