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Computational modeling of pancreatic cancer patients receiving FOLFIRINOX and gemcitabine-based therapies identifies optimum intervention strategies

Pancreatic ductal adenocarcinoma (PDAC) exhibits a variety of phenotypes with regard to disease progression and treatment response. This variability complicates clinical decision-making despite the improvement of survival due to the recent introduction of FOLFIRINOX (FFX) and nab-paclitaxel. Questio...

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Autores principales: Yamamoto, Kimiyo N., Nakamura, Akira, Liu, Lin L., Stein, Shayna, Tramontano, Angela C., Kartoun, Uri, Shimizu, Tetsunosuke, Inoue, Yoshihiro, Asakuma, Mitsuhiro, Haeno, Hiroshi, Kong, Chung Yin, Uchiyama, Kazuhisa, Gonen, Mithat, Hur, Chin, Michor, Franziska
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485645/
https://www.ncbi.nlm.nih.gov/pubmed/31026288
http://dx.doi.org/10.1371/journal.pone.0215409
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author Yamamoto, Kimiyo N.
Nakamura, Akira
Liu, Lin L.
Stein, Shayna
Tramontano, Angela C.
Kartoun, Uri
Shimizu, Tetsunosuke
Inoue, Yoshihiro
Asakuma, Mitsuhiro
Haeno, Hiroshi
Kong, Chung Yin
Uchiyama, Kazuhisa
Gonen, Mithat
Hur, Chin
Michor, Franziska
author_facet Yamamoto, Kimiyo N.
Nakamura, Akira
Liu, Lin L.
Stein, Shayna
Tramontano, Angela C.
Kartoun, Uri
Shimizu, Tetsunosuke
Inoue, Yoshihiro
Asakuma, Mitsuhiro
Haeno, Hiroshi
Kong, Chung Yin
Uchiyama, Kazuhisa
Gonen, Mithat
Hur, Chin
Michor, Franziska
author_sort Yamamoto, Kimiyo N.
collection PubMed
description Pancreatic ductal adenocarcinoma (PDAC) exhibits a variety of phenotypes with regard to disease progression and treatment response. This variability complicates clinical decision-making despite the improvement of survival due to the recent introduction of FOLFIRINOX (FFX) and nab-paclitaxel. Questions remain as to the timing and sequence of therapies and the role of radiotherapy for unresectable PDAC. Here we developed a computational analysis platform to investigate the dynamics of growth, metastasis and treatment response to FFX, gemcitabine (GEM), and GEM+nab-paclitaxel. Our approach was informed using data of 1,089 patients treated at the Massachusetts General Hospital and validated using an independent cohort from Osaka Medical College. Our framework establishes a logistic growth pattern of PDAC and defines the Local Advancement Index (LAI), which determines the eventual primary tumor size and predicts the number of metastases. We found that a smaller LAI leads to a larger metastatic burden. Furthermore, our analyses ascertain that i) radiotherapy after induction chemotherapy improves survival in cases receiving induction FFX or with larger LAI, ii) neoadjuvant chemotherapy improves survival in cases with resectable PDAC, and iii) temporary cessations of chemotherapies do not impact overall survival, which supports the feasibility of treatment holidays for patients with FFX-associated adverse effects. Our findings inform clinical decision-making for PDAC patients and allow for the rational design of clinical strategies using FFX, GEM, GEM+nab-paclitaxel, neoadjuvant chemotherapy, and radiation.
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spelling pubmed-64856452019-05-09 Computational modeling of pancreatic cancer patients receiving FOLFIRINOX and gemcitabine-based therapies identifies optimum intervention strategies Yamamoto, Kimiyo N. Nakamura, Akira Liu, Lin L. Stein, Shayna Tramontano, Angela C. Kartoun, Uri Shimizu, Tetsunosuke Inoue, Yoshihiro Asakuma, Mitsuhiro Haeno, Hiroshi Kong, Chung Yin Uchiyama, Kazuhisa Gonen, Mithat Hur, Chin Michor, Franziska PLoS One Research Article Pancreatic ductal adenocarcinoma (PDAC) exhibits a variety of phenotypes with regard to disease progression and treatment response. This variability complicates clinical decision-making despite the improvement of survival due to the recent introduction of FOLFIRINOX (FFX) and nab-paclitaxel. Questions remain as to the timing and sequence of therapies and the role of radiotherapy for unresectable PDAC. Here we developed a computational analysis platform to investigate the dynamics of growth, metastasis and treatment response to FFX, gemcitabine (GEM), and GEM+nab-paclitaxel. Our approach was informed using data of 1,089 patients treated at the Massachusetts General Hospital and validated using an independent cohort from Osaka Medical College. Our framework establishes a logistic growth pattern of PDAC and defines the Local Advancement Index (LAI), which determines the eventual primary tumor size and predicts the number of metastases. We found that a smaller LAI leads to a larger metastatic burden. Furthermore, our analyses ascertain that i) radiotherapy after induction chemotherapy improves survival in cases receiving induction FFX or with larger LAI, ii) neoadjuvant chemotherapy improves survival in cases with resectable PDAC, and iii) temporary cessations of chemotherapies do not impact overall survival, which supports the feasibility of treatment holidays for patients with FFX-associated adverse effects. Our findings inform clinical decision-making for PDAC patients and allow for the rational design of clinical strategies using FFX, GEM, GEM+nab-paclitaxel, neoadjuvant chemotherapy, and radiation. Public Library of Science 2019-04-26 /pmc/articles/PMC6485645/ /pubmed/31026288 http://dx.doi.org/10.1371/journal.pone.0215409 Text en © 2019 Yamamoto et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Yamamoto, Kimiyo N.
Nakamura, Akira
Liu, Lin L.
Stein, Shayna
Tramontano, Angela C.
Kartoun, Uri
Shimizu, Tetsunosuke
Inoue, Yoshihiro
Asakuma, Mitsuhiro
Haeno, Hiroshi
Kong, Chung Yin
Uchiyama, Kazuhisa
Gonen, Mithat
Hur, Chin
Michor, Franziska
Computational modeling of pancreatic cancer patients receiving FOLFIRINOX and gemcitabine-based therapies identifies optimum intervention strategies
title Computational modeling of pancreatic cancer patients receiving FOLFIRINOX and gemcitabine-based therapies identifies optimum intervention strategies
title_full Computational modeling of pancreatic cancer patients receiving FOLFIRINOX and gemcitabine-based therapies identifies optimum intervention strategies
title_fullStr Computational modeling of pancreatic cancer patients receiving FOLFIRINOX and gemcitabine-based therapies identifies optimum intervention strategies
title_full_unstemmed Computational modeling of pancreatic cancer patients receiving FOLFIRINOX and gemcitabine-based therapies identifies optimum intervention strategies
title_short Computational modeling of pancreatic cancer patients receiving FOLFIRINOX and gemcitabine-based therapies identifies optimum intervention strategies
title_sort computational modeling of pancreatic cancer patients receiving folfirinox and gemcitabine-based therapies identifies optimum intervention strategies
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485645/
https://www.ncbi.nlm.nih.gov/pubmed/31026288
http://dx.doi.org/10.1371/journal.pone.0215409
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