# Therapy-Induced Neutropenia and Poor Prognosis in Patients with Locally Advanced Esophageal Cancer Who Underwent Concurrent Chemoradiotherapy with Docetaxel, Cisplatin, and 5-Fluorouracil

## TL;DR

Severe neutropenia during esophageal cancer treatment is linked to worse survival and reduced immune recovery.

## Contribution

Identifies therapy-induced neutropenia as an independent predictor of poor prognosis and impaired lymphocyte recovery in esophageal cancer patients.

## Key findings

- Patients with grade 3–4 neutropenia had significantly worse overall survival compared to those with mild or no neutropenia.
- Severe neutropenia was associated with greater reductions in lymphocyte counts at cancer recurrence, suggesting impaired immune recovery.

## Abstract

Therapy-induced neutropenia is a common complication that occurs during definitive chemoradiotherapy for locally advanced esophageal cancer, but its prognostic significance is still unclear. In this study, we found that patients who developed severe neutropenia (Grade 3–4) during treatment had significantly worse overall survival compared to those with mild or no neutropenia. Notably, severe neutropenia was linked to greater reductions in lymphocyte counts at the time of cancer recurrence, indicating an impaired ability of the immune system to recover. These findings suggest that therapy-induced neutropenia not only reflects treatment toxicity but may also predict insufficient lymphocyte recovery and compromised antitumor immunity. Our results emphasize the need for further prospective studies to better understand the clinical and immunological consequences of myelosuppression in multimodal esophageal cancer therapy.

Background: The prognostic impact of therapy-induced neutropenia in patients receiving definitive chemoradiotherapy for locally advanced thoracic esophageal cancer (EC) remains inadequately characterized. This study aimed to evaluate the association between grade 3–4 neutropenia and survival outcomes following docetaxel–cisplatin–5-fluorouracil (DCF) combined with radiotherapy (DCF-RT). Methods: Fifty patients with locally advanced thoracic EC were included in this study. Chemotherapy consisted of intravenous docetaxel at 50 mg/m2 (day 1), CDDP at 60 mg/m2 (day 1), and 5-FU at 600 mg/m2 (days 1 to 4), administered every four weeks for two cycles in combination with radiotherapy (60 Gy in 30 fractions). Toxicities were assessed using the Common Terminology Criteria for Adverse Events. Overall survival (OS), progression-free survival (PFS), locoregional control and distant metastasis-free survival were compared by neutropenia grade. Results: Grade 3–4 neutropenia occurred in 80% (95% CI: 66.3–90.0) of patients. The OS rate was significantly lower in those with grade 3–4 neutropenia than in those with grade 0–2 (p = 0.006). Multivariate analysis identified grade 3–4 neutropenia (HR 3.77; 95% CI: 1.35–10.56) and complete response (CR) (HR 0.47; 95% CI: 0.25–0.87) as independent prognostic factors for OS among patients who received definitive CRT. Among 38 patients with recurrence or residual disease, those with grade 3–4 neutropenia exhibited significantly greater reductions in lymphocyte counts at recurrence versus pretreatment (p = 0.012) compared with those with grade 0–2 neutropenia. Conclusions: Therapy-induced neutropenia is an independent prognostic factor for OS in locally advanced thoracic EC patients undergoing definitive DCF-RT. It may also serve as a predictor of insufficient lymphocyte recovery following chemoradiation.