TY - JOUR

T1 - Immunohistochemical and molecular imaging biomarker signature for the prediction of failure site after chemoradiation for head and neck squamous cell carcinoma

AU - Rasmussen, Gregers Brünnich

AU - Håkansson, Katrin E

AU - Vogelius, Ivan R

AU - Rasmussen, Jacob H

AU - Friborg, Jeppe T

AU - Fischer, Barbara M

AU - Schumaker, Lisa

AU - Cullen, Kevin

AU - Therkildsen, Marianne H

AU - Bentzen, Søren M

AU - Specht, Lena

PY - 2017

Y1 - 2017

N2 - OBJECTIVE: To identify a failure site-specific prognostic model by combining immunohistochemistry (IHC) and molecular imaging information to predict long-term failure type in squamous cell carcinoma of the head and neck.PATIENT AND METHODS: Tissue microarray blocks of 196 head and neck squamous cell carcinoma cases were stained for a panel of biomarkers using IHC. Gross tumor volume (GTV) from the PET/CT radiation treatment planning CT scan, maximal Standard Uptake Value (SUVmax) of fludeoxyglucose (FDG) and clinical information were included in the model building using Cox proportional hazards models, stratified for p16 status in oropharyngeal carcinomas. Separate models were built for time to locoregional failure and time to distant metastasis.RESULTS: Higher than median p53 expression on IHC tended toward a risk factor for locoregional failure but was protective for distant metastasis, χ2for difference p = .003. The final model for locoregional failure included p53 (HR: 1.9; p: .055), concomitant cisplatin (HR: 0.41; p: .008), β-tubulin-1 (HR: 1.8; p: .08), β-tubulin-2 (HR: 0.49; p: .057) and SUVmax (HR: 2.1; p: .046). The final model for distant metastasis included p53 (HR: 0.23; p: .025), Bcl-2 (HR: 2.6; p: .08), SUVmax (HR: 3.5; p: .095) and GTV (HR: 1.7; p: .063).CONCLUSIONS: The models successfully distinguished between risk of locoregional failure and risk of distant metastasis, which is important information for clinical decision-making. High p53 expression has opposite prognostic effects for the two endpoints; increasing risk of locoregional failure, but decreasing the risk of metastatic failure, but external validation of this finding is needed.

AB - OBJECTIVE: To identify a failure site-specific prognostic model by combining immunohistochemistry (IHC) and molecular imaging information to predict long-term failure type in squamous cell carcinoma of the head and neck.PATIENT AND METHODS: Tissue microarray blocks of 196 head and neck squamous cell carcinoma cases were stained for a panel of biomarkers using IHC. Gross tumor volume (GTV) from the PET/CT radiation treatment planning CT scan, maximal Standard Uptake Value (SUVmax) of fludeoxyglucose (FDG) and clinical information were included in the model building using Cox proportional hazards models, stratified for p16 status in oropharyngeal carcinomas. Separate models were built for time to locoregional failure and time to distant metastasis.RESULTS: Higher than median p53 expression on IHC tended toward a risk factor for locoregional failure but was protective for distant metastasis, χ2for difference p = .003. The final model for locoregional failure included p53 (HR: 1.9; p: .055), concomitant cisplatin (HR: 0.41; p: .008), β-tubulin-1 (HR: 1.8; p: .08), β-tubulin-2 (HR: 0.49; p: .057) and SUVmax (HR: 2.1; p: .046). The final model for distant metastasis included p53 (HR: 0.23; p: .025), Bcl-2 (HR: 2.6; p: .08), SUVmax (HR: 3.5; p: .095) and GTV (HR: 1.7; p: .063).CONCLUSIONS: The models successfully distinguished between risk of locoregional failure and risk of distant metastasis, which is important information for clinical decision-making. High p53 expression has opposite prognostic effects for the two endpoints; increasing risk of locoregional failure, but decreasing the risk of metastatic failure, but external validation of this finding is needed.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Biomarkers/analysis

KW - Carcinoma, Squamous Cell/diagnostic imaging

KW - Chemoradiotherapy

KW - Clinical Decision-Making

KW - Female

KW - Follow-Up Studies

KW - Head and Neck Neoplasms/diagnostic imaging

KW - Humans

KW - Male

KW - Middle Aged

KW - Molecular Imaging/methods

KW - Neoplasm Recurrence, Local/diagnostic imaging

KW - Positron Emission Tomography Computed Tomography

KW - Prognosis

KW - Retrospective Studies

KW - Survival Rate

U2 - 10.1080/0284186X.2017.1364870

DO - 10.1080/0284186X.2017.1364870

M3 - Journal article

C2 - 28840766

VL - 56

SP - 1562

EP - 1570

JO - Acta Oncologica

JF - Acta Oncologica

SN - 1100-1704

IS - 11

ER -