Imaging-based biomarkers: Changes in the tumor interface of pancreatic ductal adenocarcinoma on computed tomography scans indicate response to cytotoxic therapy

Cancer. 2018 Apr 15;124(8):1701-1709. doi: 10.1002/cncr.31251. Epub 2018 Jan 25.

Abstract

Background: The assessment of pancreatic ductal adenocarcinoma (PDAC) response to therapy remains challenging. The objective of this study was to investigate whether changes in the tumor/parenchyma interface are associated with response.

Methods: Computed tomography (CT) scans before and after therapy were reviewed in 4 cohorts: cohort 1 (99 patients with stage I/II PDAC who received neoadjuvant chemoradiation and surgery); cohort 2 (86 patients with stage IV PDAC who received chemotherapy), cohort 3 (94 patients with stage I/II PDAC who received protocol-based neoadjuvant gemcitabine chemoradiation), and cohort 4 (47 patients with stage I/II PDAC who received neoadjuvant chemoradiation and were prospectively followed in a registry). The tumor/parenchyma interface was visually classified as either a type I response (the interface remained or became well defined) or a type II response (the interface became poorly defined) after therapy. Consensus (cohorts 1-3) and individual (cohort 4) visual scoring was performed. Changes in enhancement at the interface were quantified using a proprietary platform.

Results: In cohort 1, type I responders had a greater probability of achieving a complete or near-complete pathologic response (21% vs 0%; P = .01). For cohorts 1, 2, and 3, type I responders had significantly longer disease-free and overall survival, independent of traditional covariates of outcomes and of baseline and normalized cancer antigen 19-9 levels. In cohort 4, 2 senior radiologists achieved a κ value of 0.8, and the interface score was associated with overall survival. The quantitative method revealed high specificity and sensitivity in classifying patients as type I or type II responders (with an area under the receiver operating curve of 0.92 in cohort 1, 0.96 in cohort 2, and 0.89 in cohort 3).

Conclusions: Changes at the PDAC/parenchyma interface may serve as an early predictor of response to therapy. Cancer 2018;124:1701-9. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Keywords: Response Evaluation Criteria in Solid Tumors (RECIST); cytotoxic therapy; imaging biomarker; pancreatic cancer; response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Pancreatic Ductal / diagnostic imaging
  • Carcinoma, Pancreatic Ductal / pathology
  • Carcinoma, Pancreatic Ductal / therapy*
  • Chemoradiotherapy / methods
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoadjuvant Therapy / methods
  • Neoplasm Staging
  • Pancreatectomy
  • Pancreatic Ducts / diagnostic imaging*
  • Pancreatic Ducts / drug effects
  • Pancreatic Ducts / pathology
  • Pancreatic Ducts / radiation effects
  • Pancreatic Neoplasms / diagnostic imaging
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy*
  • Tomography, X-Ray Computed
  • Treatment Outcome