The Right Treatment Strategy for the Right Patient: A Biomarker-Driven Approach to Neoadjuvant vs. Surgery-First Management of Resectable and Borderline Resectable Pancreatic Cancer

Christopher B. Nahm; John Turchini; Sumit Sahni; Elizabeth Moon; Malinda Itchins; Jennifer Arena; Angela Chou; Emily K. Colvin; Viive M. Howell; Nick Pavlakis; Stephen Clarke; Jaswinder S. Samra; Anthony J. Gill; Anubhav Mittal

doi:10.3390/cancers14153620

Cancers (Jul 2022)

The Right Treatment Strategy for the Right Patient: A Biomarker-Driven Approach to Neoadjuvant vs. Surgery-First Management of Resectable and Borderline Resectable Pancreatic Cancer

Christopher B. Nahm,
John Turchini,
Sumit Sahni,
Elizabeth Moon,
Malinda Itchins,
Jennifer Arena,
Angela Chou,
Emily K. Colvin,
Viive M. Howell,
Nick Pavlakis,
Stephen Clarke,
Jaswinder S. Samra,
Anthony J. Gill,
Anubhav Mittal

Affiliations

Christopher B. Nahm: Northern Clinical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW 2565, Australia
John Turchini: Northern Clinical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW 2565, Australia
Sumit Sahni: Northern Clinical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW 2565, Australia
Elizabeth Moon: Northern Clinical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW 2565, Australia
Malinda Itchins: Northern Clinical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW 2565, Australia
Jennifer Arena: Australian Pancreatic Centre, Sydney, NSW 2565, Australia
Angela Chou: Northern Clinical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW 2565, Australia
Emily K. Colvin: Northern Clinical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW 2565, Australia
Viive M. Howell: Northern Clinical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW 2565, Australia
Nick Pavlakis: Northern Clinical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW 2565, Australia
Stephen Clarke: Northern Clinical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW 2565, Australia
Jaswinder S. Samra: Northern Clinical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW 2565, Australia
Anthony J. Gill: Northern Clinical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW 2565, Australia
Anubhav Mittal: Northern Clinical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW 2565, Australia

DOI: https://doi.org/10.3390/cancers14153620
Journal volume & issue: Vol. 14, no. 15
p. 3620

Abstract

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The genomic heterogeneity of pancreatic ductal adenocarcinoma (PDAC) is becoming increasingly appreciated. We aimed to evaluate the ability of a triple biomarker panel (S100A4, Ca-125, and mesothelin) to predict: (i) genetic PDAC subtypes; (ii) clinical phenotypes; and (iii) the optimal treatment strategy (neoadjuvant vs. surgery-first) in resectable and borderline resectable PDAC. Patients who underwent resection for resectable and borderline resectable PDAC were included from one single-institutional cohort and one multi-institutional cohort from the Australian Pancreatic Genome Initiative (APGI). Tumors were immunohistochemically evaluated for S100A4, Ca-125, and mesothelin, and a subset from the APGI cohort underwent RNA sequencing. This study included 252 and 226 patients from the single institution and the APGI cohorts, respectively. Triple-negative biomarker status correlated with non-squamous PDAC genotypes (p = 0.020), lower rates of distant recurrence (p = 0.002), and longer median overall survival (mOS) with the surgery-first approach compared with neoadjuvant treatment (33.3 vs. 22.2 mths, p = 0.038) in resectable PDAC. In contrast, the triple-positive disease was associated with longer mOS with neoadjuvant treatment compared with the surgery-first approach (29.5 vs. 13.7 mths, p = 0.021) in resectable and borderline resectable PDAC. In conclusion, the triple biomarker panel predicts genetic PDAC subtypes, clinical phenotypes, and optimal treatment strategies in resectable and borderline resectable PDAC.

Published in Cancers

ISSN: 2072-6694 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.mdpi.com/journal/cancers/

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