Short-term serial circulating tumor DNA assessment predicts therapeutic efficacy for patients with advanced pancreatic cancer

被引:6
作者
Motobayashi, Hideki [1 ]
Kitahata, Yuji [1 ]
Okada, Ken-ichi [1 ]
Miyazawa, Motoki [1 ]
Ueno, Masaki [1 ]
Hayami, Shinya [1 ]
Miyamoto, Atsushi [1 ]
Shimizu, Atsushi [1 ]
Sato, Masatoshi [1 ]
Yoshimura, Tomohiro [1 ]
Nakamura, Yuki [1 ]
Takemoto, Norio [1 ]
Nakai, Tomoki [1 ]
Hyo, Takahiko [1 ]
Matsumoto, Kyohei [1 ]
Yamaue, Hiroki [2 ]
Kawai, Manabu [1 ]
机构
[1] Wakayama Med Univ, Sch Med, Dept Surg 2, 811-1 Kimiidera, Wakayama 6418510, Japan
[2] Wakayama Med Univ, Dept Canc Immunol, Wakayama, Japan
关键词
Advanced pancreatic cancer; Systemic chemotherapy; Therapeutic efficacy; Real-time biomarkers; Molecular response; LIQUID BIOPSIES; NAB-PACLITAXEL; GEMCITABINE; FOLFIRINOX; SURVIVAL; CHEMOTHERAPY; SURROGATE;
D O I
10.1007/s00432-023-05594-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose We investigated the potential clinical utility of short-term serial KRAS-mutated circulating cell-free tumor DNA (ctDNA) assessment for predicting therapeutic response in patients undergoing first-line chemotherapy for advanced pancreatic cancer. Methods We collected 144 blood samples from 18 patients with locally advanced or metastatic cancer that were undergoing initial first-line chemotherapy of gemcitabine plus nab-paclitaxel (GEM plus nab-PTX). Analysis of KRAS-mutated ctDNA was quantified by digital droplet polymerase chain reaction (ddPCR) as mutant allele frequency (MAF). This study investigated pretreatment KRAS-mutated ctDNA status and ctDNA kinetics every few days (days 1, 3, 5 and 7) after initiation of chemotherapy and their potential as predictive indicators. Results Of the 18 enrolled patients, an increase in KRAS-mutated ctDNA MAF values from day 0-7 after initiation of chemotherapy was significantly associated with disease progression (P < 0.001). Meanwhile, positive pretreatment ctDNA status (MAF >= 0.02%) (P = 0.585) and carbohydrate antigen 19-9 (CA19-9) values above the median (P = 0.266) were not associated with disease progression. In univariate analysis, this short-term increase in ctDNA MAF values (day 0-7) was found to be associated with significantly shorter progression free survival (PFS) (hazard ration [HR], 24.234; range, (2.761-212.686); P = 0.0002). Conclusion This short-term ctDNA kinetics assessment may provide predictive information to reflect real-time therapeutic response and lead to effective refinement of regimen in patients with advanced pancreatic cancer undergoing systemic chemotherapy.
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页数:13
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共 34 条
[1]   High prevalence of mutant KRAS in circulating exosome-derived DNA from early-stage pancreatic cancer patients [J].
Allenson, K. ;
Castillo, J. ;
San Lucas, F. A. ;
Scelo, G. ;
Kim, D. U. ;
Bernard, V. ;
Davis, G. ;
Kumar, T. ;
Katz, M. ;
Overman, M. J. ;
Foretova, L. ;
Fabianova, E. ;
Holcatova, I. ;
Janout, V. ;
Meric-Bernstam, F. ;
Gascoyne, P. ;
Wistuba, I. ;
Varadhachary, G. ;
Brennan, P. ;
Hanash, S. ;
Li, D. ;
Maitra, A. ;
Alvarez, H. .
ANNALS OF ONCOLOGY, 2017, 28 (04) :741-747
[2]   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-+
[3]   Circulating Nucleic Acids Are Associated With Outcomes of Patients With Pancreatic Cancer [J].
Bernard, Vincent ;
Kim, Dong U. ;
San Lucas, F. Anthony ;
Castillo, Jonathan ;
Allenson, Kelvin ;
Mulu, Feven C. ;
Stephens, Bret M. ;
Huang, Jonathan ;
Semaan, Alexander ;
Guerrero, Paola A. ;
Kamyabi, Nabiollah ;
Zhao, Jun ;
Hurd, Mark W. ;
Koay, Eugene J. ;
Taniguchi, Cullen M. ;
Herman, Joseph M. ;
Javle, Milind ;
Wolff, Robert ;
Katz, Matthew ;
Varadhachary, Gauri ;
Maitra, Anirban ;
Alvarez, Hector A. .
GASTROENTEROLOGY, 2019, 156 (01) :108-+
[4]   Application of a Time-Varying Covariate Model to the Analysis of CA 19-9 as Serum Biomarker in Patients with Advanced Pancreatic Cancer [J].
Boeck, Stefan ;
Haas, Michael ;
Laubender, Ruediger P. ;
Kullmann, Frank ;
Klose, Christina ;
Bruns, Christiane J. ;
Wilkowski, Ralf ;
Stieber, Petra ;
Holdenrieder, Stefan ;
Buchner, Hannes ;
Mansmann, Ulrich ;
Heinemann, Volker .
CLINICAL CANCER RESEARCH, 2010, 16 (03) :986-994
[5]   Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer [J].
Buscail, Louis ;
Bournet, Barbara ;
Cordelier, Pierre .
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2020, 17 (03) :153-168
[6]   Pancreatic cancer survival by stage and age in seven high-income countries (ICBP SURVMARK-2): a population-based study [J].
Cabasag, Citadel J. ;
Arnold, Melina ;
Rutherford, Mark ;
Bardot, Aude ;
Ferlay, Jacques ;
Morgan, Eileen ;
Little, Alana ;
De, Prithwish ;
Dixon, Elijah ;
Woods, Ryan R. ;
Saint-Jacques, Nathalie ;
Evans, Sue ;
Engholm, Gerda ;
Elwood, Mark ;
Merrett, Neil ;
Ransom, David ;
O'Connell, Dianne L. ;
Bray, Freddie ;
Soerjomataram, Isabelle .
BRITISH JOURNAL OF CANCER, 2022, 126 (12) :1774-1782
[7]   Analysis of ctDNA to predict prognosis and monitor treatment responses in metastatic pancreatic cancer patients [J].
Cheng, He ;
Liu, Chen ;
Jiang, Jiahao ;
Luo, Guopei ;
Lu, Yu ;
Jin, Kaizhou ;
Guo, Meng ;
Zhang, Zhenzhen ;
Xu, Jin ;
Liu, Liang ;
Ni, Quanxing ;
Yu, Xianjun .
INTERNATIONAL JOURNAL OF CANCER, 2017, 140 (10) :2344-2350
[8]   FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer [J].
Conroy, T. ;
Hammel, P. ;
Hebbar, M. ;
Ben Abdelghani, M. ;
Wei, A. C. ;
Raoul, J. -L. ;
Chone, L. ;
Francois, E. ;
Artru, P. ;
Biagi, J. J. ;
Lecomte, T. ;
Assenat, E. ;
Faroux, R. ;
Ychou, M. ;
Volet, J. ;
Sauvanet, A. ;
Breysacher, G. ;
Di Fiore, F. ;
Cripps, C. ;
Kavan, P. ;
Texereau, P. ;
Bouhier-Leporrier, K. ;
Khemissa-Akouz, F. ;
Legoux, J. -L. ;
Juzyna, B. ;
Gourgou, S. ;
O'Callaghan, C. J. ;
Jouffroy-Zeller, C. ;
Rat, P. ;
Malka, D. ;
Castan, F. ;
Bachet, J. -B. .
NEW ENGLAND JOURNAL OF MEDICINE, 2018, 379 (25) :2395-2406
[9]   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
[10]   Circulating tumor cells (Ctc) and kras mutant circulating free Dna (cfdna) detection in peripheral blood as biomarkers in patients diagnosed with exocrine pancreatic cancer [J].
Earl, Julie ;
Garcia-Nieto, Sandra ;
Carlos Martinez-Avila, Jose ;
Montans, Jose ;
Sanjuanbenito, Alfonso ;
Rodriguez-Garrote, Mercedes ;
Lisa, Eduardo ;
Mendia, Elena ;
Lobo, Eduardo ;
Malats, Nria ;
Carrato, Alfredo ;
Guillen-Ponce, Carmen .
BMC CANCER, 2015, 15