Document Type
Article
Publication Date
10-27-2025
Abstract
BACKGROUND: Head and neck squamous-cell carcinoma (HNSCC), particularly oropharyngeal cancer (OPC), exhibits diverse prognostic factors influenced by demographic and lifestyle variables. Prognostic nomograms, such as the one developed by Fakhry et al., incorporate clinical and biological markers to predict overall survival (OS) and progression-free survival (PFS) in OPC patients. However, their applicability to European populations remains unverified. This study aimed to externally validate Fakhry's prognostic nomogram in a large European cohort of locally advanced OPC patients treated with definitive intensity-modulated radiotherapy (IMRT) with or without systemic therapy.
METHODS: This is a retrospective external validation study conducted on 805 OPC patients from 14 Southern European oncology centers, with a median follow-up of 6 years. Variables including age, smoking status, p16 expression, anemia, performance status, T and N stage, education, marital status, alcohol consumption, comorbidities (ACE-27), and caregiver presence were collected. Cox proportional hazards models and Harrell's C-index assessed discrimination and calibration of the nomogram for 2- and 5-year OS and PFS predictions. Analyses were carried out on 781 records with complete survival information.
RESULTS: The validation confirmed the robust prognostic value of Fakhry's nomogram, with a C-index of 0.75 for OS. Smoking history and p16 status were the strongest predictors, while age was less influential than previously reported. Incorporating additional variables-particularly alcohol consumption and the interaction between smoking and p16 status-significantly improved predictive accuracy (C-index up to 0.79 for OS). These findings highlight the relevance of lifestyle factors and molecular status to European OPC prognosis and support nomogram adaptation for population-specific risk stratification.
CONCLUSION: Fakhry's model is valid for European OPC patients, and its refinement by including alcohol consumption and smoking-p16 interaction enhances prognostic precision. This improved model may facilitate personalized treatment strategies and clinical trial stratification in this population.
Recommended Citation
Bossi, P.; Gili, R.; Calza, S.; Licitra, L.; Maddalo, M.; Bacigalupo, A.; Belgioia, L.; Cacicedo, J.; Facchinetti, N.; Garcia Castano, A.; Oliva, M.; Bonomo, P.; Sanguineti, G.; Franco, P.; Argiris, A.; Psyrri, A.; and Orlandi, E., "Validation of a Prognostic Nomogram for Locally Advanced Oropharyngeal Carcinoma Treated With Intensity-Modulated Radiotherapy With/Without Systemic Therapy" (2025). Kimmel Cancer Center Faculty Papers. Paper 162.
https://jdc.jefferson.edu/kimmelccfp/162
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
PubMed ID
41151202
Language
English
Included in
Diagnosis Commons, Investigative Techniques Commons, Oncology Commons, Otorhinolaryngologic Diseases Commons, Stomatognathic Diseases Commons, Therapeutics Commons
Comments
This article is the author’s final published version in ESMO Open, Volume 10, Issue 11, 2025, Article number 105859.
The published version is available at https://doi.org/10.1016/j.esmoop.2025.105859. Copyright © 2025 The Author(s).