TY - JOUR
T1 - Tumor volume and cancer stem cell expression as prognostic markers for high-dose loco-regional failure in head and neck squamous cell carcinoma - a DAHANCA 19 study
AU - Horsholt Kristensen, Morten
AU - Kristina Sørensen, Mia
AU - Tramm, Trine
AU - Alsner, Jan
AU - Singers Sørensen, Brita
AU - Maare, Christian
AU - Johansen, Jørgen
AU - Primdahl, Hanne
AU - Bratland, Åse
AU - Andrup Kristensen, Claus
AU - Andersen, Maria
AU - Kinggaard Lilja-Fischer, Jacob
AU - Ivalu Sander Holm, Anne
AU - Samsøe, Eva
AU - Rønn Hansen, Christian
AU - Zukauskaite, Ruta
AU - Overgaard, Jens
AU - Grau Eriksen, Jesper
N1 - Copyright © 2024. Published by Elsevier B.V.
PY - 2024
Y1 - 2024
N2 - BACKGROUND AND PURPOSE: Reliable and accessible biomarkers for patients with Head and Neck Squamous Cell Carcinoma (HNSCC) are warranted for biologically driven radiotherapy (RT). This study aimed to investigate the prognostic value of putative cancer stem cell (CSC) markers, hypoxia, and tumor volume using loco-regional high-dose failure (HDF) as endpoint.MATERIALS AND METHODS: Tumor tissue was retrieved from patients treated with primary chemo-(C-)RT and nimorazole for HNSCC in the Danish Head and Neck Cancer Study Group (DAHANCA) 19 study. Tumor volume, hypoxic classification, and expression of CSC markers CD44, SLC3A2, and MET were analyzed. For patients with eligible data on all parameters (n=340), the risk of HDF following primary chemo-(C-)RT were analyzed by these biomarkers as a whole and stratified for p16-positive oropharynx (p16+ OPSCC) vs p16-negative (p16-) tumors (oral cavity, p16- oropharynx, hypopharynx and larynx).RESULTS: Higher risk of HDF was seen for patients with larger primary and nodal volume (>25cm3, Hazard Ratio (HR): 3.00 [95% CI: 1.73-5.18]), high SLC3A2 (HR: 2.99 [1.28-6.99]), CD44 (>30 % positive, HR: 2.29 [1.05-5.00]), and p16- tumors (HR: 2.53 [1.05-6.11]). p16- tumors had a higher CSC marker expression than p16+ OPSCC. The factors associated with the highest risk of HDF were larger volume (HR: 3.29 [1.79-6.04]) for p16- tumors (n=178) and high SLC3A2 (HR: 6.19 [1.58-24.23]) for p16+ OPSCC (n=162).CONCLUSION: Tumor volume, p16, and CSC markers are potential biomarkers for HDF for patients with HNSCC treated with (C-)RT. Lower expression of CSC in p16+ OPSCC may contribute to better tumor control.
AB - BACKGROUND AND PURPOSE: Reliable and accessible biomarkers for patients with Head and Neck Squamous Cell Carcinoma (HNSCC) are warranted for biologically driven radiotherapy (RT). This study aimed to investigate the prognostic value of putative cancer stem cell (CSC) markers, hypoxia, and tumor volume using loco-regional high-dose failure (HDF) as endpoint.MATERIALS AND METHODS: Tumor tissue was retrieved from patients treated with primary chemo-(C-)RT and nimorazole for HNSCC in the Danish Head and Neck Cancer Study Group (DAHANCA) 19 study. Tumor volume, hypoxic classification, and expression of CSC markers CD44, SLC3A2, and MET were analyzed. For patients with eligible data on all parameters (n=340), the risk of HDF following primary chemo-(C-)RT were analyzed by these biomarkers as a whole and stratified for p16-positive oropharynx (p16+ OPSCC) vs p16-negative (p16-) tumors (oral cavity, p16- oropharynx, hypopharynx and larynx).RESULTS: Higher risk of HDF was seen for patients with larger primary and nodal volume (>25cm3, Hazard Ratio (HR): 3.00 [95% CI: 1.73-5.18]), high SLC3A2 (HR: 2.99 [1.28-6.99]), CD44 (>30 % positive, HR: 2.29 [1.05-5.00]), and p16- tumors (HR: 2.53 [1.05-6.11]). p16- tumors had a higher CSC marker expression than p16+ OPSCC. The factors associated with the highest risk of HDF were larger volume (HR: 3.29 [1.79-6.04]) for p16- tumors (n=178) and high SLC3A2 (HR: 6.19 [1.58-24.23]) for p16+ OPSCC (n=162).CONCLUSION: Tumor volume, p16, and CSC markers are potential biomarkers for HDF for patients with HNSCC treated with (C-)RT. Lower expression of CSC in p16+ OPSCC may contribute to better tumor control.
KW - Biomarkers
KW - Chemo-radiotherapy
KW - HNSCC
KW - Neoplastic Stem Cells
KW - p16 positive OPSCC
KW - Tumor volume
UR - http://www.scopus.com/inward/record.url?scp=85185471314&partnerID=8YFLogxK
U2 - 10.1016/j.radonc.2024.110149
DO - 10.1016/j.radonc.2024.110149
M3 - Journal article
C2 - 38341096
SN - 0167-8140
VL - 193
JO - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
JF - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
M1 - 110149
ER -