tbuckley/cabot-search huggingface dataset:
Does shared decision making for PSA screening empower patients?
Authors: James Austin Talcott, Maureen Bezuhly, Gina Aharanoff, Jessica Herzstein, Michael P. Osborne, Manjeet Chadha
Journal: Journal of Clinical Oncology (2017)

e549 Background: Participant characteristics affect shared decision making. In a randomized trial of physician (MD) educational interventions to improve cancer screening guideline compliance, we studied patient (PT) and MD recall of discussions and how PT characteristics affected recall. Methods: In a cluster-randomized trial of educational supports for MDs, we are enrolling an age- (30-89 years) and sex-stratified sample of 216 PTs who underwent a physical examination at two urban hospitals, 18 for each of 12 primary care MDs. Screening guideline formatting (color-coding) and academic detailing were randomly assigned in a 2x2 design. Immediate post-encounter surveys recorded PT and MD recall of screening discussions. Results: Of the first 174 participants, 92 were men. PTs were diverse (69% white) and well educated (73% college degree). When MDs reported a prostate specific antigen (PSA) screening discussion, 32% of PTs did not, and 26% of MDs disagreed when PTs reported the discussion occurred. Further, when the MD reported recommending screening, 26% of PTs disagreed, and 33% of MDs disagreed when their patients reported a recommendation. Overall, agreement between all PTs and MDs on whether screening was recommended was fair (kappa = 0.29) but there was no agreement for PTs over 70 years (kappa = -0.03). PTs reported more elements of shared decision making than MDs (data not shown). When both PT and MD or the MD alone reported that all elements of shared medical decision making had occurred, agreement on whether screening was recommended improved (kappa = 0.54 and 0.45, respectively). When PTs disagreed with their MD, they more often reported recommending for screening not against (11 vs. 4). Conclusions: In a highly educated, diverse PT population, PTs and MDs surveyed immediately after their encounter often disagreed on whether PSA screening was discussed and recommended. Disagreement was worse with older PT age but improved when both PT and MD or the MD alone reported all shared decision making elements. Clinical trial information: NCT02430948.
Identification of MEN1 mutation via next generation sequencing in the Cancer Treatment Centers of America (CTCA) database.
Authors: Eyal Meiri, Kim Kramer, Navneet Dhillon, Altovise T. Ewing, Giuseppe Del Priore
Journal: Journal of Clinical Oncology (2015)

e22083 Background: MEN1 is a syndrome associated with increased risk of non-endocrine related malignancies, including breast cancer and lung cancer. We attempted to correlate the MEN1 gene alteration incidence and the allelic frequency (AF) the MEN1 mutations detected. Methods: A retrospective review of 15 specimens (6 breast, 4 lung, 2 pancreas, 1 small intestine, 2 unknown primary cancers) with MEN1 gene alteration detected by Foundation OneTM (Foundation Medicine, Inc., MA) next generation sequencing (NGS) test was performed. DNA was extracted from biopsy specimens and sequencing was performed per previously described methodology. AF is calculated as percent of reads at the position of a variant, which support the alternate allele. The reported value is not corrected for the specimen tumor content. Results: N = 2361; Breast Cancer N = 414 (1.5%); Lung Cancer N= 369 (1.1%). Conclusions: MEN1 mutations are found in a variety of neoplasms with the majority in breast and lung carcinomas. Additional studies are underway to determine if MEN1 alterations may have a more substantial role in carcinogenesis than previously surmised. Mutation Pathology AF MEN1 Q410* Breast Neuroendocrine Carcinoma 41% MEN1 R521fs*43 Small Intestine Adenocarcinoma 25% MEN1 L278f2* Breast Neuroendocrinc Carcinoma 63% MEN1 loss Pancreas neuroendocrine tumor pNet 0 MEN1 R521fs*15 Lung large cell neuroendocrine carcinoma 44% MEN1 Q64* Breast Carcinoma 13% MEN1 P250fs*36 Lung atypical carcinoid 44% MEN1 605fs*12 + Lung Adenocarcinoma 11% MEN1 R465* Breast Carcinoma 52% MEN1 E473fs*91 Unknown Primary undifferentiated neuroendocrine carcinoma 89% MEN1 L175fs*21 Breast Carcinoma 38% MEN1 Q458fs*77 Breast Carcinoma 15% MEN1 N127fs*57 Pancreas neuroendocrine carcinoma 61% MEN1 rearrangement (exons 1-5) Lung adenocarcinoma NA MEN1 Q447* Unknown Primary Melanoma 38%
Impact of care at NCI-designated comprehensive cancer centers (NCICCC) on outcome in adolescents and young adults (AYA) with central nervous system tumors (CNSt).
Authors: Julie Anna Wolfson, Can-Lan Sun, Tongjun Kang, Smita Bhatia
Journal: Journal of Clinical Oncology (2013)

6537 Background: AYA (15-39y) have not seen survival improvement as in younger or older ages with similar cancer diagnoses, leaving an AYA Gap. Pediatric protocol use is associated with superior survival among 15-21y-olds, but impact of site of care for complex diseases with poor prognosis (such as CNSt) that require multidisciplinary, evidence-based care available at NCICCC, are unstudied. Methods: We constructed a cohort of 746 AYA with newly diagnosed CNSt, reported to the LA cancer registry from 1998-2008; 133 (18%) were treated at the 3 NCICCC in LA county. We examined clinical (WHO grade, diagnosis (dx) year, site of care) and demographic (age at dx, gender, SES, insurance, race/ethnicity) variables univariately; we included only those with p&lt;0.1 in the final multivariable model (retaining WHO and NCICCC). Analysis was stratified by time from dx (≤2y, n=746; &gt;2y, n=493) to examine impact of care at NCICCC among AYA with aggressive disease (resulting in death within 2y from dx) vs. those who survived 2y from dx – representing disease likely amenable to new strategies for control. Results: 5y overall survival (OS) was 59% and did not differ by site of care (p=0.2). Multivariable analysis restricted to the first 2y revealed an increased risk of death among those with high WHO grade (HR 4.7, p&lt;.0001); public/no insurance (HR 1.7, p=0.0006); and African American/Asian (HR 2.1, p=0.0006) or Hispanic (HR 1.4, p=0.08) origin; site of care did not impact mortality. Among 2-y survivors, high WHO grade (HR 1.7, p=0.002) continued to be associated with increased risk of death. However, receipt of care at non-NCICCC site (HR 1.6, p=0.056) was also associated with increased risk of death. Examination of access to care at NCICCC revealed that after adjusting for WHO grade and gender, older age (22-39y (OR 0.3, p&lt;0.0001), low SES (OR 0.6, p=0.04), and non-white ethnicity (OR 0.5, p=0.004), decreased likelihood of care at NCICCC. Conclusions: Population-based data reveal better OS in 2-y AYA survivors of CNSt receiving care at NCICCC. Older AYAs from low SES and non-white backgrounds are less likely to use NCICCC. AYA barriers to accessing NCICCC care are currently being explored.
Reuben Frederick Payne
Authors: Barbara Payne
Journal: BMJ (2017)

Reuben Frederick Payne (“Freddie”) was born in Lavenham, Suffolk, where his father was a general practitioner. He attended Asgarth Prep School and then Gresham’s School in Holt. During the second world war, the family lived in Plymouth. Freddie then went to Caius College, Cambridge, where he did his premedical training.

He studied medicine at Charing Cross Hospital (now Imperial College). During those years he was in the Home Guard, as were all medical students. Having completed his clinical training, he was called up for national service in the Royal Air Force, …
A phase II study of single agent mocetinostat, an oral isotype-selective histone deacetylase (HDAC) inhibitor, in patients with diffuse large cell B-cell (DLBCL) and follicular (FL) lymphomas.
Authors: Michael Crump, Charalambos Andreadis, Sarit E. Assouline, David Rizzieri, Amanda Copeland, Richard H. C. Van Der Jagt, Susan Fox, Gregory K. Reid, Jeffrey M. Besterman, Robert E. Martell, Anas Younes
Journal: Journal of Clinical Oncology (2013)

8535 Background: Mocetinostat (MGCD0103) is an orally available, isotype-selective, non-hydroxamate HDAC inhibitor targeting HDACs 1,2, 3 and 11 with single-agent activity in Hodgkin’s lymphoma and in AML and MDS (in combination with 5-azacitidine). More than 430 patients have been treated to date. Methods: This open-label, phase II trial enrolled patients with DLBCL and FL. Patients received mocetinostat at doses ranging from 70-110 mg 3x/wk every 28 days. Anticancer activity, safety, pharmacokinetics and pharmacodynamics were evaluated. Results: Sixty-nine patients with DLBCL (n=41) and FL (n=28) were enrolled for treatment at starting doses of 85-110 mg. Median age was 62 years (range: 32 to 81). Median duration of treatment was ~3 months (range: &lt;1 to 24). Objective response rate in DLBCL and FL, respectively, was 7/41 (17%; including 2 unconfirmed PRs) and 3/28 (11%; including 1 CR). Median time to response was 2.0 mos (range 1.7-21.0) and 5.3 mos (range 4.3-6.0) respectively. Stable disease was achieved by 13/41 (32%) and 14/28 (50%), respectively, for a disease control rate of 49% and 61%, respectively. Mean duration of SD in patients with DBLCL was ~4.5 mos (range 2-12 mos), with 10 patients remaining stable for ≥3 mos. Among FL patients, mean duration of SD was approximately 4.1 mos (range 1.7-13 mos), with 9 patients remaining stable for ≥3 mos. The FL CR occurred in a 62-year-old female with paratracheal, subcarinal and portal target lesions who achieved a PR after 4 cycles and CR after 12 cycles that persisted through the remaining 4 mos on study. Study drug was discontinued for adverse events in 19/69 (28%). Fatigue, weight loss or anorexia were most common (n=4 each). A total of 26 drug-related SAEs were reported among 12 patients (17%; 1-6 events per pt). There were no drug related deaths. Enrollment is complete and final data will be presented. Conclusions: Single-agent mocetinostat has activity in DLBCL and FL. Fatigue, gastrointestinal, and cardiac symptoms are the most common adverse events resulting in discontinuation of dosing. Based on the acceptable tolerability and clinical activity further development is warranted. Clinical trial information: NCT00359086.
Relationship between positive sentinel node (SN) and micrometastases (mMTS) or isolated tumor cells (ITC) with breast tumor pathological features.
Authors: Isabel Calvo, Ana Suárez, Francisco Jose Perez, Maria Fernandez Abad, Jose M Cardenas, Lina García, Paloma Alonso, Cristina Miro, Paloma Quevedo, Manuela Parras, Cristina Marquez, Mercedes Herrero, Paula Buelga, Isabel Rodriguez, Jesika Skaarup, Maria F Chereguini, Manuel Marcos, Ana Cecilia Contreras, Manuel Hidalgo, Laura García-Estevez
Journal: Journal of Clinical Oncology (2012)

e11517 Background: Aim:To study the relation of positive(pos) SN and mMTS or ITC in negative(neg) SN at surgery with tumor pathological(pathol) features (grade;carcinoma type;Ki67;Her2;hormonal status;tumor size). Methods: Cohort of 271 patients with clinically and ultrasonographically node-neg pT1-2 breast cancer and high grade or extended intraductal who received breast cancer surgery with SN biopsy alone in the last 2 years was studied. No previous chemotherapy was administered. Hormone(ER/RP) and Ki67 status were analyzed by inmunohistochemistry(IHC) while HER2 by FISH. Presence of mMTS and ITC were studied by IHC(AE1-AE3). Statistical analysis was conducted to ascertain significant relation among pos-SN or detection of mMTS/ITC in neg-SN and each of the tumor pathol features (test U-Mann-Whitney). Results: Data from 263 patients were analyzed (28 pos-SN;235 neg-SN;8 technique failures). Carcinoma type: Ductal (158;60%);lobular (46;17.5%);in-situ(53;20.2%);others(6;2.3%). Infiltrative cancer:(56% grade 2;20% grade 3;10% Her2+;9% triple-neg;81% pos-RE/RP). In-situ:(28% grade 2;64% grade 3;39% Her2+;55% pos-RE/RP). Mean pathological size 16.2mm(1-118) for infiltrative tumor and 20.1mm(1-90) for in-situ. Mean of SN found at surgery 1.98(1-5). In neg-SN, 35 cases with mMTS(14;6.2%) or ITC(21;9.2%) were found. No statistically significant relation was established between the finding of mMTS or ITC and any of the pathol features at in-situ or infiltrative tumors. In pos-SN a statistically significant relation between pos-SN and pathol size was found (p=0.003; mean pathol size 20.16mm and 15.69mm for pos and neg-SN). Conclusions: A significant relation was established with pathol size and pos-SN. In patients with neg-SN no significant relationship was found between detection of mMTS or ITC and the pathol features of the tumor.
Efficacy and safety of ustekinumab in Japanese patients with severe atopic dermatitis: a randomized, double-blind, placebo-controlled, phase II study
Authors: H. Saeki, K. Kabashima, Y. Tokura, Y. Murata, A. Shiraishi, R. Tamamura, B. Randazzo, K. Imanaka
Journal: British Journal of Dermatology (2017)

Ustekinumab, a fully human monoclonal antibody against interleukin-12/23, may potentially be effective for severe atopic dermatitis (AD) treatment.To evaluate efficacy and safety of ustekinumab 45 mg and 90 mg in patients with severe AD.In this randomized, placebo-controlled, phase II study, Japanese patients (aged 20-65 years) with severe or very severe AD entered a 12-week double-blind treatment period during which they received (1 : 1 : 1) ustekinumab 45 mg, 90 mg or placebo subcutaneous injections at weeks 0 and 4, with follow-up until week 24. The primary efficacy end point was percentage change from baseline in Eczema Area and Severity Index (EASI) score at week 12. Major secondary efficacy end points included the proportion of patients achieving EASI 50, EASI 75, Investigator's Global Assessment score 0-1, change from baseline Atopic Dermatitis Itch Scale and Dermatology Life Quality Index.A total of 79 patients were randomized [ustekinumab 45 mg (n = 24), 90 mg (n = 28), placebo (n = 27)]. Ustekinumab treatment showed nonsignificant improvement in least square mean change from baseline EASI score at week 12 [45 mg: -38·2%, 95% confidence interval (CI) -21·02-19·51; P < 0·94 and 90 mg: -39·8%, 95% CI -21·84-17·14; P < 0·81] vs. placebo (-37·5%). A nonsignificant improvement in major secondary efficacy end points was observed in both ustekinumab groups vs. placebo. The most common treatment-emergent adverse events were nasopharyngitis and worsened AD (higher in placebo vs. ustekinumab groups).Ustekinumab 45 mg and 90 mg did not demonstrate meaningful efficacy in Japanese patients with severe AD. The treatment was generally well tolerated.
Molecular screening for cancer treatment optimization (MOSCATO 01) in pediatric patients: First feasibility results of a prospective molecular stratification trial.
Authors: Birgit Geoerger, Frederic Deschamps, Stephanie Puget, Valerie Koubi-Pick, Ludovic Lacroix, Philippe Vielh, Pascale Varlet, Thierry De Baere, Francisco Bautista, Leslie Baker Tsambou, Dominique Valteau Couanet, Maud Ngo-camus, Marie-Cécile Le Deley, Veronique Minard-Colin, Jacques Grill, Laurence Brugieres, Christelle Dufour, Nathalie Gaspar, Gilles Vassal, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2014)

10050 Background: This feasibility study intends to characterize genomic alterations in recurrent tumors of an individual pediatric patient in order to select a targeted therapy approach. Methods: Pediatric patients with recurrent or refractory solid tumor were proposed to undergo on-purpose tumor biopsy or surgical resection for molecular characterization. Biopsies were obtained using 18G needles under ultrasound, CT or MRI control from primary tumor or metastatic sites. DNA extracted from fresh samples was analyzed by CGHarray 180K (if ≥ 50% tumor cells in the sample) and by sequencing for 74 target genes (if ≥ 30% tumor cells). A panel of scientists and clinicians reviewed results to determine biological signification of the alteration and match patients to the most relevant targeted therapy available (mainly in early clinical trials). Results: From December 2012 to January 2014, 12 patients were consented; 3 were screening failures. Nine enrolled patients with a median age of 7 years (range, 3-18) and a median of 3 previous treatment lines underwent dedicated intervention. Six patients (rhabdomyosarcoma (2), osteosarcoma, angiosarcoma, cervical clear cell adenocarcinoma, high-grade glioma) had biopsy, two (medulloblastoma, PNET) underwent neurosurgical resection; one with leukemic Burkitt lymphoma had blood sample for analysis. Percentage of tumor cells per sample ranged between 50 and 90% in 8 out of 9 patients. Median time between biopsy/surgery and molecular results was 21 days (14-46). At least one actionable target was identified in 6 patients (75%). Genetic alterations encompassed CDK4, EGFR, MYCN, MDM2, AR amplification, ERBB4, FGF, FGFR2, TCR gain, PTEN loss, PI3K and TP53mutation/deletion. Two patients received an adapted targeted therapy; the others could not be treated with a matched therapy due to rapid tumor progression (1) or lack of a pediatric trial (3). Conclusions: High throughput molecular analysis of recurrent/refractory malignancies in pediatric patients is feasible. Presence of multiple alterations and limited access to targeted agents within pediatric clinical trials remain the main limiting factors. Clinical trial information: NCT01566019.
Effect of nerve growth factor administered as eye-drop on visual function in children with optic glioma-associated visual impairement: A controlled, cross- over clinical trial.
Authors: Riccardo Riccardi, Antonio Chiaretti, Daniela Rizzo, Marco Piccardi, Anna Dickmann, Ilaria Lazzareschi, Antonio Ruggiero, Cesare Colosimo, Annabella Salerni, Luigi Manni, Gaspare Guglielmi, Benedetto Falsini
Journal: Journal of Clinical Oncology (2014)

10054 Background: To date, no specific therapy is available for visual dysfunction associated with optic pathway glioma (OPG). The aim of this study was to evaluate the effects on visual function of murine nerve growth factor (NGF) administered as eye drop in children with OPG and visual impairment. Methods: A controlled randomized double-blind study (EudraCT 2011-003030) was conducted in 18 pts (age range 2-23 yrs , median age 10 yrs) with OPG, off-therapy with stable disease, and visual impairment. NGF eye-drop was prepared with standards required for human use by Policlinico Gemelli Pharmacy. A single 10-day course of 1 mg topical murine NGF or placebo was administered. Assessment included visual acuity, visual field, optical coherence tomography, Ganzfeld electroretinogram photopic negative response (PhNR), and visual evoked potentials (VEPs) at baseline and 15, 30, 90 and 180 days post treatment. Brain MRI was performed at baseline and at 180 days post-treatment. Following the double-blind trial, a cross-over treatment with NGF was also performed, in open label, for patients originally receiving placebo. Results: Ten pts received placebo and eight NGF. Drug was always well tolerated. In treated pts there was an improvement of visual field by 50% (p=0.02) and 40% (p=0.05), compared to a 14% and 5% increase in the placebo group, at 30 and at 90 days post-treatment, respectively. There was a median VEP amplitude increase from baseline, compared to placebo group, at 30 days (p < 0.05). In the cross-over testing, following NGF treatment, visual field and VEP amplitudes improved from either baseline or from the values recorded after placebo . The overall NGF response rate in all 18 patients was 75% (95% CI : 65-80 % ) for visual field improvement. Conclusions: NGF administration appears to be an effective and safe treatment in patients with OPG-associated visual impairment. Clinical trial information: 2011-003030.
Diffusion of stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) in the Medicare population, 2007-2009.
Authors: James B. Yu, Pamela R. Soulos, Laura D. Cramer, Roy H. Decker, Anthony W. Kim, Cary Philip Gross
Journal: Journal of Clinical Oncology (2014)

7575 Background: Although the standard of care for early stage NSCLC is surgery, SBRT has emerged as an alternative for elderly patients who refuse surgery or are medically inoperable. As patterns of care may evolved since the introduction of SBRT for NSCLC in 2003, we investigated the adoption of SBRT vs. surgery in the Surveillance, Epidemiology, and End Results (SEER)– Medicare database in the years 2007-2009. Methods: We identified patients age > 67 who were diagnosed with stage I NSCLC from 2007 through 2009 and had undergone SBRT or surgery based on Medicare claims. Patient and hospital referral region (HRR) characteristics were recorded. Disability status (DS), a validated claims-based proxy for poor performance status, Elixhauser comorbidity index, and life expectancy (LE) were calculated using Medicare claims 12 months prior to diagnosis. The trend in receipt of SBRT was assessed for different categories of age, DS, and LE for patients whom SBRT was available in their HRR of residence. Results: There were 383 SBRT patients and 3,852 surgery patients. The proportion of patients undergoing SBRT rose from 4.4% in 2007 to 12.7% of treated patients in 2009 (p<.001). Patients who were older (Age 85-94; Odds Ratio (OR) vs. age 66-69: 5.98 [95% CI 3.34-8.08] , p<.001), female (OR 1.49 [95% CI 1.16-1.91], p=.002), with higher comorbidity (3+ conditions vs. 1: OR 4.23 [95% CI 2.97-6.02], p<.001) or disability status (Highest DS quartile vs. lowest OR 1.96 [95% CI 1.41-2.72],p<.001) were significantly more likely to undergo SBRT. The proportion of patients receiving SBRT (vs. surgery) increased in particular for patients with a shorter LE: SBRT use among patients with LE < 5 years from 11.8% in 2007 to 35.0% in 2009. In comparison, SBRT use for LE ≥ 5 years increased from 3.9% to 10.6% in the same period. Conclusions: The use of SBRT has disseminated rapidly into the care of older persons with early localized lung cancer, particularly those shorter life expectancies. Prospective studies are needed to identify patient and treatment factors associated with optimal outcomes.