tbuckley/cabot-search huggingface dataset:
Practice variance as determinant of cost in the oncology care model (OCM).
Authors: Ariel Sandhu, Prachi Kalamkar, Katherine Miller, Matthew Bigbee, Gene Grant Finley, David S. Parda, David G. Mayernik
Journal: Journal of Clinical Oncology (2018)

e18563 Background: Oncology care represents the largest driver of medical cost in the US, projected to exceed $ 173 billion per year by 2020. Previous work has identified physician behavior as a variable that results in cost differences for similar patients. Here we test this hypothesis by examining claims data from 30 physicians at Allegheny Health Network (AHN), a large group practice enrolled in the OCM. Methods: We examined reimbursement data from 5 quarterly feedback reports from 4/1/16 – 6/30/17. 592 Medicare beneficiaries with a cancer diagnosis (per ICD10) and E&M code diagnosis requiring chemotherapy were included for 5 cancers: multiple myeloma, breast, lung, prostate and colorectal. Patient metrics such as diagnosis, total cost, admission costs and counts, ED visits, home health and hospice use, HCC (Hierarchical Condition Category) risk score and death were assessed with claim derived metrics such as chemotherapy price and attributed oncologist. Per Member Per Month (PMPM) rates were calculated for costs and admissions. Results: Hospital admissions and chemotherapy contributed 40.3% and 23.7% to total costs respectively. High costs and admission rates were seen in deceased patients ($ 11655 in deceased vs $ 3833 in living patients, p < 0.001; 0.44 vs 0.06 admissions per month in deceased versus living patients, p < 0.001). Home health (HH) and hospice (H) use in deceased patients were associated with lower total costs and admission rates compared to those who died without these services ($ 11331 with HH vs $ 12008 with no HH; $ 9692 with H vs $ 15109 with no H, p: 0.01). Admission costs ($ 3727 with H vs $ 9008 with no H, p 0.002) and ER visits (0.37 with H vs 0.82 with no H, p: 0.002) fell with hospice use. 36.44% and 47.83% of deceased patients did not receive hospice and home health services respectively. Weak correlation was found between HCC risk scores and total costs (r2= 0.41), chemotherapy costs (r2= 0.174) and ER visits (r2= 0.306). Conclusions: Admissions and chemotherapy are major cost drivers subject to variance in physician practice. Hospice and home health care services are underutilized in advanced disease. Weak correlations between HCC risk score and patient metrics suggest that factors besides disease type and severity drive cost and outcomes.
Abstract 19689: Kdm3a Protects Myocardium From Ischemia/reperfusion Injury Through Targeting Akt-dependent Signaling Pathways
Authors: Guo Xin, Chen Jing, Jiang Hong, Zhang Bo-fang, Hu Qi, Yang Shuo
Journal: Circulation (2017)

Objective: The aim of the present study was to explore potential contributions of histone demethylase KDM3A in the in vivo and in vitro MIRI and the underpinning mechanisms. Methods and Results: Myocardial KDM3A expression was down-regulated under I/R injury. The global KDM3A-knocout rat, and KDM3A-overexpressed rats induced by in situ adenoviral transfection as a selective protocol due to the failure of transgenic rats generation, were utilized to investigate the effects of KDM3A in rat heart in response to I/R. The results showed that KDM3A knockout exaggerated cardiac dysfunction and necrosis, which were evidenced by reduced ejection fraction (EF) and fractional shortening (FS) as well as increased infarct size and necrotic marker enzymes. The deteriorated inflammation, mitochondria-dependent apoptosis and reactive oxygen species (ROS) were simultaneously indicated. Conversely, KDM3A overexpression developed ameliorated changes in I/R disorder. KDM3A overexpression also mitigated hypoxia/reoxygenation ...
Evaluating clinical and prognostic implications of Glypican 3 in hepatocellular carcinoma.
Authors: Sahin Lacin, Reham Abdel-Wahab, Manal Hassan, Ahmed S Shalaby, Hesham M. Amin, Robert A. Wolff, James C. Yao, Amita Mistry, Janine D. Feng, Toshihiko Ohtomo, Ahmed Omar Kaseb
Journal: Journal of Clinical Oncology (2016)

e15619 Background: Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide and its histopathological differentiation is a main factor which may affect prognosis. Precise determination of HCC differentiation is difficult, and as recently described an immunohistochemistry (IHC) marker Glypican 3 might be useful for this purpose. The goal of the current study was to investigate GPC 3 IHC staining pattern and to define the relation between its expression, clinicopathologic feature, and overall survival. Methods: 101 pathologically diagnosed HCC patients were included in the study. The Clinical parameters were retrieved from patients's medical records at the time of diagnosis. IHC procedures for GPC3 were done and according to the GPC3 staining intensity and the percentage of the stained tumor cells, patients were classified into 4 clinical score category(Clinical score category; 0 (no expression or negative), 1+ (weak intensity), 2+ (moderate intensity), and 3+ (strong intensity)).Results: Distributions of patients that according to histopathological differentiation were 27 well ,28 moderate and 12 poorly differentiated HCC. Glypican 3 expression rate in well, moderate and poorly differentiated HCC was 63 %, 86 % , and 92 %,respectively. The median OS (95% CI) was 49.9 months (35.3 - 64.6 months) for clinical score (0-1) and 30.7 months (19.4 -41.9 months) for clinical score (2-3) but this difference was not statistically significant (P = 0.06),but showed a strong trend. Conclusions: Increased Glypican 3 expression rate associated worse prognosis, and it may be a promising prognostic immunhistopathological marker for HCC.However, large-scale independent validation studies are warranted to confirm and further define the prognostic role and implications of glypican 3 expression.
TCT-706 Cardiovascular and Non-Cardiovascular Death After PCI: Insights From 32,882 Patients Enrolled in 21 Randomized Trials
Authors: Sorin Brener, Giuseppe Tarantini, Martin Leon, Patrick Serruys, Pieter Smits, Clemens von Birgelen, Aaron Crowley, Ori Ben-Yehuda, Gregg Stone
Journal: Journal of the American College of Cardiology (2018)
Pomalidomide and dexamethasone (pom-dex) with or without daratumumab (DARA) in patients (pts) with relapsed or refractory multiple myeloma (RRMM): A multicenter, randomized, phase 3 study (APOLLO).
Authors: Pieter Sonneveld, Evangelos Terpos, Meletios A. Dimopoulos, Jon Ukropec, Elena Smith, Nienke Houkes, Jordan Mark Schecter, Efstathios Kastritis
Journal: Journal of Clinical Oncology (2018)

TPS8059 Background: DARA, a human IgGκ monoclonal antibody targeting CD38, is approved in the United States and Europe for use as a monotherapy and in combination with bortezomib/dexamethasone or lenalidomide/dexamethasone in pts with RRMM. In a phase 1b study, DARA + pom-dex demonstrated efficacy and tolerability in pts with RRMM, leading to the approval of this regimen for pts with RRMM in the United States. This phase 3 study will evaluate the efficacy and safety of DARA + pom-dex versus pom-dex alone in RRMM. Methods: This is an ongoing multicenter, open-label, phase 3 study of DARA + pom-dex versus pom-dex alone. RRMM pts who have received prior antimyeloma therapy, including a proteasome inhibitor and a lenalidomide-containing regimen, have responded to prior therapy, and have progressed on or after their last regimen, are eligible. Pts who have received only 1 prior line of therapy must have progressed ≤60 days of completing the lenalidomide-containing regimen. All pts will receive pom 4 mg orally on Days 1-21 of a 28-day cycle + dex 40 mg QW (20 mg for pts ≥75 year of age). Following a protocol amendment, pts in the DARA group will receive subcutaneous DARA (1,800 mg co-formulated with recombinant human hyaluronidase [rHuPH20]) QW in Cycles 1-2, Q2W in Cycles 3-6, and Q4W thereafter. All pts will receive preinfusion medications (including diphenhydramine, paracetamol, dexamethasone, and an optional leukotriene inhibitor), and postinfusion medications (diphenhydramine, lung disease control medications, and a short-acting β2 adrenergic receptor agonist) will be recommended for pts with a higher risk of respiratory complications. Progression-free survival is the primary endpoint. Secondary endpoints include safety, overall survival, overall response rate, duration of response, and minimal-residual-disease-negative rate. Approximately 302 pts will be enrolled across 11 countries. Clinical trial information: NCT03180736.
Principles for the selection of doses in chronic rodent bioassays. ILSI Risk Science Working Group on Dose Selection.
Authors: J A Foran
Journal: Environmental Health Perspectives (1997)

Dose selection in chronic rodent bioassays has been one of the most debated issues in risk assessment. The Committee on Risk Assessment Methods of the National Research Council attempted, but failed, in 1993 to reach consensus on how to select doses for chronic rodent bioassays. However, a more recent effort conducted by the ILSI Risk Science Institute has resulted in a consensus set of principles for dose selection, including selection of the highest dose for chronic rodent bioassays. The principles encourage a move away from sole reliance on a maximum tolerated dose (MTD), as it has been traditionally defined (primarily by body weight and histopathology), and toward the use of sound scientific and toxicologic principles for the selection of all doses in the chronic bioassay. Specifically, the principles recommend that dose selection for chronic studies must be based on sound toxicologic principles; dose selection should consider human exposure; dose selection should be based on a variety of endpoints and effects derived from prechronic studies; and dose selection should consider physicochemical and other factors. Implementation of the principles internationally will have two important benefits; improvement in the quality and consistency of the rodent bioassay and international harmonization of dose selection procedures.
Urbanicity and Psychosis—Reply
Authors: Jordan E. DeVylder, Ian Kelleher, Ai Koyanagi
Journal: JAMA Psychiatry (2018)

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Circulating free DNA (cfDNA) for personalized treatment of lung cancer patients without cytopathologic diagnosis.
Authors: Aditi Puri Singh, Qin-fang Deng, Qiyu Fang, Hui Sun, Shenduo Li, Haiying Cheng, Songwen Zhou
Journal: Journal of Clinical Oncology (2018)

e21143 Background: NGS- and PCR- based platforms can detect EGFR mutations in plasma cfDNA with high accuracy. Although tissue biopsy remains the gold standard for initial diagnosis, many pts with suspected advanced NSCLC are unable to undergo biopsy, forgoing potential treatment with highly effective TKIs in pts with sensitizing EGFR mutations. Our study examines the impact of cfDNA to detect EGFR mutations in pts plasma, where tissue biopsy is not feasible. Methods: This is a prospective study of 30 Chinese pts from 09/2016 – 09/2017 with suspected advanced lung cancer (by symptoms and imaging) who were unable to have a biopsy for initial diagnosis due to comorbidities or poor performance status (PS). NGS- or PCR-based (ARMS) sequencing was used to detect EGFR mutations in pts plasma. Pts with sensitizing mutations were treated with 1st generation EGFR TKIs and followed with serial imaging. Primary endpoint was progression-free survival (PFS) and secondary end points were objective response rates (ORR) and overall survival (OS). Results: 20 of 30 pts enrolled had sensitizing EGFR mutations (9 with Exon19del, 10 with Exon21 L858R and 1 with complex mutation T790M/G719A/p. L861Q/p747_752del) in cfDNA and were started on EGFR-TKIs (gefitinib/erlotinib/icotinib). 11 pts were male and 9 female, with a median age of 67 yrs. 10 were smokers, 6 non-smokers, and smoking status was unknown for 4. All pts had an ECOG PS of 3 or 4. After 1 month on treatment, restaging scans revealed that 18 pts had a partial response and 2 had stable disease. 9 of 20 pts clinically improved and were eventually able to undergo a tissue biopsy that confirmed lung adenocarcinoma. After a median follow-up of 11 months, median PFS was 10 months and median OS had not been reached. The median OS for the 10 untreated pts was 3 months. Conclusions: In our study, pts with plasma EGFR mutations treated with TKIs showed DCR and PFS similar to historical controls that were treated based on tissue testing. This is the first prospective study showing that cfDNA genotyping provides a feasible diagnostic approach to frail lung cancer pts who are unable to undergo biopsy, which subsequently leads to EGFR-targeted therapy resulting in improved clinical outcome in a subgroup of pts.
Abstract 17173: Incidence of Cardiovascular Disease in Individuals Affected by Recent Changes in Blood Pressure Treatment Guidelines
Authors: Matthew Nayor, Meredith D Stevenson, Vanessa Xanthakis, Martin G Larson, Ramachandran S Vasan
Journal: Circulation (2015)

Introduction: The Eighth Joint National Committee (JNC 8) recently recommended important changes to blood pressure (BP) management. Specifically, JNC 8 endorsed relaxing systolic BP (SBP) targets for adults aged ≥60 years and individuals with diabetes or kidney disease. We compared the incidence of cardiovascular disease (CVD) in individuals whose BP management might be affected by these changes. Hypothesis: We hypothesized that individuals with BP and treatment status consistent with more lenient BP targets (representative of JNC 8) would demonstrate higher incidence of CVD, compared to individuals achieving more aggressive targets (representative of JNC 7). Methods: We included visits from three examination cycles of the Framingham Offspring Study (11,237 visits, mean age 46 years, 53% women), and assigned participants to one of five categories based on resting BP, treatment status, and recommendations according to JNC 7 and JNC 8 guidelines. Cox proportional hazards regression was used to assess if time to CVD varied by BP category. Results: During follow-up (mean 11.0 years), there were 1047 incident CVD events (8.5/1000 person-years). Using the group free of hypertension as referent, we observed the highest incidence of CVD in those with treated SBP 140-149 mm Hg and diastolic BP (DBP) &lt;90 mm Hg (multivariable-adjusted hazard ratio [HR] 3.53, p&lt;0.0001), which was consistent among those aged &lt;60 years (HR 3.51, p=0.0004) and ≥60 years (HR 2.74, p&lt;0.0001), Table . Participants with untreated SBP 140-149 mm Hg and DBP &lt;90 mm Hg also had increased CVD risk overall (multivariable-adjusted HR 1.88, p&lt;0.0001), as well as within those aged &lt;60 years (HR 2.25, p=0.0002), but not those ≥60 years (HR 1.28, p=0.81). Conclusions: Individuals with SBP 140-149 mm Hg and DBP &lt;90 mm Hg have increased risk of CVD, and the risk is especially high for those on treatment. Although observational, our findings may help to address concerns regarding changes proposed by the JNC 8 guidelines.
Abstract 12080: A Novel Adipokine Adipolin Prevents Pathological Vascular Remodeling Following Arterial Injury
Authors: Hayato Ogawa, Koji Ohashi, Rei Shibata, Masanori Ito, Naoya Otaka, Hiroshi Kawanishi, Toyoaki Murohara, Noriyuki Ouchi
Journal: Circulation (2016)

Introduction: Obesity is causally linked with the development of pathological remodeling of vascular wall. Previously we have demonstrated that adipolin, also known as C1q/TNF-related protein 12, is an adipokine that is down-regulated in obese rodents. Here, we investigated whether adipolin affects vascular response to injury using loss-of-function genetic manipulations. Methods and Results: No significant differences were observed in body weight, organ weights, blood pressure and blood glucose levels between adipolin-knockout (APL-KO) and wild type (WT) mice under basal conditions. APL-KO and WT mice were subjected to wire-induced injury of the left femoral artery. APL-KO mice exhibited an enhanced neointimal thickening after artery injury compared with WT mice. APL-KO mice also displayed an impaired re-endothelialization following vascular injury compared with WT mice. Treatment of human umbilical vein endothelial cells with recombinant adipolin protein promoted proliferation and reduced serum starvation-induced apoptosis. Adipolin treatment stimulated the phosphorylation of Akt and eNOS in endothelial cells. Pharmacological inhibition of PI3 kinase by treatment with LY294002 reversed the stimulatory effects of adipolin on endothelial cell growth and eNOS phosphorylation. Furthermore, APL-KO mice showed increased expression of pro-inflammatory cytokines including interleukin 6 and interleukin 1β in the injured artery as compared with WT mice. Consistently, treatment of mouse peritoneal macrophages with adipolin protein suppressed lipopolysaccharide-stimulated expression of pro-inflammatory mediators. Conclusions: Our data indicate that adipolin prevents pathological remodeling of vascular walls following injury by modulating endothelial cell function and macrophage inflammatory response.
Immune gene profiling of pretreatment tumor samples in "real-world" advanced melanoma patients treated with anti-PD-1 and/or anti-CTLA-4.
Authors: Elisa A. Rozeman, Marnix Heimen Geukes Foppen, SuFey Ong, Ruben Lacroix, Patrick Danaher, Annegien Broeks, Alessandra Cesano, Sofie Wilgenhof, Johannes V. Van Thienen, John B. A. G. Haanen, Sarah Warren, Christian U. Blank
Journal: Journal of Clinical Oncology (2018)

9585 Background: The immune checkpoint inhibitors (CI) anti-CTLA-4 (ipilimumab [IPI]) and anti-PD-1 (pembrolizumab [PEM] and nivolumab [NIVO]) have improved survival in advanced melanoma patients (pts). Because of the range of upcoming new CI combinations, there is a need for biomarkers identifying pts who benefit from anti-PD-1 monotherapy. The NanoString T cell Inflammation Signature (TIS) is an 18-gene signature including IFN-y responsive genes related to antigen presentation, chemokine expression, cytotoxic activity and adaptive immune resistance that are reflective of a pre-existing, but suppressed, adaptive immune response in the tumor. TIS was associated with positive treatment outcomes to PEM in advanced stage melanoma and other solid tumors (Ayers, JCI 2017). Here, we evaluate the TIS and other immune-related signatures in pre-treatment tumor samples obtained from “real world” pts treated with anti-PD-1 and/or IPI. Methods: RNA isolated from formalin fixed, paraffin embedded pre-treatment tumor samples from pts receiving either IPI, NIVO or PEM outside clinical trials at the Netherlands Cancer Institute were profiled with NanoString PanCancer gene expression panels. RNA samples from 97 pts treated with anti-PD-1 and 55 pts treated with IPI were profiled. Response to therapy was defined as an immune related CR or PR. Results: RNA profiling was of sufficient quality in 93 pts treated with anti-PD-1 (NIVO n = 17, PEM n = 76) and 51 pts treated with IPI. There was no significant difference in TIS between the different origins of the tumor samples. The TIS was associated with response in pts treated with IPI (p = 0.002) and first-line anti-PD-1 (p = 0.012). Pretreatment with IPI and/or targeted therapy abolished this significant association of the TIS and response to anti-PD-1 (p = 0.52), which also holds true for other signatures analyzed. Conclusions: Immune gene profiling by TIS is a valuable tool for response prediction in “real world” advanced melanoma pts treated with IPI and first-line anti-PD-1. Interestingly, this association was lost in pts treated with anti-PD-1 after targeted therapy or IPI. Validation of our observations in an independent cohort is required.
Comparison of standard versus reduced-dose pegfilgrastim on clinical outcomes and chemotherapy dose intensity in patients with advanced pancreatic cancer receiving cytotoxic combination chemotherapy (NAPPCG) in an outpatient oncology infusion clinic.
Authors: Krystal Hicks, Adam Odeh
Journal: Journal of Clinical Oncology (2017)

e15710 Background: Pegfilgrastim use has been shown to reduce the incidence of febrile neutropenia when given at recommended dosage (6 mg) following myelosuppressive chemotherapy. Despite lack of supportive data, many prescribers have adopted the practice of utilizing reduced dosages (3-4 mg) of pegfilgrastim, often citing bone pain as reason for dose reduction. We sought to explore the impact of reduced-dose pegfilgrastim on chemotherapy dose intensity in patients with pancreatic cancer treated with the triplet combination of nab-paclitaxel, cisplatin and gemcitabine (NabPlagem) at our facility. Methods: A retrospective analysis was conducted on all patients who received NabPlagem chemotherapy in combination with pegfilgrastim during the period of 1/1/16 - 9/30/16. Patients who received at least 2 cycles were considered evaluable. Chemotherapy was administered on Days 1 and 8 of a 21-day cycle with pegfilgrastim administered Days 2 and 9. Chemotherapy doses were considered full-intensity if no reduction made from original treatment schema (i.e. 125 mg/m2 nab-paclitaxel, 25 mg/m2 cisplatin and gemcitabine 1000 mg/m2) with no doses delayed or omitted from treatment plan. Results: A total of 54 chemotherapy cycles were administered, with patients receiving between 5-13 cycles. Of these 54 cycles, 14 were given with reduced-dose pegfilgrastim (26%) and 40 at full dosage (74%). In the patients receiving full dose pegfilgrastim, treatment delays and omissions were observed in 5% cycles (n = 2), with no dose reductions required. Full dose-intensity was obtained in 90% cycles (36/40). In comparison, treatment delays and omissions were observed in 14% cycles given with reduced-dose pegfilgrastim. Dose reductions were required in 10/14 cycles (71%). Full dose-intensity was observed in 28.5% cycles (4/14). Conclusions: Based on this data, dosage of pegfilgrastim dose is an important factor in maintaining dose-intensity of chemotherapy, and full dosing (6 mg) should be preferred dosing schedule when used with myelosuppressive chemotherapy.