Association Between Treatment-Related Adverse Event Trajectory and Prognosis in Esophageal Cancer Receiving Neoadjuvant Immunochemotherapy

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_adjusted, 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.