Molecular Profiling of Patients with Pancreatic Cancer: Initial Results from the Know Your Tumor Initiative
Published version of a preprint
Abstract
Purpose: To broaden access to and implementation of precision medicine in the care of patients with pancreatic cancer, the Know Your Tumor (KYT) program was initiated using a turn-key precision medicine system. Patients undergo commercially available multiomic profiling to determine molecularly rationalized clinical trials and off-label therapies. Experimental Design: Tumor samples were obtained for 640 patients from 287 academic and community practices covering 44 states. College of American Pathologists/Clinical Laboratory Improvement Amendments–accredited laboratories were used for genomic, proteomic, and phosphoprotein-based molecular profiling. Results: Tumor samples were adequate for next-generation sequencing in 96% and IHC in 91% of patients. A tumor board reviewed the results for every patient and found actionable genomic alterations in 50% of patients (with 27% highly actionable) and actionable proteomic alterations (excluding chemopredictive markers) in 5%. Actionable alterations commonly found were in DNA repair genes (BRCA1/2 or ATM mutations, 8.4%) and cell-cycle genes (CCND1/2/3 or CDK4/6 alterations, 8.1%). A subset of samples was assessed for actionable phosphoprotein markers. Among patients with highly actionable biomarkers, those who received matched therapy (n = 17) had a significantly longer median progression-free survival (PFS) than those who received unmatched therapy [n = 18; PFS = 4.1 vs. 1.9 months; HR, 0.47; 95% confidence interval (CI): 0.24–0.94; Padj = 0.03]. Conclusions: A comprehensive precision medicine system can be implemented in community and academic settings, with highly actionable findings observed in over 25% of pancreatic cancers. Patients whose tumors have highly actionable alterations and receive matched therapy demonstrated significantly increased PFS. Our findings support further prospective evaluation of precision oncology in pancreatic cancer. Clin Cancer Res; 24(20); 5018–27. ©2018 AACR.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The study validated its findings in an external cohort from PanCAN's Know Your Tumor dataset (n = 408).
“In addition, we validated our findings in an external cohort from the Pancreatic Cancer Action Network (PanCAN)’s Know Your Tumor® (KYT) Dataset38.”
From Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma (2024) · cites this paper as [38]
Cites
Austin, P. C. (2011) · Multivariate Behavioral Research · doi:10.1080/00273171.2011.568786 · Cited by 12,242 · see citing works
Siegel, R. L., Miller, K. D., & Jemal, A. (2015) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21254 · Cited by 11,854 · see citing works
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency
Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., Skora, A. D., Luber, B. S., Azad, N. S., Laheru, D., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500596 · Cited by 9,377 · see citing works
FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer
Conroy, T., Desseigne, F., Ychou, M., Bouché, O., Guimbaud, R., Bécouarn, Y., Adenis, A., Raoul, J.-L., Gourgou-Bourgade, S., de la Fouchardière, C., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1011923 · Cited by 7,810 · see citing works
Rahib, L., Smith, B. D., Aizenberg, R., Rosenzweig, A. B., Fleshman, J. M., & Matrisian, L. M. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-0155 · Cited by 7,094 · see citing works
Self-citationIncreased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine
Von Hoff, D. D., Ervin, T., Arena, F. P., Chiorean, E. G., Infante, J., Moore, M., Seay, T., Tjulandin, S. A., Ma, W. W., Saleh, M. N., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1304369 · Cited by 6,712 · see citing works
Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade
Le, D. T., Durham, J. N., Smith, K. N., Wang, H., Bartlett, B. R., Aulakh, L. K., Lu, S., Kemberling, H., Wilt, C., Luber, B. S., et al. (2017) · Science · doi:10.1126/science.aan6733 · Cited by 6,645 · see citing works
Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
Jones, S., Zhang, X., Parsons, D. W., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., et al. (2008) · Science · doi:10.1126/science.1164368 · Cited by 3,969 · see citing works
Genomic analyses identify molecular subtypes of pancreatic cancer
Bailey, P., Chang, D. K., Nones, K., Johns, A. L., Patch, A.-M., Gingras, M.-C., Miller, D. K., Christ, A. N., Bruxner, T. J. C., Quinn, M. C., et al. (2016) · Nature · doi:10.1038/nature16965 · Cited by 3,621 · cited 2× · see citing works
“Frequencies were comparable with those from other published datasets (5, 6, 23).”
ResultAnalysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden
Chalmers, Z. R., Connelly, C. F., Fabrizio, D., Gay, L., Ali, S. M., Ennis, R., Schrock, A., Campbell, B., Shlien, A., Chmielecki, J., et al. (2017) · Genome Medicine · doi:10.1186/s13073-017-0424-2 · Cited by 3,519 · see citing works
Whole genomes redefine the mutational landscape of pancreatic cancer
Initiative, A. P. C. G., Waddell, N., Pajic, M., Patch, A.-M., Chang, D. K., Kassahn, K. S., Bailey, P., Johns, A. L., Miller, D., Nones, K., et al. (2015) · Nature · doi:10.1038/nature14169 · Cited by 2,642 · cited 1× · see citing works
“This was consistent with the frequency of KRAS mutations in published studies (5, 6, 9).”
ResultDistant metastasis occurs late during the genetic evolution of pancreatic cancer
Yachida, S., Jones, S., Bozic, I., Antal, T., Leary, R., Fu, B., Kamiyama, M., Hruban, R. H., Eshleman, J. R., Nowak, M. A., et al. (2010) · Nature · doi:10.1038/nature09515 · Cited by 2,502 · see citing works
Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes
Initiative, A. P. C. G., Biankin, A. V., Waddell, N., Kassahn, K. S., Gingras, M.-C., Muthuswamy, L. B., Johns, A. L., Miller, D. K., Wilson, P. J., Patch, A.-M., et al. (2012) · Nature · doi:10.1038/nature11547 · Cited by 2,058 · see citing works
Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy
Collisson, E. A., Sadanandam, A., Olson, P., Gibb, W. J., Truitt, M., Gu, S., Cooc, J., Weinkle, J., Kim, G. E., Jakkula, L., et al. (2011) · Nature Medicine · doi:10.1038/nm.2344 · Cited by 1,967 · see citing works
Identifying differentially expressed genes using false discovery rate controlling procedures
Reiner, A., Yekutieli, D., & Benjamini, Y. (2003) · Bioinformatics · doi:10.1093/bioinformatics/btf877 · Cited by 1,765 · see citing works
Wang-Gillam, A., Li, C.-P., Bodoky, G., Dean, A., Shan, Y.-S., Jameson, G., Macarulla, T., Lee, K.-H., Cunningham, D., Blanc, J. F., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(15)00986-1 · Cited by 1,222 · cited 1× · see citing works
“4 months, which is comparable with historical controls derived from a trial of nanoliposomal irinotecan plus 5-fluorouracil [NAPOLI-1 trial (28): median PFS in experimental arm 1⁄4 3.”
BackgroundSelf-citationLe Tourneau, C., Delord, J.-P., Gonçalves, A., Gavoille, C., Dubot, C., Isambert, N., Campone, M., Trédan, O., Massiani, M.-A., Mauborgne, C., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00188-6 · Cited by 1,137 · see citing works
Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets
Witkiewicz, A. K., McMillan, E. A., Balaji, U., Baek, G., Lin, W.-C., Mansour, J., Mollaee, M., Wagner, K.-U., Koduru, P., Yopp, A., et al. (2015) · Nature Communications · doi:10.1038/ncomms7744 · Cited by 1,115 · cited 1× · see citing works
“Frequencies were comparable with those from other published datasets (5, 6, 23).”
ResultHingorani, S. R., Zheng, L., Bullock, A. J., Seery, T. E., Harris, W. P., Sigal, D. S., Braiteh, F., Ritch, P. S., Zalupski, M. M., Bahary, N., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.74.9564 · Cited by 514 · see citing works
Self-citationInfante, J. R., Somer, B. G., Park, J. O., Li, C., Scheulen, M. E., Kasubhai, S. M., Oh, D., Liu, Y., Redhu, S., Steplewski, K. M., et al. (2014) · European Journal of Cancer · doi:10.1016/j.ejca.2014.04.024 · Cited by 365 · see citing works
Schwaederle, M. C., Zhao, M. M., Lee, J. J., Lazar, V., Leyland-Jones, B. R., Schilsky, R. L., Mendelsohn, J. M., & Kurzrock, R. (2016) · JAMA Oncology · doi:10.1001/jamaoncol.2016.2129 · Cited by 349 · see citing works
Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline
Sohal, D. P. S., Mangu, P. B., Khorana, A. A., Shah, M. A., Philip, P. A., O'Reilly, E. M., Uronis, H. E., Ramanathan, R. K., Crane, C. H., Engebretson, A., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.67.1412 · Cited by 331 · see citing works
Self-citationPrecision medicine for metastatic breast cancer—limitations and solutions
Arnedos, M., Vicier, C., Loi, S., Lefèbvre, C., Michiels, S., Bonnefoi, H. R., & André, F. (2015) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2015.123 · Cited by 316 · see citing works
Bianchi, A. S., Ardini, E., Bosotti, R., Amatu, A., Valtorta, E., Somaschini, A., Raddrizzani, L., Palmeri, L., Banfi, P., Bonazzina, E. F., et al. (2015) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djv306 · Cited by 245 · see citing works
Chantrill, L. A., Nagrial, A. M., Watson, C., Johns, A. L., Martyn-Smith, M., Simpson, S. H., Mead, S., Jones, M. D., Samra, J. S., Gill, A. J., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0426 · Cited by 239 · see citing works
DiGiovanna, M. P., Stern, D. F., Edgerton, S. M., Whalen, S. G., Moore, D. H., & Thor, A. D. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.09.055 · Cited by 230 · see citing works
Lowery, M. A., Jordan, E., Baştürk, O., Ptashkin, R. N., Zehir, A., Berger, M. F., Leach, T., Herbst, B. T., Askan, G., Maynard, H., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-0899 · Cited by 212 · see citing works
Franco, J., Witkiewicz, A. K., & Knudsen, E. S. (2014) · Oncotarget · doi:10.18632/oncotarget.2270 · Cited by 207 · see citing works
Thor, A. D., Liu, S., Edgerton, S., et al. (2000) · Journal of Clinical Oncology · doi:10.1200/jco.2000.18.18.3230 · Cited by 176 · see citing works
Clinical and molecular characterization of HER2amplified-pancreatic cancer
Chou, A. S. Y., Waddell, N., Cowley, M. J., Gill, A. J., Chang, D. K.-F., Patch, A., Nones, K., Wu, J., Pinese, M., Johns, A. L., et al. (2013) · Genome Medicine · doi:10.1186/gm482 · Cited by 123 · see citing works
Wulfkuhle, J. D., Berg, D., Wolff, C., Langer, R., Tran, K., Illi, J., Espina, V. A., Pierobon, M., Deng, J., DeMichele, A. M., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-0452 · Cited by 120 · see citing works
Self-citationO'Reilly, E. M., Lee, J. W., Lowery, M. A., Capanu, M., Stadler, Z. K., Moore, M. J., Dhani, N. C., Kindler, H. L., Estrella, H., Maynard, H., et al. (2018) · Cancer · doi:10.1002/cncr.31218 · Cited by 103 · see citing works
Enrichment of PI3K-AKT–mTOR Pathway Activation in Hepatic Metastases from Breast Cancer
Pierobon, M., Ramos, C., Wong, S., Hodge, K. A., Aldrich, J., Byron, S. A., Anthony, S. P., Robert, N. J., Northfelt, D., Jahanzeb, M., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-2656 · Cited by 98 · see citing works
Self-citationProspective Clinical Study of Precision Oncology in Solid Tumors
Sohal, D. P. S., Rini, B. I., Khorana, A. A., Dreicer, R., Abraham, J., Procop, G. W., Saunthararajah, Y., Pennell, N. A., Stevenson, J. P., Pelley, R. J., et al. (2015) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djv332 · Cited by 97 · see citing works
Self-citationPrecision medicine: lessons learned from the SHIVA trial
Tsimberidou, A. M., & Kurzrock, R. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00397-6 · Cited by 88 · see citing works
Pancreatic Cancer Clinical Trials and Accrual in the United States
Hoos, W. A., James, P. M., Rahib, L., Talley, A. W., Fleshman, J. M., & Matrisian, L. M. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2013.49.4823 · Cited by 74 · see citing works
Self-citationFrogne, T., Lænkholm, A., Lyng, M., Henriksen, K. L., & Lykkesfeldt, A. E. (2009) · Breast Cancer Research · doi:10.1186/bcr2230 · Cited by 73 · see citing works
Cicenas, J., Urban, P., Küng, W., et al. (2006) · European Journal of Cancer · doi:10.1016/j.ejca.2005.11.012 · Cited by 65 · see citing works
Therapeutic Implications of Molecular Subtyping for Pancreatic Cancer.
Pishvaian, M. J., & Brody, J. R. (2017) · PubMed · Cited by 45 · see citing works
Self-citationClinical Use of Precision Oncology Decision Support
Johnson, A. M., Khotskaya, Y. B., Brusco, L., Zeng, J., Holla, V. R., Bailey, A. M., Litzenburger, B. C., Sánchez, N., Shufean, M. A., Piha-Paul, S. A., et al. (2017) · JCO Precision Oncology · doi:10.1200/po.17.00036 · Cited by 42 · see citing works
Identification of a novel metabolic-related mutation (IDH1) in metastatic pancreatic cancer
Brody, J. R., Yabar, C. S., Zarei, M., Bender, J., Matrisian, L. M., Rahib, L., Heartwell, C., Mason, K., Yeo, C. J., Peiper, S. C., et al. (2016) · Cancer Biology & Therapy · doi:10.1080/15384047.2016.1210743 · Cited by 23 · see citing works
Self-citationRao, S., Beckman, R. A., Riazi, S., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.13544 · Cited by 22 · see citing works
Dhir, M., Choudry, H. A., Holtzman, M. P., et al. (2016) · Cancer Medicine · doi:10.1002/cam4.992 · Cited by 20 · see citing works
Madhavan, S., Blais, E. M., Bender, R. J., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.36.15_suppl.6508 · Cited by 5 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Pancreatic cancer evolution and heterogeneity: integrating omics and clinical data
Connor, A. A., & Gallinger, S. (2022) · Nature Reviews Cancer · doi:10.1038/s41568-021-00418-1 · Cited by 369 · see citing works
Javle, M., Shacham-Shmueli, E., Xiao, L., Varadhachary, G., Halpern, N., Fogelman, D., Boursi, B., Uruba, S., Margalit, O., Wolff, R. A., et al. (2021) · JAMA Oncology · doi:10.1001/jamaoncol.2021.0006 · Cited by 127 · see citing works
Pancreatic ductal adenocarcinoma progression is restrained by stromal matrix
Jiang, H., Torphy, R. J., Steiger, K., Hongo, H., Ritchie, A. J., Kriegsmann, M., Horst, D., Umetsu, S. E., Joseph, N. M., McGregor, K., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci136760 · Cited by 127 · see citing works
Self-citationImpact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma
Yousef, A., Yousef, M., Chowdhury, S., Abdilleh, K., Knafl, M., Edelkamp, P., Alfaro-Munoz, K., Chacko, R., Peterson, J., Smaglo, B. G., et al. (2024) · npj Precision Oncology · doi:10.1038/s41698-024-00505-0 · Cited by 93 · see citing works
Self-citationGenetics of familial and sporadic pancreatic cancer
Wood, L. D., Yurgelun, M. B., & Goggins, M. G. (2019) · Gastroenterology · doi:10.1053/j.gastro.2018.12.039 · Cited by 91 · see citing works
Frank, K. J., Mulero-Sánchez, A., Berninger, A., Ruiz-Cañas, L., Bosma, A., Görgülü, K., Wu, N., Diakopoulos, K. N., Kaya-Aksoy, E., Ruess, D. A., et al. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100815 · Cited by 40 · see citing works
- Authors
- Pishvaian, M. J., Bender, R. J., Halverson, D., Rahib, L., Hendifar, A. E., Mikhail, S., Chung, V., Picozzi, V. J., Sohal, D., Blais, E. M., Mason, K., Lyons, E. E., Matrisian, L. M., Brody, J. R., Madhavan, S., & Petricoin, E. F.
- Affiliations
- Georgetown University Medical Center (US)
- 2Perthera, Inc, McLean, Virginia.
- Pancreatic Cancer Action Network (US)
- Cedars-Sinai Medical Center (US)
- The Ohio State University (US)
- City Of Hope National Medical Center (US)
- Virginia Mason Medical Center (US)
- Cleveland Clinic (US)
- Thomas Jefferson University (US)
- George Mason University (US)
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2018-10-15
- Volume
- 24
- Issue
- 20
- Pages
- 5018-5027
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2890048723
- Cited by
- 245
- References
- 44
- Citations by year
- 2026: 11 · 2025: 24 · 2024: 40 · 2023: 24 · 2022: 31 · 2021: 46 · 2020: 48 · 2019: 19 · 2018: 2
- FWCI
- 10.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- pancreatic cancer, precision oncology, multi-omics profiling, actionable genomic alterations, DNA repair genes, cell cycle genes, matched therapy, progression-free survival, community oncology practice
- MeSH terms
- Female, Humans, Immunohistochemistry, Male, Pancreatic Neoplasms, Prognosis, Biomarkers, Tumor, Genomics, Molecular Diagnostic Techniques, Proteomics, Microsatellite Instability, High-Throughput Nucleotide Sequencing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
