The roles of PTEN, cMET, and p16 in resistance to cetuximab in head and neck squamous cell carcinoma

There is no established biomarker for cetuximab efficacy in recurrent head and neck squamous cell carcinoma (HNSCC). The aim of the present study was to evaluate the prognostic and predictive impact of PTEN, cMET, and p16 expression in recurrent HNSCC. In this retrospective study, 112 patients with...

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Veröffentlicht in:Medical oncology (Northwood, London, England) London, England), 2019-01, Vol.36 (1), p.8-9, Article 8
Hauptverfasser: da Costa, Alexandre A. B. A., Costa, Felipe D’Almeida, Araújo, Daniel Vilarim, Camandaroba, Marcos Pedro Guedes, de Jesus, Victor Hugo Fonseca, Oliveira, Audrey, Alves, Ana Caroline Fonseca, Stecca, Carlos, Machado, Larissa, de Oliveira, Andrea Cruz Feraz, de Oliveira, Thiago Bueno, Nicolau, Ulisses Ribaldo, de Lima, Vladmir Cláudio Cordeiro
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container_issue 1
container_start_page 8
container_title Medical oncology (Northwood, London, England)
container_volume 36
creator da Costa, Alexandre A. B. A.
Costa, Felipe D’Almeida
Araújo, Daniel Vilarim
Camandaroba, Marcos Pedro Guedes
de Jesus, Victor Hugo Fonseca
Oliveira, Audrey
Alves, Ana Caroline Fonseca
Stecca, Carlos
Machado, Larissa
de Oliveira, Andrea Cruz Feraz
de Oliveira, Thiago Bueno
Nicolau, Ulisses Ribaldo
de Lima, Vladmir Cláudio Cordeiro
description There is no established biomarker for cetuximab efficacy in recurrent head and neck squamous cell carcinoma (HNSCC). The aim of the present study was to evaluate the prognostic and predictive impact of PTEN, cMET, and p16 expression in recurrent HNSCC. In this retrospective study, 112 patients with recurrent HNSCC received chemotherapy (CT) alone ( n  = 37) or chemotherapy with cetuximab ( n  = 75). PTEN, cMET, and p16 protein expression were evaluated by immunohistochemistry. The median overall survival (mOS) for the patients treated with cetuximab + CT versus CT alone was 11.4 months and 7.0 months, ( p  = 0.949). The median progression-free survival (mPFS) was 6.2 months versus 3.0 months ( p  = 0.154). Patients with PTEN loss exhibited a mOS of 5.8 months versus 10.5 months ( p  = 0.002) and a mPFS of 3.2 months versus 4.7 months ( p  = 0.019). A multivariate analysis identified an independent association between PTEN loss and OS (HR 2.27; 95% confidence 95% CI 1.27–4.08; p  = 0.006) and with PFS (HR 1.85; 95% CI 1.09–2.99; p  = 0.022). A negative prognostic impact of PTEN loss was observed in the patients treated with cetuximab + CT, and not in the CT only group. Expression of cMET and p16 showed no impact on OS or PFS. The present findings confirm that PTEN is a prognostic factor for metastatic HNSCC and they support further studies of PTEN expression to evaluate its predictive value to cetuximab response.
doi_str_mv 10.1007/s12032-018-1234-0
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B. A. ; Costa, Felipe D’Almeida ; Araújo, Daniel Vilarim ; Camandaroba, Marcos Pedro Guedes ; de Jesus, Victor Hugo Fonseca ; Oliveira, Audrey ; Alves, Ana Caroline Fonseca ; Stecca, Carlos ; Machado, Larissa ; de Oliveira, Andrea Cruz Feraz ; de Oliveira, Thiago Bueno ; Nicolau, Ulisses Ribaldo ; de Lima, Vladmir Cláudio Cordeiro</creator><creatorcontrib>da Costa, Alexandre A. B. A. ; Costa, Felipe D’Almeida ; Araújo, Daniel Vilarim ; Camandaroba, Marcos Pedro Guedes ; de Jesus, Victor Hugo Fonseca ; Oliveira, Audrey ; Alves, Ana Caroline Fonseca ; Stecca, Carlos ; Machado, Larissa ; de Oliveira, Andrea Cruz Feraz ; de Oliveira, Thiago Bueno ; Nicolau, Ulisses Ribaldo ; de Lima, Vladmir Cláudio Cordeiro</creatorcontrib><description>There is no established biomarker for cetuximab efficacy in recurrent head and neck squamous cell carcinoma (HNSCC). The aim of the present study was to evaluate the prognostic and predictive impact of PTEN, cMET, and p16 expression in recurrent HNSCC. In this retrospective study, 112 patients with recurrent HNSCC received chemotherapy (CT) alone ( n  = 37) or chemotherapy with cetuximab ( n  = 75). PTEN, cMET, and p16 protein expression were evaluated by immunohistochemistry. The median overall survival (mOS) for the patients treated with cetuximab + CT versus CT alone was 11.4 months and 7.0 months, ( p  = 0.949). The median progression-free survival (mPFS) was 6.2 months versus 3.0 months ( p  = 0.154). Patients with PTEN loss exhibited a mOS of 5.8 months versus 10.5 months ( p  = 0.002) and a mPFS of 3.2 months versus 4.7 months ( p  = 0.019). A multivariate analysis identified an independent association between PTEN loss and OS (HR 2.27; 95% confidence 95% CI 1.27–4.08; p  = 0.006) and with PFS (HR 1.85; 95% CI 1.09–2.99; p  = 0.022). A negative prognostic impact of PTEN loss was observed in the patients treated with cetuximab + CT, and not in the CT only group. Expression of cMET and p16 showed no impact on OS or PFS. 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A.</creatorcontrib><creatorcontrib>Costa, Felipe D’Almeida</creatorcontrib><creatorcontrib>Araújo, Daniel Vilarim</creatorcontrib><creatorcontrib>Camandaroba, Marcos Pedro Guedes</creatorcontrib><creatorcontrib>de Jesus, Victor Hugo Fonseca</creatorcontrib><creatorcontrib>Oliveira, Audrey</creatorcontrib><creatorcontrib>Alves, Ana Caroline Fonseca</creatorcontrib><creatorcontrib>Stecca, Carlos</creatorcontrib><creatorcontrib>Machado, Larissa</creatorcontrib><creatorcontrib>de Oliveira, Andrea Cruz Feraz</creatorcontrib><creatorcontrib>de Oliveira, Thiago Bueno</creatorcontrib><creatorcontrib>Nicolau, Ulisses Ribaldo</creatorcontrib><creatorcontrib>de Lima, Vladmir Cláudio Cordeiro</creatorcontrib><title>The roles of PTEN, cMET, and p16 in resistance to cetuximab in head and neck squamous cell carcinoma</title><title>Medical oncology (Northwood, London, England)</title><addtitle>Med Oncol</addtitle><addtitle>Med Oncol</addtitle><description>There is no established biomarker for cetuximab efficacy in recurrent head and neck squamous cell carcinoma (HNSCC). 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A negative prognostic impact of PTEN loss was observed in the patients treated with cetuximab + CT, and not in the CT only group. Expression of cMET and p16 showed no impact on OS or PFS. 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B. A. ; Costa, Felipe D’Almeida ; Araújo, Daniel Vilarim ; Camandaroba, Marcos Pedro Guedes ; de Jesus, Victor Hugo Fonseca ; Oliveira, Audrey ; Alves, Ana Caroline Fonseca ; Stecca, Carlos ; Machado, Larissa ; de Oliveira, Andrea Cruz Feraz ; de Oliveira, Thiago Bueno ; Nicolau, Ulisses Ribaldo ; de Lima, Vladmir Cláudio Cordeiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c400t-f7b3c34654b77fe9c5917281da4fd9fe8b2f2bf56c2ffb2e98ebb2d972294c773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic Agents, Immunological - therapeutic use</topic><topic>BIOLOGICAL MARKERS</topic><topic>Biomarkers, Tumor - analysis</topic><topic>CARCINOMAS</topic><topic>Cetuximab - therapeutic use</topic><topic>CHEMOTHERAPY</topic><topic>COMPUTERIZED TOMOGRAPHY</topic><topic>Cyclin-Dependent Kinase Inhibitor p18 - metabolism</topic><topic>Drug Resistance, Neoplasm - physiology</topic><topic>Female</topic><topic>HEAD</topic><topic>Head &amp; neck cancer</topic><topic>Hematology</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Internal Medicine</topic><topic>Kaplan-Meier Estimate</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>METASTASES</topic><topic>Middle Aged</topic><topic>Monoclonal antibodies</topic><topic>NECK</topic><topic>Oncology</topic><topic>Original Paper</topic><topic>Pathology</topic><topic>PATIENTS</topic><topic>Prognosis</topic><topic>Progression-Free Survival</topic><topic>Proportional Hazards Models</topic><topic>PROTEINS</topic><topic>Proto-Oncogene Proteins c-met - metabolism</topic><topic>PTEN Phosphohydrolase - metabolism</topic><topic>RADIOLOGY AND NUCLEAR MEDICINE</topic><topic>Retrospective Studies</topic><topic>Squamous cell carcinoma</topic><topic>Squamous Cell Carcinoma of Head and Neck - drug therapy</topic><topic>Squamous Cell Carcinoma of Head and Neck - mortality</topic><topic>Targeted cancer therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>da Costa, Alexandre A. 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B. A.</au><au>Costa, Felipe D’Almeida</au><au>Araújo, Daniel Vilarim</au><au>Camandaroba, Marcos Pedro Guedes</au><au>de Jesus, Victor Hugo Fonseca</au><au>Oliveira, Audrey</au><au>Alves, Ana Caroline Fonseca</au><au>Stecca, Carlos</au><au>Machado, Larissa</au><au>de Oliveira, Andrea Cruz Feraz</au><au>de Oliveira, Thiago Bueno</au><au>Nicolau, Ulisses Ribaldo</au><au>de Lima, Vladmir Cláudio Cordeiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The roles of PTEN, cMET, and p16 in resistance to cetuximab in head and neck squamous cell carcinoma</atitle><jtitle>Medical oncology (Northwood, London, England)</jtitle><stitle>Med Oncol</stitle><addtitle>Med Oncol</addtitle><date>2019-01-01</date><risdate>2019</risdate><volume>36</volume><issue>1</issue><spage>8</spage><epage>9</epage><pages>8-9</pages><artnum>8</artnum><issn>1357-0560</issn><issn>1559-131X</issn><eissn>1559-131X</eissn><abstract>There is no established biomarker for cetuximab efficacy in recurrent head and neck squamous cell carcinoma (HNSCC). The aim of the present study was to evaluate the prognostic and predictive impact of PTEN, cMET, and p16 expression in recurrent HNSCC. In this retrospective study, 112 patients with recurrent HNSCC received chemotherapy (CT) alone ( n  = 37) or chemotherapy with cetuximab ( n  = 75). PTEN, cMET, and p16 protein expression were evaluated by immunohistochemistry. The median overall survival (mOS) for the patients treated with cetuximab + CT versus CT alone was 11.4 months and 7.0 months, ( p  = 0.949). The median progression-free survival (mPFS) was 6.2 months versus 3.0 months ( p  = 0.154). Patients with PTEN loss exhibited a mOS of 5.8 months versus 10.5 months ( p  = 0.002) and a mPFS of 3.2 months versus 4.7 months ( p  = 0.019). A multivariate analysis identified an independent association between PTEN loss and OS (HR 2.27; 95% confidence 95% CI 1.27–4.08; p  = 0.006) and with PFS (HR 1.85; 95% CI 1.09–2.99; p  = 0.022). A negative prognostic impact of PTEN loss was observed in the patients treated with cetuximab + CT, and not in the CT only group. Expression of cMET and p16 showed no impact on OS or PFS. The present findings confirm that PTEN is a prognostic factor for metastatic HNSCC and they support further studies of PTEN expression to evaluate its predictive value to cetuximab response.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>30478503</pmid><doi>10.1007/s12032-018-1234-0</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-1631-0105</orcidid></addata></record>
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issn 1357-0560
1559-131X
1559-131X
language eng
recordid cdi_osti_scitechconnect_22938453
source MEDLINE; SpringerNature Journals
subjects Adult
Aged
Antineoplastic Agents, Immunological - therapeutic use
BIOLOGICAL MARKERS
Biomarkers, Tumor - analysis
CARCINOMAS
Cetuximab - therapeutic use
CHEMOTHERAPY
COMPUTERIZED TOMOGRAPHY
Cyclin-Dependent Kinase Inhibitor p18 - metabolism
Drug Resistance, Neoplasm - physiology
Female
HEAD
Head & neck cancer
Hematology
Humans
Immunotherapy
Internal Medicine
Kaplan-Meier Estimate
Male
Medicine
Medicine & Public Health
METASTASES
Middle Aged
Monoclonal antibodies
NECK
Oncology
Original Paper
Pathology
PATIENTS
Prognosis
Progression-Free Survival
Proportional Hazards Models
PROTEINS
Proto-Oncogene Proteins c-met - metabolism
PTEN Phosphohydrolase - metabolism
RADIOLOGY AND NUCLEAR MEDICINE
Retrospective Studies
Squamous cell carcinoma
Squamous Cell Carcinoma of Head and Neck - drug therapy
Squamous Cell Carcinoma of Head and Neck - mortality
Targeted cancer therapy
title The roles of PTEN, cMET, and p16 in resistance to cetuximab in head and neck squamous cell carcinoma
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