Prognostic impact of inter-metastatic heterogeneity of viable tumour cells in colorectal liver metastases.
Chemotherapeutic response
Colorectal liver metastases
Heterogeneity
Overall survival
Preoperative chemotherapy
Journal
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
ISSN: 1532-2157
Titre abrégé: Eur J Surg Oncol
Pays: England
ID NLM: 8504356
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
10
02
2022
revised:
03
03
2022
accepted:
08
03
2022
pubmed:
22
3
2022
medline:
29
6
2022
entrez:
21
3
2022
Statut:
ppublish
Résumé
Heterogenous response to neoadjuvant chemotherapy in patients with multiple colorectal liver metastases (CRLM) has been associated with an acquired resistance to systemic therapy. This study evaluated the occurrence of a heterogenous inter-metastatic tumour response with regards to the proportion of viable tumour cells, and its prognostic impact. A retrospective cohort study was conducted, including all patients with CRLM surgically treated at Karolinska University Hospital, Stockholm, Sweden, from 2013 to 2018. Factors associated with the proportion of viable tumour cells and inter-metastatic heterogeneity were analysed with regression and survival analyses. Out of 640 surgically treated patients, 405 patients (1357 CRLM), received neoadjuvant chemotherapy. Multiple CRLM were present in 314 patients (78%), out of whom 72 patients (23%) presented with a heterogenous tumour response. The median overall survival (OS) for patients with a heterogenous inter-metastatic tumour response was 36 months, compared to 57 months for patients with a homogenous inter-metastatic tumour response (p < .001). Poor OS in patients receiving preoperative chemotherapy was significantly associated with a heterogenous inter-metastatic tumour response (hazard ratio (HR) 1.68 (1.02-2.78)), right-sided primary tumour (HR 2.01 (1.29-3.43)) and CRLM diameter >5 cm (HR 1.83 (1.06-3.17)). Outcome in patients with a heterogenous inter-metastatic tumour response, illustrated by the proportion of viable tumour cells, is inferior to that of patients with a homogenous response. These results suggest that heterogeneity in treatment response is an important marker of aggressive disease and could be of clinical value for decisions on post-operative therapy.
Sections du résumé
BACKGROUND
Heterogenous response to neoadjuvant chemotherapy in patients with multiple colorectal liver metastases (CRLM) has been associated with an acquired resistance to systemic therapy. This study evaluated the occurrence of a heterogenous inter-metastatic tumour response with regards to the proportion of viable tumour cells, and its prognostic impact.
METHODS
A retrospective cohort study was conducted, including all patients with CRLM surgically treated at Karolinska University Hospital, Stockholm, Sweden, from 2013 to 2018. Factors associated with the proportion of viable tumour cells and inter-metastatic heterogeneity were analysed with regression and survival analyses.
RESULTS
Out of 640 surgically treated patients, 405 patients (1357 CRLM), received neoadjuvant chemotherapy. Multiple CRLM were present in 314 patients (78%), out of whom 72 patients (23%) presented with a heterogenous tumour response. The median overall survival (OS) for patients with a heterogenous inter-metastatic tumour response was 36 months, compared to 57 months for patients with a homogenous inter-metastatic tumour response (p < .001). Poor OS in patients receiving preoperative chemotherapy was significantly associated with a heterogenous inter-metastatic tumour response (hazard ratio (HR) 1.68 (1.02-2.78)), right-sided primary tumour (HR 2.01 (1.29-3.43)) and CRLM diameter >5 cm (HR 1.83 (1.06-3.17)).
CONCLUSION
Outcome in patients with a heterogenous inter-metastatic tumour response, illustrated by the proportion of viable tumour cells, is inferior to that of patients with a homogenous response. These results suggest that heterogeneity in treatment response is an important marker of aggressive disease and could be of clinical value for decisions on post-operative therapy.
Identifiants
pubmed: 35307250
pii: S0748-7983(22)00126-3
doi: 10.1016/j.ejso.2022.03.004
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1656-1663Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors to the article “Prognostic impact of inter-metastatic heterogeneity of viable tumour cells in colorectal liver metastases” have no conflicts of interests to declare. All authors: Cecilia Strömberg, Lilia Martinez de la Maza, Carlos Fenández Moro, Marco Gerling, Carl Jorns, Ernesto Sparrelid, Matthias Löhr and Christina Villard. Disease-free survival in patients with more than one CRLM with regards to tumour response; heterogenous tumour response, homogenous minor response, homogenous major response, and complete response b).