tbuckley/cabot-search huggingface dataset:
Cabozantinib versus other TKIs after CPI treatment in the real-world management of patients with metastatic renal cell carcinoma (mRCC).
Authors: Florence Marteau, Brooke Harrow, Christine McCarthy, Joel Wallace, Alisha Monnette, Yunfei Wang, Gurjyot K. Doshi
Journal: Journal of Clinical Oncology (2021)

293 Background: Checkpoint inhibitors (CPIs) are a treatment option for patients with metastatic renal cell carcinoma (mRCC), but there is limited clinical data on the efficacy of targeted therapies following CPI treatment. Cabozantinib is a tyrosine kinase inhibitor (TKI) that targets multiple receptor kinases implicated in tumorigenesis. In the US, cabozantinib is approved for use in patients with advanced RCC including after CPI treatment. Methods: This retrospective observational cohort study (NCT04353765) evaluated outcomes associated with cabozantinib or other TKIs (axitinib, lenvatinib, pazopanib, sorafenib, sunitinib) in patients with mRCC following CPI treatment. Eligible patients initiated TKI therapy between May 1, 2016 and Sep 31, 2019 and had received a CPI as their last systemic treatment prior to TKI therapy. Patients were identified from the US Oncology Network iKnowMed electronic health record database through structured queries and a targeted chart review. The following real-world outcomes were assessed: 6-month response rate (RR 6months ; primary); overall response rate (ORR); overall survival (OS); time to treatment discontinuation (TTD); rates of dose reductions, and discontinuation due to adverse events (AEs). The p value for RR 6months was used to test for non-inferiority. Results: Eligible patients ( n = 247) had a mean (SD) age of 65.9 (10.5) years and 74.1% were male; 75.7% ( n = 187) received cabozantinib and 24.3% ( n = 60) received other TKIs. All patients had intermediate or poor MSKCC score; more poor-risk patients received cabozantinib than other TKIs (28.9% vs 20%). Outcomes data are shown in the Table. Compared with other TKIs, cabozantinib was associated with a significantly higher RR 6months and ORR, and TTD was twice as long with cabozantinib. Discontinuation due to AEs was more frequent with other TKIs than with cabozantinib, although this was not statistically significant; 21.7% of discontinuations occurred during the first 3 months of treatment. AEs leading to discontinuation were consistent with the known safety profile of the products. Conclusions: In this mRCC population receiving routine care in the US, cabozantinib was used more frequently than other TKIs after CPI treatment. Cabozantinib was an effective and well tolerated option post-CPI, with a high response rate in the real-world setting.abozantinib was associated with a significantly higher response rate and a lower discontinuation rate due to AEs; TTD was double that of other TKIs. [Table: see text]
Assessment of Annual Cost of Substance Use Disorder in US Hospitals
Authors: Cora Peterson, Mengyao Li, Likang Xu, Christina A. Mikosz, Feijun Luo
Journal: JAMA Network Open (2021)

<h3>Importance</h3> A persistently high US drug overdose death toll and increasing health care use associated with substance use disorder (SUD) create urgency for comprehensive estimates of attributable direct costs, which can assist in identifying cost-effective ways to prevent SUD and help people to receive effective treatment. <h3>Objective</h3> To estimate the annual attributable medical cost of SUD in US hospitals from the health care payer perspective. <h3>Design, Setting, and Participants</h3> This economic evaluation of observational data used multivariable regression analysis and mathematical modeling of hospital encounter costs, controlling for patient demographic, clinical, and insurance characteristics, and compared encounters with and without secondary SUD diagnosis to statistically identify the total attributable cost of SUD. Nationally representative hospital emergency department (ED) and inpatient encounters from the 2017 Healthcare Cost and Utilization Project Nationwide Emergency Department Sample and National Inpatient Sample were studied. Statistical analysis was performed from March to June 2020. <h3>Exposures</h3> <i>International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM)</i>principal or secondary SUD diagnosis on the hospital discharge record according to the Clinical Classifications Software categories (disorders related to alcohol, cannabis, hallucinogens, inhalants, opioids, sedatives, stimulants, and other substances). <h3>Main Outcomes and Measures</h3> Annual attributable SUD medical cost in hospitals overall and by substance type (eg, alcohol). The number of encounters (ED and inpatient) with SUD diagnosis (principal or secondary) and the mean cost attributable to SUD per encounter by substance type are also reported. <h3>Results</h3> This study examined a total of 124 573 175 hospital ED encounters and 33 648 910 hospital inpatient encounters from the 2017 Healthcare Cost and Utilization Project Nationwide Emergency Department Sample and National Inpatient Sample. Total annual estimated attributable SUD medical cost in hospitals was $13.2 billion. By substance type, the cost ranged from $4 million for inhalant-related disorders to $7.6 billion for alcohol-related disorders. <h3>Conclusions and Relevance</h3> This study’s results suggest that the cost of effective prevention and treatment may be substantially offset by a reduction in the high direct medical cost of SUD hospital care. The findings of this study may inform the treatment of patients with SUD during hospitalization, which presents a critical opportunity to engage patients who are at high risk for overdose. Aligning incentives such that prevention cost savings accrue to payers and practitioners that are otherwise responsible for SUD-related medical costs in hospitals and other health care settings may encourage prevention investment.
Sustained Remission in Patients With Rheumatoid Arthritis Receiving Triple Therapy Compared to Biologic Therapy: A Swedish Nationwide Register Study
Authors: Hanna Källmark, Jon T. Einarsson, Jan‐Åke Nilsson, Tor Olofsson, Tore Saxne, Pierre Geborek, Meliha C. Kapetanovic
Journal: Arthritis & Rheumatology (2021)

Objective To compare the real‐life effectiveness of biologic therapy (a biologic disease‐modifying antirheumatic drug plus methotrexate [MTX]) versus triple therapy (MTX plus sulfasalazine plus hydroxychloroquine/chloroquine) for sustained remission of rheumatoid arthritis (RA). Methods RA patients who were registered in the nationwide Swedish Rheumatology Quality Register between 2000 and 2012 and were receiving biologic or triple therapy as a first treatment strategy after MTX monotherapy were included. Sustained remission was defined as a Disease Activity Score in 28 joints (DAS28) of &lt;2.6 for ≥6 months (short‐term sustained remission) or for ≥24 months (long‐term sustained remission). Treatment groups were compared during treatment, at 1 year, and at 2 years for 1) all patients starting therapy and 2) patients continuing to receive therapy, using propensity score–adjusted regression analyses. In addition, survival analyses were used to compare treatment groups at any time during follow‐up irrespective of therapy retention. Results A total of 1,502 patients were included (1,155 receiving biologic therapy and 347 receiving triple therapy). For patients starting therapy, the adjusted odds ratios (ORs) of achieving short‐term and long‐term remission, respectively, at 1 year after start of biologic therapy versus triple therapy were 1.79 (95% confidence interval [95% CI] 1.18–2.71) and 1.86 (95% CI 1.00–3.48). At 2 years, the ORs were 1.92 (95% CI 1.21–3.06) and 1.62 (95% CI 0.94–2.79), respectively. For patients continuing to receive therapy, corresponding results at 1 year were 1.12 (95% CI 0.72–1.75) and 1.1 (95% CI 0.59–2.16); at 2 years, 0.85 (95% CI 0.49–1.47) and 0.76 (95% CI 0.41–1.39). Hazard ratios for short‐term and long‐term sustained remission at any time during follow‐up were 1.15 (95% CI 0.91–1.46) and 1.09 (95% CI 0.77–1.54), respectively. Conclusion Among patients starting biologic or triple therapy, biologic therapy was more effective for remaining on therapy and achieving sustained remission. However, similar probabilities were found for achieving sustained remission among patients remaining on therapy and at any time during follow‐up irrespective of therapy retention. Although the likelihood of reaching sustained remission is higher with biologic therapy, for certain RA patients triple therapy may still be an alternative to biologic therapy without hampering future chances of obtaining sustained remission.
Community COVID-19 Incidence and Health Care Personnel COVID-19 Seroprevalence
Authors: Shruti K. Gohil, Susan S. Huang
Journal: JAMA Network Open (2021)

Jesse T. Jacob, MD; Julia M. Baker, PhD; Scott K. Fridkin, MD; Benjamin A. Lopman, PhD; James P. Steinberg, MD; Robert H. Christenson, PhD; Brent King, MD; Surbhi Leekha, MBBS; Lyndsay M. O'Hara, PhD; Peter Rock, MD, MBA; Gregory M. Schrank, MD; Mary K. Hayden, MD; Bala Hota, MD, MPH; Michael Y. Lin, MD, MPH; Brian D. Stein, MD, MS; Patrizio Caturegli, MD; Aaron M. Milstone, MD, MHS; Clare Rock, MD, MS; Annie Voskertchian, MPH; Sujan C. Reddy, MD; Anthony D. Harris, MD
Abstract 10983: Alcohol Intake and Heart Failure Incidence: Results From the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: P. Elliott Miller, Di Zhao, Robyn McClelland, Alan Bertoni, Joao A Lima, Eliseo Guallar, Wendy S Post
Journal: Circulation (2015)

Background: Alcohol intake has a well-described J-shaped effect on cardiovascular disease and all-cause mortality. Previous studies have shown a lower incidence of heart failure (HF) with moderate alcohol use. However, it is unknown whether alcohol intake is associated with a lower incidence of HF with reduced ejection fraction (HFrEF) or with preserved ejection fraction (HFpEF). Methods: We performed analyses of participants from the Multi-Ethnic Study of Atherosclerosis (MESA) to assess the association of alcohol and incident HF. Alcohol use was determine by self-report at baseline. Individuals were free of cardiovascular disease at baseline and were followed for a mean of 10.2 ± 2.8 years for incident events. Heart failure was classified as HFrEF (ejection fraction (EF) ≤50%) or HFpEF (EF &gt; 50%) at the time of HF diagnosis. We performed time-fixed Cox proportional hazard regression models to assess associations between alcohol use and incident heart failure. Analyses were adjusted for age, sex, race, smoking (pack-years), and education, and then additionally for systolic and diastolic blood pressures, use of antihypertensive medications, family history of CHD, diabetes, HDL-cholesterol, C-reactive protein, fibrinogen, and interim myocardial infarction as a time-varying covariate. Results: We identified 6,763 individuals with alcohol use data, which included 1,390 (20.6%) never, 1,624 (24.0%) former, and 3,749 (55.4%) current drinkers at baseline. The average age was 62.1 years with 47.2% men. There were 258 HF events with 118 classified as HFrEF, 112 as HFpEF, and 28 participants excluded from analyses due to an unknown EF. Compared to never drinkers, individuals reporting &gt; 2 drinks per day had a higher risk of developing HFpEF [HR 2.41 (95% CI 1.04, 5.60) in model 1 and HR: 2.65 (1.10-6.42) in the fully adjusted model]. There were no significant associations between alcohol use and incident overall HF (HFpEF and HFrEF combined) [HR 1.31 (0.73-2.35)] or HFrEF [HR 0.78 (0.32-1.92)]. Conclusion: In the MESA cohort, individuals who drank greater than 2 alcoholic drinks per day had an increased odds of incident HFpEF but not HFrEF. Follow-up studies are needed to understand the etiology of these differences and to investigate for differences by race and sex.
Enzalutamide plus androgen deprivation therapy (ADT) versus flutamide plus ADT in men with castration-resistant prostate cancer (CRPC): AFTERCAB.
Authors: Hiroji Uemura, Kazuki Kobayashi, Akira Yokomizo, Shiro Hinotsu, Shigeo Horie, Yoshiyuki Kakehi, Seiji Naito, Norio Nonomura, Osamu Ogawa, Mototsugu Oya, Kazuhiro Suzuki, Atsushi Saito, Satoshi Uno, Hideyuki Akaza
Journal: Journal of Clinical Oncology (2021)

81 Background: Enzalutamide has been approved for the treatment of CRPC in Japan since 2014. This study compared the efficacy and safety of enzalutamide + ADT and flutamide + ADT in the treatment of men with CRPC who progressed despite combined androgen blockade with bicalutamide + ADT. The sequential order of treatment was also investigated. Methods: The open-label, Phase 4 AFTERCAB study (NCT02918968) was conducted from November 2016–March 2020 in Japanese men aged ≥20 years with asymptomatic or mildly symptomatic CRPC (metastatic or nonmetastatic) and an Eastern Cooperative Oncology Group performance status of 0 or 1 who progressed despite bicalutamide + ADT. Patients were initially randomized to enzalutamide (160 mg/day) + ADT (enzalutamide first) or flutamide (375 mg/day [125 mg 3 × daily]) + ADT (flutamide first) as first-line therapy. Following prostate-specific antigen (PSA) progression, other disease progression, or discontinuation of first-line therapy due to an adverse event (AE), patients switched to the other treatment as second-line therapy. The primary endpoint was time to PSA progression with first-line therapy (TTPP1). Secondary endpoints included TTPP2 (TTPP1 + time to PSA progression with second-line therapy). AEs were monitored to assess safety. Results: 206 men were randomized, stratified by study site and disease stage. Baseline demographics and disease characteristics were similar between treatment arms. Median treatment exposure was 14.3 months (range 0.8–35.9) with enzalutamide first and 5.6 months (range 0.3–37.7) with flutamide first. 133 patients transitioned to second-line therapy (n=48 for enzalutamide first and n=85 for flutamide first). TTPP1 was significantly improved with enzalutamide first versus flutamide first; numerically longer TTPP2 was observed with enzalutamide first versus flutamide first (Table). With first-line therapy, 92.2% (n=94) of patients reported treatment-emergent AEs (TEAEs) and 28.4% (n=29) reported serious TEAEs for enzalutamide first. Corresponding numbers for flutamide first were 76.0% (n=79) for TEAEs and 14.4% (n=15) for serious TEAEs. Conclusions: Treatment with enzalutamide + ADT provided a significant improvement in time to PSA progression versus flutamide + ADT as first-line therapy. Both treatments were generally well tolerated, with AEs consistent with the known safety profiles. Clinical trial information: NCT02918968. [Table: see text]
Pragmatic Design of Randomized Clinical Trials for Heart Failure
Authors: Stephen J Greene, Eric J Velazquez, Kevin J Anstrom, Eric L Eisenstein, Shelly Sapp, Shelby Morgan, Tina Harding, Vandana Sachdev, Fassil Ketema, Dong-Yun Kim, Patrice Desvigne-Nickens, Bertram Pitt, Robert J Mentz
Journal: JACC Heart Failure (2021)
MASS-FIX for the detection of monoclonal proteins and light chain N-glycosylation in routine clinical practice: a cross-sectional study of 6315 patients
Authors: Patrick W. Mellors, Surendra Dasari, Mindy C. Kohlhagen, Taxiarchis Kourelis, Ronald S. Go, Eli Muchtar, Morie A. Gertz, Shaji K. Kumar, Francis. K. Buadi, Maria A. V. Willrich, John A. Lust, Prashant Kapoor, Martha Q. Lacy, David Dingli, Yi Hwa, Amie Fonder, Miriam Hobbs, Susan Hayman, Rahma Warsame, Nelson R. Leung, Yi Lin, Wilson Gonsalves, Mustaqeem Siddiqui, Robert A. Kyle, S. Vincent Rajkumar, David L. Murray, Angela Dispenzieri
Journal: Blood Cancer Journal (2021)

Immunoenrichment-based matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), termed MASS-FIX, offers several advantages over immunofixation for the detection and isotyping of serum monoclonal protein, including superior sensitivity and specificity, the ability to differentiate therapeutic monoclonal antibodies, and the rapid identification of light chain (LC) N-glycosylation. We identified 6315 patients with MASS-FIX performed at our institution since 2018. Of these, 4118 patients (65%) with a wide array of plasma cell disorders (PCD), including rare monoclonal gammopathies of clinical significance, had a positive MASS-FIX. Two-hundred twenty-one (5%) of the MASS-FIX positive patients had evidence of LC N-glycosylation, which was more commonly identified in IgM heavy chain isotype, kappa LC isotype, and in diagnoses of immunoglobulin light chain (AL) amyloidosis and cold agglutinin disease (CAD) compared to other PCD. This cross-sectional study describes the largest cohort of patients to undergo MASS-FIX in routine clinical practice. Our findings demonstrate the widespread utility of this assay, and confirm that LC N-glycosylation should prompt suspicion for AL amyloidosis and CAD in the appropriate clinical context.
Paclitaxel, ifosfamide &amp; cisplatin (TIP) as second-line therapy for germ cell tumors (GCT):Long-term follow-up and expansion cohort.
Authors: Jack Patrick Gleeson, Andrea Knezevic, Maria Bromberg, Sujata Patil, Joel Sheinfeld, Brett Stewart Carver, David Randolph Jones, Manjit S. Bains, Dean F. Bajorin, George J. Bosl, Deaglan Joseph McHugh, Samuel Aaron Funt, Robert J. Motzer, Darren R. Feldman
Journal: Journal of Clinical Oncology (2021)

386 Background: TIP was established as an effective second-line regimen in a phase II study of 46 patients (pts) with relapsed GCT and favorable risk factors (Kondagunta, JCO 2005). Here, we report long-term follow up from this trial and outcomes for additional pts who subsequently received TIP off protocol. Methods: Eligiblepts included those who received TIP on the original phase II trial (original cohort) or who received TIP following study closure but would have met the trial inclusion criteria (expansion cohort). An additional exploratory cohort was comprised of pts with unfavorable risk factors who would not have met the original trial criteria. The primary endpoint was favorable response rate (FRR), which included complete responses (CR) and partial responses with negative markers (PR-). Overall survival (OS), progression free survival (PFS), and relapse rates were also evaluated. Results: Of 204 pts who received TIP for GCT at our institution from 5/1994 to 7/2019, 87 (original cohort, n=46; expansion cohort, n=41) met the inclusion criteria and were evaluable for the main analysis. An additional 17 pts were analyzed in the exploratory cohort (unfavorable risk factor: PR- lasting &lt;6months or IR, n=13; prior adjuvant therapy, n=4). 100 pts were excluded due to participation in an ongoing clinical trial (n=17), receipt of TIP as their first regimen (n=74) or in the adjuvant (n=3) setting, or insufficient data (n=6). Baseline characteristics and efficacy data are displayed in the table below. In the main cohort, 70/87 (80%) pts achieved a favorable response. With median follow-up of 10.2 years (yrs) [original, 14.3 yrs; expansion 6.5 yrs] 26 deaths were observed. 5yr and 10yr OS rates were 72% (95% CI 63, 83) and 69% (95% CI 59, 80) respectively. 5yr and 10yr PFS were 70% (95% CI 61, 81) and 67% (95% CI 57, 78). In the exploratory cohort, there were 7 deaths at median follow-up of 6.2 yrs with 5yr OS of 56% (95% CI 35, 87) and 5yr PFS of 59% (95% CI 40, 88). Conclusions: Long-term follow-up and additional experience supports the use of TIP as second-line therapy for GCT. Similar outcomes were seen for our exploratory and main cohorts, suggesting benefit with TIP outside of those with a favorable prognosis. [Table: see text]
Abstract IA005: Immune escape during breast tumor progression
Authors: Kornelia Polyak
Journal: Cancer Research (2021)

Abstract The drivers of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) transition are poorly understood. We have analyzed genetic, gene expression, epigenetic profiles of cells composing the tumor and identified cell type-specific changes during tumor progression. Importantly, while we could not detect progression stage- stage-specific alterations in tumor epithelial cells, myoepithelial cells and cells composing the microenvironment showed consistent differences between DCIS and IDC. Overall, there is a general decline in intratumor activated GZMB+CD8+ T cells accompanied by changes in innate immune cells that promote tumor outgrowth. We demonstrate that these progression stage-specific alterations are also present in a rat model of breast cancer and that combined targeting of multiple components of the tumor ecosystem increases the efficacy of anti-cancer therapies. Our data highlight the role of microenvironmental, especially immune-related changes in driving breast tumor progression. Citation Format: Kornelia Polyak. Immune escape during breast tumor progression [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr IA005.
Distinct CDK6 complexes determine tumor cell response to CDK4/6 inhibitors and degraders
Authors: Xuewei Wu, Xiaobao Yang, Yan Xiong, Ruitong Li, Takahiro Ito, Tamer A. Ahmed, Zoi Karoulia, Christos Adamopoulos, Hong Wang, Li Wang, Ling Xie, Jing Liu, Beatrix Ueberheide, Stuart A. Aaronson, Xian Chen, Sean G. Buchanan, William R. Sellers, Jian Jin, Poulikos I. Poulikakos
Journal: Nature Cancer (2021)
Plasma exosome microRNAs in patients with advanced renal cell carcinoma treated with nivolumab and ipilimumab: Potential biomarkers of response to therapy.
Authors: Maryam Soleimani, Marisa Thi, Neetu Saxena, Daniel Joseph Khalaf, Bernhard J. Eigl, Kim N. Chi, Christian K. Kollmannsberger, Lucia Nappi
Journal: Journal of Clinical Oncology (2021)

338 Background: There is a critical unmet need for predictive biomarkers in the management of metastatic renal cell carcinoma (mRCC). We sought to quantify plasma exosome microRNAs (miRNAs) and correlate with response to first line nivolumab and ipilimumab (N/I) to potentially serve as such a biomarker. Methods: We evaluated the expression of 11 miRNAs in 19 patients with mRCC (prior to initiation of N/I) and in 32 healthy volunteers. Exosomes were extracted from 500 uL of plasma (qEV original, Izon Science) and once confirmed, were used for miRNAs extraction. MiRNAs expression was evaluated by real time polymerase chain reaction using a TaqMan miRNA assay (Applied Biosystems). The relative quantity of each miRNA in patients was compared to healthy volunteers. The expression of each miRNA was correlated to the best response to N/I, categorizing patients as either responders or non-responders. Results: Clinical characteristics are summarized in the table below. Median age at the start of systemic therapy was 64.3 years. MiR200b demonstrated a significantly higher expression in mRCC patients than in healthy volunteers (unpaired t-test; p=0.04). We observed a variable pattern of miRNA expression based on response to N/I. Although not statistically significant, 4 miRNA (miR138, 155, 200b, 221) were upregulated in non-responders, while two (miR200a and 497) were upregulated in responders. Of note, the only patient to achieve a complete response had the lowest expression of miR138 and the highest expression of miR497. Conclusions: Although preliminary and limited by a small number of patients, these initial observational results are promising and suggest a potential role for miRNAs as predictive biomarkers in mRCC. MiR138 and 497 are known to regulate CTLA-4 and PD-L1, respectively. We speculate that these miRNA are potentially involved in response to immune checkpoint therapy. Ongoing work in evaluating expression of these and other miRNAs in blood and in tissue along with clinical correlation continues. [Table: see text]