Tumour infiltrating lymphocytes and survival after adjuvant chemotherapy in patients with gastric cancer: post-hoc analysis of the CLASSIC trial.


Journal

British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635

Informations de publication

Date de publication:
06 2023
Historique:
received: 01 09 2022
accepted: 23 03 2023
revised: 16 03 2023
pmc-release: 07 04 2024
medline: 7 6 2023
pubmed: 8 4 2023
entrez: 7 4 2023
Statut: ppublish

Résumé

Only a subset of gastric cancer (GC) patients with stage II-III benefits from chemotherapy after surgery. Tumour infiltrating lymphocytes per area (TIL density) has been suggested as a potential predictive biomarker of chemotherapy benefit. We quantified TIL density in digital images of haematoxylin-eosin (HE) stained tissue using deep learning in 307 GC patients of the Yonsei Cancer Center (YCC) (193 surgery+adjuvant chemotherapy [S + C], 114 surgery alone [S]) and 629 CLASSIC trial GC patients (325 S + C and 304 S). The relationship between TIL density, disease-free survival (DFS) and clinicopathological variables was analysed. YCC S patients and CLASSIC S patients with high TIL density had longer DFS than S patients with low TIL density (P = 0.007 and P = 0.013, respectively). Furthermore, CLASSIC patients with low TIL density had longer DFS if treated with S + C compared to S (P = 0.003). No significant relationship of TIL density with other clinicopathological variables was found. This is the first study to suggest TIL density automatically quantified in routine HE stained tissue sections as a novel, clinically useful biomarker to identify stage II-III GC patients deriving benefit from adjuvant chemotherapy. Validation of our results in a prospective study is warranted.

Sections du résumé

BACKGROUND
Only a subset of gastric cancer (GC) patients with stage II-III benefits from chemotherapy after surgery. Tumour infiltrating lymphocytes per area (TIL density) has been suggested as a potential predictive biomarker of chemotherapy benefit.
METHODS
We quantified TIL density in digital images of haematoxylin-eosin (HE) stained tissue using deep learning in 307 GC patients of the Yonsei Cancer Center (YCC) (193 surgery+adjuvant chemotherapy [S + C], 114 surgery alone [S]) and 629 CLASSIC trial GC patients (325 S + C and 304 S). The relationship between TIL density, disease-free survival (DFS) and clinicopathological variables was analysed.
RESULTS
YCC S patients and CLASSIC S patients with high TIL density had longer DFS than S patients with low TIL density (P = 0.007 and P = 0.013, respectively). Furthermore, CLASSIC patients with low TIL density had longer DFS if treated with S + C compared to S (P = 0.003). No significant relationship of TIL density with other clinicopathological variables was found.
CONCLUSION
This is the first study to suggest TIL density automatically quantified in routine HE stained tissue sections as a novel, clinically useful biomarker to identify stage II-III GC patients deriving benefit from adjuvant chemotherapy. Validation of our results in a prospective study is warranted.

Identifiants

pubmed: 37029200
doi: 10.1038/s41416-023-02257-3
pii: 10.1038/s41416-023-02257-3
pmc: PMC10241786
doi:

Substances chimiques

Biomarkers 0

Types de publication

Clinical Trial Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2318-2325

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer Nature Limited.

Références

Front Immunol. 2019 Jan 29;10:71
pubmed: 30761139
J Clin Oncol. 2021 Sep 10;39(26):2903-2913
pubmed: 34133211
Cancer Med. 2021 Jul;10(14):4790-4795
pubmed: 34080777
Adv Anat Pathol. 2017 Nov;24(6):311-335
pubmed: 28777143
APMIS. 2018 Oct;126(10):814-821
pubmed: 30264431
Nature. 2014 Sep 11;513(7517):202-9
pubmed: 25079317
Ann Diagn Pathol. 2018 Aug;35:77-79
pubmed: 29886396
Lancet Oncol. 2021 Aug;22(8):1081-1092
pubmed: 34252374
Lancet Oncol. 2014 Nov;15(12):1389-96
pubmed: 25439693
Ann Surg. 2019 Aug;270(2):309-316
pubmed: 29727332
Ann Oncol. 2015 Feb;26(2):259-71
pubmed: 25214542
Ann Oncol. 2016 Sep;27(suppl 5):v38-v49
pubmed: 27664260
Lancet Oncol. 2016 Jun;17(6):717-726
pubmed: 27157491
Gastric Cancer. 2021 Jan;24(1):1-21
pubmed: 32060757
Lancet Oncol. 2018 May;19(5):629-638
pubmed: 29567071
Front Immunol. 2021 Jul 01;12:692859
pubmed: 34276684
Lancet Oncol. 2014 Jul;15(8):886-93
pubmed: 24954805
CA Cancer J Clin. 2021 May;71(3):209-249
pubmed: 33538338
JAMA Netw Open. 2022 Feb 01;5(2):e220426
pubmed: 35226081
Cancer Sci. 2019 Nov;110(11):3405-3414
pubmed: 31495054
Sci Rep. 2018 May 10;8(1):7485
pubmed: 29748589
In Vivo. 2018 Jan-Feb;32(1):151-158
pubmed: 29275313
Medicine (Baltimore). 2018 Jul;97(27):e11387
pubmed: 29979429
Gut. 2015 Nov;64(11):1721-31
pubmed: 25385008
BMJ Open. 2021 Jan 31;11(1):e044163
pubmed: 33518526
Oncotarget. 2017 Feb 7;8(6):9608-9616
pubmed: 28030810
Medicine (Baltimore). 2018 Aug;97(32):e11769
pubmed: 30095632
J Clin Oncol. 2011 Nov 20;29(33):4387-93
pubmed: 22010012
Ann Oncol. 2016 Mar;27(3):494-501
pubmed: 26673353
J Clin Oncol. 2015 Mar 20;33(9):983-91
pubmed: 25534375
Pathology. 2017 Oct;49(6):589-595
pubmed: 28843920
Nat Methods. 2019 Apr;16(4):351
pubmed: 30804552
J Clin Oncol. 2016 Apr 10;34(11):1223-30
pubmed: 26834066

Auteurs

Drolaiz H W Liu (DHW)

Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, The Netherlands.
Institute of Clinical Pathology and Molecular Pathology, Kepler University Hospital and Johannes Kepler University, Linz, Austria.

Young-Woo Kim (YW)

Department of Cancer Policy and Population Health, National Cancer Center Graduate School of Cancer Science and Policy and Center for Gastric Cancer and Department of Surgery, National Cancer Center, Goyang, Republic of Korea.

Nina Sefcovicova (N)

Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, The Netherlands.

Jon P Laye (JP)

Pathology and Data Analytics, Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.

Lindsay C Hewitt (LC)

Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, The Netherlands.
Department of Precision Medicine, GROW School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, The Netherlands.

Andrew F Irvine (AF)

Pathology and Data Analytics, Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.

Vincent Vromen (V)

Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, The Netherlands.
Cicero Zorgroep, Zuid-Limburg, The Netherlands.

Yannick Janssen (Y)

Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, The Netherlands.

Naser Davarzani (N)

Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, The Netherlands.

Gregorio E Fazzi (GE)

Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, The Netherlands.

Shahab Jolani (S)

Department of Methodology and Statistics, CAPHRI, Maastricht University, Maastricht, Netherlands.

Veerle Melotte (V)

Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, The Netherlands.
Department of Clinical Genetics, University of Rotterdam, Erasmus University Medical Center, Rotterdam, The Netherlands.

Derek R Magee (DR)

School of Computing, University of Leeds, Leeds, UK.
HeteroGenius Limited, Leeds, UK.

Myeong-Cherl Kook (MC)

Center for Gastric Cancer, Department of Pathology, National Cancer Center, Goyang, Republic of Korea.

Hyunki Kim (H)

Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.

Rupert Langer (R)

Institute of Clinical Pathology and Molecular Pathology, Kepler University Hospital and Johannes Kepler University, Linz, Austria.

Jae-Ho Cheong (JH)

Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea. jhcheong@yuhs.ac.
Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Republic of Korea. jhcheong@yuhs.ac.
Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea. jhcheong@yuhs.ac.

Heike I Grabsch (HI)

Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, The Netherlands. h.grabsch@maastrichtuniversity.nl.
Pathology and Data Analytics, Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK. h.grabsch@maastrichtuniversity.nl.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH