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 |
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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 |
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•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. Published by Elsevier B.V. All rights reserved.</rights><rights>2020. The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-4732e00256e0ccc005e200480143c0d58ed063722964a180f2388d17ea8aeb4f3</citedby><cites>FETCH-LOGICAL-c491t-4732e00256e0ccc005e200480143c0d58ed063722964a180f2388d17ea8aeb4f3</cites><orcidid>0000-0003-3435-6550 ; 0000-0001-6646-0200 ; 0000-0002-3297-2299 ; 0000-0001-9149-2247 ; 0000-0003-0624-8149 ; 0000-0001-5825-9873 ; 0000-0003-2102-3140</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0304383520305735$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33127389$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ding, Ding</creatorcontrib><creatorcontrib>Javed, Ammar A.</creatorcontrib><creatorcontrib>Cunningham, Dea</creatorcontrib><creatorcontrib>Teinor, Jonathan</creatorcontrib><creatorcontrib>Wright, Michael</creatorcontrib><creatorcontrib>Javed, Zunaira N.</creatorcontrib><creatorcontrib>Wilt, Cara</creatorcontrib><creatorcontrib>Parish, Lindsay</creatorcontrib><creatorcontrib>Hodgin, Mary</creatorcontrib><creatorcontrib>Ryan, Amy</creatorcontrib><creatorcontrib>Judkins, Carol</creatorcontrib><creatorcontrib>McIntyre, Keith</creatorcontrib><creatorcontrib>Klein, Rachel</creatorcontrib><creatorcontrib>Azad, Nilo</creatorcontrib><creatorcontrib>Lee, Valerie</creatorcontrib><creatorcontrib>Donehower, Ross</creatorcontrib><creatorcontrib>De Jesus-Acosta, Ana</creatorcontrib><creatorcontrib>Murphy, Adrian</creatorcontrib><creatorcontrib>Le, Dung T.</creatorcontrib><creatorcontrib>Shin, Eun Ji</creatorcontrib><creatorcontrib>Lennon, Anne Marie</creatorcontrib><creatorcontrib>Khashab, Mouen</creatorcontrib><creatorcontrib>Singh, Vikesh</creatorcontrib><creatorcontrib>Klein, Alison P.</creatorcontrib><creatorcontrib>Roberts, Nicholas J.</creatorcontrib><creatorcontrib>Hacker-Prietz, Amy</creatorcontrib><creatorcontrib>Manos, Lindsey</creatorcontrib><creatorcontrib>Walsh, Christi</creatorcontrib><creatorcontrib>Groshek, Lara</creatorcontrib><creatorcontrib>Brown, Caitlin</creatorcontrib><creatorcontrib>Yuan, Chunhui</creatorcontrib><creatorcontrib>Blair, Alex B.</creatorcontrib><creatorcontrib>Groot, Vincent</creatorcontrib><creatorcontrib>Gemenetzis, Georgios</creatorcontrib><creatorcontrib>Yu, Jun</creatorcontrib><creatorcontrib>Weiss, Matthew J.</creatorcontrib><creatorcontrib>Burkhart, Richard A.</creatorcontrib><creatorcontrib>Burns, William R.</creatorcontrib><creatorcontrib>He, Jin</creatorcontrib><creatorcontrib>Cameron, John L.</creatorcontrib><creatorcontrib>Narang, Amol</creatorcontrib><creatorcontrib>Zaheer, Atif</creatorcontrib><creatorcontrib>Fishman, Elliot K.</creatorcontrib><creatorcontrib>Thompson, Elizabeth 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><title>Challenges of the current precision medicine approach for pancreatic cancer: A single institution experience between 2013 and 2017</title><title>Cancer letters</title><addtitle>Cancer Lett</addtitle><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.</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 Factors</subject><subject>Tumors</subject><issn>0304-3835</issn><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtv1DAUhSMEokPhHyBkiU03Ga4fiR0WSNWIl1SJDawtj3Mz41HGDrbTwra_HIcp5bFgZev63HPv8VdVzymsKdD21WFtjR8xrxmwpbQG3j2oVlRJVstOwcNqBRxEzRVvzqonKR0AoBGyeVydcU6Z5KpbVbebvRlH9DtMJAwk75HYOUb0mUwRrUsueHLE3lnnkZhpisHYPRlCJJPxNqLJzpKyicX4mlyS5PxuROJ8yi7PeenGbxNGh0VBtphvED1hQDkxvl8u8mn1aDBjwmd353n15d3bz5sP9dWn9x83l1e1FR3NtZCcIQBrWgRrbcmCDEAooIJb6BuFPbRcMta1wlAFA-NK9VSiUQa3YuDn1ZuT7zRvSyJbMkYz6im6o4nfdTBO__3i3V7vwrVWXDaNksXg4s4ghq8zpqyPLlkcR-MxzEkz0bSCSmBtkb78R3oIc_QlXlG1TdlStYuhOKlsDClFHO6XoaAXyPqgT5D1AnmpFsil7cWfQe6bflH9nRTLd147jDrZnwB6V5hm3Qf3_wk_AE2dukc</recordid><startdate>20210128</startdate><enddate>20210128</enddate><creator>Ding, Ding</creator><creator>Javed, Ammar 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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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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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