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Prognostic value of disseminated tumor cells in unresectable pancreatic ductal adenocarcinoma: a prospective observational study

BACKGROUND: Although pancreatic ductal adenocarcinoma (PDAC) rarely metastasizes to the skeleton, disseminated tumor cells have been detected in bone marrow samples from patients with this disease. The prognostic value of such findings is currently unclear. Thus, the current study aimed to clarify t...

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Autores principales: Nordgård, Oddmund, Lapin, Morten, Tjensvoll, Kjersti, Oltedal, Satu, Edland, Karin Hestnes, Neverdahl, Nicolay Bore, Fostenes, Dmitrij, Garresori, Herish, Glenjen, Nils, Smaaland, Rune, Gilje, Bjørnar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166481/
https://www.ncbi.nlm.nih.gov/pubmed/35659265
http://dx.doi.org/10.1186/s12885-022-09714-x
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author Nordgård, Oddmund
Lapin, Morten
Tjensvoll, Kjersti
Oltedal, Satu
Edland, Karin Hestnes
Neverdahl, Nicolay Bore
Fostenes, Dmitrij
Garresori, Herish
Glenjen, Nils
Smaaland, Rune
Gilje, Bjørnar
author_facet Nordgård, Oddmund
Lapin, Morten
Tjensvoll, Kjersti
Oltedal, Satu
Edland, Karin Hestnes
Neverdahl, Nicolay Bore
Fostenes, Dmitrij
Garresori, Herish
Glenjen, Nils
Smaaland, Rune
Gilje, Bjørnar
author_sort Nordgård, Oddmund
collection PubMed
description BACKGROUND: Although pancreatic ductal adenocarcinoma (PDAC) rarely metastasizes to the skeleton, disseminated tumor cells have been detected in bone marrow samples from patients with this disease. The prognostic value of such findings is currently unclear. Thus, the current study aimed to clarify the prognostic information associated with disseminated tumor cell detection in samples from patients with PDAC. METHODS: Bone marrow aspirates were obtained from 48 patients with locally advanced (n = 11) or metastatic (n = 37) PDAC, before and after 2 months of chemotherapy. Disseminated tumor cells were detected with an mRNA panel and quantitative reverse transcription PCR. We used the highest levels measured in healthy bone marrow (n = 30) as a threshold to define the positive detection of disseminated tumor cells. Progression-free and overall survival were analyzed with Kaplan–Meier and Cox proportional hazards regression analyses. RESULTS: Disseminated tumor cells were detected in 15/48 (31%) bone marrow samples obtained before starting chemotherapy and in 8/25 (32%) samples obtained during chemotherapy. Patients with disseminated tumor cells detected before therapy had significantly shorter progression-free (p = 0.03; HR = 2.0) and overall survival (p = 0.03; HR = 2.0), compared to those without disseminated tumor cells in the bone marrow. When restricting disseminated tumor cell detection to keratins KRT7 and KRT8, the prognostic information was substantially stronger (p = 1 × 10(–6); HR = 22, and p = 2 × 10(–5); HR = 7.7, respectively). The multivariable Cox regression analysis demonstrated that disseminated tumor cell detection prior to treatment had independent prognostic value. In contrast, disseminated tumor cells detected during treatment did not have prognostic value. CONCLUSIONS: Disseminated tumor cells detected before commencing chemotherapy had prognostic value in patients with inoperable PDAC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-09714-x.
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spelling pubmed-91664812022-06-05 Prognostic value of disseminated tumor cells in unresectable pancreatic ductal adenocarcinoma: a prospective observational study Nordgård, Oddmund Lapin, Morten Tjensvoll, Kjersti Oltedal, Satu Edland, Karin Hestnes Neverdahl, Nicolay Bore Fostenes, Dmitrij Garresori, Herish Glenjen, Nils Smaaland, Rune Gilje, Bjørnar BMC Cancer Research BACKGROUND: Although pancreatic ductal adenocarcinoma (PDAC) rarely metastasizes to the skeleton, disseminated tumor cells have been detected in bone marrow samples from patients with this disease. The prognostic value of such findings is currently unclear. Thus, the current study aimed to clarify the prognostic information associated with disseminated tumor cell detection in samples from patients with PDAC. METHODS: Bone marrow aspirates were obtained from 48 patients with locally advanced (n = 11) or metastatic (n = 37) PDAC, before and after 2 months of chemotherapy. Disseminated tumor cells were detected with an mRNA panel and quantitative reverse transcription PCR. We used the highest levels measured in healthy bone marrow (n = 30) as a threshold to define the positive detection of disseminated tumor cells. Progression-free and overall survival were analyzed with Kaplan–Meier and Cox proportional hazards regression analyses. RESULTS: Disseminated tumor cells were detected in 15/48 (31%) bone marrow samples obtained before starting chemotherapy and in 8/25 (32%) samples obtained during chemotherapy. Patients with disseminated tumor cells detected before therapy had significantly shorter progression-free (p = 0.03; HR = 2.0) and overall survival (p = 0.03; HR = 2.0), compared to those without disseminated tumor cells in the bone marrow. When restricting disseminated tumor cell detection to keratins KRT7 and KRT8, the prognostic information was substantially stronger (p = 1 × 10(–6); HR = 22, and p = 2 × 10(–5); HR = 7.7, respectively). The multivariable Cox regression analysis demonstrated that disseminated tumor cell detection prior to treatment had independent prognostic value. In contrast, disseminated tumor cells detected during treatment did not have prognostic value. CONCLUSIONS: Disseminated tumor cells detected before commencing chemotherapy had prognostic value in patients with inoperable PDAC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-09714-x. BioMed Central 2022-06-03 /pmc/articles/PMC9166481/ /pubmed/35659265 http://dx.doi.org/10.1186/s12885-022-09714-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Nordgård, Oddmund
Lapin, Morten
Tjensvoll, Kjersti
Oltedal, Satu
Edland, Karin Hestnes
Neverdahl, Nicolay Bore
Fostenes, Dmitrij
Garresori, Herish
Glenjen, Nils
Smaaland, Rune
Gilje, Bjørnar
Prognostic value of disseminated tumor cells in unresectable pancreatic ductal adenocarcinoma: a prospective observational study
title Prognostic value of disseminated tumor cells in unresectable pancreatic ductal adenocarcinoma: a prospective observational study
title_full Prognostic value of disseminated tumor cells in unresectable pancreatic ductal adenocarcinoma: a prospective observational study
title_fullStr Prognostic value of disseminated tumor cells in unresectable pancreatic ductal adenocarcinoma: a prospective observational study
title_full_unstemmed Prognostic value of disseminated tumor cells in unresectable pancreatic ductal adenocarcinoma: a prospective observational study
title_short Prognostic value of disseminated tumor cells in unresectable pancreatic ductal adenocarcinoma: a prospective observational study
title_sort prognostic value of disseminated tumor cells in unresectable pancreatic ductal adenocarcinoma: a prospective observational study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166481/
https://www.ncbi.nlm.nih.gov/pubmed/35659265
http://dx.doi.org/10.1186/s12885-022-09714-x
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