The University of Southampton
University of Southampton Institutional Repository

Pathologic lymph node regression after neoadjuvant chemotherapy predicts recurrence and survival in esophageal adenocarcinoma: a multicenter study in the United Kingdom

Pathologic lymph node regression after neoadjuvant chemotherapy predicts recurrence and survival in esophageal adenocarcinoma: a multicenter study in the United Kingdom
Pathologic lymph node regression after neoadjuvant chemotherapy predicts recurrence and survival in esophageal adenocarcinoma: a multicenter study in the United Kingdom

PURPOSEThere is limited evidence regarding the prognostic effects of pathologic lymph node (LN) regression after neoadjuvant chemotherapy for esophageal adenocarcinoma, and a definition of LN response is lacking. This study aimed to evaluate how LN regression influences survival after surgery for esophageal adenocarcinoma.METHODSMulticenter cohort study of patients with esophageal adenocarcinoma treated with neoadjuvant chemotherapy followed by surgical resection at five high-volume centers in the United Kingdom. LNs retrieved at esophagectomy were examined for chemotherapy response and given a LN regression score (LNRS) - LNRS 1, complete response; 2, <10% residual tumor; 3, 10%-50% residual tumor; 4, >50% residual tumor; and 5, no response. Survival analysis was performed using Cox regression adjusting for confounders including primary tumor regression. The discriminatory ability of different LN response classifications to predict survival was evaluated using Akaike information criterion and Harrell C-index.RESULTSIn total, 17,930 LNs from 763 patients were examined. LN response classified as complete LN response (LNRS 1 ≥1 LN, no residual tumor in any LN; n = 62, 8.1%), partial LN response (LNRS 1-3 ≥1 LN, residual tumor ≥1 LN; n = 155, 20.3%), poor/no LN response (LNRS 4-5; n = 303, 39.7%), or LN negative (no tumor/regression; n = 243, 31.8%) demonstrated superior discriminatory ability. Mortality was reduced in patients with complete LN response (hazard ratio [HR], 0.35; 95% CI, 0.22 to 0.56), partial LN response (HR, 0.72; 95% CI, 0.57 to 0.93) or negative LNs (HR, 0.32; 95% CI, 0.25 to 0.42) compared with those with poor/no LN response. Primary tumor regression and LN regression were discordant in 165 patients (21.9%).CONCLUSIONPathologic LN regression after neoadjuvant chemotherapy was a strong prognostic factor and provides important information beyond pathologic TNM staging and primary tumor regression grading. LN regression should be included as standard in the pathologic reporting of esophagectomy specimens.

1527-7755
4522-4534
Moore, Jonathan L.
c8cf03a1-0a93-4e59-b785-2aa07a2d1545
Green, Michael
6ce35696-c13e-4c2b-9d5e-d1003d619a56
Santaolalla, Aida
bc60bea1-4d43-4ce4-839f-c1122076ae1f
Deere, Harriet
c46959c0-22dc-49c0-bb9e-89315af0b6ab
Evans, Richard
bb7870f5-bebf-468a-8f00-21fe5a1c86f3
Elshafie, Mona
7a1c12c2-12ba-4e21-9031-c55271b3cc82
Lavery, Anita
8f8138da-a83b-4a9d-a8d8-9ec3056eaf32
McGuigan, Andrew
eb945711-ce2d-4c7d-99d5-bcf3e2152344
Douglas, Rosalie
def139dd-0132-4aaa-a71e-0ed3bd665b35
Horne, Joanne
7769949c-aa66-4aa9-98b5-3153ea734875
Walker, Robert C.
c8fbfe1c-349d-497f-b24e-0295c84c4634
Mir, Hira
a84f2896-23ae-4298-85c2-82168f2f117d
Terlizzo, Monica
657b6616-58a9-4e13-b7b2-54779127cb34
Kamarajah, Sivesh K.
4729d9c0-d5de-40a8-bd0c-9097b0ce7e4c
Van Hemelrijck, Mieke
da132489-5270-4a1d-a6ad-1dc4b440f630
Maisey, Nick
9ea36448-8f66-46c5-9ebf-27af07416679
Sita-Lumsden, Alisa
b745a833-ebe5-41d9-8470-1650fc301262
Ngan, Sarah
dc0ba7b6-a975-4c58-9cfa-1fbdcd53a515
Kelly, Mark
e40e2b8e-6eb7-437a-93cf-fbd5d0be8b67
Baker, Cara R.
b9e35593-89cf-4e70-a28a-70e45f39c5c1
Kumar, Sacheen
0cc30cfc-02e1-421f-ab06-38529cbb155e
Lagergren, Jesper
bb341a6a-a7de-4818-adaf-2dc4b4877c5e
Allum, William H.
88d7f205-0f96-47bd-9512-6a80331fb2b8
Gossage, James A.
c4dc214b-fde6-4a1d-9f0c-69f6496dfea6
Griffiths, Ewen A.
8ff12fdd-b682-493a-b56f-a96c6206cb2c
Grabsch, Heike I.
57b3b84e-f4d2-40b9-ada4-5bbf207fea44
Turkington, Richard C.
af72b0f2-b344-4771-b5cd-e21ceb11c547
Underwood, Timothy
8e81bf60-edd2-4b0e-8324-3068c95ea1c6
Smyth, Elizabeth C.
40c91a49-5835-49a8-b2d2-1eb906835df4
Fitzgerald, Rebecca C.
e5724cec-6f06-4b20-bcdd-9d5fe95b1131
Cunningham, David
c7d35cdf-e964-4c60-8d1b-fd18ad81cb25
Davies, Andrew R.
f8d36713-01f7-4e37-8f91-5fe6c3b466cc
Moore, Jonathan L.
c8cf03a1-0a93-4e59-b785-2aa07a2d1545
Green, Michael
6ce35696-c13e-4c2b-9d5e-d1003d619a56
Santaolalla, Aida
bc60bea1-4d43-4ce4-839f-c1122076ae1f
Deere, Harriet
c46959c0-22dc-49c0-bb9e-89315af0b6ab
Evans, Richard
bb7870f5-bebf-468a-8f00-21fe5a1c86f3
Elshafie, Mona
7a1c12c2-12ba-4e21-9031-c55271b3cc82
Lavery, Anita
8f8138da-a83b-4a9d-a8d8-9ec3056eaf32
McGuigan, Andrew
eb945711-ce2d-4c7d-99d5-bcf3e2152344
Douglas, Rosalie
def139dd-0132-4aaa-a71e-0ed3bd665b35
Horne, Joanne
7769949c-aa66-4aa9-98b5-3153ea734875
Walker, Robert C.
c8fbfe1c-349d-497f-b24e-0295c84c4634
Mir, Hira
a84f2896-23ae-4298-85c2-82168f2f117d
Terlizzo, Monica
657b6616-58a9-4e13-b7b2-54779127cb34
Kamarajah, Sivesh K.
4729d9c0-d5de-40a8-bd0c-9097b0ce7e4c
Van Hemelrijck, Mieke
da132489-5270-4a1d-a6ad-1dc4b440f630
Maisey, Nick
9ea36448-8f66-46c5-9ebf-27af07416679
Sita-Lumsden, Alisa
b745a833-ebe5-41d9-8470-1650fc301262
Ngan, Sarah
dc0ba7b6-a975-4c58-9cfa-1fbdcd53a515
Kelly, Mark
e40e2b8e-6eb7-437a-93cf-fbd5d0be8b67
Baker, Cara R.
b9e35593-89cf-4e70-a28a-70e45f39c5c1
Kumar, Sacheen
0cc30cfc-02e1-421f-ab06-38529cbb155e
Lagergren, Jesper
bb341a6a-a7de-4818-adaf-2dc4b4877c5e
Allum, William H.
88d7f205-0f96-47bd-9512-6a80331fb2b8
Gossage, James A.
c4dc214b-fde6-4a1d-9f0c-69f6496dfea6
Griffiths, Ewen A.
8ff12fdd-b682-493a-b56f-a96c6206cb2c
Grabsch, Heike I.
57b3b84e-f4d2-40b9-ada4-5bbf207fea44
Turkington, Richard C.
af72b0f2-b344-4771-b5cd-e21ceb11c547
Underwood, Timothy
8e81bf60-edd2-4b0e-8324-3068c95ea1c6
Smyth, Elizabeth C.
40c91a49-5835-49a8-b2d2-1eb906835df4
Fitzgerald, Rebecca C.
e5724cec-6f06-4b20-bcdd-9d5fe95b1131
Cunningham, David
c7d35cdf-e964-4c60-8d1b-fd18ad81cb25
Davies, Andrew R.
f8d36713-01f7-4e37-8f91-5fe6c3b466cc

Moore, Jonathan L., Green, Michael, Santaolalla, Aida, Deere, Harriet, Evans, Richard, Elshafie, Mona, Lavery, Anita, McGuigan, Andrew, Douglas, Rosalie, Horne, Joanne, Walker, Robert C., Mir, Hira, Terlizzo, Monica, Kamarajah, Sivesh K., Van Hemelrijck, Mieke, Maisey, Nick, Sita-Lumsden, Alisa, Ngan, Sarah, Kelly, Mark, Baker, Cara R., Kumar, Sacheen, Lagergren, Jesper, Allum, William H., Gossage, James A., Griffiths, Ewen A., Grabsch, Heike I., Turkington, Richard C., Underwood, Timothy, Smyth, Elizabeth C., Fitzgerald, Rebecca C., Cunningham, David and Davies, Andrew R. (2023) Pathologic lymph node regression after neoadjuvant chemotherapy predicts recurrence and survival in esophageal adenocarcinoma: a multicenter study in the United Kingdom. Journal of Clinical Oncology, 41 (28), 4522-4534. (doi:10.1200/JCO.23.00139).

Record type: Article

Abstract

PURPOSEThere is limited evidence regarding the prognostic effects of pathologic lymph node (LN) regression after neoadjuvant chemotherapy for esophageal adenocarcinoma, and a definition of LN response is lacking. This study aimed to evaluate how LN regression influences survival after surgery for esophageal adenocarcinoma.METHODSMulticenter cohort study of patients with esophageal adenocarcinoma treated with neoadjuvant chemotherapy followed by surgical resection at five high-volume centers in the United Kingdom. LNs retrieved at esophagectomy were examined for chemotherapy response and given a LN regression score (LNRS) - LNRS 1, complete response; 2, <10% residual tumor; 3, 10%-50% residual tumor; 4, >50% residual tumor; and 5, no response. Survival analysis was performed using Cox regression adjusting for confounders including primary tumor regression. The discriminatory ability of different LN response classifications to predict survival was evaluated using Akaike information criterion and Harrell C-index.RESULTSIn total, 17,930 LNs from 763 patients were examined. LN response classified as complete LN response (LNRS 1 ≥1 LN, no residual tumor in any LN; n = 62, 8.1%), partial LN response (LNRS 1-3 ≥1 LN, residual tumor ≥1 LN; n = 155, 20.3%), poor/no LN response (LNRS 4-5; n = 303, 39.7%), or LN negative (no tumor/regression; n = 243, 31.8%) demonstrated superior discriminatory ability. Mortality was reduced in patients with complete LN response (hazard ratio [HR], 0.35; 95% CI, 0.22 to 0.56), partial LN response (HR, 0.72; 95% CI, 0.57 to 0.93) or negative LNs (HR, 0.32; 95% CI, 0.25 to 0.42) compared with those with poor/no LN response. Primary tumor regression and LN regression were discordant in 165 patients (21.9%).CONCLUSIONPathologic LN regression after neoadjuvant chemotherapy was a strong prognostic factor and provides important information beyond pathologic TNM staging and primary tumor regression grading. LN regression should be included as standard in the pathologic reporting of esophagectomy specimens.

Text
Lymph Node Regression AAM - Accepted Manuscript
Download (3MB)

More information

Accepted/In Press date: 16 May 2023
e-pub ahead of print date: 27 July 2023
Published date: 1 October 2023
Additional Information: Funding Information: There were no study specific sources of funding. OCCAMS was funded by a Program Grant from Cancer Research UK (RG66287, A15874). OCCAMS2 was funded by a Program Grant from Cancer Research UK (RG81771/RG84119, A22720/A22131). Publisher Copyright: © American Society of Clinical Oncology.

Identifiers

Local EPrints ID: 478776
URI: http://eprints.soton.ac.uk/id/eprint/478776
ISSN: 1527-7755
PURE UUID: 746712b6-e32c-4349-9b02-a8a190466362
ORCID for Timothy Underwood: ORCID iD orcid.org/0000-0001-9455-2188

Catalogue record

Date deposited: 10 Jul 2023 16:35
Last modified: 16 May 2024 04:01

Export record

Altmetrics

Contributors

Author: Jonathan L. Moore
Author: Michael Green
Author: Aida Santaolalla
Author: Harriet Deere
Author: Richard Evans
Author: Mona Elshafie
Author: Anita Lavery
Author: Andrew McGuigan
Author: Rosalie Douglas
Author: Joanne Horne
Author: Robert C. Walker
Author: Hira Mir
Author: Monica Terlizzo
Author: Sivesh K. Kamarajah
Author: Mieke Van Hemelrijck
Author: Nick Maisey
Author: Alisa Sita-Lumsden
Author: Sarah Ngan
Author: Mark Kelly
Author: Cara R. Baker
Author: Sacheen Kumar
Author: Jesper Lagergren
Author: William H. Allum
Author: James A. Gossage
Author: Ewen A. Griffiths
Author: Heike I. Grabsch
Author: Richard C. Turkington
Author: Elizabeth C. Smyth
Author: Rebecca C. Fitzgerald
Author: David Cunningham
Author: Andrew R. Davies

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×