Chemoradiotherapy, with adjuvant surgery for local control, confers a durable survival advantage in adenocarcinoma and squamous cell carcinoma of the oesophagus
Abstract Introduction Oesophageal cancer usually presents with systemic disease, necessitating systemic therapy. Neo-adjuvant chemoradiotherapy improves short-term survival, but its long-term impact is disputed because of limited accrual, treatment-protocol heterogeneity and a short follow-up of ran...
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description | Abstract Introduction Oesophageal cancer usually presents with systemic disease, necessitating systemic therapy. Neo-adjuvant chemoradiotherapy improves short-term survival, but its long-term impact is disputed because of limited accrual, treatment-protocol heterogeneity and a short follow-up of randomised trials. Aims Long-term results of two simultaneous randomised controlled trials (RCTs) comparing neo-adjuvant chemo-radiotherapy and surgery (MMT) with surgical monotherapy were examined, and the response of adenocarcinoma (AC) and squamous cell carcinoma (SCC) to identical regimens compared. Methods Between 1990 and 1997, two RCTs were undertaken on 211 patients. Patients with AC ( n = 113) or SCC ( n = 98) were separately-randomised to identical protocols of MMT or surgical monotherapy. Results 211 patients were followed to 206 months; 104 patients were randomised to MMT (58 AC and 46 SCC, respectively) and 107 to surgery. MMT provided a significant survival-advantage over surgical monotherapy for AC ( P = 0.004), SCC ( P = 0.01). There was a 54% relative risk-reduction in lymph-node metastasis following MMT, compared with surgery (64% versus 29%, P < 0.001). MMT produced a pathologic complete response (pCR) in 25% and 31% of AC and SCC, respectively. Survival advantage accrued to MMT, pCR and node-negative patients: AC pCR versus surgical monotherapy ( P = 0.001); residual disease following MMT versus surgical monotherapy ( P = 0.008); SCC pCR versus surgical monotherapy ( P = 0.033). Conclusions A survival advantage for MMT persisted long-term in AC and was replicated in SCC. MMT produced loco-regional tumour down-staging to extinction in 25–31% of patients, potentially permitting personalised treatment in this cohort that avoids the morbidity and mortality associated with resection. Node-negative patients with residual localised disease following MMT had a survival advantage over node-negative patients following surgery alone, supporting a systemic effect on micro-metastatic disease. |
doi_str_mv | 10.1016/j.ejca.2013.12.022 |
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Neo-adjuvant chemoradiotherapy improves short-term survival, but its long-term impact is disputed because of limited accrual, treatment-protocol heterogeneity and a short follow-up of randomised trials. Aims Long-term results of two simultaneous randomised controlled trials (RCTs) comparing neo-adjuvant chemo-radiotherapy and surgery (MMT) with surgical monotherapy were examined, and the response of adenocarcinoma (AC) and squamous cell carcinoma (SCC) to identical regimens compared. Methods Between 1990 and 1997, two RCTs were undertaken on 211 patients. Patients with AC ( n = 113) or SCC ( n = 98) were separately-randomised to identical protocols of MMT or surgical monotherapy. Results 211 patients were followed to 206 months; 104 patients were randomised to MMT (58 AC and 46 SCC, respectively) and 107 to surgery. MMT provided a significant survival-advantage over surgical monotherapy for AC ( P = 0.004), SCC ( P = 0.01). There was a 54% relative risk-reduction in lymph-node metastasis following MMT, compared with surgery (64% versus 29%, P < 0.001). MMT produced a pathologic complete response (pCR) in 25% and 31% of AC and SCC, respectively. Survival advantage accrued to MMT, pCR and node-negative patients: AC pCR versus surgical monotherapy ( P = 0.001); residual disease following MMT versus surgical monotherapy ( P = 0.008); SCC pCR versus surgical monotherapy ( P = 0.033). Conclusions A survival advantage for MMT persisted long-term in AC and was replicated in SCC. MMT produced loco-regional tumour down-staging to extinction in 25–31% of patients, potentially permitting personalised treatment in this cohort that avoids the morbidity and mortality associated with resection. Node-negative patients with residual localised disease following MMT had a survival advantage over node-negative patients following surgery alone, supporting a systemic effect on micro-metastatic disease.</description><identifier>ISSN: 0959-8049</identifier><identifier>EISSN: 1879-0852</identifier><identifier>DOI: 10.1016/j.ejca.2013.12.022</identifier><identifier>PMID: 24480403</identifier><language>eng</language><publisher>Kidlington: Elsevier</publisher><subject>Adenocarcinoma - surgery ; Adenocarcinoma - therapy ; Adult ; Aged ; Biological and medical sciences ; Carcinoma, Squamous Cell - surgery ; Carcinoma, Squamous Cell - therapy ; Chemoradiotherapy ; Cohort Studies ; Combined Modality Therapy ; Esophageal Neoplasms - surgery ; Esophageal Neoplasms - therapy ; Esophagus - drug effects ; Esophagus - radiation effects ; Esophagus - surgery ; Female ; Follow-Up Studies ; Hematology, Oncology and Palliative Medicine ; Humans ; Lymphatic Metastasis ; Male ; Medical sciences ; Middle Aged ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Pharmacology. Drug treatments ; Randomized Controlled Trials as Topic ; Survival Analysis ; Treatment Outcome ; Tumors</subject><ispartof>European journal of cancer (1990), 2014-04, Vol.50 (6), p.1065-1075</ispartof><rights>Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2014 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c388t-d3c2a2b74a32d1fd8616f928414f73c14c76420bd106bedb25f27e7c7114cf993</citedby><cites>FETCH-LOGICAL-c388t-d3c2a2b74a32d1fd8616f928414f73c14c76420bd106bedb25f27e7c7114cf993</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28800482$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24480403$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bass, G.A</creatorcontrib><creatorcontrib>Furlong, H</creatorcontrib><creatorcontrib>O’Sullivan, K.E</creatorcontrib><creatorcontrib>Hennessy, T.P.J</creatorcontrib><creatorcontrib>Walsh, T.N</creatorcontrib><title>Chemoradiotherapy, with adjuvant surgery for local control, confers a durable survival advantage in adenocarcinoma and squamous cell carcinoma of the oesophagus</title><title>European journal of cancer (1990)</title><addtitle>Eur J Cancer</addtitle><description>Abstract Introduction Oesophageal cancer usually presents with systemic disease, necessitating systemic therapy. Neo-adjuvant chemoradiotherapy improves short-term survival, but its long-term impact is disputed because of limited accrual, treatment-protocol heterogeneity and a short follow-up of randomised trials. Aims Long-term results of two simultaneous randomised controlled trials (RCTs) comparing neo-adjuvant chemo-radiotherapy and surgery (MMT) with surgical monotherapy were examined, and the response of adenocarcinoma (AC) and squamous cell carcinoma (SCC) to identical regimens compared. Methods Between 1990 and 1997, two RCTs were undertaken on 211 patients. Patients with AC ( n = 113) or SCC ( n = 98) were separately-randomised to identical protocols of MMT or surgical monotherapy. Results 211 patients were followed to 206 months; 104 patients were randomised to MMT (58 AC and 46 SCC, respectively) and 107 to surgery. MMT provided a significant survival-advantage over surgical monotherapy for AC ( P = 0.004), SCC ( P = 0.01). There was a 54% relative risk-reduction in lymph-node metastasis following MMT, compared with surgery (64% versus 29%, P < 0.001). MMT produced a pathologic complete response (pCR) in 25% and 31% of AC and SCC, respectively. Survival advantage accrued to MMT, pCR and node-negative patients: AC pCR versus surgical monotherapy ( P = 0.001); residual disease following MMT versus surgical monotherapy ( P = 0.008); SCC pCR versus surgical monotherapy ( P = 0.033). Conclusions A survival advantage for MMT persisted long-term in AC and was replicated in SCC. MMT produced loco-regional tumour down-staging to extinction in 25–31% of patients, potentially permitting personalised treatment in this cohort that avoids the morbidity and mortality associated with resection. Node-negative patients with residual localised disease following MMT had a survival advantage over node-negative patients following surgery alone, supporting a systemic effect on micro-metastatic disease.</description><subject>Adenocarcinoma - surgery</subject><subject>Adenocarcinoma - therapy</subject><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Squamous Cell - surgery</subject><subject>Carcinoma, Squamous Cell - therapy</subject><subject>Chemoradiotherapy</subject><subject>Cohort Studies</subject><subject>Combined Modality Therapy</subject><subject>Esophageal Neoplasms - surgery</subject><subject>Esophageal Neoplasms - therapy</subject><subject>Esophagus - drug effects</subject><subject>Esophagus - radiation effects</subject><subject>Esophagus - surgery</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</subject><subject>Pharmacology. Drug treatments</subject><subject>Randomized Controlled Trials as Topic</subject><subject>Survival Analysis</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><issn>0959-8049</issn><issn>1879-0852</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFks1u1DAUhSMEotPCC7BA3iCxaILtOImzQapGFJAqsQDW1o19PeOQxFM7GTRvw6PiaIay8s_9zvHVPc6yN4wWjLL6Q19gr6HglJUF4wXl_Fm2YbJpcyor_jzb0LZqc0lFe5Vdx9hTShsp6MvsiguRrmm5yf5s9zj6AMb5eY8BDqdb8tvNewKmX44wzSQuYYfhRKwPZPAaBqL9NAc_3K4biyESIGYJ0A24wkd3TAyYVQw7JG5KB5ySMmg3-REITIbExwVGv0SicUiOTzVvSeqDeIz-sIfdEl9lLywMEV9f1pvs5_2nH9sv-cO3z1-3dw-5LqWcc1NqDrxrBJTcMGtkzWrbcimYsE2pmdBNLTjtDKN1h6bjleUNNrphqWTbtrzJ3p99D8E_LhhnNbq4NgcTpj4Vq9LMaSVKkVB-RnXwMQa06hDcCOGkGFVrMqpXazJqTUYxrlIySfT24r90I5onyb8oEvDuAkBMU7YBJu3if05KSoVcjT6eOUzTODoMSg9ucknyC08Ye7-EKQ1KMRXTy-r7-gnWP8BEyp-KqvwLx5ywFQ</recordid><startdate>20140401</startdate><enddate>20140401</enddate><creator>Bass, G.A</creator><creator>Furlong, H</creator><creator>O’Sullivan, K.E</creator><creator>Hennessy, T.P.J</creator><creator>Walsh, T.N</creator><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20140401</creationdate><title>Chemoradiotherapy, with adjuvant surgery for local control, confers a durable survival advantage in adenocarcinoma and squamous cell carcinoma of the oesophagus</title><author>Bass, G.A ; Furlong, H ; O’Sullivan, K.E ; Hennessy, T.P.J ; Walsh, T.N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c388t-d3c2a2b74a32d1fd8616f928414f73c14c76420bd106bedb25f27e7c7114cf993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adenocarcinoma - surgery</topic><topic>Adenocarcinoma - therapy</topic><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Squamous Cell - surgery</topic><topic>Carcinoma, Squamous Cell - therapy</topic><topic>Chemoradiotherapy</topic><topic>Cohort Studies</topic><topic>Combined Modality Therapy</topic><topic>Esophageal Neoplasms - surgery</topic><topic>Esophageal Neoplasms - therapy</topic><topic>Esophagus - drug effects</topic><topic>Esophagus - radiation effects</topic><topic>Esophagus - surgery</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Lymphatic Metastasis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</topic><topic>Pharmacology. Drug treatments</topic><topic>Randomized Controlled Trials as Topic</topic><topic>Survival Analysis</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bass, G.A</creatorcontrib><creatorcontrib>Furlong, H</creatorcontrib><creatorcontrib>O’Sullivan, K.E</creatorcontrib><creatorcontrib>Hennessy, T.P.J</creatorcontrib><creatorcontrib>Walsh, T.N</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of cancer (1990)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bass, G.A</au><au>Furlong, H</au><au>O’Sullivan, K.E</au><au>Hennessy, T.P.J</au><au>Walsh, T.N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chemoradiotherapy, with adjuvant surgery for local control, confers a durable survival advantage in adenocarcinoma and squamous cell carcinoma of the oesophagus</atitle><jtitle>European journal of cancer (1990)</jtitle><addtitle>Eur J Cancer</addtitle><date>2014-04-01</date><risdate>2014</risdate><volume>50</volume><issue>6</issue><spage>1065</spage><epage>1075</epage><pages>1065-1075</pages><issn>0959-8049</issn><eissn>1879-0852</eissn><abstract>Abstract Introduction Oesophageal cancer usually presents with systemic disease, necessitating systemic therapy. Neo-adjuvant chemoradiotherapy improves short-term survival, but its long-term impact is disputed because of limited accrual, treatment-protocol heterogeneity and a short follow-up of randomised trials. Aims Long-term results of two simultaneous randomised controlled trials (RCTs) comparing neo-adjuvant chemo-radiotherapy and surgery (MMT) with surgical monotherapy were examined, and the response of adenocarcinoma (AC) and squamous cell carcinoma (SCC) to identical regimens compared. Methods Between 1990 and 1997, two RCTs were undertaken on 211 patients. Patients with AC ( n = 113) or SCC ( n = 98) were separately-randomised to identical protocols of MMT or surgical monotherapy. Results 211 patients were followed to 206 months; 104 patients were randomised to MMT (58 AC and 46 SCC, respectively) and 107 to surgery. MMT provided a significant survival-advantage over surgical monotherapy for AC ( P = 0.004), SCC ( P = 0.01). There was a 54% relative risk-reduction in lymph-node metastasis following MMT, compared with surgery (64% versus 29%, P < 0.001). MMT produced a pathologic complete response (pCR) in 25% and 31% of AC and SCC, respectively. Survival advantage accrued to MMT, pCR and node-negative patients: AC pCR versus surgical monotherapy ( P = 0.001); residual disease following MMT versus surgical monotherapy ( P = 0.008); SCC pCR versus surgical monotherapy ( P = 0.033). Conclusions A survival advantage for MMT persisted long-term in AC and was replicated in SCC. MMT produced loco-regional tumour down-staging to extinction in 25–31% of patients, potentially permitting personalised treatment in this cohort that avoids the morbidity and mortality associated with resection. Node-negative patients with residual localised disease following MMT had a survival advantage over node-negative patients following surgery alone, supporting a systemic effect on micro-metastatic disease.</abstract><cop>Kidlington</cop><pub>Elsevier</pub><pmid>24480403</pmid><doi>10.1016/j.ejca.2013.12.022</doi><tpages>11</tpages></addata></record> |
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subjects | Adenocarcinoma - surgery Adenocarcinoma - therapy Adult Aged Biological and medical sciences Carcinoma, Squamous Cell - surgery Carcinoma, Squamous Cell - therapy Chemoradiotherapy Cohort Studies Combined Modality Therapy Esophageal Neoplasms - surgery Esophageal Neoplasms - therapy Esophagus - drug effects Esophagus - radiation effects Esophagus - surgery Female Follow-Up Studies Hematology, Oncology and Palliative Medicine Humans Lymphatic Metastasis Male Medical sciences Middle Aged Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Pharmacology. Drug treatments Randomized Controlled Trials as Topic Survival Analysis Treatment Outcome Tumors |
title | Chemoradiotherapy, with adjuvant surgery for local control, confers a durable survival advantage in adenocarcinoma and squamous cell carcinoma of the oesophagus |
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