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Multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma

BACKGROUND: This multicentre cohort study sought to define a robust pathological indicator of clinically meaningful response to neoadjuvant chemotherapy in oesophageal adenocarcinoma. METHODS: A questionnaire was distributed to 11 UK upper gastrointestinal cancer centres to determine the use of asse...

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Autores principales: Noble, F, Lloyd, M A, Turkington, R, Griffiths, E, O'Donovan, M, O'Neill, J R, Mercer, S, Parsons, S L, Fitzgerald, R C, Underwood, T J, Noorani, A, Fels Elliott, R, Abdullahi, Z, de la Rue, R, Bornschein, J, MacRae, S, Nutzinger, B, Grehan, N, Contino, G, Crawte, J, Edwards, P A W, Miremadi, A, Malhotra, S, Hayden, A, Walker, R, Peters, C, Hannah, G, Hardwick, R, Davies, J, Ford, H, Gilligan, D, Safranek, P, Hindmarsh, A, Sujendran, V, Carroll, N, McManus, D, Hayes, S J, Ang, Y, Preston, S R, Oakes, S, Bagwan, I, Skipworth, R J E, Save, V, Hupp, T R, Puig, S, Bedford, M, Taniere, P, Whiting, J, Byrne, J, Kelly, J, Owsley, J, Crichton, C, Barr, H, Shepherd, N, Old, O, Lagergren, J, Gossage, J, Davies, A, Chang, F, Zylstra, J, Sanders, G, Berrisford, R, Harden, C, Bunting, D, Lewis, M, Cheong, E, Kumar, B, Saunders, J H, Soomro, I N, Vohra, R, Duffy, J, Kaye, P, Grabowska, A, Lovat, L, Haidry, R, Eneh, V, Igali, L, Welch, I, Scott, M, Sothi, S, Suortamo, S, Lishman, S, Beardsmore, D, Sutaria, R, Secrier, M, Eldridge, M D, Bower, L, Lynch, A G, Tavaré, S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725679/
https://www.ncbi.nlm.nih.gov/pubmed/28944954
http://dx.doi.org/10.1002/bjs.10627
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author Noble, F
Lloyd, M A
Turkington, R
Griffiths, E
O'Donovan, M
O'Neill, J R
Mercer, S
Parsons, S L
Fitzgerald, R C
Underwood, T J
Noorani, A
Fels Elliott, R
Abdullahi, Z
de la Rue, R
Bornschein, J
MacRae, S
Nutzinger, B
Grehan, N
Contino, G
Crawte, J
Edwards, P A W
Miremadi, A
Malhotra, S
Hayden, A
Walker, R
Peters, C
Hannah, G
Hardwick, R
Davies, J
Ford, H
Gilligan, D
Safranek, P
Hindmarsh, A
Sujendran, V
Carroll, N
McManus, D
Hayes, S J
Ang, Y
Preston, S R
Oakes, S
Bagwan, I
Skipworth, R J E
Save, V
Hupp, T R
Puig, S
Bedford, M
Taniere, P
Whiting, J
Byrne, J
Kelly, J
Owsley, J
Crichton, C
Barr, H
Shepherd, N
Old, O
Lagergren, J
Gossage, J
Davies, A
Chang, F
Zylstra, J
Sanders, G
Berrisford, R
Harden, C
Bunting, D
Lewis, M
Cheong, E
Kumar, B
Saunders, J H
Soomro, I N
Vohra, R
Duffy, J
Kaye, P
Grabowska, A
Lovat, L
Haidry, R
Eneh, V
Igali, L
Welch, I
Scott, M
Sothi, S
Suortamo, S
Lishman, S
Beardsmore, D
Sutaria, R
Secrier, M
Eldridge, M D
Bower, L
Lynch, A G
Tavaré, S
author_facet Noble, F
Lloyd, M A
Turkington, R
Griffiths, E
O'Donovan, M
O'Neill, J R
Mercer, S
Parsons, S L
Fitzgerald, R C
Underwood, T J
Noorani, A
Fels Elliott, R
Abdullahi, Z
de la Rue, R
Bornschein, J
MacRae, S
Nutzinger, B
Grehan, N
Contino, G
Crawte, J
Edwards, P A W
Miremadi, A
Malhotra, S
Hayden, A
Walker, R
Peters, C
Hannah, G
Hardwick, R
Davies, J
Ford, H
Gilligan, D
Safranek, P
Hindmarsh, A
Sujendran, V
Carroll, N
McManus, D
Hayes, S J
Ang, Y
Preston, S R
Oakes, S
Bagwan, I
Skipworth, R J E
Save, V
Hupp, T R
Puig, S
Bedford, M
Taniere, P
Whiting, J
Byrne, J
Kelly, J
Owsley, J
Crichton, C
Barr, H
Shepherd, N
Old, O
Lagergren, J
Gossage, J
Davies, A
Chang, F
Zylstra, J
Sanders, G
Berrisford, R
Harden, C
Bunting, D
Lewis, M
Cheong, E
Kumar, B
Saunders, J H
Soomro, I N
Vohra, R
Duffy, J
Kaye, P
Grabowska, A
Lovat, L
Haidry, R
Eneh, V
Igali, L
Welch, I
Scott, M
Sothi, S
Suortamo, S
Lishman, S
Beardsmore, D
Sutaria, R
Secrier, M
Eldridge, M D
Bower, L
Lynch, A G
Tavaré, S
author_sort Noble, F
collection PubMed
description BACKGROUND: This multicentre cohort study sought to define a robust pathological indicator of clinically meaningful response to neoadjuvant chemotherapy in oesophageal adenocarcinoma. METHODS: A questionnaire was distributed to 11 UK upper gastrointestinal cancer centres to determine the use of assessment of response to neoadjuvant chemotherapy. Records of consecutive patients undergoing oesophagogastric resection at seven centres between January 2000 and December 2013 were reviewed. Pathological response to neoadjuvant chemotherapy was assessed using the Mandard Tumour Regression Grade (TRG) and lymph node downstaging. RESULTS: TRG (8 of 11 centres) was the most widely used system to assess response to neoadjuvant chemotherapy, but there was discordance on how it was used in practice. Of 1392 patients, 1293 had TRG assessment; data were available for clinical and pathological nodal status (cN and pN) in 981 patients, and TRG, cN and pN in 885. There was a significant difference in survival between responders (TRG 1–2; median overall survival (OS) not reached) and non-responders (TRG 3–5; median OS 2·22 (95 per cent c.i. 1·94 to 2·51) years; P < 0·001); the hazard ratio was 2·46 (95 per cent c.i. 1·22 to 4·95; P = 0·012). Among local non-responders, the presence of lymph node downstaging was associated with significantly improved OS compared with that of patients without lymph node downstaging (median OS not reached versus 1·92 (1·68 to 2·16) years; P < 0·001). CONCLUSION: A clinically meaningful local response to neoadjuvant chemotherapy was restricted to the small minority of patients (14·8 per cent) with TRG 1–2. Among local non-responders, a subset of patients (21·3 per cent) derived benefit from neoadjuvant chemotherapy by lymph node downstaging and their survival mirrored that of local responders.
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spelling pubmed-57256792017-12-12 Multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma Noble, F Lloyd, M A Turkington, R Griffiths, E O'Donovan, M O'Neill, J R Mercer, S Parsons, S L Fitzgerald, R C Underwood, T J Noorani, A Fels Elliott, R Abdullahi, Z de la Rue, R Bornschein, J MacRae, S Nutzinger, B Grehan, N Contino, G Crawte, J Edwards, P A W Miremadi, A Malhotra, S Hayden, A Walker, R Peters, C Hannah, G Hardwick, R Davies, J Ford, H Gilligan, D Safranek, P Hindmarsh, A Sujendran, V Carroll, N McManus, D Hayes, S J Ang, Y Preston, S R Oakes, S Bagwan, I Skipworth, R J E Save, V Hupp, T R Puig, S Bedford, M Taniere, P Whiting, J Byrne, J Kelly, J Owsley, J Crichton, C Barr, H Shepherd, N Old, O Lagergren, J Gossage, J Davies, A Chang, F Zylstra, J Sanders, G Berrisford, R Harden, C Bunting, D Lewis, M Cheong, E Kumar, B Saunders, J H Soomro, I N Vohra, R Duffy, J Kaye, P Grabowska, A Lovat, L Haidry, R Eneh, V Igali, L Welch, I Scott, M Sothi, S Suortamo, S Lishman, S Beardsmore, D Sutaria, R Secrier, M Eldridge, M D Bower, L Lynch, A G Tavaré, S Br J Surg Original Article BACKGROUND: This multicentre cohort study sought to define a robust pathological indicator of clinically meaningful response to neoadjuvant chemotherapy in oesophageal adenocarcinoma. METHODS: A questionnaire was distributed to 11 UK upper gastrointestinal cancer centres to determine the use of assessment of response to neoadjuvant chemotherapy. Records of consecutive patients undergoing oesophagogastric resection at seven centres between January 2000 and December 2013 were reviewed. Pathological response to neoadjuvant chemotherapy was assessed using the Mandard Tumour Regression Grade (TRG) and lymph node downstaging. RESULTS: TRG (8 of 11 centres) was the most widely used system to assess response to neoadjuvant chemotherapy, but there was discordance on how it was used in practice. Of 1392 patients, 1293 had TRG assessment; data were available for clinical and pathological nodal status (cN and pN) in 981 patients, and TRG, cN and pN in 885. There was a significant difference in survival between responders (TRG 1–2; median overall survival (OS) not reached) and non-responders (TRG 3–5; median OS 2·22 (95 per cent c.i. 1·94 to 2·51) years; P < 0·001); the hazard ratio was 2·46 (95 per cent c.i. 1·22 to 4·95; P = 0·012). Among local non-responders, the presence of lymph node downstaging was associated with significantly improved OS compared with that of patients without lymph node downstaging (median OS not reached versus 1·92 (1·68 to 2·16) years; P < 0·001). CONCLUSION: A clinically meaningful local response to neoadjuvant chemotherapy was restricted to the small minority of patients (14·8 per cent) with TRG 1–2. Among local non-responders, a subset of patients (21·3 per cent) derived benefit from neoadjuvant chemotherapy by lymph node downstaging and their survival mirrored that of local responders. Oxford University Press 2017-09-25 /pmc/articles/PMC5725679/ /pubmed/28944954 http://dx.doi.org/10.1002/bjs.10627 Text en © 2017 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by/4.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Article
Noble, F
Lloyd, M A
Turkington, R
Griffiths, E
O'Donovan, M
O'Neill, J R
Mercer, S
Parsons, S L
Fitzgerald, R C
Underwood, T J
Noorani, A
Fels Elliott, R
Abdullahi, Z
de la Rue, R
Bornschein, J
MacRae, S
Nutzinger, B
Grehan, N
Contino, G
Crawte, J
Edwards, P A W
Miremadi, A
Malhotra, S
Hayden, A
Walker, R
Peters, C
Hannah, G
Hardwick, R
Davies, J
Ford, H
Gilligan, D
Safranek, P
Hindmarsh, A
Sujendran, V
Carroll, N
McManus, D
Hayes, S J
Ang, Y
Preston, S R
Oakes, S
Bagwan, I
Skipworth, R J E
Save, V
Hupp, T R
Puig, S
Bedford, M
Taniere, P
Whiting, J
Byrne, J
Kelly, J
Owsley, J
Crichton, C
Barr, H
Shepherd, N
Old, O
Lagergren, J
Gossage, J
Davies, A
Chang, F
Zylstra, J
Sanders, G
Berrisford, R
Harden, C
Bunting, D
Lewis, M
Cheong, E
Kumar, B
Saunders, J H
Soomro, I N
Vohra, R
Duffy, J
Kaye, P
Grabowska, A
Lovat, L
Haidry, R
Eneh, V
Igali, L
Welch, I
Scott, M
Sothi, S
Suortamo, S
Lishman, S
Beardsmore, D
Sutaria, R
Secrier, M
Eldridge, M D
Bower, L
Lynch, A G
Tavaré, S
Multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma
title Multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma
title_full Multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma
title_fullStr Multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma
title_full_unstemmed Multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma
title_short Multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma
title_sort multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725679/
https://www.ncbi.nlm.nih.gov/pubmed/28944954
http://dx.doi.org/10.1002/bjs.10627
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