Bio


Dr. Chen is a board-certified, fellowship-trained specialist in oncology and hematology. He is also an Assistant Professor in the Division of Oncology in the Department of Medicine at Stanford University School of Medicine.

Dr. Chen delivers comprehensive, compassionate care for patients in need of early drug development clinical trials and patients with gastrointestinal cancers. As a researcher, he leads the early drug development group and studies how tumor heterogeneity limits the clinical benefit of anticancer therapies in order to accelerate development of novel therapeutic strategies. Dr. Chen’s work has appeared in the New England Journal of Medicine, JAMA, Journal of Clinical Oncology, Science Advances, Journal of Oncology Practice, and Health Services Research.

Dr. Chen attended Harvard College, where he graduated summa cum laude and Phi Beta Kappa in molecular biology. He went to medical school at Washington University in St. Louis on a full-tuition merit scholarship, graduating with Alpha Omega Alpha honors, and did his residency training in internal medicine at Massachusetts General Hospital and hematology/oncology fellowship in the combined Harvard Dana-Farber Cancer Institute/Massachusetts General Hospital program. As a fellow, he received the NIH T-32 Ruth L. Kirchstein-National Service Research Award in Cancer Biology for his work exploring the molecular structure of metastatic solid tumors.

Dr. Chen is a member of the American Society of Clinical Oncology, European Society for Medical Oncology, and American Association for Cancer Research.

Clinical Focus


  • Developmental Therapeutics
  • GI Oncology
  • Medical Oncology

Academic Appointments


Administrative Appointments


  • Director, Early Drug Development, Stanford Cancer Institute (2023 - Present)
  • Clinical Director, Early Drug Development, Stanford Cancer Institute (2021 - 2023)
  • Team Science Division Representative, Department of Medicine (2022 - Present)

Honors & Awards


  • ISP Star Award, Stanford Medicine (2023)
  • Shmunis Family Innovation Award in Cancer Therapeutics, Stanford Cancer Institute (2022-2023)
  • Andrea Lynn Scott Memorial Research Fellowship, Cholangiocarcinoma Foundation (2021-2022)
  • FDA-AACR Oncology Education Fellow, FDA / AACR (2020-2021)
  • T32 Ruth L. Kirschstein-National Service Research Award in Cancer Biology, NIH (2018-2020)

Professional Education


  • Medical Education: Washington University in St Louis School of Medicine (2014) MO
  • Board Certification: American Board of Internal Medicine, Medical Oncology (2020)
  • Board Certification: American Board of Internal Medicine, Hematology (2020)
  • Board Certification, American Board of Internal Medicine, Medical Oncology (2020)
  • Fellowship: Dana Farber Cancer Institute Hematology Oncology Fellowship (2020) MA
  • Board Certification: American Board of Internal Medicine, Internal Medicine (2017)
  • Residency: Massachusetts General Hospital Internal Medicine Residency (2017) MA
  • BA, Harvard College, Molecular Biology, Economics, Health Policy (2010)

Clinical Trials


  • A Study to Evaluate KIN-2787 in Participants With BRAF and/or NRAS Mutation Positive Solid Tumors Recruiting

    The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of KIN-2787 in adults with BRAF/NRAS-mutated advanced or metastatic solid tumors.

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  • Brightline-2: A Study to Test Whether Brigimadlin (BI 907828) Helps People With Cancer in the Biliary Tract, Pancreas, Lung or Bladder Recruiting

    This study is open to adults with advanced cancer in the biliary tract, pancreas, lung, or bladder. This is a study for people for whom previous treatment was not successful or no treatment exists. The purpose of this study is to find out whether a medicine called BI 907828 helps people with cancer in the biliary tract, pancreas, lung, or bladder. BI 907828 is a so-called MDM2 inhibitor that is being developed to treat cancer. All participants take BI 907828 as a tablet once every 3 weeks. Participants may continue to take BI 907828 as long as they benefit from treatment and can tolerate it. They visit the study site regularly. At the study site, doctors regularly check the size of the tumour and whether it has spread to other parts of the body. The doctors also regularly check participants' health and take note of any unwanted effects.

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  • Study of GS-1811 Given Alone or With Zimberelimab in Adults With Advanced Solid Tumors Recruiting

    This is a first-in-human (FIH) study to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of GS-1811 as monotherapy and in combination with zimberelimab in participants with advanced solid tumors. This study will be conducted in 6 parts (Parts A, B, and E: monotherapy, Parts C and D: combination therapy, and Part F for both monotherapy and combination therapy) in participants with advanced solid tumors who have received, been intolerant to, or been ineligible for all treatments known to confer clinical benefit or in participants with select solid tumors.

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  • Study of GS-2121 Given Alone or in Combination in Adults With Advanced Solid Tumors Recruiting

    The main goal of this first-in-human (FIH) study is to learn about the safety and dosing of GS-2121 when given alone or in combination with zimberelimab (ZIM) in participants with advanced solid tumors. The primary objectives of this study are: * To assess the safety and tolerability of GS-2121 as monotherapy and GS-2121 in combination with zimberelimab in participants with advanced solid tumors. * To identify the maximum tolerated dose (MTD) / maximum administered dose (MAD) and/or the recommended phase 2 dose (RP2D) of GS-2121 as monotherapy and in combination with zimberelimab in participants with advanced solid tumors.

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  • A Phase 1 in Patients With HLA-A*0201+ and WT1+ Recurrent/Metastatic Cancers Not Recruiting

    This is a Phase 1, open-label, 2-part, multi-center study evaluating the safety, tolerability, PK, pharmacodynamics (PD), immunogenicity, and antitumor activity of CUE-102 intravenous (IV) monotherapy in HLA-A\*0201 positive patients with WT1 positive recurrent/metastatic solid tumors who have failed conventional therapies.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • A Study of PY314 in Subjects With Advanced Solid Tumors Not Recruiting

    This is an open-label, multicenter, first in human, Phase 1a/1b study of PY314 in subjects with locally advanced (unresectable) and/or metastatic solid tumors that are refractory or relapsed to standard of care (including pembrolizumab, if approved for that indication).

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors Not Recruiting

    The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of escalating doses of RMC-6291 (KRAS G12C(ON) inhibitor) monotherapy in adult subjects with advanced solid tumors and to identify the maximum tolerated dose (MTD), and the recommended Phase 2 dose.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • Glycan Mediated Immune Regulation With a Bi-Sialidase Fusion Protein (GLIMMER-01) Not Recruiting

    This is a Phase 1/2, first-in-human, open-label, dose escalation and dose-expansion study of E-602, administered alone and in combination with cemiplimab.

    Stanford is currently not accepting patients for this trial. For more information, please contact Debjani Ghoshal, 650-725-5903.

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  • Milademetan in Advanced/Metastatic Solid Tumors Not Recruiting

    Phase 2, multicenter, single-arm, open-label basket study designed to evaluate the safety and efficacy of milademetan in patients with advanced or metastatic solid tumors refractory or intolerant to standard-of-care therapy that exhibit wild-type (WT) TP53 and MDM2 copy number (CN) ≥ 8 using prespecified biomarker criteria.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • Safety, Tolerability, Pharmacokinetics, and Antitumor Study of ADCT-601 to Treat Advanced Solid Tumors Not Recruiting

    This study evaluates the safety, tolerance, pharmacokinetics (PK), and antitumor activity of ADCT-601 in patients with advanced solid tumors.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • Study of ADCT-301 in Patients With Selected Advanced Solid Tumors Not Recruiting

    This study evaluates ADCT-301 in patients with Selected Advanced Solid Tumors. Patients will participate in a Treatment Period with 3-week cycles and a Follow-up Period every 12 weeks for up to 1 year after treatment discontinuation.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • Study of ORIC-101 in Combination With Anticancer Therapy Not Recruiting

    The purpose of this study is to establish the recommended Phase 2 dose (RP2D), safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of ORIC-101 in combination with nab-paclitaxel or other anticancer therapies when administered to patients with advanced or metastatic solid tumors.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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All Publications


  • Redefining Available Therapy in Oncology Accelerated Approval Decisions. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Patel, S. R., Ramachandran, M., Ai, A., Chen, C. T. 2024: JCO2400892

    Abstract

    When weighing rapid approval for follow-on drugs, should @FDAOncology recognize the drugs that came before?

    View details for DOI 10.1200/JCO.24.00892

    View details for PubMedID 39454117

  • NCCN Guidelines Insights: Colorectal Cancer Screening, Version 1.2024. Journal of the National Comprehensive Cancer Network : JNCCN Ness, R. M., Llor, X., Abbass, M. A., Bishu, S., Chen, C. T., Cooper, G., Early, D. S., Friedman, M., Fudman, D., Giardiello, F. M., Glaser, K., Gurudu, S., Hall, M., Huang, L. C., Issaka, R., Katona, B., Kidambi, T., Lazenby, A. J., Maratt, J., Markowitz, A. J., Marsano, J., May, F. P., Mayer, R. J., Olortegui, K., Patel, S., Peter, S., Porter, L. D., Shafi, M., Stanich, P. P., Terdiman, J., Vu, P., Weiss, J. M., Wood, E., Cassara, C. J., Sambandam, V. 2024; 22 (7): 438-446

    Abstract

    The NCCN Guidelines for Colorectal Cancer (CRC) Screening describe various colorectal screening modalities as well as recommended screening schedules for patients at average or increased risk of developing sporadic CRC. They are intended to aid physicians with clinical decision-making regarding CRC screening for patients without defined genetic syndromes. These NCCN Guidelines Insights focus on select recent updates to the NCCN Guidelines, including a section on primary and secondary CRC prevention, and provide context for the panel's recommendations regarding the age at which to initiate screening in average-risk individuals and those with increased risk based on personal history of childhood, adolescent, and young adult cancer.

    View details for DOI 10.6004/jnccn.2024.0047

    View details for PubMedID 39236750

  • ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Nab-Paclitaxel in Patients with Advanced Solid Tumors. Cancer research communications Chen, C. T., Khanna, V., Kummar, S., Abdul-Karim, R. M., Sommerhalder, D., Tolcher, A. W., Ueno, N. T., Davis, S. L., Orr, D. W., Hamilton, E., Patel, M. R., Spira, A. I., Jauhari, S., Florou, V., Duff, M., Xu, R., Wang, J., Barkund, S. R., Zhou, H., Pankov, A., Kong, W., Jahchan, N. S., Jackson, E. L., Sun, J. D., Junttila, M. R., Multani, P. S., Daemen, A., Chow Maneval, E., Munster, P. N. 2024

    Abstract

    PURPOSE: In preclinical models, glucocorticoid receptor (GR) signaling drives resistance to taxane chemotherapy in multiple solid tumors via upregulation of anti-apoptotic pathways. ORIC-101 is a potent and selective GR antagonist that was investigated in combination with taxane chemotherapy as an anticancer regimen preclinically and in a phase 1 clinical trial.PATIENTS AND METHODS: The ability of ORIC-101 to reverse taxane resistance was assessed in cell lines and xenograft models, and a phase 1 study (NCT03928314) was conducted in patients with advanced solid tumors to determine the dose, safety, and antitumor activity of ORIC-101 with nab-paclitaxel.RESULTS: ORIC-101 reversed chemoprotection induced by glucocorticoids in vitro and achieved tumor regressions when combined with paclitaxel in both taxane-naive and -resistant xenograft models. In the phase 1 study, 21 patients were treated in dose escalation and 62 patients were treated in dose expansion. All patients in dose expansion had previously progressed on a taxane-based regimen. In dose escalation, 5 objective responses were observed. A pre-planned futility analysis in dose expansion showed a 3.2% (95% CI 0.4, 11.2) ORR with a median PFS of 2 months (95% CI 1.8, 2.8) across all 4 cohorts, leading to study termination. Pharmacodynamic analysis of tissue and plasma showed GR pathway downregulation in most patients in cycle 1.CONCLUSIONS: ORIC-101 with nab-paclitaxel showed limited clinical activity in taxane-resistant solid tumors. Despite clear inhibition of GR pathway signaling, the insufficient clinical signal underscores the challenges of targeting a single resistance pathway when multiple mechanisms of resistance may be in play.

    View details for DOI 10.1158/2767-9764.CRC-24-0115

    View details for PubMedID 39177285

  • Reflections and Roadmaps: Career Development Beyond the FDA-AACR Oncology Educational Fellowship. Clinical cancer research : an official journal of the American Association for Cancer Research Patel, T., Chen, C., Al Hadidi, S., Kadry, Y., Sridhara, R., Purcell, E., Wisch, L., Retzlaff, J., Foti, M., Pazdur, R., Kluetz, P., Gao, J. 2024

    Abstract

    In 2020, the U.S. Food and Drug Administration's Oncology Center of Excellence, in collaboration with the American Association for Cancer Research, launched a novel educational partnership known as the FDA-AACR Oncology Educational Fellowship. This year-long program is aimed for hematology/oncology fellows, scientists, and early-career investigators, offering an in-depth exploration of the regulatory review process by blending didactic learning with practical cases discussing oncology drug approvals. The fellowship has been met with enthusiastic feedback, with participants lauding its role in demystifying the regulatory landscape and enhancing their professional careers. This paper reflects on the experiences of four alumni, showcasing the program's transformative impact across diverse oncology career paths in government, academia, and industry.

    View details for DOI 10.1158/1078-0432.CCR-24-1444

    View details for PubMedID 38856702

  • Correlation of baseline ENPP1 and cGAS expression in advanced solid tumors with intratumoral immune activation and clinical outcomes after treatment with the first-in-class oral ENPP1 inhibitor RBS2418, alone or in combination with pembrolizumab Marron, T., Wainberg, Z. A., Spira, A. I., Gordon, M. S., Chen, C., Segar, J., Boccia, R. V., Berlin, J., Csiki, I., Schanzer, J., Huang, N., Glen, J., Klumpp, K., Misleh, J. LIPPINCOTT WILLIAMS & WILKINS. 2024
  • Phase 2 study of novel HER2-targeting, TLR7/8 immune-stimulating antibody conjugate (ISAC) BDC-1001 (trastuzumab imbotolimod) plus /- pertuzumab (P) in patients (pts) with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab deruxtecan (T-DXd) Pegram, M. D., Calfa, C., Chen, C., Salgado, A., Heeke, A., Kang, I., Pistilli, B., Pohlmann, P. R., Rugo, H. S., Saura, C., Vicier, C., Pearson, C., Mangeshkar, M., Yu, T., Alonso, M. N., Colburn, D. E., Perez, E. A., Drago, J. Z. LIPPINCOTT WILLIAMS & WILKINS. 2024
  • A phase 1/2 study of BDC-3042, a novel dectin-2 agonistic antibody, in patients with advanced cancers. Salkeni, M., Vandross, A. L., Dumbrava, E., Giordano, A., Chen, C., Kenkel, J., Cai, D., Xu, L., Alonso, M. N., Ackerman, S., Yu, T., Colburn, D. E., Perez, E. A., Wilks, S. LIPPINCOTT WILLIAMS & WILKINS. 2024
  • Phase II trial of organ preservation program using short-course radiation and FOLFOXIRI for rectal cancer (SHORT-FOX). Pollom, E. L., Fisher, G. A., Shelton, A., Johnson, T., Chen, C., Jackson, S., Shaheen, S., Holden, T., Bien, J., King, D., Morris, A. M., Kin, C., Dawes, A., Kirilcuk, N., Gahagan, J., Vitzthum, L., Sheth, V., Brown, E., Pratapneni, A., Chang, D. LIPPINCOTT WILLIAMS & WILKINS. 2024
  • A phase 1, open-label, dose escalation, and expansion study of CUE-102, a novel WT1-pHLA-IL2-Fc fusion protein, in patients with HLA-A*0201-positive disease and WT1-positive recurrent/metastatic cancers Uboha, N., Saenger, Y. M., Alese, O. B., Kim, D., Zheng, L., Chaves, J., Fu, S., Gong, J., Jin, Z., Powderly, J. D., Gabrail, N., Bekaii-Saab, T. S., Alistar, A., Chen, C., Agensky, L., Goel, A., Margossian, S., Quayle, S. N., Levisetti, M., Selfridge, J. LIPPINCOTT WILLIAMS & WILKINS. 2024
  • Toward Precision Perioperative Therapy in GI Malignancies. JCO precision oncology Glover, M. J., Bien, J., Chen, C. T. 2023; 7: e2200381

    Abstract

    The term precision oncology typically refers to molecularly guided therapies against cancer. Less appreciated but also critically important is molecular identification of patients with resectable disease who are most likely to benefit from perioperative drugs, and tailored selection of such drugs. We call this idea precision perioperative therapy. Over the past several years, use of precision perioperative approaches for patients with localized GI cancers has expanded in clinical trials and practice. Here, we summarize the status of the field and highlight areas of future innovation.Using PubMed, we reviewed articles published from 2017 to 2023 in English. We used search terms "adjuvant," "perioperative," "neoadjuvant," and "precision medicine" for various types of GI malignancies. Information about ongoing clinical trials was accessed through ClinicalTrials.gov, accessed January 2023.Paradigms such as minimal residual disease detection via circulating tumor DNA and perioperative immunotherapy in lieu of chemotherapy for mismatch repair-deficient disease may lead to reduced toxicity and improved long-term outcomes in select populations. Molecularly targeted drugs that have shown activity against metastatic disease may also hold promise in the curable setting.The field is very much in development, but emerging data demonstrate early promise. We are optimistic that ongoing research efforts will increasingly bring precision perioperative therapy to patients with resectable GI malignancies.

    View details for DOI 10.1200/PO.22.00381

    View details for PubMedID 37625103

  • Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study. The Lancet. Oncology Strickler, J. H., Cercek, A., Siena, S., André, T., Ng, K., Van Cutsem, E., Wu, C., Paulson, A. S., Hubbard, J. M., Coveler, A. L., Fountzilas, C., Kardosh, A., Kasi, P. M., Lenz, H. J., Ciombor, K. K., Elez, E., Bajor, D. L., Cremolini, C., Sanchez, F., Stecher, M., Feng, W., Bekaii-Saab, T. S. 2023; 24 (5): 496-508

    Abstract

    HER2 is an actionable target in metastatic colorectal cancer. We assessed the activity of tucatinib plus trastuzumab in patients with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer.MOUNTAINEER is a global, open-label, phase 2 study that enrolled patients aged 18 years and older with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer at 34 sites (clinics and hospitals) in five countries (Belgium, France, Italy, Spain, and the USA). Initially, the study was designed as a single-cohort study, which was expanded following an interim analysis to include more patients. Initially, patients were given tucatinib (300 mg orally twice daily) plus intravenous trastuzumab (8 mg/kg as an initial loading dose, then 6 mg/kg every 21 days; cohort A) for the duration of treatment (until progression), and after expansion, patients were randomly assigned (4:3), using an interactive web response system and stratified by primary tumour location, to either tucatinib plus trastuzumab (cohort B) or tucatinib monotherapy (cohort C). The primary endpoint was confirmed objective response rate per blinded independent central review (BICR) for cohorts A and B combined and was assessed in patients in the full analysis set (ie, patients with HER2-positive disease who received at least one dose of study treatment). Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT03043313, and is ongoing.Between Aug 8, 2017, and Sept 22, 2021, 117 patients were enrolled (45 in cohort A, 41 in cohort B, and 31 in cohort C), of whom 114 patients had locally assessed HER2-positive disease and received treatment (45 in cohort A, 39 in cohort B, and 30 in cohort C; full analysis set), and 116 patients received at least one dose of study treatment (45 in cohort A, 41 in cohort B, and 30 in cohort C; safety population). In the full analysis set, median age was 56·0 years (IQR 47-64), 66 (58%) were male, 48 (42%) were female, 88 (77%) were White, and six (5%) were Black or African American. As of data cutoff (March 28, 2022), in 84 patients from cohorts A and B in the full analysis set, the confirmed objective response rate per BICR was 38·1% (95% CI 27·7-49·3; three patients had a complete response and 29 had a partial response). In cohorts A and B, the most common adverse event was diarrhoea (55 [64%] of 86), the most common grade 3 or worse adverse event was hypertension (six [7%] of 86), and three (3%) patients had tucatinib-related serious adverse events (acute kidney injury, colitis, and fatigue). In cohort C, the most common adverse event was diarrhoea (ten [33%] of 30), the most common grade 3 or worse adverse events were increased alanine aminotransferase and aspartate aminotransferase (both two [7%]), and one (3%) patient had a tucatinib-related serious adverse event (overdose). No deaths were attributed to adverse events. All deaths in treated patients were due to disease progression.Tucatinib plus trastuzumab had clinically meaningful anti-tumour activity and favourable tolerability. This treatment is the first US Food and Drug Administration-approved anti-HER2 regimen for metastatic colorectal cancer and is an important new treatment option for chemotherapy-refractory HER2-positive metastatic colorectal cancer.Seagen and Merck & Co.

    View details for DOI 10.1016/S1470-2045(23)00150-X

    View details for PubMedID 37142372

  • Trials in progress: a global phase 1/1b clinical trial evaluating exarafenib (KIN-2787), a highly selective pan-RAF inhibitor, in adult patients with BRAF-altered solid tumors and NRAS mutant melanoma Spira, A., Gambardella, V., Kato, S., Perez, C., Mckean, M., Cao, M., Kim, R., Chen, C. T., Italiano, A., Cassier, P., Mehnert, J., Chmielowski, B., Lee, G., Severson, P., Unger, C., Guan, X., Williams, R., Long, G. AMER ASSOC CANCER RESEARCH. 2023
  • GLIMMER-01: initial results from a phase 1 dose escalation trial of a first-in-class bi-sialidase (E-602) in solid tumors Luke, J. J., Johnson, M., Tolcher, A., Chen, C. T., Dai, T., Curti, B. D., El-Khoueiry, A., Sznol, M., Henick, B. S., Horak, C., Jayaraman, P., Cole, C. B., Wilson, D., Cao, L., Peng, L., Feltquate, D., Lathers, D., Sharma, M. R. AMER ASSOC CANCER RESEARCH. 2023
  • A PHASE 1/2 DOSE ESCALATION/EXPANSION STUDY EVALUATING THE SAFETY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTITUMOR ACTIVITY OF E-602, A BI-SIALIDASE FUSION PROTEIN, IN ADVANCED CANCER (GLIMMER-01) Sharma, M., Lathers, D., Johnson, M., Luke, J., Puzanov, I., Curti, B., Chen, C., El-Khoueiry, A., Henick, B., Callahan, M., Sznol, M., Patel, S., Wilson, D., Ricker, M., Cao, L., Jayaraman, P., Che, J., Peng, L., Feltquate, D., Tolcher, A. BMJ PUBLISHING GROUP. 2022: A803
  • The Clinical Landscape of Cell-Free DNA Alterations in 1,671 Patients with Advanced Biliary Tract Cancer. Annals of oncology : official journal of the European Society for Medical Oncology Berchuck, J. E., Facchinetti, F., DiToro, D. F., Baiev, I., Majeed, U., Reyes, S., Chen, C., Zhang, K., Sharman, R., Junior, P. L., Maurer, J., Shroff, R. T., Pritchard, C. C., Wu, M., Catenacci, D. V., Javle, M., Friboulet, L., Hollebecque, A., Bardeesy, N., Zhu, A. X., Lennerz, J. K., Tan, B., Borad, M., Parikh, A. R., Kiedrowski, L. A., Kelley, R. K., Mody, K., Juric, D., Goyal, L. 2022

    Abstract

    BACKGROUND: Targeted therapies have transformed clinical management of advanced biliary tract cancer (BTC). Cell-free DNA (cfDNA) analysis is an attractive approach for cancer genomic profiling that overcomes many limitations of traditional tissue-based analysis. We examined cfDNA as a tool to inform clinical management of patients with advanced BTC and generate novel insights into BTC tumor biology.PATIENTS AND METHODS: We analyzed next-generation sequencing data of 2,068 cfDNA samples from 1,671 patients with advanced BTC generated with Guardant360. We performed clinical annotation on a multi-institutional subset (n=225) to assess intra-patient cfDNA-tumor concordance and the association of cfDNA variant allele fraction (VAF) with clinical outcomes.RESULTS: Genetic alterations were detected in cfDNA in 84% of patients, with targetable alterations detected in 44% of patients. FGFR2 fusions, IDH1 mutations, and BRAF V600E were clonal in majority of cases, affirming these targetable alterations as early driver events in BTC. Concordance between cfDNA and tissue for mutation detection was high for IDH1 mutations (87%) and BRAF V600E (100%), and low for FGFR2 fusions (18%). cfDNA analysis uncovered novel putative mechanisms of resistance to targeted therapies, including mutation of the cysteine residue (FGFR2 C492F) to which covalent FGFR inhibitors bind. High pre-treatment cfDNA VAF associated with poor prognosis and shorter response to chemotherapy and targeted therapy. Finally, we report the frequency of promising targets in advanced BTC currently under investigation in other advanced solid tumors, including KRAS G12C (1.0%), KRAS G12D (5.1%), PIK3CA mutations (6.8%), and ERBB2 amplifications (4.9%).CONCLUSIONS: These findings from the largest and most comprehensive study to date of cfDNA from patients with advanced BTC highlight the utility of cfDNA analysis in current management of this disease. Characterization of oncogenic drivers and mechanisms of therapeutic resistance in this study will inform drug development efforts to reduce mortality for patients with BTC.

    View details for DOI 10.1016/j.annonc.2022.09.150

    View details for PubMedID 36089135

  • Rectosigmoid Cancer-Rectal Cancer or Sigmoid Cancer? American journal of clinical oncology Hui, C., Baclay, R., Liu, K., Sandhu, N., Loo, P., von Eyben, R., Chen, C., Sheth, V., Vitzthum, L., Chang, D., Pollom, E. 2022

    Abstract

    OBJECTIVES: We aimed to determine the optimal treatment for patients with locally advanced rectosigmoid cancers, and to determine whether this can be guided by distance from anal verge (AV) and/or anatomic landmarks such as the sacral promontory and peritoneal reflection (PR).MATERIALS AND METHODS: We retrospectively reviewed patients with T3-T4 and/or node-positive rectosigmoid cancers who underwent surgery from 2006 to 2018 with available pelvic imaging. We included tumors at 9 to 20cm from the AV on either staging imaging, or colonoscopy. Patients were stratified into those who received neoadjuvant therapy, and those who underwent upfront surgery. Comparisons of characteristics were performed using chi2 test and Fischer exact test. Locoregional failure (LRF) and overall survival were compared using Cox regressions and Kaplan-Meier analysis.RESULTS: One hundred sixty-one patients were included. Ninety-seven patients had neoadjuvant therapy, and 64 patients had upfront surgery. Median follow-up time was 45.1 months. Patients who had neoadjuvant therapy had tumors that were higher cT stage (P<0.01) with more positive/close circumferential resection margins seen on imaging by radiologists (28.9% vs. 1.6%, P=0.015). The 2-year rate of LRF, distant metastases, or overall survival was not significantly different between the 2 groups. None of 15 patients with tumors below the PR treated with neoadjuvant therapy had LRF, but 1 (25%) of 4 patients with tumors below the PR treated with adjuvant therapy experienced LRF (P=0.05).CONCLUSIONS: Patients with tumors below the PR may benefit more from neoadjuvant therapy. The PR on imaging may be a reliable landmark in addition to the distance from the AV to determine the most appropriate treatment option.

    View details for DOI 10.1097/COC.0000000000000931

    View details for PubMedID 35848736

  • Phase 1b/2 trial of tucatinib plus trastuzumab plus /- chemotherapy or pembrolizumab in patients with metastatic HER2+GI cancers Shitara, K., Park, H., Bekaii-Saab, T., Kim, S. S., Kamath, S., Pishvaian, M. J., Chen, C., Zhen, D. B., Mayor, J., Tan, Q., Strickler, J. H. ELSEVIER. 2022: S502
  • Effect of camidanlumab tesirine (Cami) as monotherapy and in combination with pembrolizumab ( PEM) on the immune cell profile in patients with selected advanced solid tumors Puzanov, I., Chen, C. T., LoRusso, P., Papadopoulos, K. P., Kummar, S., Hamilton, E., LeBruchec, Y., Havenith, K., Pantano, S., Toukam, M., Wuerthner, J., Boni, J. AMER ASSOC CANCER RESEARCH. 2022
  • Chromatin modifier alterations confer resistance to endocrine deprivation and CDK4/6 inhibitors in ER plus breast cancer and drive convergent evolution in patient autopsy lesions Leshchiner, E., Leshchiner, I., Martin, E. E., Chen, C. T., Zhang, T., Pinto, C., Rhrissorrakrai, K., Utro, F., Levovitz, C., Jacobs, R. A., Danysh, B. P., Slowik, K., Broudo, M., Parida, L., Juric, D., Getz, G. AMER ASSOC CANCER RESEARCH. 2022
  • A phase 2 study of the MDM2 inhibitor milademetan in patients with TP53-wild type and MDM2-amplified advanced or metastatic solid tumors (MANTRA-2) Dumbrava, E., Hanna, G. J., Cote, G., Stinchcombe, T., Johnson, M., Chen, C., Devarakonda, S., Shah, N., Xu, F., Doebele, R., Gounder, M. M. LIPPINCOTT WILLIAMS & WILKINS. 2022
  • Severe Lactic Acidosis Complicated by Insulin-Resistant Hyperosmolar Hyperglycemic Syndrome in a Patient With Metastatic Breast Cancer Undergoing AKT-Inhibitor Therapy. JCO precision oncology Stamou, M. I., Chen, C., Wander, S. A., Supko, J. G., Juric, D., Bardia, A., Wexler, D. J. 2022; 6: e2100428

    View details for DOI 10.1200/PO.21.00428

    View details for PubMedID 35700410

  • A Novel Framework for the Next Generation of Precision Oncology Targets. JAMA oncology Chen, C. T., Ford, J. M. 2022

    View details for DOI 10.1001/jamaoncol.2022.0760

    View details for PubMedID 35587343

  • Phase II trial of organ preservation program using short-course radiation and folfoxiri for rectal cancer (SHORT-FOX) Pollom, E. L., Shelton, A., Fisher, G. A., Bien, J., King, D., Johnson, T., Chen, C., Shaheen, S., Chong, C., Vitzthum, L., Kirilcuk, N., Morris, A. M., Kin, C., Dawes, A., Sheth, V., Sundaram, V., Brown, E., Chang, D. LIPPINCOTT WILLIAMS & WILKINS. 2022
  • Phase 1b/2, open-label, dose-escalation and expansion trial of tucatinib in combination with trastuzumab with and without oxaliplatin-based chemotherapy or pembrolizumab in patients with unresectable or metastatic HER2+gastrointestinal cancers (trial in progress) Park, H., Bekaii-Saab, T. S., Kim, S. S., Kamath, S., Pishvaian, M. J., Chen, C., Zhen, D., Mayor, J., Tan, Q., Strickler, J. H. LIPPINCOTT WILLIAMS & WILKINS. 2022
  • Proteogenomic characterization of CDK4/6 inhibitor-resistant ER plus breast cancer Chen, C. T., Leshchiner, I., Martin, L., Kane, H., Rhrissorrakrai, K., Utro, F., Levovitz, C., Gillette, M., Satpathy, S., Pinto, C., McLoughlin, D., Allen, R., Danysh, B. P., Slowik, K., Jacobs, R. A., Carr, S., Parida, L., Getz, G., Juric, D. AMER ASSOC CANCER RESEARCH. 2021
  • Paving a pathway for drug development in HER2-positive biliary tract cancer. The Lancet. Oncology Chen, C. T., Goyal, L. 2021; 22 (9): 1204-1206

    View details for DOI 10.1016/S1470-2045(21)00465-4

    View details for PubMedID 34478661

  • A phase 1b, open-label, dose-escalation study to evaluate camidanlumab tesirine (Cami) as monotherapy in patients (pts) with advanced solid tumors. Puzanov, I., LoRusso, P., Papadopoulos, K. P., Chen, C. T., LeBruchec, Y., He, X., Cousin, T., Havenith, K., Boni, J., Bendell, J. C. LIPPINCOTT WILLIAMS & WILKINS. 2021
  • Case 8-2021: A 34-Year-Old Woman with Cholangiocarcinoma. The New England journal of medicine Goyal, L. n., Chen, C. T., Pierce, T. T., Deshpande, V. n. 2021; 384 (11): 1054–64

    View details for DOI 10.1056/NEJMcpc2027092

    View details for PubMedID 33730458

  • Cell-free DNA captures tumor heterogeneity and driver alterations in rapid autopsies with pre-treated metastatic cancer. Nature communications Pereira, B., Chen, C. T., Goyal, L., Walmsley, C., Pinto, C. J., Baiev, I., Allen, R., Henderson, L., Saha, S., Reyes, S., Taylor, M. S., Fitzgerald, D. M., Broudo, M. W., Sahu, A., Gao, X., Winckler, W., Brannon, A. R., Engelman, J. A., Leary, R., Stone, J. R., Campbell, C. D., Juric, D. 2021; 12 (1): 3199

    Abstract

    In patients with metastatic cancer, spatial heterogeneity of somatic alterations may lead to incomplete assessment of a cancer's mutational profile when analyzing a single tumor biopsy. In this study, we perform sequencing of cell-free DNA (cfDNA) and distinct metastatic tissue samples from ten rapid autopsy cases with pre-treated metastatic cancer. We show that levels of heterogeneity in genetic biomarkers vary between patients but that gene expression signatures representative of the tumor microenvironment are more consistent. Across nine patients with plasma samples available, we are able to detect 62/62 truncal and 47/121 non-truncal point mutations in cfDNA. We observe that mutation clonality in cfDNA is correlated with the number of metastatic lesions in which the mutation is detected and use this result to derive a clonality threshold to classify truncal and non-truncal driver alterations with reasonable specificity. In contrast, mutation truncality is more often incorrectly assigned when studying single tissue samples. Our results demonstrate the utility of a single cfDNA sample relative to that of single tissue samples when treating patients with metastatic cancer.

    View details for DOI 10.1038/s41467-021-23394-4

    View details for PubMedID 34045463

  • Characterization of spatial and temporal heterogeneity of ER positive metastatic breast cancer using serial biopsies Allen, R. K., Pinto, C. J., Fitzgerald, D. M., Huynh, T. G., Chen, C. T., Juric, D. AMER ASSOC CANCER RESEARCH. 2020
  • Plasma sequencing demonstrates that breast cancer patients have a higher prevalence of clonal and multiple PIK3CA mutations than other solid tumor patients Chen, C., Sahu, A., Price, K., Pinto, C., Allen, R., Wang, X., Szabolcs, A., Goyal, L., Ting, D., Liu, S., Juric, D. AMER ASSOC CANCER RESEARCH. 2020
  • Overcoming Resistance to Targeted Therapies in Gastrointestinal Cancers: Progress to Date and Progress to Come. American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting Chen, C. n., Di Bartolomeo, M. n., Corallo, S. n., Strickler, J. H., Goyal, L. n. 2020; 40: 161–73

    Abstract

    Targeted therapies have transformed the treatment paradigm in diseases such as non-small cell lung cancer and melanoma but have shown relatively modest clinical benefit in gastrointestinal malignancies. Anti-EGFR therapy in RAS wild-type colorectal cancer, anti-HER2 therapy in HER2- amplified esophagogastric cancer, and FGFR and isocitrate dehydrogenase 1 (IDH1) inhibitors in FGFR2 fusion-positive and IDH1-mutant biliary tract cancers offer antitumor efficacy, but the clinical benefit and durability of response in each case are typically limited. We review targeted therapies in each of these therapeutic areas and discuss their clinical efficacy, mechanisms of primary and acquired resistance, and strategies to overcome this resistance. We discuss lessons learned that we hope will lead to an expanded role for molecularly targeted therapy options for patients with gastrointestinal cancers.

    View details for DOI 10.1200/EDBK_280871

    View details for PubMedID 32421451

  • Response rates and lesion-level progression patterns of solid tumor patients in an academic phase I program: implications for tumour heterogeneity Chen, C., Pinto, C., Walmsley, C., Allen, R., Muzikansky, A., Henderson, L., Broudo, M., Wolfgang, J., Fitzgerald, D. M., Hong, T., Juric, D. OXFORD UNIV PRESS. 2019
  • Pharmacological inhibition of β-catenin/BCL9 interaction overcomes resistance to immune checkpoint blockades by modulating Treg cells. Science advances Feng, M., Jin, J. Q., Xia, L., Xiao, T., Mei, S., Wang, X., Huang, X., Chen, J., Liu, M., Chen, C., Rafi, S., Zhu, A. X., Feng, Y. X., Zhu, D. 2019; 5 (5): eaau5240

    Abstract

    The Wnt/β-catenin (β-cat) pathway plays a critical role in cancer. Using hydrocarbon-stapled peptide technologies, we aim to develop potent, selective inhibitors targeting this pathway by disrupting the interaction of β-cat with its coactivators B-cell lymphoma 9 (BCL9) and B-cell lymphoma 9-like (B9L). We identified a set of peptides, including hsBCL9CT-24, that robustly inhibits the activity of β-cat and suppresses cancer cell growth. In animal models, these peptides exhibit potent anti-tumor effects, favorable pharmacokinetic profiles, and minimal toxicities. Markedly, these peptides promote intratumoral infiltration of cytotoxic T cells by reducing regulatory T cells (Treg) and increasing dendritic cells (DCs), therefore sensitizing cancer cells to PD-1 inhibitors. Given the strong correlation between Treg infiltration and APC mutation in colorectal cancers, it indicates our peptides can reactivate anti-cancer immune response suppressed by the oncogenic Wnt pathway. In summary, we report a promising strategy for cancer therapy by pharmacological inhibition of the Wnt/β-cat signaling.

    View details for DOI 10.1126/sciadv.aau5240

    View details for PubMedID 31086813

    View details for PubMedCentralID PMC6506245

  • Efficacy, Safety, and Regulatory Approval of Food and Drug Administration-Designated Breakthrough and Nonbreakthrough Cancer Medicines. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Hwang, T. J., Franklin, J. M., Chen, C. T., Lauffenburger, J. C., Gyawali, B., Kesselheim, A. S., Darrow, J. J. 2018; 36 (18): 1805-1812

    Abstract

    Purpose The breakthrough therapy program was established in 2012 to expedite the development and review of new medicines. We evaluated the times to approval, efficacy, and safety of breakthrough-designated versus non-breakthrough-designated cancer drugs approved by the US Food and Drug Administration (FDA). Methods We studied all new cancer drugs approved by the FDA between January 2012 and December 2017. Regulatory and therapeutic characteristics (time to FDA approval, pivotal trial efficacy end point, novelty of mechanism of action) were compared between breakthrough-designated and non-breakthrough-designated cancer drugs. Random-effects meta-regression was used to assess the association between breakthrough therapy designation and hazard ratios for progression-free survival (PFS), response rates (RRs) for solid tumors, serious adverse events, and deaths not attributed to disease progression. Results Between 2012 and 2017, the FDA approved 58 new cancer drugs, 25 (43%) of which received breakthrough therapy designation. The median time to first FDA approval was 5.2 years for breakthrough-designated drugs versus 7.1 years for non-breakthrough-designated drugs (difference, 1.9 years; P = .01). There were no statistically significant differences between breakthrough-designated and non-breakthrough-designated drugs in median PFS gains (8.6 v 4.0 months; P = .11), hazard ratios for PFS (0.43 v 0.51; P = .28), or RRs for solid tumors (37% v 39%; P = .74). Breakthrough therapy-designated drugs were not more likely to act via a novel mechanism of action (36% v 39%; P = 1.00). Rates of deaths (6% v 4%; P = .99) and serious adverse events (38% v 36%; P = 0.93) were also similar in breakthrough-designated and non-breakthrough-designated drugs. Conclusion Breakthrough-designated cancer drugs were associated with faster times to approval, but there was no evidence that these drugs provide improvements in safety or novelty; nor was there a statistically significant efficacy advantage when compared with non-breakthrough-designated drugs.

    View details for DOI 10.1200/JCO.2017.77.1592

    View details for PubMedID 29688832

  • Medicare Spending for Breast, Prostate, Lung, and Colorectal Cancer Patients in the Year of Diagnosis and Year of Death. Health services research Chen, C. T., Li, L. n., Brooks, G. n., Hassett, M. n., Schrag, D. n. 2018; 53 (4): 2118–32

    Abstract

    To characterize spending patterns for Medicare patients with incident breast, prostate, lung, and colorectal cancer.2007-2012 data from the Surveillance, Epidemiology, and End Results Program linked with Medicare fee-for-service claims.We calculate per-patient monthly and yearly mean and median expenditures, by cancer type, stage at diagnosis, and spending category, over the years of diagnosis and death.Over the year of diagnosis, mean spending was $35,849, $26,295, $55,597, and $63,063 for breast, prostate, lung, and colorectal cancer, respectively. Over the year of death, spending was similar across different cancer types and stage at diagnosis.Characterization of Medicare spending according to clinically meaningful categories may assist development of oncology alternative payment models and cost-effectiveness models.

    View details for DOI 10.1111/1475-6773.12745

    View details for PubMedID 28748564

    View details for PubMedCentralID PMC6051983

  • Walk-in clinics versus physician offices and emergency rooms for urgent care and chronic disease management. Cochrane database of systematic reviews Chen, C. E., Chen, C. T., Hu, J., Mehrotra, A. 2017; 2: CD011774-?

    Abstract

    Walk-in clinics are growing in popularity around the world as a substitute for traditional medical care delivered in physician offices and emergency rooms, but their clinical efficacy is unclear.To assess the quality of care and patient satisfaction of walk-in clinics compared to that of traditional physician offices and emergency rooms for people who present with basic medical complaints for either acute or chronic issues.We searched CENTRAL, MEDLINE, Embase, six other databases, and two trials registers on 22 March 2016 together with reference checking, citation searching, and contact with study authors to identify additional studies. We applied no restrictions on language, publication type, or publication year.Study design: randomized trials, non-randomized trials, and controlled before-after studies.standalone physical clinics not requiring advance appointments or registration, that provided basic medical care without expectation of follow-up. Comparisons: traditional primary care practices or emergency rooms.We used standard methodological procedures expected by Cochrane and the Cochrane Effective Practice and Organisation of Care (EPOC) Group.The literature search identified 6587 citations, of which we considered 65 to be potentially relevant. We reviewed the abstracts of all 65 potentially relevant studies and retrieved the full texts of 12 articles thought to fit our study criteria. However, following independent author assessment of the full texts, we excluded all 12 articles.Controlled trial evidence about the mortality, morbidity, quality of care, and patient satisfaction of walk-in clinics is currently not available.

    View details for DOI 10.1002/14651858.CD011774.pub2

    View details for PubMedID 28211045

  • Journey of Generic Imatinib: A Case Study in Oncology Drug Pricing. Journal of oncology practice Chen, C. T., Kesselheim, A. S. 2017; 13 (6): 352–55

    View details for DOI 10.1200/JOP.2016.019737

    View details for PubMedID 28445102

  • Transforming healthcare delivery: Why and how accountable care organizations must evolve. Journal of hospital medicine Chen, C. T., Ackerly, D. C., Gottlieb, G. n. 2016; 11 (9): 658–61

    Abstract

    Accountable care organizations (ACOs) have shown promise in reducing healthcare spending growth, but have proven to be financially unsustainable for many healthcare organizations. Even ACOs with shared savings have experienced overall losses because the shared savings bonuses have not covered the costs of delivering population health. As physicians and former ACO leaders, we believe in the concept of accountable care, but ACOs need to evolve if they are to have a viable future. We propose the novel possibility of allowing ACOs to bill fee-for-service for their population health interventions, a concept we call population health billing. Journal of Hospital Medicine 2016;11:658-661. © 2016 Society of Hospital Medicine.

    View details for DOI 10.1002/jhm.2589

    View details for PubMedID 27596543

  • Disruptive innovation in academic medical centers: balancing accountable and academic care. Academic medicine : journal of the Association of American Medical Colleges Stein, D. n., Chen, C. n., Ackerly, D. C. 2015; 90 (5): 594–98

    Abstract

    Numerous academic medicine leaders have argued that academic referral centers must prepare for the growing importance of accountability-driven payment models by adopting population health initiatives. Although this shift has merit, execution of this strategy will prove significantly more problematic than most observers have appreciated. The authors describe how successful implementation of an accountable care health strategy within a referral academic medical center (AMC) requires navigating a critical tension: The academic referral business model, driven by tertiary-level care, is fundamentally in conflict with population health. Referral AMCs that create successful value-driven population health systems within their organizations will in effect disrupt their own existing tertiary care businesses. The theory of disruptive innovation suggests that balancing the push and pull of academic and accountable care within a single organization is achievable. However, it will require significant shifts in resource allocation and changes in management structure to enable AMCs to make the inherent difficult choices and trade-offs that will ensue. On the basis of the theories of disruptive innovation, the authors present recommendations for how academic health systems can successfully navigate these issues as they transition toward accountability-driven care.

    View details for DOI 10.1097/ACM.0000000000000606

    View details for PubMedID 25517702

  • Readmission penalties and health insurance expansions: a dispatch from Massachusetts. Journal of hospital medicine Chen, C., Scheffler, G., Chandra, A. 2014; 9 (11): 681-7

    Abstract

    Payers are penalizing hospitals for high readmission rates. It is unknown whether major changes in population insurance coverage can affect readmission rates, despite the Affordable Care Act's coverage expansions coming into effect this year.To evaluate the impact of a large-scale insurance expansion on hospital readmissions, using Massachusetts' 2006 health reform as a natural experiment.Difference-in-difference time-series design.All Massachusetts acute-care hospitals.Inpatient visits from 2004 to 2010.Primary outcome was the hospital 30-day readmission rate. Readmissions to any Massachusetts hospital were tracked.Decreases in uninsurance rates during and after reform were largely limited to the hospital quartile with the highest prereform uninsurance rates (from 14% uninsured at the start of the reform to 2.9% by the end of the study period). The other hospitals collectively experienced a smaller decline in their uninsured admissions (5.9% at the start of reform to 2.5% by the end of the study period). According to difference-in-difference regression analysis, the highest uninsured hospital quartile experienced a modest increase in their unadjusted readmission rate of 0.6 percentage points (95% confidence interval: 0.1%-1.1%) during the reform period as compared to the other hospital quartiles (P = 0.01). This represents a relative increase of 4.5% in the readmission rate. Risk-adjusted readmission rates showed no corresponding change.The Affordable Care Act's insurance expansion may be associated with an increase in unadjusted readmission rates among hospitals that cared for disproportionate numbers of uninsured patients. Risk-adjustment appears to take this effect into account.

    View details for DOI 10.1002/jhm.2213

    View details for PubMedID 24945696

  • Beyond ACOs and bundled payments: Medicare's shift toward accountability in fee-for-service. JAMA Chen, C. n., Ackerly, D. C. 2014; 311 (7): 673–74

    View details for DOI 10.1001/jama.2014.11

    View details for PubMedID 24549543

  • Massachusetts' health care reform and emergency department utilization. The New England journal of medicine Chen, C., Scheffler, G., Chandra, A. 2011; 365 (12): e25

    View details for DOI 10.1056/NEJMp1109273

    View details for PubMedID 21899444