Neoadjuvant therapy versus upfront surgery for potentially resectable pancreatic cancer: a Markov decision analysis

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Abstract

Background Neoadjuvant therapy has emerged as an alternative treatment strategy for potentially resectable pancreatic cancer. In the absence of large randomized controlled trials offering a direct comparison, this study aims to use Markov decision analysis to compare efficacy of traditional surgery first (SF) and neoadjuvant treatment (NAT) pathways for potentially resectable pancreatic cancer. Methods An advanced Markov decision analysis model was constructed to compare SF and NAT pathways for potentially resectable pancreatic cancer. Transition probabilities were calculated from randomized control and Phase II/III trials after comprehensive literature search. Utility outcomes were measured in overall and quality-adjusted life months (QALMs) on an intention-to-treat basis as the primary outcome. Markov cohort analysis of treatment received was the secondary outcome. Model uncertainties were tested with one and twoway deterministic and probabilistic Monte Carlo sensitivity analysis. Results SF gave 23.72 months (18.51 QALMs) versus 20.22 months (16.26 QALMs). Markov Cohort Analysis showed that where all treatment modalities were received NAT gave 35.05 months (29.87 QALMs) versus 30.96 months (24.86QALMs) for R0 resection and 34.08 months (29.87 QALMs) versus 25.85 months (20.72 QALMs) for R1 resection. One-way deterministic sensitivity analysis showed that NAT was superior if the resection rate was greater than 51.04% or below 75.68% in SF pathway. Two-way sensitivity analysis showed that pathway superiority depended on obtaining multimodal treatment in either pathway Conclusion Whilst NAT is a viable alternative to traditional SF approach, superior pathway selection depends on the individual patient's likelihood of receiving multimodal treatment in either pathway.

LanguageEnglish
Article numbere0212805
Number of pages20
JournalPLoS ONE
Volume14
Issue number2
DOIs
Publication statusPublished - 28 Feb 2019

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pancreatic neoplasms
Neoadjuvant Therapy
Decision Support Techniques
Decision theory
Pancreatic Neoplasms
Surgery
surgery
Quality of Life
resection
therapeutics
Sensitivity analysis
Combined Modality Therapy
Cohort Studies
model uncertainty
Uncertainty
Therapy
Decision analysis
Cancer
Therapeutics
Randomized Controlled Trials

Keywords

  • neoadjuvant therapy
  • pancreatic cancer
  • Markov decision analysis

Cite this

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title = "Neoadjuvant therapy versus upfront surgery for potentially resectable pancreatic cancer: a Markov decision analysis",
abstract = "Background Neoadjuvant therapy has emerged as an alternative treatment strategy for potentially resectable pancreatic cancer. In the absence of large randomized controlled trials offering a direct comparison, this study aims to use Markov decision analysis to compare efficacy of traditional surgery first (SF) and neoadjuvant treatment (NAT) pathways for potentially resectable pancreatic cancer. Methods An advanced Markov decision analysis model was constructed to compare SF and NAT pathways for potentially resectable pancreatic cancer. Transition probabilities were calculated from randomized control and Phase II/III trials after comprehensive literature search. Utility outcomes were measured in overall and quality-adjusted life months (QALMs) on an intention-to-treat basis as the primary outcome. Markov cohort analysis of treatment received was the secondary outcome. Model uncertainties were tested with one and twoway deterministic and probabilistic Monte Carlo sensitivity analysis. Results SF gave 23.72 months (18.51 QALMs) versus 20.22 months (16.26 QALMs). Markov Cohort Analysis showed that where all treatment modalities were received NAT gave 35.05 months (29.87 QALMs) versus 30.96 months (24.86QALMs) for R0 resection and 34.08 months (29.87 QALMs) versus 25.85 months (20.72 QALMs) for R1 resection. One-way deterministic sensitivity analysis showed that NAT was superior if the resection rate was greater than 51.04{\%} or below 75.68{\%} in SF pathway. Two-way sensitivity analysis showed that pathway superiority depended on obtaining multimodal treatment in either pathway Conclusion Whilst NAT is a viable alternative to traditional SF approach, superior pathway selection depends on the individual patient's likelihood of receiving multimodal treatment in either pathway.",
keywords = "neoadjuvant therapy, pancreatic cancer, Markov decision analysis",
author = "Alison Bradley and {Van Der Meer}, Robert",
year = "2019",
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AU - Bradley, Alison

AU - Van Der Meer, Robert

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N2 - Background Neoadjuvant therapy has emerged as an alternative treatment strategy for potentially resectable pancreatic cancer. In the absence of large randomized controlled trials offering a direct comparison, this study aims to use Markov decision analysis to compare efficacy of traditional surgery first (SF) and neoadjuvant treatment (NAT) pathways for potentially resectable pancreatic cancer. Methods An advanced Markov decision analysis model was constructed to compare SF and NAT pathways for potentially resectable pancreatic cancer. Transition probabilities were calculated from randomized control and Phase II/III trials after comprehensive literature search. Utility outcomes were measured in overall and quality-adjusted life months (QALMs) on an intention-to-treat basis as the primary outcome. Markov cohort analysis of treatment received was the secondary outcome. Model uncertainties were tested with one and twoway deterministic and probabilistic Monte Carlo sensitivity analysis. Results SF gave 23.72 months (18.51 QALMs) versus 20.22 months (16.26 QALMs). Markov Cohort Analysis showed that where all treatment modalities were received NAT gave 35.05 months (29.87 QALMs) versus 30.96 months (24.86QALMs) for R0 resection and 34.08 months (29.87 QALMs) versus 25.85 months (20.72 QALMs) for R1 resection. One-way deterministic sensitivity analysis showed that NAT was superior if the resection rate was greater than 51.04% or below 75.68% in SF pathway. Two-way sensitivity analysis showed that pathway superiority depended on obtaining multimodal treatment in either pathway Conclusion Whilst NAT is a viable alternative to traditional SF approach, superior pathway selection depends on the individual patient's likelihood of receiving multimodal treatment in either pathway.

AB - Background Neoadjuvant therapy has emerged as an alternative treatment strategy for potentially resectable pancreatic cancer. In the absence of large randomized controlled trials offering a direct comparison, this study aims to use Markov decision analysis to compare efficacy of traditional surgery first (SF) and neoadjuvant treatment (NAT) pathways for potentially resectable pancreatic cancer. Methods An advanced Markov decision analysis model was constructed to compare SF and NAT pathways for potentially resectable pancreatic cancer. Transition probabilities were calculated from randomized control and Phase II/III trials after comprehensive literature search. Utility outcomes were measured in overall and quality-adjusted life months (QALMs) on an intention-to-treat basis as the primary outcome. Markov cohort analysis of treatment received was the secondary outcome. Model uncertainties were tested with one and twoway deterministic and probabilistic Monte Carlo sensitivity analysis. Results SF gave 23.72 months (18.51 QALMs) versus 20.22 months (16.26 QALMs). Markov Cohort Analysis showed that where all treatment modalities were received NAT gave 35.05 months (29.87 QALMs) versus 30.96 months (24.86QALMs) for R0 resection and 34.08 months (29.87 QALMs) versus 25.85 months (20.72 QALMs) for R1 resection. One-way deterministic sensitivity analysis showed that NAT was superior if the resection rate was greater than 51.04% or below 75.68% in SF pathway. Two-way sensitivity analysis showed that pathway superiority depended on obtaining multimodal treatment in either pathway Conclusion Whilst NAT is a viable alternative to traditional SF approach, superior pathway selection depends on the individual patient's likelihood of receiving multimodal treatment in either pathway.

KW - neoadjuvant therapy

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