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Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis.

Identifieur interne : 000528 ( PubMed/Corpus ); précédent : 000527; suivant : 000529

Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis.

Auteurs : Benjamin Lacas ; Jean Bourhis ; Jens Overgaard ; Qiang Zhang ; Vincent Grégoire ; Matthew Nankivell ; Björn Zackrisson ; Zbigniew Szutkowski ; Rafał Suwi Ski ; Michael Poulsen ; Brian O'Sullivan ; Renzo Corv ; Sarbani Ghosh Laskar ; Carlo Fallai ; Hideya Yamazaki ; Werner Dobrowsky ; Kwan Ho Cho ; Adam S. Garden ; Johannes A. Langendijk ; Celia Maria Pais Viegas ; John Hay ; Mohamed Lotayef ; Mahesh K B. Parmar ; Anne Aupérin ; Carla Van Herpen ; Philippe Maingon ; Andy M. Trotti ; Cai Grau ; Jean-Pierre Pignon ; Pierre Blanchard

Source :

RBID : pubmed:28757375

English descriptors

Abstract

The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials.

DOI: 10.1016/S1470-2045(17)30458-8
PubMed: 28757375

Links to Exploration step

pubmed:28757375

Le document en format XML

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<name sortKey="Zhang, Qiang" sort="Zhang, Qiang" uniqKey="Zhang Q" first="Qiang" last="Zhang">Qiang Zhang</name>
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<name sortKey="Poulsen, Michael" sort="Poulsen, Michael" uniqKey="Poulsen M" first="Michael" last="Poulsen">Michael Poulsen</name>
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<name sortKey="O Sullivan, Brian" sort="O Sullivan, Brian" uniqKey="O Sullivan B" first="Brian" last="O'Sullivan">Brian O'Sullivan</name>
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<name sortKey="Corv, Renzo" sort="Corv, Renzo" uniqKey="Corv R" first="Renzo" last="Corv">Renzo Corv</name>
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<name sortKey="Laskar, Sarbani Ghosh" sort="Laskar, Sarbani Ghosh" uniqKey="Laskar S" first="Sarbani Ghosh" last="Laskar">Sarbani Ghosh Laskar</name>
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<nlm:affiliation>Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, India.</nlm:affiliation>
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<name sortKey="Fallai, Carlo" sort="Fallai, Carlo" uniqKey="Fallai C" first="Carlo" last="Fallai">Carlo Fallai</name>
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<nlm:affiliation>Department of Radiotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.</nlm:affiliation>
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<name sortKey="Yamazaki, Hideya" sort="Yamazaki, Hideya" uniqKey="Yamazaki H" first="Hideya" last="Yamazaki">Hideya Yamazaki</name>
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<nlm:affiliation>Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka, Japan.</nlm:affiliation>
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<name sortKey="Dobrowsky, Werner" sort="Dobrowsky, Werner" uniqKey="Dobrowsky W" first="Werner" last="Dobrowsky">Werner Dobrowsky</name>
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<nlm:affiliation>Department of Clinical Oncology, Freeman Hospital, Newcastle, UK.</nlm:affiliation>
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<name sortKey="Cho, Kwan Ho" sort="Cho, Kwan Ho" uniqKey="Cho K" first="Kwan Ho" last="Cho">Kwan Ho Cho</name>
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<name sortKey="Langendijk, Johannes A" sort="Langendijk, Johannes A" uniqKey="Langendijk J" first="Johannes A" last="Langendijk">Johannes A. Langendijk</name>
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<name sortKey="Viegas, Celia Maria Pais" sort="Viegas, Celia Maria Pais" uniqKey="Viegas C" first="Celia Maria Pais" last="Viegas">Celia Maria Pais Viegas</name>
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<nlm:affiliation>Radiation Oncology Department, Instituto Nacional de Cancer, Brasil National Cancer Institute, Rio de Janeiro, Brazil.</nlm:affiliation>
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<name sortKey="Lotayef, Mohamed" sort="Lotayef, Mohamed" uniqKey="Lotayef M" first="Mohamed" last="Lotayef">Mohamed Lotayef</name>
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<name sortKey="Grau, Cai" sort="Grau, Cai" uniqKey="Grau C" first="Cai" last="Grau">Cai Grau</name>
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<nlm:affiliation>Department of Experimental Clinical Oncology, Aarhus, Denmark.</nlm:affiliation>
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<name sortKey="Pignon, Jean Pierre" sort="Pignon, Jean Pierre" uniqKey="Pignon J" first="Jean-Pierre" last="Pignon">Jean-Pierre Pignon</name>
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<nlm:affiliation>Ligue Nationale Contre le Cancer Meta-Analysis Platform, Service de Biostatistique et d'Epidémiologie, Gustave Roussy Cancer Campus, INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France. Electronic address: jean-pierre.pignon@gustaveroussy.fr.</nlm:affiliation>
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<name sortKey="Blanchard, Pierre" sort="Blanchard, Pierre" uniqKey="Blanchard P" first="Pierre" last="Blanchard">Pierre Blanchard</name>
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<name sortKey="Overgaard, Jens" sort="Overgaard, Jens" uniqKey="Overgaard J" first="Jens" last="Overgaard">Jens Overgaard</name>
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<nlm:affiliation>Department of Experimental Clinical Oncology, Aarhus, Denmark.</nlm:affiliation>
</affiliation>
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<author>
<name sortKey="Zhang, Qiang" sort="Zhang, Qiang" uniqKey="Zhang Q" first="Qiang" last="Zhang">Qiang Zhang</name>
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<nlm:affiliation>NRG Oncology Statistics and Data Management Center (formerly RTOG), Philadelphia, PA, USA.</nlm:affiliation>
</affiliation>
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<name sortKey="Gregoire, Vincent" sort="Gregoire, Vincent" uniqKey="Gregoire V" first="Vincent" last="Grégoire">Vincent Grégoire</name>
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<nlm:affiliation>Radiation Oncology Department, UCL-Cliniques Universitaires St-Luc, Brussels, Belgium.</nlm:affiliation>
</affiliation>
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<name sortKey="Nankivell, Matthew" sort="Nankivell, Matthew" uniqKey="Nankivell M" first="Matthew" last="Nankivell">Matthew Nankivell</name>
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<nlm:affiliation>Medical Research Council Clinical Trials Unit, University College London, London, UK.</nlm:affiliation>
</affiliation>
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<name sortKey="Zackrisson, Bjorn" sort="Zackrisson, Bjorn" uniqKey="Zackrisson B" first="Björn" last="Zackrisson">Björn Zackrisson</name>
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<nlm:affiliation>Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.</nlm:affiliation>
</affiliation>
</author>
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<name sortKey="Szutkowski, Zbigniew" sort="Szutkowski, Zbigniew" uniqKey="Szutkowski Z" first="Zbigniew" last="Szutkowski">Zbigniew Szutkowski</name>
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<nlm:affiliation>Department of Radiotherapy, Cancer Center, Marie Curie-Sklodowska Memorial Institute, Warsaw, Poland.</nlm:affiliation>
</affiliation>
</author>
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<name sortKey="Suwi Ski, Rafal" sort="Suwi Ski, Rafal" uniqKey="Suwi Ski R" first="Rafał" last="Suwi Ski">Rafał Suwi Ski</name>
<affiliation>
<nlm:affiliation>Radiotherapy and Chemotherapy Clinic and Teaching Hospital, Marie Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Poulsen, Michael" sort="Poulsen, Michael" uniqKey="Poulsen M" first="Michael" last="Poulsen">Michael Poulsen</name>
<affiliation>
<nlm:affiliation>Radiation Oncology Services, Mater Centre, Brisbane, QLD, Australia.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="O Sullivan, Brian" sort="O Sullivan, Brian" uniqKey="O Sullivan B" first="Brian" last="O'Sullivan">Brian O'Sullivan</name>
<affiliation>
<nlm:affiliation>Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Corv, Renzo" sort="Corv, Renzo" uniqKey="Corv R" first="Renzo" last="Corv">Renzo Corv</name>
<affiliation>
<nlm:affiliation>IRCCS San Martino-IST, Genoa, Italy.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Laskar, Sarbani Ghosh" sort="Laskar, Sarbani Ghosh" uniqKey="Laskar S" first="Sarbani Ghosh" last="Laskar">Sarbani Ghosh Laskar</name>
<affiliation>
<nlm:affiliation>Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, India.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Fallai, Carlo" sort="Fallai, Carlo" uniqKey="Fallai C" first="Carlo" last="Fallai">Carlo Fallai</name>
<affiliation>
<nlm:affiliation>Department of Radiotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Yamazaki, Hideya" sort="Yamazaki, Hideya" uniqKey="Yamazaki H" first="Hideya" last="Yamazaki">Hideya Yamazaki</name>
<affiliation>
<nlm:affiliation>Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka, Japan.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Dobrowsky, Werner" sort="Dobrowsky, Werner" uniqKey="Dobrowsky W" first="Werner" last="Dobrowsky">Werner Dobrowsky</name>
<affiliation>
<nlm:affiliation>Department of Clinical Oncology, Freeman Hospital, Newcastle, UK.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Cho, Kwan Ho" sort="Cho, Kwan Ho" uniqKey="Cho K" first="Kwan Ho" last="Cho">Kwan Ho Cho</name>
<affiliation>
<nlm:affiliation>Proton Therapy Center, Research Institute and Hospital, National Cancer Center, Goyang, South Korea.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Garden, Adam S" sort="Garden, Adam S" uniqKey="Garden A" first="Adam S" last="Garden">Adam S. Garden</name>
<affiliation>
<nlm:affiliation>Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Langendijk, Johannes A" sort="Langendijk, Johannes A" uniqKey="Langendijk J" first="Johannes A" last="Langendijk">Johannes A. Langendijk</name>
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<nlm:affiliation>Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.</nlm:affiliation>
</affiliation>
</author>
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<name sortKey="Viegas, Celia Maria Pais" sort="Viegas, Celia Maria Pais" uniqKey="Viegas C" first="Celia Maria Pais" last="Viegas">Celia Maria Pais Viegas</name>
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<nlm:affiliation>Radiation Oncology Department, Instituto Nacional de Cancer, Brasil National Cancer Institute, Rio de Janeiro, Brazil.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Hay, John" sort="Hay, John" uniqKey="Hay J" first="John" last="Hay">John Hay</name>
<affiliation>
<nlm:affiliation>Division of Radiation Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Lotayef, Mohamed" sort="Lotayef, Mohamed" uniqKey="Lotayef M" first="Mohamed" last="Lotayef">Mohamed Lotayef</name>
<affiliation>
<nlm:affiliation>Radiation Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Parmar, Mahesh K B" sort="Parmar, Mahesh K B" uniqKey="Parmar M" first="Mahesh K B" last="Parmar">Mahesh K B. Parmar</name>
<affiliation>
<nlm:affiliation>Medical Research Council Clinical Trials Unit, University College London, London, UK.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Auperin, Anne" sort="Auperin, Anne" uniqKey="Auperin A" first="Anne" last="Aupérin">Anne Aupérin</name>
<affiliation>
<nlm:affiliation>Ligue Nationale Contre le Cancer Meta-Analysis Platform, Service de Biostatistique et d'Epidémiologie, Gustave Roussy Cancer Campus, INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Van Herpen, Carla" sort="Van Herpen, Carla" uniqKey="Van Herpen C" first="Carla" last="Van Herpen">Carla Van Herpen</name>
<affiliation>
<nlm:affiliation>Department of Medical Oncology, Radboud University Medical Center, Nijmegen, Netherlands.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Maingon, Philippe" sort="Maingon, Philippe" uniqKey="Maingon P" first="Philippe" last="Maingon">Philippe Maingon</name>
<affiliation>
<nlm:affiliation>European Organisation for Research and Treatment of Cancer, Radiation Oncology Group, Brussels, Belgium; Service d'Oncologie, Radiothérapie, Hôpitaux Universitaires Pitié Salpêtrière, Charles Foix, Paris, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Trotti, Andy M" sort="Trotti, Andy M" uniqKey="Trotti A" first="Andy M" last="Trotti">Andy M. Trotti</name>
<affiliation>
<nlm:affiliation>Moffitt Cancer Center, Department of Radiation Oncology, Tampa, FL, USA.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Grau, Cai" sort="Grau, Cai" uniqKey="Grau C" first="Cai" last="Grau">Cai Grau</name>
<affiliation>
<nlm:affiliation>Department of Experimental Clinical Oncology, Aarhus, Denmark.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Pignon, Jean Pierre" sort="Pignon, Jean Pierre" uniqKey="Pignon J" first="Jean-Pierre" last="Pignon">Jean-Pierre Pignon</name>
<affiliation>
<nlm:affiliation>Ligue Nationale Contre le Cancer Meta-Analysis Platform, Service de Biostatistique et d'Epidémiologie, Gustave Roussy Cancer Campus, INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France. Electronic address: jean-pierre.pignon@gustaveroussy.fr.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Blanchard, Pierre" sort="Blanchard, Pierre" uniqKey="Blanchard P" first="Pierre" last="Blanchard">Pierre Blanchard</name>
<affiliation>
<nlm:affiliation>Department of Radiation Therapy, Gustave Roussy Cancer Campus, INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.</nlm:affiliation>
</affiliation>
</author>
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<series>
<title level="j">The Lancet. Oncology</title>
<idno type="eISSN">1474-5488</idno>
<imprint>
<date when="2017" type="published">2017</date>
</imprint>
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<term>Carcinoma, Squamous Cell (mortality)</term>
<term>Carcinoma, Squamous Cell (pathology)</term>
<term>Carcinoma, Squamous Cell (radiotherapy)</term>
<term>Dose Fractionation</term>
<term>Head and Neck Neoplasms (mortality)</term>
<term>Head and Neck Neoplasms (pathology)</term>
<term>Head and Neck Neoplasms (radiotherapy)</term>
<term>Humans</term>
</keywords>
<keywords scheme="MESH" qualifier="mortality" xml:lang="en">
<term>Carcinoma, Squamous Cell</term>
<term>Head and Neck Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en">
<term>Carcinoma, Squamous Cell</term>
<term>Head and Neck Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="radiotherapy" xml:lang="en">
<term>Carcinoma, Squamous Cell</term>
<term>Head and Neck Neoplasms</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Dose Fractionation</term>
<term>Humans</term>
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<div type="abstract" xml:lang="en">The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials.</div>
</front>
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<pubmed>
<MedlineCitation Status="MEDLINE" Owner="NLM">
<PMID Version="1">28757375</PMID>
<DateCreated>
<Year>2017</Year>
<Month>07</Month>
<Day>31</Day>
</DateCreated>
<DateCompleted>
<Year>2017</Year>
<Month>09</Month>
<Day>25</Day>
</DateCompleted>
<DateRevised>
<Year>2017</Year>
<Month>09</Month>
<Day>25</Day>
</DateRevised>
<Article PubModel="Print-Electronic">
<Journal>
<ISSN IssnType="Electronic">1474-5488</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>18</Volume>
<Issue>9</Issue>
<PubDate>
<Year>2017</Year>
<Month>Sep</Month>
</PubDate>
</JournalIssue>
<Title>The Lancet. Oncology</Title>
<ISOAbbreviation>Lancet Oncol.</ISOAbbreviation>
</Journal>
<ArticleTitle>Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis.</ArticleTitle>
<Pagination>
<MedlinePgn>1221-1237</MedlinePgn>
</Pagination>
<ELocationID EIdType="pii" ValidYN="Y">S1470-2045(17)30458-8</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/S1470-2045(17)30458-8</ELocationID>
<Abstract>
<AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials.</AbstractText>
<AbstractText Label="METHODS" NlmCategory="METHODS">For this updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered fractionation radiotherapy (comparison 1) or conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone (comparison 2). Eligible trials had to start randomisation on or after Jan 1, 1970, and completed accrual before Dec 31, 2010; had to have been randomised in a way that precluded prior knowledge of treatment assignment; and had to include patients with non-metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing first-line curative treatment. Trials including a non-conventional radiotherapy control group, investigating hypofractionated radiotherapy, or including mostly nasopharyngeal carcinomas were excluded. Trials were grouped in three types of altered fractionation: hyperfractionated, moderately accelerated, and very accelerated. Individual patient data were collected and combined with a fixed-effects model based on the intention-to-treat principle. The primary endpoint was overall survival.</AbstractText>
<AbstractText Label="FINDINGS" NlmCategory="RESULTS">Comparison 1 (conventional fractionation radiotherapy vs altered fractionation radiotherapy) included 33 trials and 11 423 patients. Altered fractionation radiotherapy was associated with a significant benefit on overall survival (hazard ratio [HR] 0·94, 95% CI 0·90-0·98; p=0·0033), with an absolute difference at 5 years of 3·1% (95% CI 1·3-4·9) and at 10 years of 1·2% (-0·8 to 3·2). We found a significant interaction (p=0·051) between type of fractionation and treatment effect, the overall survival benefit being restricted to the hyperfractionated group (HR 0·83, 0·74-0·92), with absolute differences at 5 years of 8·1% (3·4 to 12·8) and at 10 years of 3·9% (-0·6 to 8·4). Comparison 2 (conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone) included five trials and 986 patients. Overall survival was significantly worse with altered fractionation radiotherapy compared with concomitant chemoradiotherapy (HR 1·22, 1·05-1·42; p=0·0098), with absolute differences at 5 years of -5·8% (-11·9 to 0·3) and at 10 years of -5·1% (-13·0 to 2·8).</AbstractText>
<AbstractText Label="INTERPRETATION" NlmCategory="CONCLUSIONS">This update confirms, with more patients and a longer follow-up than the first version of MARCH, that hyperfractionated radiotherapy is, along with concomitant chemoradiotherapy, a standard of care for the treatment of locally advanced head and neck squamous cell cancers. The comparison between hyperfractionated radiotherapy and concomitant chemoradiotherapy remains to be specifically tested.</AbstractText>
<AbstractText Label="FUNDING" NlmCategory="BACKGROUND">Institut National du Cancer; and Ligue Nationale Contre le Cancer.</AbstractText>
<CopyrightInformation>Copyright © 2017 Elsevier Ltd. All rights reserved.</CopyrightInformation>
</Abstract>
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<Author ValidYN="Y">
<LastName>Lacas</LastName>
<ForeName>Benjamin</ForeName>
<Initials>B</Initials>
<AffiliationInfo>
<Affiliation>Ligue Nationale Contre le Cancer Meta-Analysis Platform, Service de Biostatistique et d'Epidémiologie, Gustave Roussy Cancer Campus, INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Bourhis</LastName>
<ForeName>Jean</ForeName>
<Initials>J</Initials>
<AffiliationInfo>
<Affiliation>Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.</Affiliation>
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</Author>
<Author ValidYN="Y">
<LastName>Overgaard</LastName>
<ForeName>Jens</ForeName>
<Initials>J</Initials>
<AffiliationInfo>
<Affiliation>Department of Experimental Clinical Oncology, Aarhus, Denmark.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Zhang</LastName>
<ForeName>Qiang</ForeName>
<Initials>Q</Initials>
<AffiliationInfo>
<Affiliation>NRG Oncology Statistics and Data Management Center (formerly RTOG), Philadelphia, PA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Grégoire</LastName>
<ForeName>Vincent</ForeName>
<Initials>V</Initials>
<AffiliationInfo>
<Affiliation>Radiation Oncology Department, UCL-Cliniques Universitaires St-Luc, Brussels, Belgium.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Nankivell</LastName>
<ForeName>Matthew</ForeName>
<Initials>M</Initials>
<AffiliationInfo>
<Affiliation>Medical Research Council Clinical Trials Unit, University College London, London, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Zackrisson</LastName>
<ForeName>Björn</ForeName>
<Initials>B</Initials>
<AffiliationInfo>
<Affiliation>Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Szutkowski</LastName>
<ForeName>Zbigniew</ForeName>
<Initials>Z</Initials>
<AffiliationInfo>
<Affiliation>Department of Radiotherapy, Cancer Center, Marie Curie-Sklodowska Memorial Institute, Warsaw, Poland.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Suwiński</LastName>
<ForeName>Rafał</ForeName>
<Initials>R</Initials>
<AffiliationInfo>
<Affiliation>Radiotherapy and Chemotherapy Clinic and Teaching Hospital, Marie Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Poulsen</LastName>
<ForeName>Michael</ForeName>
<Initials>M</Initials>
<AffiliationInfo>
<Affiliation>Radiation Oncology Services, Mater Centre, Brisbane, QLD, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>O'Sullivan</LastName>
<ForeName>Brian</ForeName>
<Initials>B</Initials>
<AffiliationInfo>
<Affiliation>Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Corvò</LastName>
<ForeName>Renzo</ForeName>
<Initials>R</Initials>
<AffiliationInfo>
<Affiliation>IRCCS San Martino-IST, Genoa, Italy.</Affiliation>
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<Author ValidYN="Y">
<LastName>Laskar</LastName>
<ForeName>Sarbani Ghosh</ForeName>
<Initials>SG</Initials>
<AffiliationInfo>
<Affiliation>Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, India.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Fallai</LastName>
<ForeName>Carlo</ForeName>
<Initials>C</Initials>
<AffiliationInfo>
<Affiliation>Department of Radiotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Yamazaki</LastName>
<ForeName>Hideya</ForeName>
<Initials>H</Initials>
<AffiliationInfo>
<Affiliation>Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Dobrowsky</LastName>
<ForeName>Werner</ForeName>
<Initials>W</Initials>
<AffiliationInfo>
<Affiliation>Department of Clinical Oncology, Freeman Hospital, Newcastle, UK.</Affiliation>
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<LastName>Cho</LastName>
<ForeName>Kwan Ho</ForeName>
<Initials>KH</Initials>
<AffiliationInfo>
<Affiliation>Proton Therapy Center, Research Institute and Hospital, National Cancer Center, Goyang, South Korea.</Affiliation>
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<Author ValidYN="Y">
<LastName>Garden</LastName>
<ForeName>Adam S</ForeName>
<Initials>AS</Initials>
<AffiliationInfo>
<Affiliation>Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.</Affiliation>
</AffiliationInfo>
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<LastName>Langendijk</LastName>
<ForeName>Johannes A</ForeName>
<Initials>JA</Initials>
<AffiliationInfo>
<Affiliation>Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.</Affiliation>
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</Author>
<Author ValidYN="Y">
<LastName>Viegas</LastName>
<ForeName>Celia Maria Pais</ForeName>
<Initials>CMP</Initials>
<AffiliationInfo>
<Affiliation>Radiation Oncology Department, Instituto Nacional de Cancer, Brasil National Cancer Institute, Rio de Janeiro, Brazil.</Affiliation>
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</Author>
<Author ValidYN="Y">
<LastName>Hay</LastName>
<ForeName>John</ForeName>
<Initials>J</Initials>
<AffiliationInfo>
<Affiliation>Division of Radiation Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Lotayef</LastName>
<ForeName>Mohamed</ForeName>
<Initials>M</Initials>
<AffiliationInfo>
<Affiliation>Radiation Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt.</Affiliation>
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</Author>
<Author ValidYN="Y">
<LastName>Parmar</LastName>
<ForeName>Mahesh K B</ForeName>
<Initials>MKB</Initials>
<AffiliationInfo>
<Affiliation>Medical Research Council Clinical Trials Unit, University College London, London, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Aupérin</LastName>
<ForeName>Anne</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>Ligue Nationale Contre le Cancer Meta-Analysis Platform, Service de Biostatistique et d'Epidémiologie, Gustave Roussy Cancer Campus, INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.</Affiliation>
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</Author>
<Author ValidYN="Y">
<LastName>van Herpen</LastName>
<ForeName>Carla</ForeName>
<Initials>C</Initials>
<AffiliationInfo>
<Affiliation>Department of Medical Oncology, Radboud University Medical Center, Nijmegen, Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Maingon</LastName>
<ForeName>Philippe</ForeName>
<Initials>P</Initials>
<AffiliationInfo>
<Affiliation>European Organisation for Research and Treatment of Cancer, Radiation Oncology Group, Brussels, Belgium; Service d'Oncologie, Radiothérapie, Hôpitaux Universitaires Pitié Salpêtrière, Charles Foix, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Trotti</LastName>
<ForeName>Andy M</ForeName>
<Initials>AM</Initials>
<AffiliationInfo>
<Affiliation>Moffitt Cancer Center, Department of Radiation Oncology, Tampa, FL, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Grau</LastName>
<ForeName>Cai</ForeName>
<Initials>C</Initials>
<AffiliationInfo>
<Affiliation>Department of Experimental Clinical Oncology, Aarhus, Denmark.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Pignon</LastName>
<ForeName>Jean-Pierre</ForeName>
<Initials>JP</Initials>
<AffiliationInfo>
<Affiliation>Ligue Nationale Contre le Cancer Meta-Analysis Platform, Service de Biostatistique et d'Epidémiologie, Gustave Roussy Cancer Campus, INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France. Electronic address: jean-pierre.pignon@gustaveroussy.fr.</Affiliation>
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</Author>
<Author ValidYN="Y">
<LastName>Blanchard</LastName>
<ForeName>Pierre</ForeName>
<Initials>P</Initials>
<AffiliationInfo>
<Affiliation>Department of Radiation Therapy, Gustave Roussy Cancer Campus, INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<CollectiveName>MARCH Collaborative Group</CollectiveName>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y">
<Grant>
<GrantID>U10 CA180822</GrantID>
<Acronym>CA</Acronym>
<Agency>NCI NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant>
<GrantID>U10 CA180868</GrantID>
<Acronym>CA</Acronym>
<Agency>NCI NIH HHS</Agency>
<Country>United States</Country>
</Grant>
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<PublicationTypeList>
<PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D017418">Meta-Analysis</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic">
<Year>2017</Year>
<Month>07</Month>
<Day>27</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo>
<Country>England</Country>
<MedlineTA>Lancet Oncol</MedlineTA>
<NlmUniqueID>100957246</NlmUniqueID>
<ISSNLinking>1470-2045</ISSNLinking>
</MedlineJournalInfo>
<SupplMeshList>
<SupplMeshName Type="Disease" UI="C535575">Carcinoma, squamous cell of head and neck</SupplMeshName>
</SupplMeshList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList>
<MeshHeading>
<DescriptorName UI="D002294" MajorTopicYN="N">Carcinoma, Squamous Cell</DescriptorName>
<QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
<QualifierName UI="Q000532" MajorTopicYN="Y">radiotherapy</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D019583" MajorTopicYN="Y">Dose Fractionation</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D006258" MajorTopicYN="N">Head and Neck Neoplasms</DescriptorName>
<QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
<QualifierName UI="Q000532" MajorTopicYN="Y">radiotherapy</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
</MeshHeadingList>
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<ForeName>Pierre</ForeName>
<Initials>P</Initials>
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<Investigator ValidYN="Y">
<LastName>Bourhis</LastName>
<ForeName>Jean</ForeName>
<Initials>J</Initials>
</Investigator>
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<LastName>Lacas</LastName>
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<Initials>B</Initials>
</Investigator>
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<ForeName>Jean Pierre</ForeName>
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</Investigator>
<Investigator ValidYN="Y">
<LastName>Bernier</LastName>
<ForeName>Jacques</ForeName>
<Initials>J</Initials>
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<ForeName>Quynh-Thu</ForeName>
<Initials>QT</Initials>
</Investigator>
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<ForeName>Jens</ForeName>
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<ForeName>Masheh Kb</ForeName>
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<Initials>B</Initials>
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<Initials>J</Initials>
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