tbuckley/cabot-search huggingface dataset:
Predicting Oncotype DX score with clinicopathological variables.
Authors: Valmarie Ramos-Lamboy, Fernando Cabanillas, Miguel M. Echenique, Victor Carlo, Viviana Negron, Orestes Antonio Pavia, Margarita Bruno, Karen J. Santiago
Journal: Journal of Clinical Oncology (2012)

e11015 Background: Oncotype Dx (OD) is a commercially available gene-profiling test that has been shown to be effective in predicting risk of recurrence after therapy with CMF or Tamoxifen. The aim of our study is to develop a method that uses easily available clinical data to predict cases with favorable OD category (ODC). Methods: We identified 145 ER+/Her-2 neg cases that had information on histologic grade (HG), PR status and Oncotype Dx Category (ODC). Of these, 75 also had information on Ki-67. We evaluated HG, ER status, PR status, Nottingham score and tumor size for their correlation with ODC using multiple regression analysis. Results: The median tumor size was 12.0 mm (0.6-45). 33.7% were HG 1, 54% were grade 2, and 12% were grade 3. 88% were invasive ductal carcinomas, 9% were invasive lobular carcinomas, 3% were other types. The median OD score was 15 (0-57) with 86 (59%) ODC=1, 53 (37%) ODC=2 and 6 (4%) ODC=3; median Ki-67 was 11% (1-50). In a multivariate analysis excluding Ki-67, the only factors that were significantly correlated with ODC were PR status and HG (p= 0.004). PR status had the strongest overall association with ODC (P=0.008). Defining PR&gt; 60% with HG=1 as a positive result we calculated the positive predictive value (PPV) or the capacity to predict cases with ODC=1, as 85% and negative predictive value (NPV) as 46%. None of the cases with PR&gt; 60% and HG=1 had an ODC=3 (high risk). A patient with a favorable ODC=1 was considered as a positive case for purpose of calculating PPV, NPV, sensitivity and specificity. Sensitivity to detect positive cases was 26% and specificity was 93%. We explored a 2nd model that included Ki-67 and found that only PR &gt;60% and Ki-67 &gt;11% significantly correlated with ODC (p=0.004). PR status again had the strongest overall association with ODC (P=0.007) followed by Ki-67 (P=0.019). HG was not significant in the 2 nd multivariate model because of its strong correlation with Ki-67. PPV for this 2 nd model was 79% and NPV=50%. Conclusions: 1-Pts who have PR&gt;60% with HG=1 are highly likely to have a favorable ODC=1, however the ODC of pts with either PR&lt;60% or HG&gt;1 is not predictable with either of our two models. 2- The use of Ki-67 doesn’t add much to the capacity of the model to predict ODC. 3- PR is the strongest predictive factor in the model.
Mazabraud’s Syndrome Mimicking Metastases on FDG PET/CT in a Patient With Colon Cancer
Authors: Sonia Mahajan, Reema Goel, Christopher Riedl, Gary A. Ulaner
Journal: Clinical Nuclear Medicine (2018)

Mazabraud's, a syndrome consisting of fibrous dysplasia and soft tissue myxomas, is a rare disorder with less than 100 cases reported in the literature. Appearance of lesions in Mazabraud's syndrome on FDG PET/CT scan in an oncological scenario can be misinterpreted as malignancy. We present the case of a 69-year-old woman, diagnosed with metastatic colon carcinoma and suspected osseous as well as soft tissue metastases, who was later found to have concomitant Mazabraud's syndrome. This case describes the diagnostic dilemma associated with this unusual entity and importance of differentiating benign and malignant etiologies on FDG PET/CT scan.
A phase II study of nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer (mTNBC).
Authors: Romualdo Barroso-Sousa, Hao Guo, William Thomas Barry, Grace Winship, Beth Overmoyer, Dan G. Duda, Sara M. Tolaney
Journal: Journal of Clinical Oncology (2018)

TPS1119 Background: Patients with mTNBC have a poor prognosis, and new therapies are needed. Vascular endothelial growth factor (VEGF)-A and myeloid-derived suppressors cells (MDSCs) have been recognized as critical players of tumor immune suppression of T-cell mediated responses. We hypothesize that cabozantinib, a multikinase inhibitor that blocks the VEGF receptor 2, and reduces MDSCs while increasing the number of T cells, will enhance the activity of the anti-PD-1 checkpoint blocker nivolumab in mTNBC. Methods: This is a phase II, single arm, single-center study assessing the efficacy of nivolumab (480 mg intravenously on day 1, every 28 days) plus cabozantinib (40 mg daily by mouth) in patients with mTNBC (NCT03316586). Eligibility Criteria include patients with mTNBC, or estrogen and progesterone receptor low positive ( < 10%) breast cancer, with measurable disease, and who have received 0-3 prior lines of chemotherapy in the advanced setting. The primary aim is to evaluate the efficacy of the combination, as defined by ORR according to RECIST 1.1. Secondary objectives include to determine the ORR according to immune-related criteria, the progression-free survival, the clinical benefit rate, the safety and the tolerability of the combination. Tumor biopsies and peripheral blood will be obtained at baseline, on treatment and at disease progression for immunoprofiling and to examine biomarkers of treatment response. Using the Simons “optimal” method, in the first stage, 18 patients will be enrolled. If there are least 3 responses, accrual will continue to the second stage where up to 17 additional patients will be enrolled. If at least 7 of these 35 patients have an objective response the regimen will be considered worthy of further study. With this design, if the true response rate is 10%, the chance the regimen is declared worthy of further study is less than 5% (exact alpha = 0.047). If the true response rate is 30%, the chance that the regimen is declared worthy of further study is 90%. The trial opened in December 2017 and has accrued 5 patients with a target accrual of 35 patients. Accrual should be completed in 12 months. Clinical trial information: 03316586.
Antithrombotic Therapy for Peripheral Artery Disease in 2018
Authors: Connie N. Hess, William R. Hiatt
Journal: JAMA (2018)

Anna Franzone, MD; Raffaele Piccolo, MD; Giuseppe Gargiulo, MD; Sara Ariotti, MD; Marcello Marino, MD; Andrea Santucci, MD; Andrea Baldo, MD; Giulia Magnani, MD, PhD; Aris Moschovitis, MD; Stephan Windecker, MD; Marco Valgimigli, MD, PhD
Inflammatory cytokines, life-threatening arrhythmias and premature mortality in chronic inflammatory arthritis: time to focus on
Authors: Pietro Enea Lazzerini, Franco Laghi Pasini, Maurizio Acampa, Pier Leopoldo Capecchi
Journal: Annals of the Rheumatic Diseases (2018)

We read with much interest the paper by Ntari et al 1 and would like to highlight how the high prevalence of fatal arrhythmic events that they found in Tg197 mice might have relevant implications in the clinical setting.

A solid body of data supports the evidence that in patients with chronic inflammatory arthritis (CIA), particularly rheumatoid arthritis (RA), the risk of death is significantly higher than in the general population, and that such a premature mortality is largely related to fatal cardiovascular events.2 In this regard, two population-based studies provided evidence that the prevalence of cardiac arrest (CA) and sudden cardiac death (SCD) is ~2 times higher in patients with RA than in those with no RA.3 4 In addition, in patients with RA, the onset of an acute coronary syndrome is characterised by an increased short-term case …
Abstract 79: Sex-dependent Role of Macrophage-derived Insulin-like Growth Factor-1 in Body Growth, Cardiac Homeostasis and Responses to Cardiac Tissue Stress
Authors: Alexei Ilinykh, Christopher Chan, Micheal A McLellan, Galen T Squiers, Jane Branca, Grant R Drummond, Nadia A Rosenthal, Alexander R Pinto
Journal: Circulation Research (2017)

Biological sex is a key factor influencing the development and progression of cardiovascular disease. While sexual dimorphism has been identified in cardiac physiology and sex-based differences are observed in clinical contexts, the molecular and cellular bases for these differences are not understood. Recently, we found for the first time that female and male hearts are different in their cellular composition. Female hearts comprise significantly greater numbers of resident mesenchymal cells, including cardiac fibroblasts, compared to male hearts, and female hearts consist of differing proportions of multiple leukocyte subsets. We found that these differences are regulated by gonadal hormones. Extending on our previous work, this study investigates sexual dimorphism in cell-specific IGF-1 production and its impact on cardiac inflammatory responses. IGF-1 is a growth factor that is essential for development and injury responses, and that has been previously shown to function in a sex-dependent manner. Using genetic, transcriptomic and high-dimensional flow cytometry approaches, we found that macrophages and fibroblasts are the principle IGF-1 producing cells in the heart, with macrophages from female mouse hearts producing twice as much IGF-1 as in males. This contributed to a ~20% greater level of IGF-1 found in the hearts of females compared to males. Furthermore, constitutive genetic ablation of macrophage-derived IGF-1 resulted in ~30% reduction in total IGF-1 in hearts of female mice, whereas no reduction was observed in male hearts. Surprisingly, we also found that ablation of macrophage-derived IGF-1 reduces body weight in female mice by ~10%. Finally, we found that macrophage-derived IGF-1 regulates cardiac inflammatory responses in a sex-dependent manner. To our knowledge, this is the first study to demonstrate that a macrophage-derived growth factor is essential for normal body growth and plays a sex-dependent role in cardiac inflammatory responses. Our observations provide a cellular and molecular basis for the sexual dimorphism observed in cardiac physiology and pathology, and underscore the importance of considering biological sex in experimental models of cardiac development and disease.
Efficacy analyses of central laboratory pCR results from the LILAC study comparing the biosimilar ABP 980 and trastuzumab.
Authors: Hans-Christian Kolberg, Zorica Tomasevic, Georgia Demetriou, Yasuhiro Fujiwara, Marco Colleoni, Hans Tesch, Patricia Xavier Santi, Vladimir Hanes, Nan Zhang
Journal: Journal of Clinical Oncology (2018)

583 Background: The phase 3 LILAC Study compared ABP 980 with trastuzumab (TRAS) on pathologic complete response (pCR) in women with HER2+ early breast cancer. The primary efficacy results, based on local laboratory evaluation of tumor samples, have been reported previously. Here we report the results of pCR analysis based on central laboratory evaluation of tumor samples. Methods: After run-in anthracycline-based chemotherapy, patients were randomized 1:1 to ABP 980 or TRAS plus paclitaxel Q3W x 4 or Q1W x 12. The co-primary endpoints were risk difference (RD) and risk ratio (RR) of pCR adjusted for baseline covariates in breast tissue and axillary lymph nodes. Clinical similarity was supported by the central pathology evaluation as the 2-sided 90% CIs were within the equivalence margin for RD (-13% to 13%) and RR (0.759 to 1.318). Representative samples of tumor material were sent to the central laboratory for evaluation. Samples were determined to be adequate for evaluation based on the presence of tumor bed and integrity of nuclear detail. Each sample was evaluated by 2 independent central pathologists, who were blinded to patients’ treatment and to each other’s assessment. If discordance between the 2 pathologists was found, the case was sent to a third blinded pathologist to determine the outcome. Results: 725 patients were randomized; 696 (ABP 980: n = 358; TRAS: n = 338) were included in the pCR evaluable population. pCR was achieved in 48.0% for ABP 980 and 40.5% for TRAS, based on local review. RD of pCR was 7.3% (90% CI: 1.2%, 13.4%); RR was 1.19 (90% CI: 1.033, 1.366). The upper limit of the CIs slightly exceeded the equivalence margin. Based on central review, pCR was achieved in 47.8% for ABP 980 and 41.8% for TRAS. RD was 5.8% (90% CI: -0.5, 12.0%); RR was 1.14 (90% CI: 0.993, 1.312). Both RR and RD were contained within the equivalence margin. Conclusions: Results based on central evaluations support clinical equivalence of ABP 980 and TRAS. All sensitivity analyses based on central pathology evaluation were within the prespecified equivalence margins. This study demonstrates the feasibility of including central laboratory review of pCR rates in a large multicenter, multinational study. Clinical trial information: NCT01901146.
Hospitals’ reported £1bn deficit masks true scale of financial woes, say analysts
Authors: Nigel Hawkes
Journal: BMJ (2018)

Hospitals spent almost £1bn more in 2017-18 than they were paid, show data published by NHS Improvement.1

The provider sector as a whole ended the year with a deficit of £960m (€1.1bn; $1.3bn), which is almost exactly balanced by a projected underspend of £955m by healthcare commissioners reported last week by NHS England.

The NHS as a whole is therefore “broadly in balance,” said NHS Improvement, which oversees providers of NHS services. However, analysts questioned the conclusion, claiming that it was achieved only by one-off savings and a non-recurrent £1.8bn transfer from the sustainability and transformation fund set up to help transform NHS services.2

If these were discounted, said Sally Gainsbury, senior policy analyst at the think tank the Nuffield Trust, the true provider deficit …
Safety and efficacy of eflapegrastim in reducing severe neutropenia in patients treated with myelosuppressive chemotherapy in a phase 3 randomized controlled trial compared to pegfilgrastim (ADVANCE trial).
Authors: Lee Steven Schwartzberg, Zandong Yang, Julio Antonio Peguero, Richy Agajanian, Jayaram S. Bharadwaj, Alvaro Restrepo, Osama Hlalah, Inderjit Mehmi, Gajanan Bhat, Patrick Wayne Cobb
Journal: Journal of Clinical Oncology (2018)

e12513 Background: Eflapegrastim is a novel investigational biologic comprised of recombinant human G-CSF covalently linked to the human immunoglobulin G4FC fragment using proprietary LAPSCOVERY™ technology with potentially unique distribution to areas rich in FcRn receptors. The current study was a randomized, phase 3 study to demonstrate the non-inferiority (NI) of eflapegrastim to pegfilgrastim in patients receiving chemotherapy for breast cancer. Methods: Patients with Stage I to Stage IIIA breast cancer were treated on Day 1 of each of four cycles with adjuvant/neo-adjuvant docetaxel and cyclophosphamide (TC). On Day 2 of each cycle patients received a single subcutaneous dose of either eflapegrastim 13.2 mg/0.6 mL (equivalent to 3.6 mg G-CSF) or pegfilgrastim (6 mg) in a 1:1 ratio. Patients had CBCs drawn daily on Day 1 and day 4-15 or until recovery of neutropenia in each cycle. The primary endpoint was to demonstrate non-inferiority of eflapegrastim to pegfilgrastim as measured by the mean duration of severe neutropenia (DSN) in Cycle 1 with NI margin of < 0.62 day. Results: In a total of 406 intent-to-treat patients (randomized to 196 eflapegrastim; 210 pegfilgrastim), median age was 61 years (range 24 to 84 years); mean (SD) DSN was 0.19 (0.478) days for eflapegrastim and 0.34 (0.668) days for pegfilgrastim, demonstrating the non-inferiority (95% CI of ∆DSN: [-0.260, -0.035]; p < 0.0001). The non-inferiority of eflapegrastim for DSN was maintained across all 4 cycles. There were no statistically significant differences in secondary endpoints of time to ANC recovery, depth of ANC nadir and incidence of FN at Cycle 1. The adverse events observed in ≥10% of patients were similar across both arms and were mainly hematologic including neutropenia, lymphopenia, anemia and leukopenia. Conclusions: Eflapegrastim, a novel long acting G-CSF was non-inferior to pegfilgrastim in the reduction of DSN in Cycles 1-4, in breast cancer patients treated with TC. Eflapegrastim was safe and well-tolerated with a similar safety profile to pegfilgrastim. Clinical trial information: NCT02643420.
Pain relief after musculoskeletal trauma
Authors: Gijs Helmerhorst
Journal: British Journal of Sports Medicine (2018)

I investigated the effects of opioid pain medications versus non-opioid pain medications on pain relief, satisfaction with pain relief and disability after musculoskeletal trauma. The main objectives were to: (1) evaluate the differences in pain management after extremity fractures in the Netherlands and the USA, (2) test if current analgesic prescription management in fracture patients is suitable and (3) find factors associated with continued use of opioids after surgery for musculoskeletal trauma in the USA.

There is substantial variation in the management of pain relief for patients after musculoskeletal trauma. The USA and Canada are in the midst of a crisis of opioid use, misuse, overdose and deaths related to overdose, and most musculoskeletal trauma patients are given opioids. In Europe, the number of …
Prevalence of knee osteoarthritis features on magnetic resonance imaging in asymptomatic uninjured adults: a systematic review and meta-analysis
Authors: Adam G Culvenor, Britt Elin Øiestad, Harvi F Hart, Joshua J Stefanik, Ali Guermazi, Kay M Crossley
Journal: British Journal of Sports Medicine (2018)

Background Knee MRI is increasingly used to inform clinical management. Features associated with osteoarthritis are often present in asymptomatic uninjured knees; however, the estimated prevalence varies substantially between studies. We performed a systematic review with meta-analysis to provide summary estimates of the prevalence of MRI features of osteoarthritis in asymptomatic uninjured knees. Methods We searched six electronic databases for studies reporting MRI osteoarthritis feature prevalence (ie, cartilage defects, meniscal tears, bone marrow lesions and osteophytes) in asymptomatic uninjured knees. Summary estimates were calculated using random-effects meta-analysis (and stratified by mean age: &lt;40 vs ≥40 years). Meta-regression explored heterogeneity. Results We included 63 studies (5397 knees of 4751 adults). The overall pooled prevalence of cartilage defects was 24% (95% CI 15% to 34%) and meniscal tears was 10% (7% to 13%), with significantly higher prevalence with age: cartilage defect &lt;40 years 11% (6%to 17%) and ≥40 years 43% (29% to 57%); meniscal tear &lt;40 years 4% (2% to 7%) and ≥40 years 19% (13% to 26%). The overall pooled estimate of bone marrow lesions and osteophytes was 18% (12% to 24%) and 25% (14% to 38%), respectively, with prevalence of osteophytes (but not bone marrow lesions) increasing with age. Significant associations were found between prevalence estimates and MRI sequences used, physical activity, radiographic osteoarthritis and risk of bias. Conclusions Summary estimates of MRI osteoarthritis feature prevalence among asymptomatic uninjured knees were 4%–14% in adults aged &lt;40 years to 19%–43% in adults ≥40 years. These imaging findings should be interpreted in the context of clinical presentations and considered in clinical decision-making.
Diabetes outcomes in patients with a history of breast cancer.
Authors: Leslie J. Hinyard, Martin W Schoen, Jiajing Chen, Yifan Tu, Miriam B. Rodin
Journal: Journal of Clinical Oncology (2018)

8 Background: While diabetes is known to worsen breast cancer (BC) outcomes, little is known about the effect of BC on diabetes outcomes. This study examined differences in outcomes diabetic patients with and without a history of BC. Methods: Data from NHANES 2010 – 2016 was used to identify female patients self-reporting diabetes mellitus (DM). Comparisons of DM outcomes for persons reporting a history of BC versus without any cancer were made using Chi-Square and separate analyses were conducted for younger (less than 65) and older (65 and older) respondents. Analyses were conducted using SAS survey procedures (Cary, NC) and were weighted to account for the sampling scheme. Results: The analytic cohort consisted of 1347 patients, of which 80 (6.3%, weighted) reported a history of breast cancer. 785 (62.4%, weighted) of the full sample was under age 65. Of those under 65, 3% (weighted) reported history of BC and 11.8% (weighted) of those over 65% reported BC. In diabetics under 65, respondents with BC were more likely to report physical limitations keep them from working and physical, mental, and emotional limitations (p = .001, and p = 0.03, respectively) and were less likely to use insulin (p = .01) than respondents without BC. In respondents 65 and older, women with BC were more likely to report problems with memory and confusion (p = .002) and less likely to rate their general health as excellent or very good (p = .01) compared to those without BC. No differences were found for demographic characteristics, retinopathy, heart disease, or stroke for either age group. Conclusions: In this population of patients with diabetes, history of BC was associated with physical and emotional limitations in younger patients and general health status and memory and confusion in older patients. Understanding the intersection of multiple chronic conditions is important for improving quality of life and clinical outcomes in BC survivors.
A randomized phase II trial of carboplatin with or without nivolumab in first- or second-line metastatic TNBC.
Authors: Ana Christina Garrido-Castro, William Thomas Barry, Tiffany A. Traina, Robert Wesolowski, Nadine M. Tung, Tanya Keenan, Eliezer Mendel Van Allen, Nancy U. Lin, Eric P. Winer, Ian E. Krop, Sara M. Tolaney
Journal: Journal of Clinical Oncology (2018)

TPS1118 Background: Triple negative breast cancer (TNBC) has an aggressive clinical course with higher relapse rates and shorter overall survival compared to patients with hormone receptor-positive or HER2-positive disease. Increasing data suggest that interaction with the immune system is critical for outcomes in TNBC. Tumor infiltrating lymphocytes (TIL) correlate with improved prognosis and response to several PD-1/-L1 inhibitors. However, response rates with single agent checkpoint inhibitors reach only ≈ 25% in first-line TNBC. Platinum agents are DNA crosslinkers that cause accumulation of genotoxic stress, which stimulates immune activation via IFN-γ signaling. In preclinical models, platinum has been shown to generate CD8-driven anti-tumor immune response, making the combination with nivolumab (PD-1 antibody) an attractive strategy to enhance the benefit of either agent alone. Methods: This Phase II open-label, multicenter trial will enroll 132 patients with metastatic TNBC randomized 1:1 to receive carboplatin (AUC 6) with or without nivolumab (360 mg) IV every 3 weeks. Eligible patients must have unresectable locally advanced or metastatic TNBC treated with 0 to 1 prior line of chemotherapy in the metastatic setting. Prior platinum exposure is allowed in the neo/adjuvant setting if ≥12 months elapsed since the end of adjuvant therapy to the development of metastatic disease. The primary objective is to compare the efficacy, defined as progression-free survival (PFS) per RECIST 1.1, of carboplatin in combination with nivolumab versus carboplatin alone. Key secondary objectives include objective response rate, overall survival, clinical benefit rate, and duration and time to objective response. Patients must be willing to undergo mandatory paired research biopsies, one at baseline and one after 2 cycles of therapy, if safely accessible, to assess the correlation between TIL and PFS, and to explore pharmacodynamic changes in TIL and other biomarkers of response and resistance to treatment. Additional correlative studies, including analyses of circulating tumor DNA, peripheral blood mononuclear cells and intestinal microbiome, are planned. Clinical trial information: NCT03414684.