tbuckley/cabot-search huggingface dataset:
Increased FDG avidity in lymphoid tissue associated with response to combined immune checkpoint blockade
Authors: Katy K. Tsai, Miguel H. Pampaloni, Charity Hope, Alain P. Algazi, Britt-Marie Ljung, Laura Pincus, Adil I. Daud
Journal: Journal for ImmunoTherapy of Cancer (2016)

Antibodies against programmed death 1 (PD-1) receptor and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) have transformed the systemic treatment of melanoma and many other cancers. Understanding the spectrum of benign findings and atypical response patterns seen in immune checkpoint blockade is important for accurately assessing treatment response as these immunotherapies become more widely used.We report a 63-year-old man with metastatic melanoma successfully treated with combination CTLA-4 and PD-1 blockade (ipilimumab and nivolumab), after non-response to pembrolizumab monotherapy. The initial impression of disease progression, based on cutaneous and PET/CT findings of increased fluoro-2-deoxy-D-glucose (FDG) uptake in benign lymphoid tissue, proved to be erroneous after assiduous review of radiographic imaging and correlative pathology.These findings indicate that increased FDG uptake in benign lymphoid tissue seen on PET/CT may be a surrogate marker of immune activation and treatment response. Prospective studies will be invaluable in validating immune-related radiographic findings as a prognostic biomarker of response in cancer patients being treated with immune checkpoint blockade.
Use of a multiplatform analysis of plasma cytokines and angiogenic factors (CAFs) to identify baseline CAFs associated with pazopanib response and tumor burden in renal cell carcinoma (RCC) patients.
Authors: H. T. Tran, Y. Liu, Y. Lin, A. Martin, K. L. Baker, H. A. Fritsche, A. J. Zurita, L. Pandite, J. Heymach
Journal: Journal of Clinical Oncology (2010)

4522 Background: In a phase II RCC study of pazopanib (VEG102616) a response rate of 34.7% and disease control rate (CR + PR +SD) of 80% were observed (Hutson, JCO 2009). Previous analysis using AVANTRAT Biochips (Decision Biomarkers) in a subset of 129/215 patients (pts) with greatest versus least tumor shrinkage (TS) identified that lower baseline levels of plasma HGF, IL-6, and IL-8 were significantly correlated with greater TS, while elevated E-Selectin and lower IL-6 were associated with longer progression-free survival (PFS) (Heymach, ACCR-NCI-EORTC 2009). The validation was conducted using Searchlight (SL) (Aushon) and ELISA (EL) assays. Methods: Candidate markers (HGF, IL-6, IL-8, E-Selectin, and VEGF) were validated in 215 pts including the initial 129 pts. Spearman correlations were performed across the three platforms. CAF levels were correlated with maximum change from baseline in TS by linear regression; PFS by Cox regression; baseline tumor burden using baseline sum of longest tumor diameter by Spearman. Results: CAF levels were highly correlated among the three platforms (R>0.70, p <0.0001 across all comparisons). Lower levels of HGF (SL p=0.0477, EL p=0.0104), IL8 (SL p=0.0328, EL not performed (NP)) and IL-6 (SL p=0.0415, EL p=0.0251) were significantly correlated with greater TS. Higher levels of E-Selectin (SL p=0.0410, EL NP), lower IL-6 (SL p=0.0019, EL p=0.0052) and HGF (SL p=0.0234, EL p=0.0354) have a longer median PFS 83.9 versus 39.29 weeks for the overall study population (215 pts). Higher levels of IL-6 (SL p <0.0001), IL-8 (SL p= 0.0003), and VEGF (SL p <0.0001) were significantly correlated with greater baseline tumor burden. Conclusions: The three platforms demonstrated consistent results that lower baseline levels of HGF and IL-6 are correlated with greater TS. Elevated levels of E-Selectin, lower levels of IL-6 and HGF are correlated with longer PFS. Higher levels of IL-6 and IL-8 correlated with greater tumor burden. CAF profiling is a feasible approach to assess pts who may derive benefit from pazopanib. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline
Adherence to osteoporosis screening guidelines in seniors with breast cancer treated with anti-estrogen therapy: A population-based study.
Authors: David Henault, Sue-Ling Chang, Sinizana Dumitra, Richard Kramer, Nancy Mayo, Ari Meguerditchian
Journal: Journal of Clinical Oncology (2015)

72 Background: Aromatase inhibitors (AI) improve recurrence and survival rates in women ≥ 65 with hormone-receptor positive (HR+) breast cancer (BC). However, AI’s are associated to increased bone demineralization in a population already at risk for osteoporosis. Bone mineral densitometry (BMD) is therefore recommended at treatment start, to minimize treatment-related toxicity. This study assesses compliance to BMD recommendations in older BC survivors treated with an AI and identifies predictors of non-adherence to guidelines. Methods: A population-based historical prospective cohort study was conducted in Quebec (Canada), where universal health insurance provides medical and pharmaceutical services. All women ≥ 65 with incident stage I, II or III BC (1998-2012) were identified from the provincial cancer registry. Administrative claims were accessed to track receipt of BMD (±12 months from treatment start) and potential predictors: age, economic status, Charlson comorbidity index, breast and axillary surgery, chemotherapy, radiotherapy, bisphosphonate use, adherence to anti-estrogen therapy (AET), physician specialty and having a primary care physician (PCP). Multivariate logistic regression was performed using generalized estimating equations to identify predictors of BMD, adjusting for clustering within physicians. Results: Of 16,480 patients, 36.1% had a BMD at AET start. This increased to 58.4% for women on AI. Factors predicting baseline BMD non-use in AI patients were: older age (OR 0.42; 95% CI, 0.36 – 0.49), lower annual income (OR 0.57; 95%CI, 0.47 – 0.70), not having a PCP (OR 0.77; 95%CI, 0.68 – 0.86), chemotherapy and radiotherapy outside of guidelines (OR 0.80; 95%CI, 0.66 – 0.96 and 0.69; 95%CI, 0.54 – 0.87, respectively), non-surgical specialist managing AET (OR 0.81; 95%CI, 0.67 – 0.98), older physicians (OR 0.61; 95% CI, 0.46 – 0.81), and non-adherence to AET (OR 0.69; 95%CI 0.60-0.79). The same predictors persisted in patients on any AET. Conclusions: Bone health management in seniors receiving AET is suboptimal. Factors related to underutilization of BMD can be easily identified and used to optimize chronic care of older BC survivors.
Antitumor effect of Chinese herb oridonin on human non-small cell lung cancer (NSCLC).
Authors: Siyu Chen, Wei Tian, Ai-Hong Ma, Sonal Desai, Krysteena Tolentino, Yantong Guo, Tianhong Li
Journal: Journal of Clinical Oncology (2012)

e13526 Background: Oridonin, a diterpenoid purified from the Chinese herb Rabdosia rubescens, has anti-inflammatory and potentially anti-tumor property. We aimed to study the antitumor effect of oridonin on a panel of human non-small cell lung cancer (NSCLC) cell lines. Methods: Human NSCLC cell lines with a wild-type EGFR gene and a RAS gene mutation were treated with escalating dose concentration of oridonin (from 2.5 to 50 µM). Antitumor effect was measured by 72-hr growth inhibition by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell morphology was observed under microscope. Ongoing experiments will identify potential drug target(s) by assessing changes in global gene expression. Results: Oridonin exhibited a dose-dependent and time-dependent cytotoxic effect on a panel of NSCLC cell lines. Table 1 summarizes the molecular and histological features of these NSCLC cells, and their cytotoxicity to oridinin, erlotinib and pemetrexed. In those NSCLC cells that were sensitive to oridonin, morphological changes were consistent with autophagy and apoptosis. Potential drug targets will be verified by RT-PCR and immunoblotting. Conclusions: Oridonin exerts a distinct cytotoxicity that is independent of the sensitivity of NSCLC cells to erlotinib or pemetrexed. Further mechanistic and animal studies are warranted to understand its anti-tumor property and toxicity profile in preclinical evaluation. [Table: see text]
Phase I trial of weekly and every 3 weeks ixabepilone (Ix) and sunitinib (S) in advanced solid tumors (STs).
Authors: M. Kittaneh, A. J. Montero, K. Kovacs, V. D. Guardiola Amado, A. M. Flores, A. Ferrell, M. Vulfovich, M. D. Pegram, P. W. Benedetto, C. M. S. Rocha Lima, J. R. Merchan
Journal: Journal of Clinical Oncology (2011)

3081 Background: Ix is a cytotoxic microtubule-stabilizing agent with anti-proliferative and anti-angiogenic properties. S is a multi-targeted receptor tyrosine kinase inhibitor. IX and S combination may be synergistic, since S may increase delivery of Ix to the tumor by inducing vascular normalization. Methods: Patients (pts) with advanced STs were enrolled in a phase I, dose-escalation study to assess safety, pharmacokinetics (PK), angiogenesis biomarkers and to determine the recommended phase II dose. Eligibility: age > 18, ≤ 4 prior systemic therapies (tx), ECOG PS 0-2, measurable/evaluable disease and good organ function. Treatment schedules: A (weekly Ix, 3 out of 4-weeks): starting dose 7.5 mg/m2 IV (1A), 15 mg/m2 IV (2A) and 20 mg/m2 IV (3A). Schedule B (every 3 weeks): starting dose 20 mg/m2 IV (1B), 30 mg/m2 IV (2B) and 40 mg/m2 IV (3B). In both schedules, S was given continuously starting on day 8 of cycle 1 at 37.5 mg PO daily. A standard 3 + 3 design was used and dose-limiting toxicities (DLTs) assessed in the first cycle. Results: 30 patients were enrolled. Two pts withdrew before starting tx. Baseline characteristics: median age: 61.5 (25-78); males/females: 19/9; most frequent STs: colorectal -CRC- (16), pancreas (2), prostate (2); median PS: 1; median of prior tx: 3. Number of pts evaluable for toxicity/dose escalation/efficacy: 28/23/21. One DLT was observed in schedule 3A (grade (gr) 3 DVT) and 2 in schedule 3B (gr 4 mucositis/gr 3 dehydration; gr4 neutropenia). Other gr 3 /4 AEs (non DLTs): leukopenia (18%), neutropenia (25%), lymphopenia (21%), anemia (14%), thrombocytopenia (7%), leukocytosis (4%), fatigue (25%), neuropathy (7%), mucositis (7%), nausea (7%), vomiting (4%), hyperglycemia (4%), syncope (4%), abdominal pain (4%) and GI bleed (4%). Median # of cycles (evaluable pts): 3 (range1-10). Three pts achieved PR (2 with CRC). Eight patients had SD (5 with CRC). 10 patients had PD. Conclusions: The combination of Ix and S appears to have acceptable toxicity and encouraging activity in heavily pretreated pts. The recommended phase II dose for S is 37.5 mg po daily with Ix 20 mg/m2 in Schedule A and Ix 30 mg/m2 in schedule B. Angiogenesis biomarkers and PK analyses are underway.
Pain and Physical Function Following Bariatric Surgery
Authors: Alberto Soriano-Maldonado, Manuel Ferrer Márquez, Enrique G. Artero
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Utilization of Magee equation 3 in ER-positive, HER2-negative/equivocal tumors to determine pathologic response to neoadjuvant therapy.
Authors: Daniel J. Farrugia, Alessandra Landmann, Emilia Diego, Priscilla F. McAuliffe, Ronald Johnson, Marguerite Bonaventura, Atilla Soran, David J. Dabbs, Shannon Puhalla, Rachel Catherine Jankowitz, Adam Brufsky, Barry C. Lembersky, Priya Rastogi, Nancy E. Davidson, Gretchen M. Ahrendt, Rohit Bhargava
Journal: Journal of Clinical Oncology (2016)

11594 Background: Magee Equations (ME) were derived to estimate Oncotype DX scores (Mod Pathol. 2013;26:658-64). ME3 uses only the immunohistochemical/FISH data for ER, PR, HER2 and Ki-67 for calculation (24.30812+ERIHC*(−0.02177)+PRIHC*(−0.02884)+(0 for HER2-ve, 1.46495 for equivocal, 12.75525 for HER2+ve)+Ki-67*0.18649). We hypothesized that ME3 scores from pre-therapy core biopsy can be used to predict response to NAT. Methods: A retrospective chart review was conducted of patients who received NAT from 2010-2014 at a single institution. Of 595 patients that had tumor ER status, HER2 status and pathologic complete response (pCR) information available, we excluded 359 tumors that were ER -ve or showed unequivocal HER2 gene amplification. pCR was defined as absence of invasive tumor in the breast and regional lymph nodes (LN). ME3 scores were grouped into 3 categories similar to Oncotype DX, i.e. 0 to <18, 18 to <31, and ≥31. Univariate analyses were performed using Fisher exact test. Results: 236 ER+, HER2 -ve/equivocal tumors were eligible for consideration. Mean followup was 33.3 months. Table 1 shows that pCR rate increases with higher ME3 score categories (RR 27 for ME3 ≥31 vs <18). For patients that do not achieve pCR, ME3 score ≥31 correlates with increased risk of overall recurrence, with the majority occurring in patients with +ve LN in the resection specimen (Table 2). Conclusions: ME3 score ≥31 predicts for pCR in the neoadjuvant setting and paradoxically for tumor recurrence when pCR is not achieved. These results validate the use of ME3 in selecting patients who will benefit from chemotherapy but require validation outside a single institution. ME3 Score n Age (y) Ki-67 ER H-Score ypLN+ (%) Recurrence (%) pCR pCR (%) RR 95% CI p <18 69 57 15.56 273.1 41 (59) 5 (7.3) 1 (1.4) 18-30 116 54.1 37.63 225.9 69 (59) 13 (11.2) 5 (4.3) 2.97 0.35, 24.9 0.413 ≥31 51 50.3 80.98 72.7 17 (33) 14 (27.5) 20 (39.2) 27.1 3.75, 195.1 <0.0001 ME3 Score n Recurrence in patients without pCR Recurrence (%) RR 95% CI p <18 68 5 (7.35) 18-30 111 13 (11.71) 1.59 0.59, 4.27 0.446 ≥31 31 14 (45.16) 6.14 2.4, 15.5 <0.0001 ypLN +ve subset <18 41 4 (9.76) 18-30 69 11 (15.94) 1.63 0.56, 4.80 0.407 ≥31 16 10 (62.5) 6.41 2.34, 17.5 0.0001
O-024 Circulating tumor DNA extended RAS mutational analysis as a surrogate of mutational status of tumor samples in metastatic colorectal cancer and its impact on patient selection for anti-EGFR therapy
Authors: J. Grasselli, E. Elez, G. Caratù, J. Matito, C. Santos, T. Macarulla, J. Vidal, M. Garcia, J.M. Viéitez, D. Paéz, E. Falcó, C. Lopez Lopez, E. Aranda, F. Jones, V. Sikri, P. Nuciforo, R. Dienstmann, C. Montagut, J. Tabernero, D. Azuara, R. Salazar, A. Vivancos
Journal: Annals of Oncology (2016)
In ICH associated with antiplatelet therapy, platelet transfusion increased death or dependence
Authors: David Barer
Journal: Annals of Internal Medicine (2016)

Source Citation Baharoglu MI, Cordonnier C, Salman RA, et al, PATCH Investigators. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial. Lancet. 2016 May 9. [Epub ahead of print] 27178479
Cancer-related fatigue in patients with and survivors of Hodgkin's lymphoma: a longitudinal study of the German Hodgkin Study Group
Authors: Stefanie Kreissl, Horst Mueller, Helen Goergen, Axel Mayer, Corinne Brillant, Karolin Behringer, Teresa Veronika Halbsguth, Felicitas Hitz, Martin Soekler, Oluwatoyin Shonukan, Jens Ulrich Rueffer, Hans-Henning Flechtner, Michael Fuchs, Volker Diehl, Andreas Engert, Peter Borchmann
Journal: The Lancet Oncology (2016)
Abstract 20218: Comparative Effectiveness of Dabigatran and Rivaroxaban versus Warfarin in Patients With Non-Valvular Atrial Fibrillation
Authors: Lindsay Bengtson, Lin Chen, Richard MacLehose, Pamela Lutsey, Alvaro Alonso
Journal: Circulation (2014)

Background: In randomized trials, the new oral anticoagulants (NOAC) dabigatran and rivaroxaban have been at least as efficacious as warfarin in the prevention of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF). Information on the effectiveness of NOACs versus warfarin in real-world populations in the US is more limited. Methods: We used data from the US MarketScan Commercial and Medicare Supplemental databases in the period 2010-12. We selected patients initiating oral anticoagulants after NVAF diagnosis, and with at least 6 months of enrollment before first anticoagulant use. Patients initiating dabigatran or rivaroxaban were matched with up to 5 warfarin users by age, sex, and time in the database. Outcomes of interest (ischemic stroke, intracranial bleeding, and gastrointestinal [GI] bleeding) were defined according to validated algorithms. Information on other comorbidities and medication use was obtained from inpatient, outpatient, and pharmacy claims. High-dimensional propensity score-adjusted Cox proportional hazards regression was used to estimate the association of NOACs vs warfarin with each outcome of interest. Results: The analysis included 32,918 dabigatran, 3,301 rivaroxaban and 92,633 warfarin users with NVAF. During an average 13-month follow-up (6 for rivaroxaban, 15 for dabigatran), 1035 ischemic strokes, 225 intracranial bleeds, and 1842 GI bleeds were identified. Rate of ischemic stroke was similar in patients initiating NOACs compared to those on warfarin. However, rate of intracranial bleeding was lower in patients using NOACs compared to warfarin users, while GI bleeding rate was higher in dabigatran users than warfarin users (Table). Conclusion: In this large real-world patient population, effectiveness of NOACs (compared to warfarin) for diverse outcomes was comparable to efficacy reported in the RE-LY and ROCKET-AF trials.
Biomimetic Microfluidic Networks: Fabrication of 3D Biomimetic Microfluidic Networks in Hydrogels (Adv. Healthcare Mater. 17/2016)
Authors: Keely A. Heintz, Michael E. Bregenzer, Jennifer L. Mantle, Kelvin H. Lee, Jennifer L. West, John H. Slater
Journal: Advanced Healthcare Materials (2016)

Slater and co-workers demonstrate fabrication of three-dimensional, biomimetic microfluidic networks embedded in poly(ethylene glycol) diacrylate hydrogels by combining laser-based degradation with image-guided laser control on page 2153. Generation of high-density, capillary-like microfluidic networks that recapitulate the architecture of in vivo microvasculature as well as the ability to induce internetwork transport between two independent microfluidic systems is presented. Recapitulating in vivo-like transport using biomimetic microfluidic networks may prove advantageous in fabricating advanced in vitro tissue models.
Canadian employers' awareness of and willingness to include intravenous cancer medicines on employee benefit private insurance plans.
Authors: L. Blair, S. Yunger, T. Benn, S. R. Sehdev, D. Shum, D. Milliken
Journal: Journal of Clinical Oncology (2010)

e16526 Background: In Canada, the Canada Health Act (CHA) provides the legal framework for public funding of intravenous cancer drugs (IVCD). Since IVCD are typically administered in a hospital setting, private insurers take the position that funding is the responsibility of the provincial governments. However, recent data has shown that more than half of insurers are approving IVCD for patients when special requests are made for employer consideration. This study evaluated employers' awareness of their coverage for IVCD and identified their willingness to include IVCD on their private benefit plans (PBP) rather than approving on a case-by-case basis. Methods: A telephone and online survey was conducted of employers with decision-making influence over their companies PBP between July and August 2009. 276 employers completed the survey, 45% with less than 500 employees and 55% above. There was a margin of error ± 4.8%, 19 times out of 20. Results: While 55% of respondents stated that IVCD were included on their PBP, 37% of employers were unsure. When deciding to fund an IVCD for an individual patient, 83% confirmed that a drug offering a cure is the main deciding factor, 77% if it offers a return to work, 72% if it extends life and 71% look at the cost of coverage. 63% stated that the method of administration (IV versus oral) and 51% stated that the location of delivery (private clinic or hospital) should not affect a drug being listed on a PBP. 38% stated that IVCD should definitely be included in the PBP as a standard inclusion, while 45% responded “yes, maybe.” Similar results were seen in all employers. Conclusions: Employers have some awareness that IVCD are not covered by PBP, however most believe they are covered or are unsure. The majority of employers feel that PBP should cover all IVCD as a standard inclusion. As such, employers and employees must be educated on current gaps in IVCD coverage in PBP. As well, employers should assess their willingness to include IVCD on their PBP to meet employee healthcare needs. The high value placed on cure, overall survival and cost is consistent with decision-making criteria normally used by Canadian public payers, however a patients return to work is unique to employers. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Roche