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

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 pa...

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Veröffentlicht in:Cancer letters 2021-01, Vol.497, p.221-228
Hauptverfasser: Ding, Ding, Javed, Ammar A., Cunningham, Dea, Teinor, Jonathan, Wright, Michael, Javed, Zunaira N., Wilt, Cara, Parish, Lindsay, Hodgin, Mary, Ryan, Amy, Judkins, Carol, McIntyre, Keith, Klein, Rachel, Azad, Nilo, Lee, Valerie, Donehower, Ross, De Jesus-Acosta, Ana, Murphy, Adrian, Le, Dung T., Shin, Eun Ji, Lennon, Anne Marie, Khashab, Mouen, Singh, Vikesh, Klein, Alison P., Roberts, Nicholas J., Hacker-Prietz, Amy, Manos, Lindsey, Walsh, Christi, Groshek, Lara, Brown, Caitlin, Yuan, Chunhui, Blair, Alex B., Groot, Vincent, Gemenetzis, Georgios, Yu, Jun, Weiss, Matthew J., Burkhart, Richard A., Burns, William R., He, Jin, Cameron, John L., Narang, Amol, Zaheer, Atif, Fishman, Elliot K., Thompson, Elizabeth D., Anders, Robert, Hruban, Ralph H., Jaffee, Elizabeth, Wolfgang, Christopher L., Zheng, Lei, Laheru, Daniel A.
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container_end_page 228
container_issue
container_start_page 221
container_title Cancer letters
container_volume 497
creator Ding, Ding
Javed, Ammar A.
Cunningham, Dea
Teinor, Jonathan
Wright, Michael
Javed, Zunaira N.
Wilt, Cara
Parish, Lindsay
Hodgin, Mary
Ryan, Amy
Judkins, Carol
McIntyre, Keith
Klein, Rachel
Azad, Nilo
Lee, Valerie
Donehower, Ross
De Jesus-Acosta, Ana
Murphy, Adrian
Le, Dung T.
Shin, Eun Ji
Lennon, Anne Marie
Khashab, Mouen
Singh, Vikesh
Klein, Alison P.
Roberts, Nicholas J.
Hacker-Prietz, Amy
Manos, Lindsey
Walsh, Christi
Groshek, Lara
Brown, Caitlin
Yuan, Chunhui
Blair, Alex B.
Groot, Vincent
Gemenetzis, Georgios
Yu, Jun
Weiss, Matthew J.
Burkhart, Richard A.
Burns, William R.
He, Jin
Cameron, John L.
Narang, Amol
Zaheer, Atif
Fishman, Elliot K.
Thompson, Elizabeth D.
Anders, Robert
Hruban, Ralph H.
Jaffee, Elizabeth
Wolfgang, Christopher L.
Zheng, Lei
Laheru, Daniel A.
description 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. •Clinical genomic profiling approach for PDAC patients in routine practice is feasible.•Delayed ordering of genomic testing in the clinical course and limited targetable alterations lead to the low percentage of patients who receive matched therapy.•A comprehensive real-time platform combining early ordering and potentially actionable alteration identification is urgently needed.
doi_str_mv 10.1016/j.canlet.2020.10.039
format Article
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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. •Clinical genomic profiling approach for PDAC patients in routine practice is feasible.•Delayed ordering of genomic testing in the clinical course and limited targetable alterations lead to the low percentage of patients who receive matched therapy.•A comprehensive real-time platform combining early ordering and potentially actionable alteration identification is urgently needed.</description><identifier>ISSN: 0304-3835</identifier><identifier>EISSN: 1872-7980</identifier><identifier>DOI: 10.1016/j.canlet.2020.10.039</identifier><identifier>PMID: 33127389</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Actionable alteration ; Adenocarcinoma ; Aged ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biomarkers, Tumor - genetics ; Biopsy ; Carcinoma, Pancreatic Ductal - genetics ; Carcinoma, Pancreatic Ductal - secondary ; Carcinoma, Pancreatic Ductal - therapy ; Clinical decision making ; Clinical genomic testing ; Clinical medicine ; Clinical trials ; Combined Modality Therapy ; Decision making ; FDA approval ; Feasibility Studies ; Female ; Follow-Up Studies ; Genomes ; High-Throughput Nucleotide Sequencing ; Humans ; Lymphatic Metastasis ; Male ; Matched therapy ; Medicine ; Metastasis ; Middle Aged ; Molecular Targeted Therapy - standards ; Mutation ; Next-generation sequencing ; Pancreatic cancer ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - pathology ; Pancreatic Neoplasms - therapy ; Pancreaticoduodenectomy ; Patients ; Precision Medicine ; Prognosis ; Retrospective Studies ; Surgery ; Survival analysis ; Time Factors ; Tumors</subject><ispartof>Cancer letters, 2021-01, Vol.497, p.221-228</ispartof><rights>2020 The Authors</rights><rights>Copyright © 2020 The Authors. 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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. •Clinical genomic profiling approach for PDAC patients in routine practice is feasible.•Delayed ordering of genomic testing in the clinical course and limited targetable alterations lead to the low percentage of patients who receive matched therapy.•A comprehensive real-time platform combining early ordering and potentially actionable alteration identification is urgently needed.</description><subject>Actionable alteration</subject><subject>Adenocarcinoma</subject><subject>Aged</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biopsy</subject><subject>Carcinoma, Pancreatic Ductal - genetics</subject><subject>Carcinoma, Pancreatic Ductal - secondary</subject><subject>Carcinoma, Pancreatic Ductal - therapy</subject><subject>Clinical decision making</subject><subject>Clinical genomic testing</subject><subject>Clinical medicine</subject><subject>Clinical trials</subject><subject>Combined Modality Therapy</subject><subject>Decision making</subject><subject>FDA approval</subject><subject>Feasibility Studies</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Genomes</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Matched therapy</subject><subject>Medicine</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Molecular Targeted Therapy - standards</subject><subject>Mutation</subject><subject>Next-generation sequencing</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Pancreatic Neoplasms - therapy</subject><subject>Pancreaticoduodenectomy</subject><subject>Patients</subject><subject>Precision Medicine</subject><subject>Prognosis</subject><subject>Retrospective Studies</subject><subject>Surgery</subject><subject>Survival analysis</subject><subject>Time 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Wright, Michael ; Javed, Zunaira N. ; Wilt, Cara ; Parish, Lindsay ; Hodgin, Mary ; Ryan, Amy ; Judkins, Carol ; McIntyre, Keith ; Klein, Rachel ; Azad, Nilo ; Lee, Valerie ; Donehower, Ross ; De Jesus-Acosta, Ana ; Murphy, Adrian ; Le, Dung T. ; Shin, Eun Ji ; Lennon, Anne Marie ; Khashab, Mouen ; Singh, Vikesh ; Klein, Alison P. ; Roberts, Nicholas J. ; Hacker-Prietz, Amy ; Manos, Lindsey ; Walsh, Christi ; Groshek, Lara ; Brown, Caitlin ; Yuan, Chunhui ; Blair, Alex B. ; Groot, Vincent ; Gemenetzis, Georgios ; Yu, Jun ; Weiss, Matthew J. ; Burkhart, Richard A. ; Burns, William R. ; He, Jin ; Cameron, John L. ; Narang, Amol ; Zaheer, Atif ; Fishman, Elliot K. ; Thompson, Elizabeth D. ; Anders, Robert ; Hruban, Ralph H. ; Jaffee, Elizabeth ; Wolfgang, Christopher L. ; Zheng, Lei ; Laheru, Daniel 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D.</creatorcontrib><creatorcontrib>Anders, Robert</creatorcontrib><creatorcontrib>Hruban, Ralph H.</creatorcontrib><creatorcontrib>Jaffee, Elizabeth</creatorcontrib><creatorcontrib>Wolfgang, Christopher L.</creatorcontrib><creatorcontrib>Zheng, Lei</creatorcontrib><creatorcontrib>Laheru, Daniel A.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ding, Ding</au><au>Javed, Ammar A.</au><au>Cunningham, Dea</au><au>Teinor, Jonathan</au><au>Wright, Michael</au><au>Javed, Zunaira N.</au><au>Wilt, Cara</au><au>Parish, Lindsay</au><au>Hodgin, Mary</au><au>Ryan, Amy</au><au>Judkins, Carol</au><au>McIntyre, Keith</au><au>Klein, Rachel</au><au>Azad, Nilo</au><au>Lee, Valerie</au><au>Donehower, Ross</au><au>De Jesus-Acosta, Ana</au><au>Murphy, Adrian</au><au>Le, Dung T.</au><au>Shin, Eun Ji</au><au>Lennon, Anne Marie</au><au>Khashab, Mouen</au><au>Singh, Vikesh</au><au>Klein, Alison P.</au><au>Roberts, Nicholas J.</au><au>Hacker-Prietz, Amy</au><au>Manos, Lindsey</au><au>Walsh, Christi</au><au>Groshek, Lara</au><au>Brown, Caitlin</au><au>Yuan, Chunhui</au><au>Blair, Alex B.</au><au>Groot, Vincent</au><au>Gemenetzis, Georgios</au><au>Yu, Jun</au><au>Weiss, Matthew J.</au><au>Burkhart, Richard A.</au><au>Burns, William R.</au><au>He, Jin</au><au>Cameron, John L.</au><au>Narang, Amol</au><au>Zaheer, Atif</au><au>Fishman, Elliot K.</au><au>Thompson, Elizabeth D.</au><au>Anders, Robert</au><au>Hruban, Ralph H.</au><au>Jaffee, Elizabeth</au><au>Wolfgang, Christopher L.</au><au>Zheng, Lei</au><au>Laheru, Daniel A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Challenges of the current precision medicine approach for pancreatic cancer: A single institution experience between 2013 and 2017</atitle><jtitle>Cancer letters</jtitle><addtitle>Cancer Lett</addtitle><date>2021-01-28</date><risdate>2021</risdate><volume>497</volume><spage>221</spage><epage>228</epage><pages>221-228</pages><issn>0304-3835</issn><eissn>1872-7980</eissn><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. •Clinical genomic profiling approach for PDAC patients in routine practice is feasible.•Delayed ordering of genomic testing in the clinical course and limited targetable alterations lead to the low percentage of patients who receive matched therapy.•A comprehensive real-time platform combining early ordering and potentially actionable alteration identification is urgently needed.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>33127389</pmid><doi>10.1016/j.canlet.2020.10.039</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-3435-6550</orcidid><orcidid>https://orcid.org/0000-0001-6646-0200</orcidid><orcidid>https://orcid.org/0000-0002-3297-2299</orcidid><orcidid>https://orcid.org/0000-0001-9149-2247</orcidid><orcidid>https://orcid.org/0000-0003-0624-8149</orcidid><orcidid>https://orcid.org/0000-0001-5825-9873</orcidid><orcidid>https://orcid.org/0000-0003-2102-3140</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0304-3835
ispartof Cancer letters, 2021-01, Vol.497, p.221-228
issn 0304-3835
1872-7980
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8375587
source MEDLINE; Elsevier ScienceDirect Journals
subjects Actionable alteration
Adenocarcinoma
Aged
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biomarkers, Tumor - genetics
Biopsy
Carcinoma, Pancreatic Ductal - genetics
Carcinoma, Pancreatic Ductal - secondary
Carcinoma, Pancreatic Ductal - therapy
Clinical decision making
Clinical genomic testing
Clinical medicine
Clinical trials
Combined Modality Therapy
Decision making
FDA approval
Feasibility Studies
Female
Follow-Up Studies
Genomes
High-Throughput Nucleotide Sequencing
Humans
Lymphatic Metastasis
Male
Matched therapy
Medicine
Metastasis
Middle Aged
Molecular Targeted Therapy - standards
Mutation
Next-generation sequencing
Pancreatic cancer
Pancreatic Neoplasms - genetics
Pancreatic Neoplasms - pathology
Pancreatic Neoplasms - therapy
Pancreaticoduodenectomy
Patients
Precision Medicine
Prognosis
Retrospective Studies
Surgery
Survival analysis
Time Factors
Tumors
title Challenges of the current precision medicine approach for pancreatic cancer: A single institution experience between 2013 and 2017
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