tbuckley/cabot-search huggingface dataset:
A co-clinical phase II trial of carboplatin and docetaxel as neoadjuvant treatment for triple negative breast cancer with genomic discovery analysis.
Authors: Foluso Olabisi Ademuyiwa, Shunqiang Li, Tracy Skinner, Jason Hoshower, Jingqin Luo, Cynthia X. Ma, Katherine N. Weilbaecher, Michael Naughton, Leonel Fernando Hernandez-Aya, Elaine R. Mardis, Matthew James Ellis
Journal: Journal of Clinical Oncology (2016)

TPS1099 Background: Patients with TNBC who do not achieve a pathologic complete response (pCR) or near pCR have high rates of relapse, due to chemotherapy resistance, within the first few years after diagnosis. Molecular biomarkers predictive for chemotherapy sensitivity are lacking. This ongoing trial is evaluating carboplatin and docetaxel in the neoadjuvant setting to determine whether these drugs will increase the pCR rate compared to historical controls. Correlative studies include exome and transcriptome sequencing on samples acquired from patients as a means to decipher the genomic architecture and clonal evolution of those who achieved a pCR compared to those who did not. The simultaneous development of patient derived xenografts (PDX) from host tumors is also planned. Methods: Patients with clinical stage 2 or 3 TNBC will receive six cycles of neoadjuvant carboplatin AUC 6 and docetaxel 75 mg/m2 every 3 weeks, followed by definitive surgery. Forty-one eligible patients will be treated according to protocol, permitting us to attain a power of 83% to detect our expected pCR rate of 54% compared to the historical 35% rate, based on a two-sided exact binomial test at the 4.8% significance level. Eligibility: tumor size at least 2 cm, adequate organ and bone marrow function, no bilateral or inflammatory disease, no invasive cancer within 5 years, ECOG performance status of ≤ 2, no prior sentinel node biopsy. Tissue collection for xenografting and correlative studies will occur at baseline, at cycle 1 day 3, and at surgery. The primary objective is to determine the pCR rate, defined as the absence of invasive cancer in breast or nodes at surgery. Secondary and exploratory objectives include xenografting rates, evaluation of mutational signatures of chemotherapy resistance and response, and comparison of chemotherapy responses between patients and their xenografts. The study was activated on 7/7/2014 and is still recruiting. Twenty patients have been enrolled and have had baseline tissue banked. Fourteen patients have completed protocol therapy. Three patients have tissue at all 3 time points (9 samples), and are presently being studied by exome and transcriptome sequencing. Clinical trial information: NCT02124902.
Biomarker-Based Phase II Trial of Savolitinib in Patients With Advanced Papillary Renal Cell Cancer
Authors: Toni K. Choueiri, Elizabeth Plimack, Hendrik-Tobias Arkenau, Eric Jonasch, Daniel Y.C. Heng, Thomas Powles, Melanie M. Frigault, Edwin A. Clark, Amir A. Handzel, Humphrey Gardner, Shethah Morgan, Laurence Albiges, Sumanta Kumar Pal
Journal: Journal of Clinical Oncology (2017)

Purpose Patients with advanced papillary renal cell carcinoma (PRCC) have limited therapeutic options. PRCC may involve activation of the MET pathway, for example, through gene amplification or mutations. Savolitinib (AZD6094, HMPL-504, volitinib) is a highly selective MET tyrosine kinase inhibitor. We report results of a single-arm, multicenter, phase II study evaluating the safety and efficacy of savolitinib in patients with PRCC according to MET status. Patients and Methods Patients with histologically confirmed locally advanced or metastatic PRCC were enrolled and received savolitinib 600 mg orally once daily. MET-driven PRCC was defined as any of the following: chromosome 7 copy gain, focal MET or HGF gene amplification, or MET kinase domain mutations. Efficacy was assessed according to MET status. Safety, toxicity, and patient-reported health-related quality-of-life outcomes were assessed in all patients. Results Of 109 patients treated, PRCC was MET driven in 44 (40%) and MET independent in 46 (42%); MET status was unknown in 19 (17%). MET-driven PRCC was strongly associated with response; there were eight confirmed partial responders with MET-driven disease (18%), but none with MET-independent disease ( P = .002). Median progression-free survival for patients with MET-driven and MET-independent PRCC was 6.2 months (95% CI, 4.1 to 7.0 months) and 1.4 months (95% CI, 1.4 to 2.7 months), respectively (hazard ratio, 0.33; 95% CI, 0.20 to 0.52; log-rank P &lt; .001). The most frequent adverse events associated with savolitinib were nausea, fatigue, vomiting, and peripheral edema. Conclusion These data show activity and tolerability of savolitinib in the subgroup of patients with MET-driven PRCC. Furthermore, molecular characterization of MET status was more predictive of response to savolitinib than a classification based on pathology. These findings justify investigating savolitinib in MET-driven PRCC.
Adjuvant chemotherapy in colorectal cancer: Its impact in the real world
Authors: A White, D Fennelly, K Sheahan, H Mulcahy, JM Hyland, DP O'Donoghue
Journal: Endoscopy (2005)

Advancing age is the biggest risk factor for development of bowel cancer yet trials of adjuvant therapy either fail to mention age or do not include patients over 70 years.
Solitary Choroidal Metastasis From Lung Adenocarcinoma on FDG PET/CT
Authors: Zu-Gui Li
Journal: Clinical Nuclear Medicine (2017)

Solitary choroidal metastasis as an initial presentation of lung cancer is rare. A 67-year-old woman who initially presented with a 3-month history of blurred vision in the right eye was suggestive of choroidal melanoma on MRI. Preoperatively, a pulmonary mass was found on x-ray. She was referred for an FDG PET/CT imaging, which revealed a choroidal lesion with minimal FDG uptake in right eye and increased FDG activity in the known lung mass. A pathological diagnosis of metastatic lung adenocarcinoma was made after enucleation of the right eyeball.
A clinician’s plea to test glioma patients for CMV
Authors: Nicole Lydia Goerig, Benjamin Frey, Klaus Überla, Udo Gaipl, Rainer Fietkau
Journal: Neuro-Oncology (2017)

during therapy: 19/26 patients were positive for anti-CMV IgG at all serum collection time points (Table 1).Only 3/26 patients were positive for anti-CMV IgM and those were also positive for anti-CMV IgG, indicating a reactivation rather than a primary CMV infection.None of the patients was positive for CMV DNA in peripheral blood despite use of a highly sensitive PCR assay. 3Nineteen of 26 patients received dexamethasone during RT, 4 patients before RT but stopped during RT, and 3 patients did not receive dexamethasone.The mean cumulative dosage of dexamethasone before RT was 228.0 mg (SD 80.9 mg) in the CMV IgM-positive patients and 180.2 mg (SD 175.3 mg) in the CMV IgM-negative patients (Mann-Whitney U test P = 0.259).The cumulative dosage of dexamethasone during RT was similar between these 2 patient groups-188.7 mg (SD 151.1) versus 111.4 mg (SD 100.8) (Mann-Whitney U test P = 0.313) and 4.5 mg per day (SD 3.4) versus 4.0 (SD 3.6) (Mann Whitney U Test P = 0.491).Of note, lower dosages of the corticosteroid were administered at all time points compared with the prior study. 1 Glucocorticoids play an important role in CMV replication: dexamethasone treatment of fibroblasts enhances replication of CMV 4 and initiates the transcription cascade of CMV. 5 In concordance, Goerig et al 1 found an association between CMV reactivation and dexamethasone treatment of glioblastoma patients.In contrast, we didn't find an association between RT or dexamethasone treatment and CMV reactivation.None of our patients had CMV viremia and only 3 patients were positive for anti-CMV IgM during treatment.Nevertheless, glucocorticoid dosages used in the present patients were clearly lower than in the previous study.Standard glucocorticoid dosages used in the treatment of glioblastoma may have to be optimized to reduce the risk of CMV reactivation and disease.
The effect of celebrity health disclosures on demand for health care: Trends in BRCA testing in 2013 and subsequent health services use.
Authors: Megan Roberts, Stacie Dusetzina
Journal: Journal of Clinical Oncology (2016)

e13106 Background: Celebrity health disclosures through the media increase awareness of important health issues and may increase health services use. In May 2013 an internationally-renowned celebrity, Angelina Jolie, disclosed her receipt of BRCA1 and BRCA2 testing and subsequent double mastectomy in a highly publicized editorial in the New York Times. This study’s objectives were to describe trends in BRCA1/2 testing before and after Jolie’s disclosure, and in subsequent health services use. Methods: We used 2012-2013 MarketScan Commercial Claims and Encounters data, which include claims and demographic data for non-retired employees and their dependents enrolled in commercial health insurance plans. We identified women aged 18-64 who received BRCA testing in 2013 and were continuously enrolled for one year prior to testing. We used interrupted time series analysis to compare trends in BRCA testing prior to and after Jolie’s New York Times editorial, using a Poisson distribution and log link and controlling for patient and health plan covariates. Models were stratified by cancer history status (i.e., personal/family vs. none). We used generalized estimating equations with a binomial distribution and log link to estimate risks and risk ratios for subsequent health services use (surgical consult, mastectomy, MRI and genetic counseling) within three months after BRCA testing. Results: Uptake of BRCA testing increased from 10.5 to 15.8 tests per 100000 women following publication of Jolie’s editorial. Although testing increased among all women, the likelihood of receiving cancer-related follow-up services declined among those with a personal/family history seeking testing after Jolie’s disclosure. Conclusions: This celebrity health disclosure had a significant impact on genetic testing uptake both among women with a personal/family cancer history, as well as among women without a cancer history. Our results suggest that celebrity disclosures through popular media influence health behavior, both among individuals who are and are not indicated to receive such services.
Erratum: 'U' curve association of blood pressure and mortality in hemodialysis (Kidney International (1998) 54 (561-569))
Authors: P. G. Zager, J. Nikolic, R. H. Brown, M. A. Campbell, W. C. Hunt, D. Peterson, J. Van Stone, A. Levey, K. B. Meyer, M. J. Klag, H. K. Johnson, E. Clark, J. H. Sadler, P. Teredesai
Journal: Kidney International (1998)
Association of Charcot-Marie-Tooth gene, SBF2, with taxane-induced peripheral neuropathy in African Americans.
Authors: Bryan P. Schneider, Dongbing Lai, Fei Shen, Guanglong Jiang, Milan Radovich, Lang Li, Laura Gardner, Kathy D. Miller, Anne M. O'Neill, Joseph A. Sparano, Gloria Xue, Tatiana Foroud, George W. Sledge
Journal: Journal of Clinical Oncology (2016)

1026 Background: Taxane-induced peripheral neuropathy (TIPN) is one of the most important survivorship issues for cancer patients. African Americans (AA) have previously been shown to have an increased risk for this toxicity. Germline predictive biomarkers hold promise to help identify a priori which patients might be at extraordinarily high risk for this toxicity. Methods: We performed whole exome sequencing on germline DNA from AA patients who received a standard dose and schedule of paclitaxel in the adjuvant, randomized phase III breast cancer trial, E5103. Evaluable cases were defined as those with either grade 3-4 (n = 56) or grade 2-4 (n = 121) TIPN and were compared to evaluable controls (n = 59) who had no evidence of TIPN. We retained for analysis rare variants with a minor allele frequency < 3% and which were predicted to be deleterious by protein prediction programs. A gene-based, case-control analysis using SKAT was performed to identify genes that harbored an imbalance of deleterious variants associated with increased risk of TIPN. Results: Five genes had a p-value < 10-4 for grade 3-4 TIPN analysis and three genes had a p-value < 10-4 for the grade 2-4 TIPN analysis. For the grade 3-4 TIPN analysis, SET binding factor 2 (SBF2) was significantly associated with TIPN (p-value = 4.35 x10-6). Five variants were predicted to be deleterious in SBF2. Inherited mutations in SBF2 have previously been associated with autosomal recessive, Type 4B2 Charcot-Marie-Tooth (CMT) disease. Conclusions: Rare variants in SBF2, a CMT gene, predict an increased risk of TIPN in AA patients receiving paclitaxel.
Abstract 11194: Classic Pattern Dyssynchrony is Associated With Left Bundle Branch Block in Pediatric Dilated Cardiomyopathy
Authors: Daniel Forsha, Cameron Slorach, Ching Kit Chen, Niels Risum, Christoph Hornik, Peter Sogaard, Luc Mertens, Piers Barker, Joseph Kisslo, Mark K Friedberg
Journal: Circulation (2013)

Classic pattern dyssynchrony (CPD) has been associated with > 90% response to cardiac resynchronization therapy (CRT) in adults with dilated cardiomyopathy (DCM), but has not been evaluated in pedi...
Survival and outcome data observed in 98 patients affected by acute myeloid leukemia undergoing chemotherapy consolidation courses treatment followed by autologous bone marrow transplantation (auto-BMT).
Authors: Giovanni Marconi, Cristina Papayannidis, Federico Mosna, Michele Gottardi, Elena Tenti, Eugenia Franchini, Andrea Ghelli Luserna di Rorà, Emanuela Ottaviani, Maria Chiara Fontana, Giorgia Simonetti, Viviana Guadagnuolo, Marco Manfrini, Debora Capelli, Piero Galieni, Andrea Piccin, Giuseppe Visani, Francesco Rodeghiero, Cristina Tecchio, Filippo Gherlinzoni, Giovanni Martinelli
Journal: Journal of Clinical Oncology (2016)

e18520 Background: In a specific subset of patients, Auto-BMT may represent a good therapeutic option. It is used worldwide in consolidation of both low risk, and standard risk AML without an available HLA matched donor. Were analyzed all patients who received Auto-BMT from 2005 to 2014 in several Italian institution. Methods: From 2005, 98 AML patients underwent Auto-BMT; 89/98 patients are evaluable for survival and outcome data. Molecular monitoring by specific fusion transcripts was performed in positive patients at the time of diagnosis, and at fixed time points. According to ELN risk stratification 41 patients had a low risk (LR) AML, 4 patients with a high risk (HR) AML and 44 patients with a standard risk (SR) AML. Results: Patients received a median of 2 consolidation courses of chemotherapy (range 1-4) before proceeding to Auto-BMT, performed in 1stCR in most of them. Six patients (6.7%) received auto-BMT in first relapse. Forty-one patients relapsed after auto-BMT. With a median follow up of 6 years, the median Overall Survival (OS) of the entire population was 64.3 months (range 5.8-294.2 months). To assess the role of the number of consolidation courses we compared patients who received none or 1 consolidation course with patients who received 2 or more courses, who showed a better OS (p= 0.0061). Moreover, we compared patients who did not achieve a negative minimal residual disease status before auto-BMT (n=9) with patients who did (n=37). MRD negativity show to define better outcome in terms of 5-years OS (83.4% and 50% respectively). Conclusions: Auto-BMT offers a chance to achieve long-term DFS and OS both in patients with LR and SR AML, avoiding overtreatment. The major role is played in MRD negative patients, offering the best chances to achieve a long-term OS. We suggest a therapy schedule including two or more consolidation courses in patients who obtain a first CR, and to proceed then to auto-BMT. Akcnowledgments: work supported by ELN, AIL, AIRC, Progetto Regione-Università 2010-12 (L.Bolondi), FP7 NGS-PTL project.
Pegylated Full-Length Recombinant Factor VIII with Extended Half-Life in Previously Treated Pediatric Patients with Hemophilia Α: Efficacy of Prophylaxis and Treatment By Time (of Day/of Week) of Occurrence of Bleeding
Authors: Eric S. Mullins, Christine M. Knoll, Amy L. Dunn, Werner Engl, Marlies Sharkhawy, Brigitt E. Abbuehl
Journal: Blood (2016)
Does endocrine therapy in mucinous and tubular breast cancer improve outcome?
Authors: Nicola Jane Mitchell, David James Porter
Journal: Journal of Clinical Oncology (2014)

566 Background: Mucinous and tubular breast cancer (ca) have better prognosis than infiltrating ductal carcinoma (IDC). Patients (pts) often receive adjuvant (adj) treatment as if their risk was standard but questions arise about which pts could safely avoid treatment. We aimed to establish the current local practices and assess outcomes. Methods: We identified pts with early-stage mucinous and tubular breast ca using prospectively collected data from the Auckland Breast Cancer Registry between June 2000 and June 2012. Pts were case matched with IDC according to size, grade, nodal status and age. Because endocrine therapy (ET) use increased with higher Nottingham Prognostic Index (NPI), survival outcomes were also analysed by NPI group. Results: 161 mucinous and 201 tubular ca were identified. Baseline characteristics and treatment received are shown below. ET was used more in IDC than mucinous (54% vs 40%) or tubular ca (23% vs 12%). Median follow up was 4.3 yrs for mucinous and 4.8 yrs for tubular ca. RFS was superior in mucinous cf matched IDC (HR 0.3, p=0.0012) as well as DDFS (HR 0.2, p=0.011). A trend towards improved OS with ET in mucinous ca was seen in the overall group (HR 0.3, p=0.056), despite ET use being more common in higher NPI groups. RFS (HR 0.7, p=0.38) and DDFS (HR 0.1, p=0.083) were similar in tubular cf matched IDC. Of 182 pts with EPG tubular ca, only 10 received ET with no improvement in OS (HR 2.8, p=0.21). Conclusions :In this study, mucinous ca has an inherently better survival than IDC but women at higher risk may still benefit from ET. The good prognosis in tubular ca appears to be due to low stage at presentation. No benefit of ET was seen in tubular or EPG mucinous ca, suggesting selected women may be safely spared the side effects and costs of treatment. Mucinous n = 161 Tubular n = 201 Median age in years (quartiles) 63 (52,75) 57 (50, 65) Median size, mm (quartiles) 18 (12, 27) 9 (6, 13) Grade 1 107 (66%) 189 (94%) 2 47 (29%) 8 (4%) 3 4 (2.5%) 1 (0.5%) Unknown 3 (1.9%) 3 (1.5%) Nodal status 0 129 (80%) 174 (87%) 1 to 3 13 (8%) 9 (4%) 4 + 4 (2%) 0 (0%) Unknown 15 (9%) 18 (9%) NPI Excellent (EPG) 65 (40%) 182 (91%) Good (GPG) 58 (36%) 12 (6%) Moderate (MPG) 32 (20%) 7 (3%) Poor (PPG) 6 (4%) 0 (0%) Adj chemotherapy (%) 15 (9%) 6 (3%) Adj endocrine therapy (%) 64 (40%) 25 (12%)
Risk factors for head injury events in professional rugby union: a video analysis of 464 head injury events to inform proposed injury prevention strategies
Authors: Ross Tucker, Martin Raftery, Simon Kemp, James Brown, Gordon Fuller, Ben Hester, Matthew Cross, Ken Quarrie
Journal: British Journal of Sports Medicine (2017)

The tackle is responsible for the majority of head injuries during rugby union. In order to address head injury risk, risk factors during the tackle must first be identified. This study analysed tackle characteristics in the professional game in order to inform potential interventions.464 tackles resulting in a head injury assessment (HIA) were analysed in detail, with tackle type, direction, speed, acceleration, nature of head contact and player body position the characteristics of interest.Propensity to cause an HIA was significantly greater for active shoulder tackles, front-on tackles, high speeder tackles and an accelerating tackler. Head contact between a tackler's head and ball carrier's head or shoulder was significantly more likely to cause an HIA than contact below the level of the shoulder (incident rate ratio (IRR) 4.25, 95%-CI 3.38 to 5.35). The tackler experiences the majority (78%) of HIAs when head-to-head contact occurs. An upright tackler was 1.5 times more likely to experience an HIA than a bent at the waist tackler (IRR 1.44, 95% CI 1.18 to 1.76).This study confirms that energy transfer in the tackle is a risk factor for head injury, since direction, type and speed all influence HIA propensity. The study provides evidence that body position and the height of tackles should be a focus for interventions, since lowering height and adopting a bent at the waist body position is associated with reduced risk for both tacklers and ball carriers. To this end, World Rugby has implemented law change based on the present data.
Factors affecting mortality in patients with post-operative enterocutaneous fistulae
Authors: AL Gidwani, S Gidwani
Journal: Endoscopy (2005)

Aim: Enterocutaneous fistulae encompass a wide spectrum of disease entities with significant morbidity and mortality. This study aims to analyse the risk factors which influence the outcome of patients with post-operative enterocutaneous fistulae.
Issue of quality control was not addressed
Authors: S. Adlakha, P. G Cachia, M. J Pippard, P. G Davey, B. M Goudie
Journal: BMJ (1996)

Radcliffe Hospital and Oxfordshire Health Authorities decided to collaborate in producing their own card.This is now in wide use throughout the county, having replaced the national card not only at the Oxford Radcliffe Hospital but also, more importantly in numerical terms, in all general practice surgeries and community pharmacies.It has also been offered to the other trusts in the county to use if they wish.The card was approved by the Royal Pharma- ceutical Society before the substitution was made.The Department of Health was also given notice of our intentions and raised no objection.A further concern arose about the need for guidance as to when the card should and should not be issued.A double sided, A4 sized advice sheet was therefore produced, using the best available evidence, and sent to all general practi- tioners and community pharmacists with the first batch of the new steroid cards.Part of its intention is to rationalise the issuing of the steroid cards.They are not, for instance, recom- mended for patients receiving low doses of inhaled corticosteroids, in whom there is no increased risk from chickenpox.The same guidance sheet also includes locally tailored advice as to what should be done if a patient at risk who is receiving corticosteroids does come into contact with chickenpox or shingles.