Treatment-related lymphopenia predicts long-term survival in locally advanced head and neck cancer: Post-Hoc analysis of a randomized phase III trial.

To evaluate the prognostic value of treatment related decline of peripheral absolute lymphocyte count (ALC) in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) after preoperative radiation therapy (RT) with or without chemotherapy. This post-hoc analysis was performed using data of 222 patients from a phase III, randomized controlled trial in LA-HNSCC. ALCs were measured before, during, and after RT. The ALC decline was defined as the difference between pre-treatment ALC and the nadir ALC observed during RT. Optimal cut-off values for hematologic and nutritional indices were determined by ROC analysis. Survival outcomes were estimated using Kaplan-Meier analysis and compared with the log-rank test. Prognostic factors were identified using LASSO regression and multivariable Cox models. A nomogram was constructed based on independent prognostic variables. With a median follow-up of 132.0 (IQR: 104.17-151.73) months, no significant difference was observed in the 10-year overall survival (OS) and progression-free survival (PFS) between treatment groups. Lymphopenia during RT occurred in 197 patients (88.7%), including grade 3 in 112 (50.5%) and grade 4 in 10 (4.5%). An ALC decline > 0.74×109/L was independently associated with poorer OS and PFS. The nomogram integrating T stage, N stage, ALC decline, and neutrophil-to-albumin ratio (NAR) yielded a C-index of 0.66, a 5-year AUC of 0.738, good calibration, and favorable net benefit on DCA. Treatment-related ALC decline is an independent adverse prognostic factor in LA-HNSCC. A nomogram incorporating ALC decline performs favorably in individualized survival prediction.