Assessment of gene expressions from squamous cell carcinoma of the head and neck to predict radiochemotherapy-related xerostomia and dysphagia

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung



PURPOSE: We tested the hypothesis that gene expressions from biopsies of locally advanced head and neck squamous cell carcinoma (HNSCC) patients can supplement dose-volume parameters to predict dysphagia and xerostomia following primary radiochemotherapy (RCTx).

MATERIAL AND METHODS: A panel of 178 genes previously related to radiochemosensitivity of HNSCC was considered for nanoString analysis based on tumour biopsies of 90 patients with locally advanced HNSCC treated by primary RCTx. Dose-volume parameters were extracted from the parotid, submandibular glands, oral cavity, larynx, buccal mucosa, and lips. Normal tissue complication probability (NTCP) models were developed for acute, late, and for the improvement of xerostomia grade ≥2 and dysphagia grade ≥3 using a cross-validation-based least absolute shrinkage and selection operator (LASSO) approach combined with stepwise logistic regression for feature selection. The final signatures were included in a logistic regression model with optimism correction. Performance was assessed by the area under the receiver operating characteristic curve (AUC).

RESULTS: NTCP models for acute and late xerostomia and the improvement of dysphagia resulted in optimism-corrected AUC values of 0.84, 0.76, and 0.70, respectively. The minimum dose to the contralateral parotid was selected for both acute and late xerostomia and the minimum dose to the larynx was selected for dysphagia improvement. For the xerostomia endpoints, the following gene expressions were selected: RPA2 (cellular response to DNA damage), TCF3 (salivary gland cells development), GBE1 (glycogen storage and regulation), and MAPK3 (regulation of cellular processes). No gene expression features were selected for the prediction of dysphagia.

CONCLUSION: This hypothesis-generating study showed the potential of improving NTCP models using gene expression data for HNSCC patients. The presented models require independent validation before potential application in clinical practice.


Seiten (von - bis)856-863
FachzeitschriftActa Oncologica
Frühes Online-Datum3 Juni 2022
PublikationsstatusVeröffentlicht - 2022

Externe IDs

Scopus 85131589809
Mendeley b88b1eba-54ed-33b0-bcf4-853b65e2f124
WOS 000805690200001
unpaywall 10.1080/0284186x.2022.2081931
ORCID /0000-0002-7017-3738/work/142254022
ORCID /0000-0002-5256-1497/work/153110537


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  • Carcinoma, Squamous Cell/genetics, Chemoradiotherapy/adverse effects, Deglutition Disorders/genetics, Gene Expression, Head and Neck Neoplasms/complications, Humans, Parotid Gland, Radiotherapy, Intensity-Modulated/methods, Squamous Cell Carcinoma of Head and Neck/complications, Xerostomia/genetics