tbuckley/cabot-search huggingface dataset:
BMA backs doctors fighting government over “discriminating” NHS pension scheme
Authors: Zosia Kmietowicz
Journal: BMJ (2019)

The BMA is to support doctors intending to sue the government because it believes that many were forced to join a pension scheme that will make them worse off when they retire.

Solicitors for the BMA have written to England’s health secretary, Matt Hancock, warning him of the intention to take legal action. Letters have also been sent to the Scottish and Northern Ireland governments.

Trevor Pickersgill, interim BMA treasurer, explained that in 2015 the NHS closed two sections …
Abstract MP62: Associations of Timing of Complementary Feeding Introduction and Adiposity Throughout Childhood and Adolescence
Authors: Veronique Gingras, Izzuddin M Aris, Sheryl L Rifas-Shiman, Karen M Switkowski, Emily Oken, Marie-France Hivert
Journal: Circulation (2019)

Introduction: Complementary feeding includes introducing food or beverages other than breastmilk or formula to infants. We previously showed associations of early complementary feeding (&lt;4 months old) with higher obesity risk at 3 years old in formula-fed children only. Hypothesis: We hypothesized that associations with adiposity would persist into early adolescence. Methods: Among 991 children from Project Viva, a pre-birth prospective cohort, we examined associations of complementary feeding timing with later body mass index (BMI) z-scores, waist circumference, and dual-energy radiograph absorptiometry (DXA) measured adiposity in mid-childhood (mean: 7.8, SD 0.8 years old; N=681) and in early adolescence (mean: 13.2, SD 0.9 years old; N=637). We used linear regression models adjusted for socio-demographic characteristics, parental BMI, and change in weight-for-age z-score from 0 to 4 months (as a marker of early infant growth); the reference group for all analyses was complementary feeding initiation between 4 to &lt;6 months. We ran separate models for infants who were breastfed for ≥4 months (breastfed) and infants who were never breastfed or weaned &lt;4 months of age (formula-fed). As a secondary analysis, we fitted individual BMI trajectories using mixed-effect models with natural cubic spline functions (N=952), and then examined the association of timing of complementary feeding with age at BMI rebound derived from the trajectories, using linear regression models, adjusting for previously listed covariates. Results: At 4 months of life, 66% (654 of 991) of children were breastfed and 34% (337 of 991) were formula-fed. Complementary feeding was introduced &lt;4 months for 19% (188 of 991), between 4 to &lt;6 months for 68% (674 of 991; reference group), and ≥6 months for 13% (129 of 991) of children. Complementary feeding &lt;4 months was associated with higher waist circumference in both formula-fed (β 2.60, 95% CI [0.35, 4.86] cm) and breastfed children (1.98 [0.07, 3.89] cm) in mid-childhood, while in early adolescence, it was associated with higher BMI z-score (0.36 [0.04, 0.68]) in formula-fed children, and with higher waist circumference in both formula-fed (4.99 [1.14, 8.84] cm) and breastfed children (3.12 [0.02, 6.21] cm). Complementary feeding &lt;4 months was additionally associated with an earlier age at BMI rebound (-7.6 [-12.6, -2.5] months) in breastfed children. Complementary feeding initiated ≥6 months was associated with higher BMI z-score (0.50 [0.04, 0.97]) in mid-childhood and with an earlier age at BMI rebound (-11.5 [-20.0, -2.9] months) in formula-fed children only. Conclusions: We found associations of both early and late introduction of complementary feeding with BMI z-score in formula-fed infants and with waist circumference in breastfed and formula-fed infants throughout childhood.
A phase II study of cabozantinib as first-line treatment in metastatic collecting ducts carcinoma: The BONSAI trial.
Authors: Giuseppe Procopio, Raffaele Ratta, Maurizio Colecchia, Marialuisa Sensi, Pierangela Sepe, Melanie Claps, Licia Rivoltini, Filippo G. De Braud, Filippo Pagani, Elena Verzoni
Journal: Journal of Clinical Oncology (2019)

578 Background: Metastatic collecting ducts carcinoma (mCDC) is a rare and aggressive disease, characterized by a poor prognosis; its treatment represents an unmet medical need. We aimed to evaluate the activity and safety of cabozantinib (cabo) in mCDC. Methods: This is a prospective, monocentric, single-arm phase II trial evaluating cabo in patients (pts) with untreated mCDC. Cabo was administered at the dose of 60 mg orally once daily until disease progression (evaluated by RECIST 1.1 criteria) or unacceptable toxicity. Primary endpoint was objective response rate. Secondary endpoints were progression-free survival, overall survival and safety profile. Exploratory objectives include the identification of somatic mutations and the mutational load on tissue samples; plasma and viable peripheral blood mononuclear cells were studied for immune related biomarker profiling. Results will be crossed with clinical data in terms of response rate, to detect any predictive value of blood immune cell profiling. A central pathological review before study entry is mandatory. The study design is based on a Simon’s two stage optimal design: in the first step at least 2 responses in 9 pts enrolled are needed to go to the second stage of the study (14 additional pts). Results: From January 2018 to September 2018, 11 pts with mCDC have been so far enrolled, nine of which started study treatment. Median age was 58 years, 8 pts were male and 1 female, 7 pts received a previous nephrectomy. The most common metastatic sites were bone and abdominal lymphnodes (5 pts each), followed by liver and lung (2 pts each). Two pts had a partial response as best response, 2 had a stable disease, 3 had a progressive disease and 3 pts died for early progression. Treatment was feasible and well tolerated. All pts reported at least one grade (G) 1-2 adverse events (AEs): the most common were asthenia, diarrhea, anorexia and nausea, hand-foot syndrome, hypertension and dysgeusia. No G3-4 AEs were reported. Genetic and immunological essays are ongoing to assess the immunomodulatory properties of cabozantinib and potential predictive factors. Conclusions: Cabo was safe and active in CDC. The second stage and biomarkers analyses are ongoing. Clinical trial information: NCT03354884.
Endoscopic tissue shielding to prevent bleeding after endoscopic submucosal dissection: a prospective multicenter randomized controlled trial
Authors: Yosuke Kataoka, Yosuke Tsuji, Kingo Hirasawa, Kengo Takimoto, Tomonori Wada, Satoshi Mochizuki, Ken Ohata, Yoshiki Sakaguchi, Keiko Niimi, Satoshi Ono, Shinya Kodashima, Nobutake Yamamichi, Mitsuhiro Fujishiro, Kazuhiko Koike
Journal: Endoscopy (2019)

Bleeding after endoscopic submucosal dissection (ESD) is a severe adverse event. Recent reports have described the efficacy of the endoscopic shielding method with polyglycolic acid (PGA) sheets and fibrin glue for the prevention of adverse events after ESD. The aim of the present study was to investigate whether the PGA shielding method provides additional benefit in preventing post-ESD bleeding compared with standard care.This was a prospective, multicenter, randomized controlled trial. Patients at high risk of post-ESD bleeding were enrolled in the study. Before ESD, patients were randomized to either the PGA group or the control group. After completing ESD in the PGA group, PGA sheets were placed onto the ulcer floor and adhered with fibrin glue. The primary end point was the post-ESD bleeding rate.140 eligible patients were enrolled from September 2014 to September 2016, and 137 were included in the intention-to-treat analysis (67 in the PGA group and 70 in the control group). Post-ESD bleeding occurred in three patients (4.5 %) in the PGA group and in four patients (5.7 %) in the control group; there was no significant difference between the two groups (P > 0.99). Post-ESD bleeding tended to occur later in the control group than in the PGA group (median 12.5 days [range 8 - 14] vs. 2 days [range 0 - 7], respectively).The PGA shielding method did not demonstrate a significant effect on the prevention of post-ESD bleeding.
Abstract MP35: Physical Activity and Risk of Cardiovascular Events and All-Cause Mortality Among Kidney Transplant Recipients
Authors: Augustine Kang, Hongseok Kim, Carol E Garber, Charles Eaton, Patricia M Risica, Andrew G Bostom
Journal: Circulation (2019)

Introduction: Insufficient physical activity (PA) may increase the risk of all-cause mortality and cardiovascular disease (CVD) morbidity and mortality among kidney transplant recipients (KTRs), but limited research is available. We examine the relationship between PA and the development of CVD events and all-cause mortality among a cohort of KTRs. Methods: N = 4377 participants were examined from a large, multiethnic, multicenter trial (37% female; mean age 51.9 ± 9.4 years; 75% White; 20% with prevalent CVD). PA was measured at baseline and was derived from a modified PA summary score from the Yale Physical Activity Survey (YPAS) and divided into tertiles (T1, T2, T3), from lowest to highest PA. Kaplan-Meier survival curves were used to graph the risk of CVD events and all-cause mortality between PA tertiles. Cox proportional hazards regression models were constructed to examine the association of baseline PA levels with CVD events (e.g. stroke, myocardial infarction, CVD death) and all-cause mortality over time. There was no violation of the proportional hazards assumption. Covariates include age, sex, race, smoking status, diastolic blood pressure, blood lipids, BMI, transplant vintage, and donor type. Results: Participants were followed up to 2,500 days. The cohort reported 486 CVD events and 419 deaths. Fully adjusted models revealed that compared to the lowest tertile, the highest tertile had significantly lower risk of: CVD events (HR, 0.628, 95% CI, 0.499-0.790) and all-cause mortality (HR, 0.533, 95% CI, 0.414-0.688). Compared to middle T2 scores, T3 of PA scores had significantly lower: risk of CVD events (HR, 0.709, 95% CI, 0.563-0.895) and all-cause mortality (HR, 0.635, 95% CI, 0.491-0.822). Results were similar in unadjusted models. Conclusion: Physical activity was associated in a dose-response manner with a reduced risk of CVD events and all-cause mortality in kidney transplant recipients. These observed associations in a large, international sample of KTRs, even when controlling for traditional CVD risk factors, indicate the potential importance of PA in reducing CVD and death among KTRs. Future work to confirm these associations and to determine whether increasing PA will reduce risk in KTRs is needed, which may help inform if PA should be integrated into lifestyle management strategies among KTRs.
Evaluating traditional phase 2 trial design of systemic therapies in recurrent/advanced cervical cancer: A NRG Oncology/Gynecologic Oncology Group (GOG) ancillary data study.
Authors: Lilian Tran Gien, Wei Deng, Gillian Thomas
Journal: Journal of Clinical Oncology (2015)

e16592 Background: The identification of effective systemic agents for recurrent cervical cancer has been illusive despite multiple phase 2 studies. This analysis of ancillary data from phase 2 GOG studies was conducted to explore whether traditional endpoints of tumor response, progression-free survival (PFS) and overall survival (OS), were reflected in subsequent phase 3 trials. The aim was to generate hypotheses for refining future trial designs and to identify prognostic factors for response to treatment. Methods: From 1995 to 2012, all 35 phase 2 trials in recurrent cervix cancer were included. Patient, treatment, and outcome data were collected from a database and individual chart review. Generalized estimating equations estimated overall response rates; multivariate analysis determined factors associated with tumor response. PFS and OS were compared based on agents that went forward to phase 3, and by clusters of prognostic factors as defined by the Moore criteria. Results: 1237 eligible patients were included. Only 11% (95% CL 8-15%) had a complete or partial response. Factors associated with better tumor response included performance status of 0, time to first relapse > 1 year, no prior platinum chemotherapy, and non-African-American race. The odds for low risk patients (0-1 factors) to respond to therapy was 6.03 times (95% CL 1.69 – 21.59, p = 0.0057) the odds for high risk patients (4-5 factors). The number of risk factors influences overall survival (high risk vs low risk patients HR 1.9 [1.42-2.55], p < 0.0001). There were no statistically significant differences in PFS (p = 0.09) or OS (p = 0.20) for patients on studies of drugs rejected vs accepted for phase 3 study. Conclusions: Factors prognostic for response to treatment include performance status, time to first relapse, prior platinum chemotherapy, and race. Stratifying risk groups should be strongly considered during the design of future trials. It is unclear what criteria should be used to select agents for subsequent phase 3 studies, as current criteria are not robust. This information drives the need for refining clinical trial design and selection criteria for effectiveness.
Does chronic lymphocytic leukemia occur in younger adults in Turkey?
Authors: Gultekin Pekcan, Erden Atilla, Sinem Civriz Bozdag, Selami Kocak Toprak, Meltem Kurt Yuksel, Pervin Topcuoglu, Hamdi Akan, Osman Ilhan, Gunhan Gurman, Muhit Ozcan, Onder Arslan
Journal: Journal of Clinical Oncology (2015)

e18037 Background: Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in the Western world and affects mainly elderly patients. Median age at diagnosis is 72. Our aim, in this retrospective study is to present our CLL patients’ demographic data. Methods: We retrospectively included 99 patients diagnosed as CLL which is defined by a circulating B lymphocyte > 5000mm3 and flow cytometry confirmation of immunophenotype with CD5, CD19, CD20, CD23,CD79b and surface Ig light chain restriction. Therapy decision at diagnosis or follow up was given according to IWCLL 2008 criteria. Performance status of the patients before therapy was peformed by using CIRS criteria in most of the patients who were evaluated for the ongoing clinical trials. Rest of them were arbitirarly categorized as fit or unfit at the discretion of the physician. Results: Median age of the patients at diagnosis was 52 (32-98) years while 60 of the patients (60%) were male. The distrubition of the age was as follows: 27.3% ≤ 50, 29.3% 51-60, 30.3% 61-70 and 13.1% > 70. Rai stages at diagnosis from 0 to IV were 15%, 14%, 25%, 16% and 29% respectively. FISH abnormalities documented in 19 (20%) of the patients at diagnosis. Most common genetic abnormality was del 13q (10%). Del17p was detected in 5% of the patients after diagnosis. Fifty-two patients (53%) (27 fit, 18 unfit, 7 unknown) needed therapy at diagnosis or their folow up period. 1st line therapy in fit patients were mainly R-FC (25%), R-CVP, FC, or R-Benda. In unfit patients first line therapy distrubution was R-FClite (61%), Clb alone, R- Clb. The most common given second line therapy was R-FC for fit patients and R-FClite for the unfit patients. Conclusions: CLL has a wide range of genetic variations with different clinical onsets. We detected CLL in younger adults in our cohort although the known incidence is greatest in older individuals in Western World. This data should be confirmed in larger studies.
A survey to determine patients’ (pts) opinions of a clinical trial (CT) comparing intermittent (int) versus continuous (cont) androgen receptor signaling inhibitor (ARSi) therapy for the treatment of advanced prostate cancer.
Authors: Cameron Phillips, Seanthel Delos Santos, Robert Mason, Urban Emmenegger
Journal: Journal of Clinical Oncology (2019)

295 Background: Several therapies have shown a survival benefit and improvements in pt-reported quality of life in metastatic prostate cancer (mPC) including ARSis, such as abiraterone (A) and enzalutamide (E). While both are fairly well tolerated, there is a wide range of side effects associated with them. In addition, both of these medications are costly. The purpose of this study was to obtain pts’ opinions regarding potential participation in a randomized CT comparing int to cont treatment with A and E. Methods: We approached ambulatory pts diagnosed with mPC between August 2018 and October 2018 to complete a questionnaire eliciting their preferences regarding participation in a CT comparing int to cont treatment with A or E. A total of 105 patients completed the survey. We collected information regarding pts’ current/prior therapies, their interest in being treated with an int strategy and reasons for or against participating in a randomized CT with int versus cont treatment. Results: The median age of our pts was 72 years (IQR: 67 -78). 30% of patients had prior experience with an ARSi (A 10%, E 20%). 51% of pts were receiving either A (28%) or E (23%) at the time of the survey. 76% of pts indicated that they would generally be interested (27%) or very interested (49%) in participating in CTs, and 65% of patients were interested (19%) or very interested (46%) in participating in a CT involving int ARSi therapy. The reasons for participating include the prospect of less side effects (49%), less medication burden (39%), and cost-savings (15%). The reasons for not participating include the possibility of the cancer worsening off treatment (55%), the possibility of worse overall survival (48%), and the possibility of developing cancer-related symptoms in the off-phase (39%). Conclusions: The majority of pts surveyed would be interested in participating in a randomized CT that would include int versus cont treatment with an ARSi. In a complementary study, we are surveying oncologists to determine the ideal patient cohort for such a study, as well as acceptable triggers for treatment interruption and resumption.
Validated five-factor prognostic model for survival of patients (pts) with metastatic urothelial carcinoma (mUC) receiving different post-platinum PD-L1 inhibitors.
Authors: Guru Sonpavde, Daniel Hennessy, Juliane Manitz, Guenter Niegisch, Thomas Powles, Jonathan E. Rosenberg, Dean F. Bajorin, Andrea B. Apolo, Gregory Russell Pond
Journal: Journal of Clinical Oncology (2019)

476 Background: A prognostic model for overall survival (OS) of mUC was previously reported in the setting of post-platinum atezolizumab (Pond GR, GU ASCO 2018). This model was limited by employing only atezolizumab treated pts, small size of the validation dataset and unclear applicability to other PD-1/L1 inhibitors. Hence, we constructed a robust prognostic model utilizing the combined atezolizumab cohort as the discovery dataset and used a validation dataset comprised of post-platinum avelumab-treated pts. Methods: The discovery dataset consisted of pt level data from 2 phase I/II trials (IMvigor210 and PCD4989g) evaluating atezolizumab (n = 405). Pts enrolled on a phase I/II trial that received post-platinum avelumab (n = 242) comprised the validation dataset (EMR 100070-001). Cox regression analyses evaluated the association of candidate prognostic factors with OS. Factors were dichotomized and laboratory values were normalized by logarithmic transformation. Stepwise selection was employed to propose an optimal model using the discovery dataset. Discrimination (via c-statistic) and calibration were assessed in the avelumab dataset following the validation procedure by Royston and Altman (2013). Results: The 5 factors included in the optimal prognostic model in the discovery dataset were ECOG-PS (1 vs. 0; HR 1.80; 95% CI [1.36-2.36]), presence/absence of liver metastasis (HR 1.55; 95% CI [1.20-2.00]), number of platelets (HR 2.22; 95% CI [1.54-3.18]), neutrophil-lymphocyte ratio (NLR; HR 1.94; 95% CI [1.57-2.40]) and lactate dehydrogenase (LDH; HR 1.60; 95% CI [1.28-1.99]). The c-statistic for prediction of survival was 0.692 and 0.671 in the discovery and validation datasets, respectively. Acceptable or good calibration of expected 1-year survival was observed. Conclusions: A 5-factor externally validated prognostic model for OS is proposed employing a large dataset of 647 pts overall in the setting of post-platinum PD-L1 inhibitors for mUC. This model may assist in prognostic stratification and interpreting nonrandomized trials of post-platinum PD1/L1 inhibitors.
Time efficiency and feasibility of Lesion Dashboard workflow for computing RECIST (Response Evaluation Criteria in Solid Tumors) treatment response assessment.
Authors: Manish Sharma, Merlijn Sevenster, Andrea Cowhy, Piotr Obara, Joost F Peters, William Trost, Lauren Wall, Charles W Westin, PAUL J Chang
Journal: Journal of Clinical Oncology (2015)

e17675 Background: Lesion measurements in oncology research subjects are communicated in radiology reports and manually tabulated by clinical research associates (CRAs) in most clinical research centers. This workflow is inefficient, error prone and suffers from dissociating measurement and image data. We evaluate time efficiency and feasibility of Lesion Dashboard (LD), a software application that consumes a patient's structured measurements directly from the Picture Archiving Communication System (PACS), gives an image-integrated, longitudinal quantitative disease review and enables RECIST assessment. Methods: CT exams, reports and RECIST worksheets of 16 oncology research subjects on therapeutic clinical trials were obtained retrospectively. LD was developed presenting longitudinal measurements, collected by Lesion Tracker (LT), a PACS tool used by Radiology, and gives one-click access to pertinent image slices and reports. The images of the 16 patients were annotated with LT. Part 1: 4 CRAs tabulated measurements from the reports into worksheets, mimicking the traditional workflow. Part 2: 4 oncologists and 4 CRAs (same as in Part 1) completed RECIST assessment in LD and were surveyed thereafter. Time to complete a case was measured in both parts. Results: Completing RECIST assessment in LD required 77.8 seconds on average per patient case (oncologists: 107.9s; CRAs: 47.8s). In the traditional workflow, CRAs were less efficient per case (240.5s). The difference is significant for each CRA (paired t-test; P < .0001). On average per case, oncologists opened images of 2.0 lesions and 0.1 reports. In the survey, all 8 participants agreed that LD was intuitive and easy to use. All 4 oncologists strongly preferred LD over traditional workflow and strongly agreed that populating LD with LT data is a value-add to Radiology's service. Conclusions: LD creates a more efficient workflow for computing response assessment that is error-free due to automated propagation of measurement data and gives one-click access to image data. User survey results indicate that the new workflow is feasible and preferred compared to the traditional workflow.