Background: The hypopharyngeal region is among the most aggressive sites of head and neck squamous cell carcinoma, often presenting at an advanced stage with poor survival outcomes. However, there are only a limited number of biomarkers available to predict the prognosis of this aggressive disease. Recent interest has focused on immunonutritional biomarkers that may improve prognostication. The C-reactive protein–albumin–lymphocyte (CALLY) index has emerged as a composite biomarker integrating systemic inflammation, nutritional status, and immune competence. However, its clinical relevance in hypopharyngeal cancer has not been established. Methods: This retrospective, single-center study included patients with histologically confirmed hypopharyngeal squamous cell carcinoma treated with definitive chemoradiotherapy between 2010 and 2024. Patients were excluded from the study if they had incomplete laboratory data, had a concomitant malignancy, were undergoing induction chemotherapy, or had diseases affecting inflammatory and immunological markers. The CALLY index was calculated using pre-treatment laboratory values. Receiver operating characteristic (ROC) analysis determined the optimal cut-off value for overall survival (OS). Kaplan–Meier survival estimates and Cox regression analyses were used to assess associations between the CALLY index and progression-free survival (PFS), local recurrence-free survival (LRFS), and OS. Results: A total of 71 patients were included. The optimal CALLY cut-off was 1.47 (AUC = 0.70, p = 0.006). Patients with a CALLY index ≥ 1.47 had significantly improved median PFS (37 vs. 9 months, p = 0.003), LRFS (39 vs. 9 months, p = 0.002), and OS (61 vs. 11 months, p = 0.002). In multivariate analysis, the CALLY index and T stage remained independent prognostic factors of all three survival outcomes. Conclusions: The pretreatment CALLY index is a practical, accessible biomarker that independently predicts survival in hypopharyngeal cancer. Its integration into clinical practice may enhance risk stratification and guide individualized management strategies.

Backround: The purpose of this study was to evaluate the outcomes of different radiotherapy techniques used in routine clinical practice for the radical treatment of hypopharyngeal cancer and to assess improvements over the last few decades. Methods: We compared the outcomes of patients with hypopharyngeal squamous cell carcinoma treated with curative radiotherapy (RT) or chemoradiotherapy between January 1992 and December 2020, using 2D-RT, 3D-CRT/IMRT, and VMAT techniques. A retrospective analysis was conducted on eighty-one patients with hypopharyngeal cancer. Results: The median follow-up time was 26 months (range: 6-290). In multivariate analysis, radiotherapy technique, Karnofsky Performance Status (KPS), nodal stage, and clinical stage were identified as statistically significant factors affecting overall survival and local-regional relapse-free survival. Grade 2-4 early and late side effects were significantly more frequent in Group I patients (treated with 2D Conventional Radiotherapy) (20.3%) compared to Group II patients (treated with 3DCRT/IMRT and VMAT techniques) (3.1%) Conclusion: KPS, stage, and advanced RT techniques independently significantly affected outcomes. Moreover, advanced RT techniques were associated with a significant reduction in side effects.