Precision Oncology in Pancreatic Cancer: Experiences and Challenges of the CCCMunichLMU Molecular Tumor Board

被引：13

作者：

Dorman, Klara ^{[1
,2
,3
]}

Zhang, Danmei ^{[1
,2
,3
]}

Heinrich, Kathrin ^{[1
,2
,3
]}

Reeh, Laurens ^{[1
,2
,4
]}

Weiss, Lena ^{[1
,2
]}

Haas, Michael ^{[1
,2
]}

Beyer, Georg ^{[5
,6
]}

Roessler, Daniel ^{[5
,6
]}

Goni, Elisabetta ^{[5
,6
]}

Renz, Bernhard W. ^{[3
,7
]}

D'Haese, Jan G. ^{[7
]}

Kunz, Wolfgang G. ^{[8
]}

Seidensticker, Max ^{[8
]}

Corradini, Stefanie ^{[9
]}

Niyazi, Maximilian ^{[3
,6
,9
]}

Ormanns, Steffen ^{[3
,10
]}

Kumbrink, Joerg ^{[3
,10
]}

Jung, Andreas ^{[3
,10
]}

Klauschen, Frederick ^{[3
,10
]}

Werner, Jens ^{[3
,6
,7
]}

Mayerle, Julia ^{[3
,5
,6
]}

von Bergwelt-Baildon, Michael ^{[1
,2
,3
]}

Boeck, Stefan ^{[1
,2
,3
]}

Heinemann, Volker ^{[1
,2
,3
]}

Westphalen, C. Benedikt ^{[1
,2
,3
]}

机构：

[1] Ludwig Maximilian Univ Munich, Univ Hosp, Dept Internal Medicine3, Klinikum Grosshadern, Marchioninistr 15, D-81377 Munich, Germany

[2] Ludwig Maximilian Univ Munich, Univ Hosp, Comprehens Canc Ctr, Klinikum Grosshadern, Marchioninistr 15, D-81377 Munich, Germany

[3] German Canc Consortium DKTK, Partner Site Munich, Munich, Germany

[4] Klinikum Dritter Orden, Dept Pediat & Adolescent Med, Munich, Germany

[5] Ludwig Maximilians Univ Munchen, Univ Hosp, Dept Med 2, Munich, Germany

[6] Bavarian Canc Res Ctr BZKF, Partner Site Munich, Munich, Germany

[7] Ludwig Maximilians Univ Munchen, Univ Hosp, Dept Gen Visceral & Transplant Surg, Munich, Germany

[8] Ludwig Maximilians Univ Munchen, Univ Hosp, Dept Radiol, Munich, Germany

[9] Ludwig Maximilians Univ Munchen, Univ Hosp, Dept Radiat Oncol, Munich, Germany

[10] Ludwig Maximilians Univ Munchen, Inst Pathol, Fac Med, Munich, Germany

来源：

TARGETED ONCOLOGY | 2023年 / 18卷 / 02期

关键词：

THERAPY;

D O I：

10.1007/s11523-023-00950-0

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BackgroundIn pancreatic cancer, systemic treatment options in addition to chemotherapy remain scarce, and so far only a small proportion of patients benefit from targeted therapies.ObjectiveThe patients with pancreatic cancer discussed in the CCCMunich(LMU) Molecular Tumor Board were reviewed to gain a better real-world understanding of the challenges and chances of precision oncology in this hard-to-treat cancer.MethodsPatients with pancreatic cancer who received comprehensive genomic profiling and were discussed in the interdisciplinary Molecular Tumor Board between May 2017 and July 2022 were included. These patients' medical charts, comprehensive genomic profiling results, and Molecular Tumor Board recommendations were analyzed in this retrospective cohort study.ResultsMolecular profiles of 165 patients with pancreatic cancer were discussed in the Molecular Tumor Board. In the 149 cases where comprehensive genomic profiling was successful, KRAS mutations were detected in 87.9%, TP53 in 53.0%, and CDKN2A in 14.1%. 33.3% of KRAS wild-type patients harbored targetable mutations, while these were only found in 19.1% of patients with the KRAS mutation; however, this difference was not statistically significant. 63.8% of patients with successful testing received a targeted treatment recommendation by the Molecular Tumor Board; however, only 3.2% of these were put into practice. Compared to a historic cohort of patients with pancreatic cancer with synchronous metastatic disease diagnosed between 2010 and 2017, the patients from the pancreatic cancer cohort with synchronous metastatic disease had a longer survival.ConclusionsThis single-center experience emphasizes the challenges of targeted treatment in pancreatic cancer. Very few patients ultimately received the recommended therapies, highlighting the need for more and better targeted treatment options in pancreatic cancer, early comprehensive genomic profiling to allow sufficient time to put Molecular Tumor Board recommendations into practice, and close cooperation with clinical trial units to give patients access to otherwise not available targeted treatments.

引用

页码：257 / 267

页数：11

共 31 条

[1]

[Anonymous], KREBS BAUCHSPEICHELD

[2] Evaluation of worldwide clinical trials by gender: An FDA perspective [J].

Ayuso, Emily ;

Geller, Ruth J. ;

Wang, Junyang ;

Whyte, John ;

Jenkins, Marjorie .

CONTEMPORARY CLINICAL TRIALS, 2019, 80 :16-21

[3] 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-+

[4] 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

[5] Evolving Landscape of Molecular Prescreening Strategies for Oncology Early Clinical Trials [J].

Dienstmann, Rodrigo ;

Garralda, Elena ;

Aguilar, Susana ;

Sala, Gemma ;

Viaplana, Cristina ;

Ruiz-Pace, Fiorella ;

Gonzalez-Zorelle, Jenifer ;

Grazia LoGiacco, Deborah ;

Ogbah, Zighereda ;

Ramos Masdeu, Laia ;

Mancuso, Francesco ;

Fasani, Roberta ;

Jimenez, Jose ;

Martinez, Paola ;

Oaknin, Ana ;

Saura, Cristina ;

Oliveira, Mafalda ;

Balmana, Judith ;

Carles, Joan ;

Macarulla, Teresa ;

Elez, Elena ;

Alsina, Maria ;

Brana, Irene ;

Felip, Enriqueta ;

Tabernero, Josep ;

Rodon, Jordi ;

Nuciforo, Paolo ;

Vivancos, Ana .

JCO PRECISION ONCOLOGY, 2020, 4 :505-513

[6] Challenges of the current precision medicine approach for pancreatic cancer: A single institution experience between 2013 and 2017 [J].

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. .

CANCER LETTERS, 2021, 497 :221-228

[7] Serum biomarker panel diagnostics in pancreatic ductal adenocarcinoma: the clinical utility of soluble interleukins, IFN-γ, TNF-α and PD-1/PD-L1 in comparison to established serum tumor markers [J].

Dorman, Klara ;

Gerckens, Miriam ;

Kruger, Stephan ;

Krueger, Kimberly ;

Mayer, Zsuzsanna ;

Rupp, Alexander ;

Zhang, Danmei ;

Weiss, Lena ;

Westphalen, C. Benedikt ;

Haas, Michael ;

Guenther, Michael ;

Ormanns, Steffen ;

Klawonn, Frank ;

Werner, Jens ;

von Bergwelt-Baildon, Michael ;

Heinemann, Volker ;

Boeck, Stefan ;

Holdenrieder, Stefan .

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2023, 149 (06) :2463-2474

[8] Novel systemic treatment approaches for metastatic pancreatic cancer [J].

Dorman, Klara ;

Heinemann, Volker ;

Kobold, Sebastian ;

Von Bergwelt-Baildon, Michael ;

Boeck, Stefan .

EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2022, 31 (03) :249-262

[9] Lessons learned: the first consecutive 1000 patients of the CCCMunichLMU Molecular Tumor Board [J].

Heinrich, Kathrin ;

Miller-Phillips, Lisa ;

Ziemann, Frank ;

Hasselmann, Korbinian ;

Ruehlmann, Katharina ;

Flach, Madeleine ;

Biro, Dorottya ;

von Bergwelt-Baildon, Michael ;

Holch, Julian ;

Herold, Tobias ;

von Baumgarten, Louisa ;

Greif, Philip A. ;

Jeremias, Irmela ;

Wuerstlein, Rachel ;

Casuscelli, Jozefina ;

Spitzweg, Christine ;

Seidensticker, Max ;

Renz, Bernhard ;

Corradini, Stefanie ;

Baumeister, Philipp ;

Goni, Elisabetta ;

Tufman, Amanda ;

Jung, Andreas ;

Kumbrink, Joerg ;

Kirchner, Thomas ;

Klauschen, Frederick ;

Metzeler, Klaus H. ;

Heinemann, Volker ;

Westphalen, C. Benedikt .

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2023, 149 (05) :1905-1915

[10] Protective autophagy elicited by RAF→MEK→ERK inhibition suggests a treatment strategy for RAS-driven cancers [J].

Kinsey, Conan G. ;

Camolotto, Soledad A. ;

Boespflug, Amelie M. ;

Guillen, Katrin P. ;

Foth, Mona ;

Truong, Amanda ;

Schuman, Sophia S. ;

Shea, Jill E. ;

Seipp, Michael T. ;

Yap, Jeffrey T. ;

Burrell, Lance D. ;

Lum, David H. ;

Whisenant, Jonathan R. ;

Gilcrease, G. Weldon, III ;

Cavalieri, Courtney C. ;

Rehbein, Kaitrin M. ;

Cutler, Stephanie L. ;

Affolter, Kajsa E. ;

Welm, Alana L. ;

Welm, Bryan E. ;

Scaife, Courtney L. ;

Snyder, Eric L. ;

McMahon, Martin .

NATURE MEDICINE, 2019, 25 (04) :620-+

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