Genomic testing for pancreatic cancer in clinical practice as real-world evidence

被引:32
作者
Hayashi, Hideyuki [1 ]
Tanishima, Shigeki [2 ]
Fujii, Kyoko [1 ]
Mori, Ryo [2 ]
Okamura, Yasunobu [2 ]
Yanagita, Emmy [1 ]
Matsuoka, Ryosuke [1 ]
Amano, Toraji [3 ]
Kinoshita, Ichiro [4 ]
Komatsu, Yoshito [5 ]
Dosaka-Akita, Hirotoshi [1 ,4 ]
Nishihara, Hiroshi [1 ]
机构
[1] Hokkaido Univ Hosp, Div Clin Canc Genom, Sapporo, Hokkaido, Japan
[2] Mitsubishi Space Software Co Ltd, Dept Biomed Informat Dev, Tokyo, Japan
[3] Hokkaido Univ Hosp, Clin Res & Med Innovat Ctr, Sapporo, Hokkaido, Japan
[4] Hokkaido Univ, Grad Sch Med, Dept Med Oncol, Sapporo, Hokkaido, Japan
[5] Hokkaido Univ Hosp, Canc Ctr, Dept Canc Chemotherapy, Sapporo, Hokkaido, Japan
关键词
Clinical sequencing; Gene alterations; Precision medicine; Turnaround time; DUCTAL ADENOCARCINOMA; MUTATIONAL LANDSCAPE; PRECISION MEDICINE; MUTANT KRAS; PHASE-III; GEMCITABINE; THERAPY; IMMUNOTHERAPY; DIAGNOSIS; GENETICS;
D O I
10.1016/j.pan.2018.07.006
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: Precision medicine guided by comprehensive genome sequencing represents a potential treatment strategy for pancreatic cancer. However, clinical sequencing for pancreatic cancer entails several practical difficulties. We have launched an in-house clinical sequencing system and started genomic testing for patients with cancer in clinical practice. We have analyzed the clinical utility of this system in pancreatic cancer. Methods: We retrospectively reviewed 20 patients with pancreatic cancer who visited our division. Genomic DNA was extracted from both tumor tissue and peripheral blood mononuclear cells obtained from the patients. We performed a comprehensive genomic testing using targeted amplicon sequencing for 160 cancer-related genes. The primary endpoints were the detection rates of potential actionable and druggable gene alterations. The secondary endpoints were the detection rate of secondary germline findings, the rate of re-biopsy required for genome sequencing, survival time after the initial visit (postsequencing survival time), and turnaround time. Results: Although re-biopsy was required for 25% (5/20) of all patients, genomic testing was performed in all patients. Actionable and druggable gene alterations were detected in 100% (20/20) and 35% (7/20) of patients, respectively, whereas secondary germline findings were detected in 5% (1/20) of patients. The median turnaround times for physicians and patients were 20 and 26 days, respectively. The median post-sequencing survival time was 10.3 months. Only 10% (2/20) of all patients were treated with therapeutic agents based on the outcomes of genomic testing. Conclusions: The clinical application of comprehensive genomic testing for pancreatic cancer was feasible and promising in clinical practice. (C) 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:647 / 654
页数:8
相关论文
共 37 条
[1]   Genomic analyses identify molecular subtypes of pancreatic cancer [J].
Bailey, Peter ;
Chang, David K. ;
Nones, Katia ;
Johns, Amber L. ;
Patch, Ann-Marie ;
Gingras, Marie-Claude ;
Miller, David K. ;
Christ, Angelika N. ;
Bruxner, Tim J. C. ;
Quinn, Michael C. ;
Nourse, Craig ;
Murtaugh, L. Charles ;
Harliwong, Ivon ;
Idrisoglu, Senel ;
Manning, Suzanne ;
Nourbakhsh, Ehsan ;
Wani, Shivangi ;
Fink, Lynn ;
Holmes, Oliver ;
Chin, Vencssa ;
Anderson, Matthew J. ;
Kazakoff, Stephen ;
Leonard, Conrad ;
Newell, Felicity ;
Waddell, Nick ;
Wood, Scott ;
Xu, Qinying ;
Wilson, Peter J. ;
Cloonan, Nicole ;
Kassahn, Karin S. ;
Taylor, Darrin ;
Quek, Kelly ;
Robertson, Alan ;
Pantano, Lorena ;
Mincarelli, Laura ;
Sanchez, Luis N. ;
Evers, Lisa ;
Wu, Jianmin ;
Pinese, Mark ;
Cowley, Mark J. ;
Jones, Marc D. ;
Colvin, Emily K. ;
Nagrial, Adnan M. ;
Humphrey, Emily S. ;
Chantrill, Lorraine A. ;
Mawson, Amanda ;
Humphris, Jeremy ;
Chou, Angela ;
Pajic, Marina ;
Scarlett, Christopher J. .
NATURE, 2016, 531 (7592) :47-+
[2]   Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: A randomized trial [J].
Burris, HA ;
Moore, MJ ;
Andersen, J ;
Green, MR ;
Rothenberg, ML ;
Madiano, MR ;
Cripps, MC ;
Portenoy, RK ;
Storniolo, AM ;
Tarassoff, P ;
Nelson, R ;
Dorr, FA ;
Stephens, CD ;
VanHoff, DD .
JOURNAL OF CLINICAL ONCOLOGY, 1997, 15 (06) :2403-2413
[3]   Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden [J].
Chalmers, Zachary R. ;
Connelly, Caitlin F. ;
Fabrizio, David ;
Gay, Laurie ;
Ali, Siraj M. ;
Ennis, Riley ;
Schrock, Alexa ;
Campbell, Brittany ;
Shlien, Adam ;
Chmielecki, Juliann ;
Huang, Franklin ;
He, Yuting ;
Sun, James ;
Tabori, Uri ;
Kennedy, Mark ;
Lieber, Daniel S. ;
Roels, Steven ;
White, Jared ;
Otto, Geoffrey A. ;
Ross, Jeffrey S. ;
Garraway, Levi ;
Miller, Vincent A. ;
Stephens, Phillip J. ;
Frampton, Garrett M. .
GENOME MEDICINE, 2017, 9
[4]   Precision Medicine for Advanced Pancreas Cancer: The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) Trial [J].
Chantrill, Lorraine A. ;
Nagrial, Adnan M. ;
Watson, Clare ;
Johns, Amber L. ;
Martyn-Smith, Mona ;
Simpson, Skye ;
Mead, Scott ;
Jones, Marc D. ;
Samra, Jaswinder S. ;
Gill, Anthony J. ;
Watson, Nicole ;
Chin, Venessa T. ;
Humphris, Jeremy L. ;
Chou, Angela ;
Brown, Belinda ;
Morey, Adrienne ;
Pajic, Marina ;
Grimmond, Sean M. ;
Chang, David K. ;
Thomas, David ;
Sebastian, Lucille ;
Sjoquist, Katrin ;
Yip, Sonia ;
Pavlakis, Nick ;
Asghari, Ray ;
Harvey, Sandra ;
Grimison, Peter ;
Simes, John ;
Biankin, Andrew V. .
CLINICAL CANCER RESEARCH, 2015, 21 (09) :2029-2037
[5]   FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer [J].
Conroy, Thierry ;
Desseigne, Francoise ;
Ychou, Marc ;
Bouche, Olivier ;
Guimbaud, Rosine ;
Becouarn, Yves ;
Adenis, Antoine ;
Raoul, Jean-Luc ;
Gourgou-Bourgade, Sophie ;
de la Fouchardiere, Christelle ;
Bennouna, Jaafar ;
Bachet, Jean-Baptiste ;
Khemissa-Akouz, Faiza ;
Pere-Verge, Denis ;
Delbaldo, Catherine ;
Assenat, Eric ;
Chauffert, Bruno ;
Michel, Pierre ;
Montoto-Grillot, Christine ;
Ducreux, Michel .
NEW ENGLAND JOURNAL OF MEDICINE, 2011, 364 (19) :1817-1825
[6]   Improving pancreatic cancer diagnosis using circulating tumor cells: prospects for staging and single-cell analysis [J].
Court, Colin M. ;
Ankeny, Jacob S. ;
Hou, Shuang ;
Tseng, Hsian-Rong ;
Tomlinson, James S. .
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS, 2015, 15 (11) :1491-1504
[7]   Basket Trials in Oncology: A Trade-Off Between Complexity and Efficiency [J].
Cunanan, Kristen M. ;
Gonen, Mithat ;
Shen, Ronglai ;
Hyman, David M. ;
Riely, Gregory J. ;
Begg, Colin B. ;
Iasonos, Alexia .
JOURNAL OF CLINICAL ONCOLOGY, 2017, 35 (03) :271-+
[8]   PD-1/PD-L1 and immunotherapy for pancreatic cancer [J].
Feng, Mengyu ;
Xiong, Guangbing ;
Cao, Zhe ;
Yang, Gang ;
Zheng, Suli ;
Song, Xujun ;
You, Lei ;
Zheng, Lianfang ;
Zhang, Taiping ;
Zhao, Yupei .
CANCER LETTERS, 2017, 407 :57-65
[9]   Prevalence of Germline Mutations in Cancer Predisposition Genes in Patients With Pancreatic Cancer [J].
Grant, Robert C. ;
Selander, Iris ;
Connor, Ashton A. ;
Selvarajah, Shamini ;
Borgida, Ayelet ;
Briollais, Laurent ;
Petersen, Gloria M. ;
Lerner-Ellis, Jordan ;
Holter, Spring ;
Gallinger, Steven .
GASTROENTEROLOGY, 2015, 148 (03) :556-564
[10]   Utility of Assessing the Number of Mutated KRAS, CDKN2A, TP53, and SMAD4 Genes Using a Targeted Deep Sequencing Assay as a Prognostic Biomarker for Pancreatic Cancer [J].
Hayashi, Hideyuki ;
Kohno, Takashi ;
Ueno, Hideki ;
Hiraoka, Nobuyoshi ;
Kondo, Shunsuke ;
Saito, Motonobu ;
Shimada, Yoko ;
Ichikawa, Hitoshi ;
Kato, Mamoru ;
Shibata, Tatsuhiro ;
Morizane, Chigusa ;
Sakamoto, Yasunari ;
Shimada, Kazuaki ;
Komatsu, Yoshito ;
Sakamoto, Naoya ;
Okusaka, Takuji .
PANCREAS, 2017, 46 (03) :335-340