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

Authors: Yamamoto, K. N.; Nakamura, A.; Liu, L. L.; Stein, S.; Tramontano, A. C.; Kartoun, U.; Shimizu, T.; Inoue, Y.; Asakuma, M.; Haeno, H.; Kong, C. Y.; Uchiyama, K.; Gonen, M.; Hur, C.; Michor, F.
Article Title: Computational modeling of pancreatic cancer patients receiving FOLFIRINOX and gemcitabine-based therapies identifies optimum intervention strategies
Abstract: 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. © 2019 Yamamoto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: adult; cancer survival; controlled study; treatment response; aged; major clinical study; overall survival; fluorouracil; cancer combination chemotherapy; cancer growth; monotherapy; gemcitabine; paclitaxel; cancer patient; cancer radiotherapy; phenotype; metastasis; tumor volume; cohort analysis; mathematical model; irinotecan; folinic acid; pancreas adenocarcinoma; clinical decision making; neoadjuvant chemotherapy; oxaliplatin; stochastic model; japan; induction chemotherapy; massachusetts; medical school; general hospital; oncological parameters; human; male; female; article; local advancement index
Journal Title: PLoS ONE
Volume: 14
Issue: 4
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2019-04-26
Start Page: e0215409
Language: English
DOI: 10.1371/journal.pone.0215409
PUBMED: 31026288
PROVIDER: scopus
PMCID: PMC6485645
Notes: Article -- Export Date: 3 June 2019 -- Source: Scopus
Citation Impact
MSK Authors
  1. Mithat Gonen
    864 Gonen