tbuckley/cabot-search huggingface dataset:
Differences in survival between usual practice and clinical trial participants in advanced NSCLC by age.
Authors: Ana Laura Ortega Granados, Nuria Cárdenas Quesada, Capilla de la Torre Cabrera, Mónica Fernández Navarro, María Ruiz Sanjuan, Juan Francisco Marin Pozo, Rosa Millán García, Francisco José García Verdejo, Natalia Luque Caro, David Fernández Garay, Yessica Plata Fernández, Pedro López Leiva, Victor Navarro Pérez, Esther Martínez Ortega, Rosario Dueñas García, Maria Lomas Garrido, Maria Carmen Álamo de la Gala, Ana Jaén Morago, Miguel Angel Moreno Jimenez, Pedro Sánchez Rovira
Journal: Journal of Clinical Oncology (2017)

e20515 Background: It is known that outcome of patients included in clinical trials have a better outcome than patients treated with standard therapy. This is a retrospective case-control study of outcome of patients with stage III and IV non-small cell lung cáncer (NSCLC) recruited in clinical trials vs advanced NSCLC patients in usual clinical practice in our institution. Methods: We performed a case-control study matching all patients participating in trials with chemotherapy and/or TKis (immunotherapy was not included) in a 5 year period (January 2010-November 2014) in 1 st line setting, matching them in a ratio 1:2 with individuals in usual clinical practice. There were 36 patients in trials and 72 patients treated by our protocol. Cases were matched by age ( &lt; 65 and &gt; 65), histology (adenocarcinoma and squamous), EGFR status (mutated and wild-type). All patients were WHO performance status 0-1. Results: Patients in each group were matched for stage, histological subtype, previous surgery and systemic therapy. Median follow up for patients treated on a trial was 3.3 years, compared with 2.9 years for matched patients who received standard 1 st line therapy. Median overall survival for patients included a trial was 19.6 months, and 15.7 months for control group. The difference between groups was not significant (Log rank test, HR 0.81, 95% CI: 0.42 to 1.30, p = 0.53). Median overall survival in younger patients in trials ( &lt; 65) was 19.3 months, and in elderly patients was 19.8 months. The median progression-free survival in the two groups was 6.8 and 5.5 months respectively (HR 0.72, 95% CI 0.30 to 1.43, p = 0.21). Conclusions: In our institution, we didn’t found significant differences for overall survival or progression-free survival, but there is a trend for a better outcome for those items. Benefit seems to be similar in younger patients than in older patients, so this encourages recruiting of selected elderly patients.
Effect of EGFR mutations on outcomes in NSCLC with brain metastases.
Authors: Kumar Prabhash, Vijaya Raj Bhatt, Sanyo P D'souza, Lynette Smith, Alison M Cushman-Vokoun, Vanita Noronha, Vivek Verma, Amit Joshi, Anuradha Chougule, N. A. Jambhekar, M. Anne Kessinger, Alissa S. Marr, Vijay Maruti Patil, Shripad Dinanath Banavali, Apar Kishor Ganti
Journal: Journal of Clinical Oncology (2016)

e20644 Background: Prior studies have suggested the possibility of more epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancers (NSCLC) from patients with brain metastasis. These studies however, did not adjust for any effects of potential confounding variables. Methods: This retrospective study included 1522 consecutive NSCLC patients, whose tumors were diagnosed and tested for EGFR mutations at the University of Nebraska Medical Center, US and Tata Memorial Hospital, India between 2007 and 2014. Univariate analysis (Chi-square or Fisher's exact tests) and multivariate logistic regression were used to identify any association between EGFR status and clinical factors. Results: EGFR mutations were more common in females than males (38% vs. 24%, p < 0.0001), Asians than Caucasians (31% vs. 13%), non-smokers than smokers (40% vs. 14%, p < 0.0001), alcohol non-consumers than users (32% vs. 15%, p < 0.0001), adenocarcinoma than other histologies (32% vs. 10%, p < 0.0001) and patients with brain metastasis than extracranial or no metastasis (39% vs. 29% vs. 15%, p < 0.0001). Multivariate analysis demonstrated a higher likelihood of an EGFR mutation among patients with brain metastasis (OR 1.8, p = 0.0002). The median overall survival (OS) was 19.8 months (95% CI, 17.9, 21.7 months). Patients with an EGFR mutation had a longer median OS compared to those without (25.1 vs. 16.8 months; p = 0.0001). Patients with tumors harboring an exon 19 deletion had a numerically better median OS compared to L858R mutation (27.1 vs. 21.1 months; Hazard ratio 0.73; 95% CI, 0.53, 1.01; p = 0.056). Patients with brain metastases had a shorter OS compared to those without (15 vs. 20.6 months; p = 0.02). However in patients with EGFR mutation positive tumors, there was no difference in OS between patients with and without brain metastases (20.8 vs. 25.1 months; p = 0.11). Conclusions: There is a nearly two-fold higher incidence of EGFR mutations in NSCLC among patients with brain metastasis at diagnosis. The presence of an exon 19 deletion may confer a better prognosis than other EGFR mutations. In patients with EGFR mutation-positive tumors, the presence of brain metastases did not adversely affect prognosis.
TCT-784 Relationship between enzymatic infarct size and total platelet aggregability during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction
Authors: Shinnosuke Kikuchi, Kengo Tsukahara, Shinya Ichikawa, Yugo Minamimoto, Kozo Okada, Yasushi Matsuzawa, Masaaki Konishi, Nobuhiko Maejima, Noriaki Iwahashi, Kiyoshi Hibi, Masami Kosuge, Toshiaki Ebina, Kouichi Tamura, Kazuo Kimura
Journal: Journal of the American College of Cardiology (2018)
Phase 1/2a study of BAL101553, a novel tumor checkpoint controller (TCC), administered as 48-hour infusion in adult patients with advanced solid tumors.
Authors: Markus Joerger, Ioannis Metaxas, Anastasios Stathis, Dagmar Hess, Michael Thomas Mark, Franziska Hutter, Nicole Levy, Silvia Stuedeli, Simona Berardi, Michèle Landau-Salzberg, Marc Frederick Engelhardt, Patrice Larger, Thomas Kaindl, Peter Hafner, Phil McKernan, Heidi A Lane, Roger Anton Fredy Von Moos, Cristiana Sessa
Journal: Journal of Clinical Oncology (2018)

2529 Background: BAL101553 is the prodrug of BAL27862, a small molecule TCC that binds microtubules and promotes tumor cell death by activation of the spindle assembly checkpoint. In a study of BAL101553 administered as a 2-h infusion on Days 1, 8 and 15 of a 28-day cycle (NCT01397929, Lopez et al. JCO 34, 2016; 2525), vascular toxicities were observed and appeared to be Cmax related. Nonclinical models indicate that the antiproliferative effects of BAL27862 are AUC driven; this trial was intended to determine whether prolonged infusion reduces Cmax-related toxicity and increases the AUC at the recommended phase 2 dose (RP2D) (NCT02895360, Joerger et al. JCO 2017; TPS2602). Methods: Patients with advanced solid tumors received 48-h infusions of BAL101553 using an elastomeric pump on Days 1, 8 and 15 of consecutive 28-day cycles using a 3+3 dose-escalation design to determine the maximum-tolerated dose (MTD). During Cycle 2, patients received BAL101553 orally QD (Days 15–21) instead of IV in order to assess oral bioavailability. Adverse events (AEs) were assessed by CTCAEv4.03 grade (G); tumor response by RECIST 1.1 every two cycles; pharmacokinetics were assessed during the first two cycles. Results: Phase 1 enrollment was completed with 20 patients (7M/13F; median age 60 years; median 3 prior chemotherapies) receiving IV BAL101553 at doses of 30, 45, 70 or 90 mg/m2. Dose-limiting toxicities included transient G3 hypotension at 70 mg/m2 and reversible G3 hyponatremia, G3 neutropenia, G2 hallucinations and ataxia at 90 mg/m2. There were no relevant vascular toxicities. Of 16 evaluable patients, one had a confirmed partial response (ovarian cancer) and one had stable disease for 6 months (endometrial cancer). BAL27862 exposures (AUC) were near dose-proportional. At 70 mg/m2, the BAL27862 Cycle 1/Day 1 Cmax was 144 ng/mL and AUC was 8580 ng.h/mL. Oral bioavailability was estimated to be > 80%. Conclusions: The MTD/RP2D of BAL101553 48-h infusion was 70 mg/m2. At this dose the AUC/Cmax ratio was ~4× higher compared to the 2-h infusion regimen at the RP2D of 30 mg/m2. There were indications of potential clinical benefits in patients with ovarian and endometrial cancers. Clinical trial information: NCT02895360.
Safety of biweekly α<sub>1</sub>-antitrypsin treatment in the RAPID programme
Authors: Timm Greulich, Jan Chlumsky, Marion Wencker, Oliver Vit, Michael Fries, Thomas Chung, Amgad Shebl, Claus Vogelmeier, Kenneth R. Chapman, Noel G. McElvaney
Journal: European Respiratory Journal (2018)

α1-antitrypsin (α1-AT) deficiency is a hereditary disorder characterised by an abnormally low concentration of functional α1-AT in blood and tissues [1]. The primary role of α1-AT is to protect elastin-containing tissues, most notably the lung, against the destructive activity of proteolytic enzymes [2]. Patients with severe α1-AT deficiency present with serum α1-AT concentrations <11 μM and are prone to destruction of the lung tissue, often developing respiratory symptoms and emphysema in the fourth or fifth decade of life [3, 4]. Administration of 120 mg·kg−1 α1-antitrypsin on a biweekly basis was safe and well tolerated <http://ow.ly/CVbz30lUBum> Michael Riley and Barbara Boggetti (Trilogy Writing and Consulting GmbH, Frankfurt, Germany) provided medical writing support on behalf of CSL Behring.
PSA response in black and white patients treated with abiraterone acetate (AA) for metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Sundhar Ramalingam, Michael Sandon Humeniuk, Rachel Hu, Julia Rasmussen, Patrick Healy, Yuan Wu, Michael Roger Harrison, Andrew J. Armstrong, Daniel J. George, Tian Zhang
Journal: Journal of Clinical Oncology (2016)

5033 Background: Pivotal trials of AA for patients with mCRPC enrolled few black patients (pts), a population with a higher mortality from prostate cancer. Evidence suggests differences in androgen receptor signaling between black (B) and white (W) PC pts; therefore, we retrospectively investigated PSA response in B vs W pts treated with AA. Methods: We performed a 2:1, W vs B case-control study. Pts were identified through pharmacy records for AA use in mCRPC between May 1, 2008 and June 16, 2015 at Duke University, with pts matched for prior docetaxel use. Pts with prior enzalutamide were excluded. Baseline prognostic factors of performance status, PSA, Gleason score, alkaline phosphatase, albumin and hemoglobin (hgb) were identified. The primary objective was to compare the rate of a ≥ 90% PSA decline from baseline PSA with AA therapy between groups. Results: Baseline characteristics among pts (n = 45 B, n = 90 W) were similar with the exception of median hgb (B = 11.4 g/dl, W = 12.3 g/dl). The proportion of black pts achieving a ≥ 90% PSA decline was 37.8%, vs. 28.9% for white pts (p = 0.296; Table). Statistically significant differences were found in the proportion of pts achieving a ≥ 50% PSA decline [B = 68.9%, W = 48.9% (p = 0.028)] and ≥ 30% PSA decline [B = 77.8%, W = 54.4% (p = 0.008)]. Primary AA-refractory disease (PSA increase as best response) trended to be more in W = 31.1% than in B = 15.6% pts (p = 0.052). Median treatment duration (B = 9.36 months, W = 8.25 months) did not differ (Wilcoxon p = 0.44). Median overall survival [B = 27.3 months (95% CI, 13.9, not estimable), W = 24.8 months (95% CI 19, 31.6) (p = 0.669)] and median time to PSA progression [B = 11.0 months (95% CI 4.3, 18.0), W = 9.4 months (95% CI: 6.2, 13.0) (p = 0.917)] did not differ. Conclusions: Black pts may have a higher PSA response to AA than white pts. An ongoing prospective clinical study (NCT01940276) is evaluating outcomes between black and white pts treated with AA. PSA response outcome # Black pts (n = 45) % Black pts # White pts (n = 90) % White pts P-value ≥ 30% PSA decline 35 77.8% 49 54.4% 0.008 ≥ 50% PSA decline 31 68.9% 44 48.9% 0.028 ≥ 90% PSA decline 17 37.8% 26 28.9% 0.296 PSA increase as best response 7 15.6% 28 31.1% 0.052
Adherence to 'Choosing Wisely' recommendations for radiation therapy in a commercially insured breast cancer population.
Authors: Joshua A. Roth, Jean A. McDougall, Lia Moriguchi Halasz, Catherine R. Fedorenko, Qin Sun, Bernardo H. L. Goulart, Shilpen A. Patel
Journal: Journal of Clinical Oncology (2017)

e18267 Background: ASTRO ‘Choosing Wisely recommendations’ (CWr) note radiation therapy (RT) interventions lacking evidence of benefit in cancer care. This study evaluates adherence to the 2013 CWr to ‘not routinely use intensity modulated radiotherapy (IMRT) to deliver whole breast radiotherapy as part of breast conservation therapy’ using a novel linkage between the Western WA Cancer Surveillance System (CSS) and claims from two large commercial insurance plans. No studies have evaluated adherence to this CWr in a commercial insurance setting. Methods: CSS records for first primary Stage I/II breast cancer cases (2008-2015) were linked with Premera Blue Cross and Regence Blue Shield claims. Included cases had coverage for ≥12-months before/after diagnosis (or until death), lumpectomy within 6 months of diagnosis, and RT within 6 months of lumpectomy. We used generalized estimating equations (GEE) to evaluate associations between demographic (age, race) and tumor (grade, laterality, diagnosis year) variables and use of IMRT vs conventional conformal RT within 1 year of diagnosis. Results: We identified 1,048 first primary Stage I/II breast cancer cases that met inclusion criteria. Mean age was 61, 91% were white, 52% were left-side cases. The non-adherent proportions are in the table below. In GEE analysis, only left-side cases (OR=6.4, p&lt;0.001) and years of age (OR=1.03, p&lt;0.01) were independently associated with IMRT use. Conclusions: Patients with IMRT vs. conventional conformal RT after lumpectomy may incur additional cost without commensurate clinical benefit. In the first study of adherence to a CWr against IMRT in this setting, we found that left-side cases were 6-fold more likely to be non-adherent vs right-side cases. This association suggests that IMRT is being used to reduce radiation dose to the heart, though not supported by evidence. Overall, the small non-adherent proportion before/after the CWr suggests alignment between guidelines and use of IMRT in Western WA. Future studies should evaluate IMRT use in other regions and develop strategies to improve CWr adherence in left-side cases. [Table: see text]
Abstract 20301: Reversible Oxidation Of Metabolic Protein Triosephosphate Isomerase in the Type 2 Diabetic Heart
Authors: Lauren E Smith, Brett Hambly, Stuart Cordwell, Melanie White
Journal: Circulation (2016)

Introduction: Type 2 diabetes (T2D) impairs the ability of the heart to switch between fatty acid metabolism and glycolysis. This metabolic inflexibility is particularly damaging during I/R, as the...
Infographic. Effectiveness of multicomponent lower extremity injury prevention programmes in team-sport athletes: an umbrella review
Authors: Pedro L Valenzuela, Romana Brunner, Adrián Castillo-García, Bernd Friesenbichler, Nicola C Casartelli, Javier S Morales, Nicola A Maffiuletti, Mario Bizzini, Karin Niedermann
Journal: British Journal of Sports Medicine (2019)

The incidence of sports injuries has been reported to reach ~26 and 34 injuries per 1000 persons in the USA1 and the European Union,2 respectively, with the majority of these injuries occurring in the lower extremity (eg, ankle and knee sprains, hamstring strains, ACL tears).1 Sports injuries have important negative physical, psychological and medical consequences for the athlete, as well as technical, tactical and economical consequences for the team. Moreover, sports injuries have relevant implications for healthcare systems associated with the treatment costs.3 4 …
Association of Met-BDNF allele with pre-existing peripheral neuropathy in breast cancer patients.
Authors: David Azoulay, Anca Leibovici, Rivka Sharoni, Hadassah Goldberg
Journal: Journal of Clinical Oncology (2017)

e21702 Background: We previously published preliminary results suggesting an association between the met-BDNF allele and vulnerability to paclitaxel-induced peripheral neuropathy (PIPN) in breast cancer patients. Here we present updated data obtained from our extended study. Methods: 35 patients; 34 women (33 with breast cancer and 1 with ovarian cancer) and one man (breast cancer) completed their follow-up. Peripheral neuropathy (PN) was assessed at diagnosis and along the treatment protocol, using the reduced version of Total Neuropathy Score (TNSr). Patients with TNSr≥2 at diagnosis were determined with pre-existing PN (Pre-PN). Allelic discrimination of BDNF polymorphism (rs6265) was determined by Sanger sequencing. Results: BDNF genotype Val/Val was found in 20 patients (57.14%), Val/Met in 15 patients (42.86%). No patient had the Met/Met genotype. 10 patients (28.57%) were diagnosed with Pre-PN, 3 of them with diabetic-related neuropathy. A higher incidences of the Met-BDNF allele was found in patients with Pre-PN as compared to patients with no Pre-PN (7/10 (70%) vs. 8/25 (32%) Val/Met in Pre-PN and no Pre-PN respectively, prob &gt; ChiSq &lt; 0.05). The three patients with diabetic related Pre-PN were genotyped Met-BDNF. The maximal TNSr scores developed by each patient during follow-up were higher in Met-BDNF patients compare to Val/Val patients. (Maximal TNSr mean ± SEM in Val/Val 4.80±0.62 vs. 7.73±1.34 in Val/Met BDNF, prob &lt; t 0.04). No difference in the maximal TNSr scores between Met-BDNF and Val/Val patients were shown after excluding the patients with Pre-PN (Maximal TNSr mean ± SEM in Val/Val 5.05±0.78 vs. 5.25±0.62 in Val/Met BDNF, prob &lt; t 0.44). Conclusions: Our data demonstrate an association between met-BDNF and Pre-PN. Higher maximal TNSr scores in our met-BDNF patients is generally the consequence of their higher Pre-PN.
SV-BR-1-GM a whole-cell targeted immunotherapy for breast cancer: Preliminary clinical data.
Authors: Jarrod P. Holmes, William Williams, George Earl Peoples, Markus Lacher, Elizabeth Tan-Chiu, Charles L. Wiseman
Journal: Journal of Clinical Oncology (2018)

e15165 Background: SV-BR-1-GM is a GM-CSF transfected breast cancer cell line which expresses HLA class I & II antigens. In a previous clinical trial, a partial response of widely metastatic breast cancer was seen in a patient who matched SV-BR-1-GM at HLA-DRB3*02:02. Methods: Subjects received low-dose cyclophosphamide 2-3d prior to ID injection of SV-BR-1-GM (20x106 cells divided into 4 sites) and interferon-α into the inoculation sites ~2 & 4 days subsequently. Cycles were q2 weeks x3 then q mo x 3 Results: In clinical trial NCT03066947 , 6 patients have been inoculated (Table). T umor regression was seen in 2 patients. 01-002 presented with liver, bone and 20 classic miliary lung metastases (up to 9mm). This subject previously failed 7 chemo regimens. She matched SV-BR-1-GM at Class I & II HLA loci. Imaging at 3 mo showed virtually complete regression of all 20 identifiable lesions in the lungs. This response was maintained at 6 mo. but the subject was taken off protocol because of disease progression (liver and bone). 01-005, matching HLA-A*24:02, had notable regression of cutaneous lesions, but progressed in pleural and pericardial effusions, had irreversible cardiac arrest (unlikely related). 02-004 with inflammatory breast cancer withdrew due to worsening breast inflammation. There were no serious or unexpected adverse events., local injection-site irritation was the most common toxicity. Conclusions: SV-BR-1-GM in this regimen appears to be safe and well-tolerated and is associated with objective regression of metastatic breast cancer. HLA matching is being studied as a predictor of response. Clinical trial information: NCT03066947.Table of Patients Patient Age Metastatic Sites # Prior Regimens HLA Matches # of Cycles Tumor Regression? 01-001 46 Pleura Lymph Nodes 7 chemo/bio 5 hormonal DRB3*02:02 1 No 01-002 73 Lung Liver Bone 7 chemo 1 hormonal A*24:02 DRB3*02:02 8 Lungs 01-005 54 Lymph nodes Pleura Skin 3 chemo/bio A*24:02 2 Skin 02-001 70 Lymph nodes 3 chemo/bio None 1 No 02-003 61 Bone Brain 3 chemo None 6 Pending 02-004 74 Lymph nodes Cutaneous 5 chemo (A*11:01) DRB3*02:02 2 Pending
Benefit–risk profile of tofacitinib in patients with moderate‐to‐severe chronic plaque psoriasis: pooled analysis across six clinical trials
Authors: B.E. Strober, A.B. Gottlieb, P.C.M. Kerkhof, L. Puig, H. Bachelez, E. Chouela, S. Imafuku, D. Thaçi, H. Tan, H. Valdez, P. Gupta, M. Kaur, V. Frajzyngier, R. Wolk
Journal: British Journal of Dermatology (2018)

Although existing psoriasis treatments are effective and well tolerated in many patients, there is still a need for new effective targeted treatment options. Tofacitinib is an oral Janus kinase inhibitor that has been investigated in patients with moderate-to-severe chronic plaque psoriasis.To consider the benefits and risks of tofacitinib in patients with moderate-to-severe psoriasis.Data were pooled from one phase II, four phase III and one long-term extension study comprising 5204 patient-years of tofacitinib treatment. Efficacy end points included patients achieving Physician's Global Assessments of 'clear' or 'almost clear', ≥ 75% and ≥ 90% reduction in Psoriasis Area and Severity Index (coprimary end points) and improvements in Dermatology Life Quality Index score, Hospital Anxiety and Depression Scale depression score and Itch Severity Item score, at weeks 16 and 52. Safety data were summarized for 3 years of tofacitinib exposure.Tofacitinib 5 and 10 mg twice daily (BID) showed superiority over placebo for all efficacy end points at week 16, with response maintained for 52 weeks of continued treatment. Tofacitinib improved patients' quality of life and was well tolerated. Rates of safety events of interest (except herpes zoster) were similar to those in the published literature and healthcare databases for other systemic psoriasis therapies. Tofacitinib 10 mg BID demonstrated greater efficacy than 5 mg BID.Tofacitinib has a benefit-risk profile in moderate-to-severe psoriasis consistent with that of other systemic treatments.