Challenges of the current precision medicine approach for pancreatic cancer: A single institution experience between 2013 and 2017

Abstract

Recent research on genomic profiling of pancreatic ductal adenocarcinoma (PDAC) has identified many potentially actionable alterations. However, the feasibility of using genomic profiling to guide routine clinical decision making for PDAC patients remains unclear. We retrospectively reviewed PDAC patients between October 2013 and December 2017, who underwent treatment at the Johns Hopkins Hospital and had clinical tumor next-generation sequencing (NGS) through commercial resources. Ninety-two patients with 93 tumors tested were included. Forty-eight (52%) patients had potentially curative surgeries. The median time from the tissue available to the NGS testing ordered was 229 days (interquartile range 62–415). A total of three (3%) patients had matched targeted therapies based on genomic profiling results. Genomic profiling guided personalized treatment for PDAC patients is feasible, but the percentage of patients who receive targeted therapy is low. The main challenges are ordering NGS testing early in the clinical course of the disease and the limited evidence of using a targeted approach in these patients. A real-time department level genomic testing ordering system in combination with an evidence-based flagging system for potentially actionable alterations could help address these shortcomings.

Epithelial-to-Mesenchymal Transition in Pancreatic Cancer is associated with Restricted Water Diffusion in Diffusion-Weighted Magnetic Resonance Imaging

“…New therapeutic strategies include exploitation of DNA repair abnormalities, targeting cancer-cell metabolism and EMT as well as components of the stroma or the tumor micromilieu [52][53][54]. However, although up to one fourth of PDAC harbour clinically actionable molecular alterations and molecularly matched therapies may improve overall survival in these patients, the percentage of PDAC patients who ultimately receive targeted therapies is very low [51,55,56]. This shows that the challenge for personalized medicine in PDAC might not only be the dearth of targeted and other novel therapy options, but rather improving patient stratification and making novel therapies more accessible to individual patients and treating physicians [51,52].…”

The Heterogeneity of the Tumor Microenvironment as Essential Determinant of Development, Progression and Therapy Response of Pancreatic Cancer

“…Thus, until today, less than 5% PDAC patients receive a targeted therapy and significant improvements of survival are still missing [ 301 ]. Current clinical trials such as the “Precision-Panc” (NCT04161417) and the “Precision Promise” studies (NCT04229004) are ongoing with the aim to validate the therapeutic efficacy of novel individualized therapies in PDAC patients [ 302 , 303 ]. However, results from these trials are still pending.…”

Does the Microenvironment Hold the Hidden Key for Functional Precision Medicine in Pancreatic Cancer?

“…This suggests that in addition to the low frequency of actionable molecular alterations in the PDAC patient population, there are further barriers that currently hinder such precision medicine programs from becoming part of routine clinical care. For example, a study at John Hopkins Hospital found that only 3 out of 92 patients (3%) received matched targeted therapy based on tumour next-generation sequencing [ 23 ]. This study identified that a significant barrier is the delay in requesting genomic profiling—it was reported that the medium time to order genomic profiling was 229 days [ 23 ].…”

“…For example, a study at John Hopkins Hospital found that only 3 out of 92 patients (3%) received matched targeted therapy based on tumour next-generation sequencing [ 23 ]. This study identified that a significant barrier is the delay in requesting genomic profiling—it was reported that the medium time to order genomic profiling was 229 days [ 23 ].…”