Clinical Trial

. 2021 Jan 28:497:221-228.

doi: 10.1016/j.canlet.2020.10.039. Epub 2020 Oct 28.

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

Ding Ding¹, Ammar A Javed², Dea Cunningham³, Jonathan Teinor², Michael Wright², Zunaira N Javed², Cara Wilt⁴, Lindsay Parish³, Mary Hodgin³, Amy Ryan⁴, Carol Judkins⁴, Keith McIntyre⁴, Rachel Klein⁴, Nilo Azad⁴, Valerie Lee⁴, Ross Donehower⁴, Ana De Jesus-Acosta⁴, Adrian Murphy⁴, Dung T Le⁴, Eun Ji Shin⁵, Anne Marie Lennon⁶, Mouen Khashab⁵, Vikesh Singh⁵, Alison P Klein⁷, Nicholas J Roberts⁷, Amy Hacker-Prietz⁸, Lindsey Manos², Christi Walsh², Lara Groshek², Caitlin Brown², Chunhui Yuan², Alex B Blair², Vincent Groot², Georgios Gemenetzis², Jun Yu², Matthew J Weiss², Richard A Burkhart², William R Burns², Jin He², John L Cameron², Amol Narang⁸, Atif Zaheer⁹, Elliot K Fishman⁹, Elizabeth D Thompson¹⁰, Robert Anders¹⁰, Ralph H Hruban¹⁰, Elizabeth Jaffee⁴, Christopher L Wolfgang¹¹, Lei Zheng¹², Daniel A Laheru¹³

Affiliations

¹ The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Surgery the Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
² The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Surgery the Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
³ The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
⁵ The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
⁶ The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA; Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA; Department of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
⁷ Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA; The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
⁸ The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
⁹ The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
¹⁰ The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
¹¹ The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Surgery the Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. Electronic address: cwolfga2@jhmi.edu.
¹² The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. Electronic address: lzheng6@jhmi.edu.
¹³ The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. Electronic address: laherda@jhmi.edu.

PMID: 33127389
PMCID: PMC8375587
DOI: 10.1016/j.canlet.2020.10.039

Clinical Trial

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

Ding Ding et al. Cancer Lett. 2021.

. 2021 Jan 28:497:221-228.

doi: 10.1016/j.canlet.2020.10.039. Epub 2020 Oct 28.

Authors

Affiliations

¹ The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Surgery the Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
² The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Surgery the Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
³ The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
⁵ The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
⁶ The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA; Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA; Department of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
⁷ Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA; The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
⁸ The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
⁹ The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
¹⁰ The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
¹¹ The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Surgery the Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. Electronic address: cwolfga2@jhmi.edu.
¹² The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. Electronic address: lzheng6@jhmi.edu.
¹³ The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. Electronic address: laherda@jhmi.edu.

PMID: 33127389
PMCID: PMC8375587
DOI: 10.1016/j.canlet.2020.10.039

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.

Keywords: Actionable alteration; Clinical genomic testing; Matched therapy.

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Conflict of interest statement

Declaration of competing interest

Lei Zheng receives grant support from Bristol-Meyer Squibb, Merck, iTeos, Amgen, NovaRock, Inxmed, and Halozyme, and received the royalty for licensing GVAX to Aduro Biotech. LZ is a paid consultant/Advisory Board Member at Biosion, Alphamab, NovaRock, Akrevia, Sound Biologics, FusunBiopharmaceutical, Foundation Medicine, Data-revive, and Mingruzhiyao. LZ holds shares at Alphamab and Mingruzhiyao.

Figures

**Fig. 1.**
The landscape of genomic alteration and frequency of all 93 tumors.

**Fig. 2.**
Computed tomography (CT) before and after PARP inhibitor treatment of a patient with mutations in BRCA2. A–C. CT before modified FOLFIRINOX treatment. **D–F**. CT after modified FOLFIRINOX before PARP inhibitor treatment. **G–I**. CT after PARP inhibitor treatment. Note: the yellow arrows indicate metastatic liver lesions; the orange arrows indicate primary lesions.

**Fig. 3.**
Schematic diagram of the pancreatic cancer precision medicine program.

See this image and copyright information in PMC

References

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

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

Authors

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Abstract

Conflict of interest statement

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