Measuring Response to Neoadjuvant Therapy Using Biomarkers in Pancreatic Cancer

A Narrative Review

Catherine Valukas; Akhil Chawla

Disclosures

Chin Clin Oncol. 2022;11(4):30 

In This Article

Abstract and Introduction

Abstract

Background and Objective: Pancreatic cancer is the 4th leading cause of cancer death in the US, with incidence increasing over the last 20 years. Recently neoadjuvant therapy (NAT) has emerged as an important tool in improving resectability and overall survival. The objective is to describe and discuss the current literature on the use of biomarkers in measuring response to NAT in pancreatic adenocarcinoma.

Methods: An electronic review of PubMed, Google Scholar and Cochrane was performed to obtain key literature on serum, imaging, clinical, and histologic biomarkers utilized to measure response to NAT in pancreatic cancer. This literature review included publications in English written between January 1, 2011 to March 31, 2022.

Key Content and Findings: An overview of four categories of biomarkers was evaluated for their utility in assessing both pathologic response and overall survival following NAT in pancreatic adenocarcinoma. Serum CA19-9 as well as CT radiomic features, FDG PET response and development of histologic grading system all show promise as markers of response to NAT.

Conclusions: While multiple promising modalities exist, all require some form of standardization in terms of predicting response to NAT. Further investigation and large-scale studies to evaluate the efficacy of various imaging modalities are necessary. Additionally, there needs to be standardization of histologic grading system post NAT, and consensus on CA19-9 cutoff values in determining NAT response.

Introduction

Pancreatic cancer is the 4th leading cause of cancer death in the US, with incidence increasing over the last 20 years.[1] Historically, treatment of localized pancreatic cancer has centered upon curative-intent surgery for those who are eligible, followed by adjuvant chemotherapy. However, multiple studies have demonstrated that over half of all patients who undergo upfront resection are unable to complete adjuvant therapy.[2] Recently, management of pancreatic ductal adenocarcinoma (PDAC) has shifted towards the use of neoadjuvant chemotherapy and chemo-radiation therapy especially in locally advanced and borderline resectable disease. The current preferred regimens in the neoadjuvant/adjuvant setting are FOLFIRINOX (or modified FOLFIRINOX) or gemcitabine + nab-paclitaxel with or without radiation. Neoadjuvant therapy (NAT) for pancreatic cancer has been shown to increase margin-negative resection rate, reduce the rate of lymph node involvement as well as slow the development of micrometastasis.[3–5] The use of NAT has the potential to improve resectability and survival in patients with PDAC, a concept which has been evaluated by a variety of recently reported clinical trials.[5–7] However, evaluating treatment response to NAT remains a challenge. This review highlights the role of biomarkers in evaluating response to neoadjuvant treatment in pancreatic cancer. A biomarker is defined by the NIH Biomarker Working Group as "a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacologic responses to therapeutic intervention".[8] To date, the most used biomarker in the detection and management of pancreatic cancer is Carbohydrate Antigen 19–9 (CA 19–9); however it is limited in its utility. Thus, multiple studies are ongoing to improve diagnosis and guide management PDAC.[8–10] This review examines current available techniques which may be utilized to predict both treatment response as well as survival outcomes. For the purpose of this review, we did not delineate between specific regimens of chemotherapy or chemotherapy and radiation. We present the following article in accordance with the Narrative Review reporting checklist (available at https://cco.amegroups.com/article/view/10.21037/cco-22-49/rc).

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