Li Zijie, Huang Shujie, Chen Rixin, Gao Zhen, Wu Junhan, Chen Yizhang, Zhong Weifeng, Wang Sichao, Qiao Guibin
Department of Thoracic Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
Shantou University Medical College, Shantou, China.
Ann Surg Oncol. 2025 Jun;32(6):4173-4180. doi: 10.1245/s10434-024-16811-7. Epub 2024 Dec 27.
Immunochemotherapy is inevitably accompanied with treatment-related adverse events (TRAEs). However, TRAEs are typically assessed at a single time point, overlooking the complexity of TRAE trajectories over time. This study aimed to characterize TRAE trajectories during multi-cycle neoadjuvant immunochemotherapy (nICT) and identify potential prognostic factors for patients with esophageal squamous cell carcinoma (ESCC).
This prospective cohort study enrolled locally advanced ESCC patients treated with nICT between July 2020 and August 2022. The study recorded and graded TRAEs according to common terminology criteria for adverse events (CTCAE) v5.0. Latent-class mixed-modeling (LCMM) was used to identify the TRAE trajectories. Prognosis and tumor response of different TRAE trajectories were further analyzed.
The study finally enrolled 75 eligible patients (mean age, 62.4 years; 77.3% male). The major TRAEs with high incidence were fatigue (90.7%), alopecia (74.7%), pruritus (60.0%), nausea (49.3%), vomiting (41.3%), and pain (33.3%). Two- and three-cluster trajectory models provided the best fit for TRAEs. Most TRAEs showed improvement over time except for the subgroups of fatigue and alopecia, which tended to worsen. Furthermore, the patients with a severe gastrointestinal TRAE trajectory had poorer overall survival than those with a mild gastrointestinal TRAE trajectory (hazard ratio, 3.97; 95% confidence interval, 1.09-14.51; p = 0.037). Higher objective tumor response rates were associated with a mild fatigue trajectory (p = 0.039) and a mild pain trajectory (p = 0.016).
For patients with locally advanced ESCC, most TRAEs such as pruritus, nausea, vomiting, and pain improved over time, whereas fatigue and alopecia tended to worsen in multi-cycle nICT. A mild gastrointestinal TRAE trajectory was associated with better survival.
免疫化疗不可避免地会伴随治疗相关不良事件（TRAEs）。然而，TRAEs通常在单一时间点进行评估，忽略了TRAEs随时间变化轨迹的复杂性。本研究旨在描述多周期新辅助免疫化疗（nICT）期间TRAEs的轨迹，并确定食管鳞状细胞癌（ESCC）患者的潜在预后因素。
这项前瞻性队列研究纳入了2020年7月至2022年8月期间接受nICT治疗的局部晚期ESCC患者。该研究根据不良事件通用术语标准（CTCAE）v5.0记录并分级TRAEs。采用潜在类别混合模型（LCMM）来识别TRAEs的轨迹。进一步分析不同TRAEs轨迹的预后和肿瘤反应。
该研究最终纳入了75例符合条件的患者（平均年龄62.4岁；77.3%为男性）。高发生率的主要TRAEs包括疲劳（90.7%）、脱发（74.7%）、瘙痒（60.0%）、恶心（49.3%）、呕吐（41.3%）和疼痛（33.3%）。两聚类和三聚类轨迹模型对TRAEs的拟合效果最佳。除了疲劳和脱发亚组有恶化趋势外，大多数TRAEs随时间推移有所改善。此外，胃肠道TRAEs轨迹严重的患者总生存期比胃肠道TRAEs轨迹轻微的患者更差（风险比，3.97；95%置信区间，1.09 - 14.51；p = 0.037）。更高的客观肿瘤反应率与轻微的疲劳轨迹（p = 0.039）和轻微的疼痛轨迹（p = 0.016）相关。
对于局部晚期ESCC患者，在多周期nICT中，大多数TRAEs如瘙痒、恶心、呕吐和疼痛随时间推移有所改善，而疲劳和脱发有恶化趋势。胃肠道TRAEs轨迹轻微与更好的生存相关。
