Christopher T Chen, MD

All Publications

• 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

  View details for DOI 10.1136/jitc-2022-SITC2022.0772

  View details for Web of Science ID 000919423400728

• 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

  View details for DOI 10.1016/j.annonc.2022.05.183

  View details for Web of Science ID 000834940400283

• 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

  View details for Web of Science ID 000892509508531

• 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

  View details for Web of Science ID 000892509505471

• 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

  View details for Web of Science ID 000863680304881

• 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

  View details for DOI 10.1200/JCO.2022.40.4_suppl.TPS218

  View details for Web of Science ID 000770995900213

• 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

  View details for DOI 10.1200/JCO.2022.40.4_suppl.TPS376

  View details for Web of Science ID 000770995900364

• 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

  View details for DOI 10.1158/1535-7163.TARG-21-P065

  View details for Web of Science ID 000776028100117

• 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

  View details for DOI 10.1200/JCO.2021.39.15_suppl.2556

  View details for Web of Science ID 000708120601077

• 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

  View details for DOI 10.1158/1538-7445.SABCS19-PD8-08

  View details for Web of Science ID 000527012503342

• 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

  View details for DOI 10.1158/1538-7445.SABCS19-P4-10-34

  View details for Web of Science ID 000527012502173

• 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

  View details for Web of Science ID 000491295501307

• 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