Validation of a 15-gene hypoxia classifier in head and neck cancer for prospective use in clinical trials

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Validation of a 15-gene hypoxia classifier in head and neck cancer for prospective use in clinical trials. / Toustrup, Kasper; Sørensen, Brita Singers; Metwally, Mohamed A Hassan; Tramm, Trine; Mortensen, Lise Saksø; Overgaard, Jens; Alsner, Jan.

In: Acta Oncologica, Vol. 55, No. 9-10, 10.05.2016, p. 1091-1098.

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@article{9ad67b5a8de9422aab142044caf353d8,
title = "Validation of a 15-gene hypoxia classifier in head and neck cancer for prospective use in clinical trials",
abstract = "In head and neck squamous cell carcinomas (HNSCC) hypoxic radioresistance can be reduced by use of the hypoxic modifier nimorazole, as shown in the DAHANCA 5 trial. Recently, a 15-gene hypoxia classifier has shown predictive impact for the effect of nimorazole by identifying 'more' and 'less' hypoxic tumors in the DAHANCA 5 cohort. A prospective multicentre EORTC-1219 study is initiated, where nimorazole and prospective use of the classifier as a predictor is tested in relation to the most recent accelerated chemoradiotherapy treatment. Validation of the gene expression classification procedures is described here.MATERIAL AND METHODS:Formalin-fixed paraffin-embedded (FFPE) tumor material from three recent HNSCC cohorts [DAHANCA 18 (n = 96), 24 (n = 40), and IAEA Hypo (n = 55)] was used to establish and validate procedures for prospective classification of patients. Repeatability was tested for the different steps in the gene expression analysis, and reproducibility was tested with xenograft tumors (FaDuDD, UTSCC33), where gene expression in complementary sections was compared after fixation and embedding locally and at international institutions, respectively. Intra-tumor heterogeneity was addressed by classifying biopsy samples from HNSCC tumors, where 2-4 biopsies from each tumor was accessible.RESULTS:Procedures were successfully established for individual classification of HNSCC patients in retrospective and prospective cohorts. Measurements of gene expression levels were reproducible between different international institutions.CONCLUSION:Technical validation of the 15-gene hypoxia classifier demonstrated that it is suitable for implementation in prospective clinical trials.",
author = "Kasper Toustrup and S{\o}rensen, {Brita Singers} and Metwally, {Mohamed A Hassan} and Trine Tramm and Mortensen, {Lise Saks{\o}} and Jens Overgaard and Jan Alsner",
year = "2016",
month = "5",
day = "10",
doi = "10.3109/0284186X.2016.1167959",
language = "English",
volume = "55",
pages = "1091--1098",
journal = "Acta Oncologica",
issn = "0284-186X",
publisher = "Taylor & francis",
number = "9-10",

}

RIS

TY - JOUR

T1 - Validation of a 15-gene hypoxia classifier in head and neck cancer for prospective use in clinical trials

AU - Toustrup, Kasper

AU - Sørensen, Brita Singers

AU - Metwally, Mohamed A Hassan

AU - Tramm, Trine

AU - Mortensen, Lise Saksø

AU - Overgaard, Jens

AU - Alsner, Jan

PY - 2016/5/10

Y1 - 2016/5/10

N2 - In head and neck squamous cell carcinomas (HNSCC) hypoxic radioresistance can be reduced by use of the hypoxic modifier nimorazole, as shown in the DAHANCA 5 trial. Recently, a 15-gene hypoxia classifier has shown predictive impact for the effect of nimorazole by identifying 'more' and 'less' hypoxic tumors in the DAHANCA 5 cohort. A prospective multicentre EORTC-1219 study is initiated, where nimorazole and prospective use of the classifier as a predictor is tested in relation to the most recent accelerated chemoradiotherapy treatment. Validation of the gene expression classification procedures is described here.MATERIAL AND METHODS:Formalin-fixed paraffin-embedded (FFPE) tumor material from three recent HNSCC cohorts [DAHANCA 18 (n = 96), 24 (n = 40), and IAEA Hypo (n = 55)] was used to establish and validate procedures for prospective classification of patients. Repeatability was tested for the different steps in the gene expression analysis, and reproducibility was tested with xenograft tumors (FaDuDD, UTSCC33), where gene expression in complementary sections was compared after fixation and embedding locally and at international institutions, respectively. Intra-tumor heterogeneity was addressed by classifying biopsy samples from HNSCC tumors, where 2-4 biopsies from each tumor was accessible.RESULTS:Procedures were successfully established for individual classification of HNSCC patients in retrospective and prospective cohorts. Measurements of gene expression levels were reproducible between different international institutions.CONCLUSION:Technical validation of the 15-gene hypoxia classifier demonstrated that it is suitable for implementation in prospective clinical trials.

AB - In head and neck squamous cell carcinomas (HNSCC) hypoxic radioresistance can be reduced by use of the hypoxic modifier nimorazole, as shown in the DAHANCA 5 trial. Recently, a 15-gene hypoxia classifier has shown predictive impact for the effect of nimorazole by identifying 'more' and 'less' hypoxic tumors in the DAHANCA 5 cohort. A prospective multicentre EORTC-1219 study is initiated, where nimorazole and prospective use of the classifier as a predictor is tested in relation to the most recent accelerated chemoradiotherapy treatment. Validation of the gene expression classification procedures is described here.MATERIAL AND METHODS:Formalin-fixed paraffin-embedded (FFPE) tumor material from three recent HNSCC cohorts [DAHANCA 18 (n = 96), 24 (n = 40), and IAEA Hypo (n = 55)] was used to establish and validate procedures for prospective classification of patients. Repeatability was tested for the different steps in the gene expression analysis, and reproducibility was tested with xenograft tumors (FaDuDD, UTSCC33), where gene expression in complementary sections was compared after fixation and embedding locally and at international institutions, respectively. Intra-tumor heterogeneity was addressed by classifying biopsy samples from HNSCC tumors, where 2-4 biopsies from each tumor was accessible.RESULTS:Procedures were successfully established for individual classification of HNSCC patients in retrospective and prospective cohorts. Measurements of gene expression levels were reproducible between different international institutions.CONCLUSION:Technical validation of the 15-gene hypoxia classifier demonstrated that it is suitable for implementation in prospective clinical trials.

UR - https://www.ncbi.nlm.nih.gov/pubmed/27161763

U2 - 10.3109/0284186X.2016.1167959

DO - 10.3109/0284186X.2016.1167959

M3 - Journal article

C2 - 27161763

VL - 55

SP - 1091

EP - 1098

JO - Acta Oncologica

JF - Acta Oncologica

SN - 0284-186X

IS - 9-10

ER -