tbuckley/cabot-search huggingface dataset:
A randomized phase II trial of the MET inhibitor tivantinib + cetuximab versus cetuximab alone in patients with recurrent/metastatic head and neck cancer.
Authors: Everett E. Vokes, Francis P. Worden, Douglas Adkins, Julie E. Bauman, Dean Lim, Ammar Sukari, Krishna A. Rao, Stephanie Ann Wagner, Kelly Kevelin Curtis, Barbara J. Gitlitz, Katharine Andress Rowe Price, James Lloyd Wade, Victoria Meucci Villaflor, Jonas A. De Souza, Theodore Karrison, Walter Michael Stadler, Tanguy Y. Seiwert
Journal: Journal of Clinical Oncology (2015)

6060 Background: MET signaling has been proposed as a mechanism of resistance to anti-EGFR therapy. MET expression is common in Head and Neck Squamous Cell Carcinomas (HNSCC) (Seiwert et al, Cancer Res 2009). We compared the oral MET inhibitor tivantinib (ARQ197) (T) in combination with cetuximab (C), with C monotherapy, in patients (pts) with recurrent/metastatic (r/m) HNSCC. Methods: 78 cetuximab-naïve pts after platinum failure were enrolled from 2012-2014, 40 on the T+C arm, and 38 on the C control arm. 31 pts (40%) were HPV-positive/p16-positive oropharyngeal (OP) cancers. T was given orally 360mg BID, C 500mg/m2 every two weeks. Cross-sectional imaging was performed every 8 weeks. Primary outcome was response rate (RECIST 1.1), and secondary outcomes included survival. Results: In 75 pts currently assessable for response, the response rate in the T+C arm was 8.5% (N = 3, including one CR), and 5.3% (N = 2) in the C alone arm (NS). Of note the response rate in HPV-positive/p16-positive oropharyngeal HNSCC pts was 0% in both arms in a combined 31 HPV-positive/p16-positive OP HNSCC. The response rate in HPV-negative pts was 12.5% (T+C)/ 8.5% (C) (NS). Median PFS in both arms was 4 months (NS), median OS 8 months (NS). Both treatments were well tolerated with a trend towards increased hematological toxicities in the T+C arm (12.5% of pts experience grade 3 leukopenia). Conclusions: Tivantinib + Cetuximab given in an unselected population of r/m HNSCC pts does not significantly improve response rate and survival. Consistent with other recent reports (Fayette et al ESMO 2014; Machiels et al ESMO 2014), EGFR inhibitors, including cetuximab appear to be less active/inactive in HPV-positive/p16-positive oropharyngeal HNSCC patients. Clinical trial information: NCT01696955.
Cost and survival analysis before and after implementation of Dana-Farber Clinical Pathways for Patients with Stage IV Non-Small Cell Lung Cancer.
Authors: Yichen Zhang, Belen Fraile, Carole Kathleen Dalby, Tom Nguyen, Julia Nagle, Christine A. Lydon, Michael S. Rabin, Kristen K. McNiff, Joseph O. Jacobson, David Michael Jackman
Journal: Journal of Clinical Oncology (2017)

3 Background: Oncologists face challenges associated with increasing cost and medical complexity. The Dana-Farber Cancer Institute (DFCI) has created a customized clinical pathways program that seeks to prospectively support and guide medical decision-making across our network. It also allows the Institute to track and learn from the medical decisions made. We have analyzed cost and outcomes data from before and after the implementation of Dana-Farber Pathways in our thoracic oncology program. Methods: Our lung cancer group created a customized clinical pathway for the treatment of non-small cell lung cancer (NSCLC). We partnered with Via Oncology to provide a web-based platform for real-time pathway navigation and post-treatment data aggregation. DFCI Pathways for NSCLC went live in January 2014. We identified all patients who were diagnosed with and treated for stage IV NSCLC in 2012 (pre-pathways) and 2014 (post-pathways). Demographics, clinical characteristics, treatments, and clinical outcomes were captured. Costs of care for each patient were determined for one year from the time of diagnosis. Results: We identified a total of 160 Stage IV NSCLC patients diagnosed in 2012, and 210 patients diagnosed in 2014. The pretreatment group had more women (61% vs. 50%) but was otherwise similarly matched in terms of smoking status and presence of targetable changes in EGFR and ALK. The total 12-month cost of care (adjusted for age, sex, race, distance to DFCI, clinical trial enrollment, and EGFR and ALK status) demonstrated a $15,013 savings after the implementation of pathways ($67,050 pre, $52,037 post). Clinical outcomes were not compromised, with no significant difference in median overall survival (10.7 months pre, 11.2 months post; p = 0.08). Conclusions: In an era where comparative outcomes analysis and value assessment are increasingly important, the implementation of a clinical pathways program can provide a means to harness and deploy institutional expertise and track and learn from care decisions. Patients treated after the implementation of a clinical pathways program in lung cancer saw preserved clinical outcomes and a significant decrease in cost of care.
Developing and evaluating new models of care in hematology.
Authors: Tom Kouroukis, Jenna Ratcliffe, Karen Running, Jonathan Sussman
Journal: Journal of Clinical Oncology (2017)

53 Background: The duration of care for patients with hematological malignancies (HM) from diagnosis to discharge can often be five years or longer, during which patients frequently visit their hematologist but may not maintain contact with their primary care physician (PCP). This can result in gaps in the care of non cancer health problems. A number of studies in solid tumors have highlighted the benefits of maintaining contact with the PCP however there has been little published on survivorship care in HM. Objective. Develop and evaluate models of care in hematology that facilitate transition to the PCP where appropriate. Methods: This study used a stepwise approach to inform the development and evaluation of care models. Models were developed using: a literature review; expert opinion; input from patient and PCP focus groups. The survivorship model (SM) was evaluated in a longitudinal, cohort of patients using validated patient surveys: Coordination of Cancer Care Questionnaire; Edmonton Symptom Assessment Scale; EQ5D-QoL. Results: Focus groups were conducted with 26 participants. Patients indicated they would be willing to engage with their PCP if primary care were more confident in their cancer care abilities, and if communication improved between specialty and PCP. PCPs felt care plans should be clear, concise and within their scope. Three new models of care were developed based on level of care need (survivorship, shared, engagement). The SM has been tested with 50 patients who have completed treatment and follow up. Survey results indicated the majority of SM patients: continued to feel well; reported high functioning; had seen their PCP since discharge; were satisfied with the coordination of their care. Fifteen PCPs responded to a follow up survey. PCPs were: satisfied with the SM care plan and aware of the repatriation process to specialty care, if needed. Conclusions: Patient involvement in model design was instrumental in the success of the project. PCPs reported that the tools developed in this pilot enhanced the care experience and provider collaboration. These findings warrant further testing of care models in a comparative study with this complex cancer population.
Weight History and All-Cause and Cause-Specific Mortality in Three Prospective Cohort Studies
Authors: Edward Yu, Sylvia H. Ley, JoAnn E. Manson, Walter Willett, Ambika Satija, Frank B. Hu, Andrew Stokes
Journal: Annals of Internal Medicine (2017)

Background: The relationship between body mass index (BMI) and mortality is controversial. Objective: To investigate the relationship between maximum BMI over 16 years and subsequent mortality. Design: 3 prospective cohort studies. Setting: Nurses' Health Study I and II and Health Professionals Follow-Up Study. Participants: 225 072 men and women with 32 571 deaths observed over a mean of 12.3 years of follow-up. Measurements: Maximum BMI over 16 years of weight history and all-cause and cause-specific mortality. Results: Maximum BMIs in the overweight (25.0 to 29.9 kg/m2) (multivariate hazard ratio [HR], 1.06 [95% CI, 1.03 to 1.08]), obese I (30.0 to 34.9 kg/m2) (HR, 1.24 [CI, 1.20 to 1.29]), and obese II (≥35.0 kg/m2) (HR, 1.73 [CI, 1.66 to 1.80]) categories were associated with increases in risk for all-cause death. The pattern of excess risk with a maximum BMI above normal weight was maintained across strata defined by smoking status, sex, and age, but the excess was greatest among those younger than 70 years and never-smokers. In contrast, a significant inverse association between overweight and mortality (HR, 0.96 [CI, 0.94 to 0.99]) was observed when BMI was defined using a single baseline measurement. Maximum overweight was also associated with increased cause-specific mortality, including death from cardiovascular disease and coronary heart disease. Limitation: Residual confounding and misclassification. Conclusion: The paradoxical association between overweight and mortality is reversed in analyses incorporating weight history. Maximum BMI may be a useful metric to minimize reverse causation bias associated with a single baseline BMI assessment. Primary Funding Source: National Institutes of Health.
Trastuzumab (T) combined with standard chemotherapy in HER+ metastatic bladder cancer (BC) patients: Interim safety results of a prospective randomized phase II study
Authors: P. Beuzeboc, E. Banu, E. Voog, G. Bousquet, F. Priou, G. Deplanque, L. Bozec, J. P. Machiels, J. M. Vannetzel, S. Oudard
Journal: Journal of Clinical Oncology (2007)

15565 Background: Almost 25% of BC patients overexpressed HER2 and 50 to 60% of them are responding to the combination of T with standard chemotherapy (gemcitabine and platinum salt). A prospective, randomized, European phase II study comparing this association with conventional chemotherapy alone is ongoing. Methods: Eligible HER+ BC pts were required to have an advanced and chemonaive bladder cancer and ECOG performance status (PS) 0–2. The aim is to demonstrate a progression-free survival benefit for investigational arm. Sample size was estimated at 126 patients, with a two-sided alpha and beta levels at 5 and 80%, respectively. Treatment-related toxicities were evaluated using CTC-NCI version 2. Fisher exact test was the main statistical method testing differences in percentage of toxicities. Results: Thirty-seven patients were included in 11 centres between February 2004 and December 2006. The planned safety interim analysis was performed after inclusion of 30 patients (15 in each arm). Median age was 59 years (range 46- 80), 93% of patients are men. Seven percent have an advanced disease, 33% have more than one single metastatic site and 83% were PS ECOG 0–1. There were no significant differences between arms concerning hematological and non-hematological all grade toxicities. Severe (grade III-IV) leucopenia, granulocytopenia, anemia and thrombocytopenia were registered in 53, 53, 33 and 60% for combined arm. Grade I-II of diarrhea was slightly more frequent for T arm. There were no differences for alopecia, constipation, nausea and edema. An asymptomatic reduction of the left ventricular ejection fraction was found in one patient in each arm. Conclusions: Combination of T with standard chemotherapy for BC patients was safe. No serious adverse events significant differences were registered, especially concerning T-related cardiac toxicities. The planned interim efficacy analysis is expected after inclusion of 60 patients. No significant financial relationships to disclose.
Exploring changes over time and characteristics associated with data retrieval across individual participant data meta-analyses: systematic review
Authors: Sarah J Nevitt, Anthony G Marson, Becky Davie, Sally Reynolds, Lisa Williams, Catrin Tudur Smith
Journal: BMJ (2017)

<h3>Abstract</h3> <h3>Objective</h3> To investigate whether the success rate of retrieving individual participant data (IPD) for use in IPD meta-analyses has increased over time, and to explore the characteristics associated with IPD retrieval. <h3>Design</h3> Systematic review of published IPD meta-analyses, supplemented by a reflection of the Cochrane Epilepsy Group's 20 years' experience of requesting IPD. <h3>Data sources</h3> Medline, CENTRAL, Scopus, Web of Science, CINAHL Plus, and PsycINFO. <h3>Eligibility criteria for study selection</h3> IPD meta-analyses of studies of all designs and all clinical areas published in English. <h3>Results</h3> 760 IPD meta-analyses which identified studies by systematic methods that had been published between 1987 and 2015 were included. Only 188 (25%) of these IPD meta-analyses retrieved 100% of the eligible IPD for analysis, with 324 (43%) of these IPD meta-analyses retrieving 80% or more of relevant IPD. There is insufficient evidence to suggest that IPD retrieval rates have improved over time. IPD meta-analyses that included only randomised trials, had an authorship policy, included fewer eligible participants, and were conducted outside of the Cochrane Database of Systematic Reviews were associated with a high or complete IPD retrieval rate. There was no association between the source of funding of the IPD meta-analyses and IPD retrieval rate. The IPD retrieval rate of the Cochrane Epilepsy Group has declined from 83% (up to 2005) to 65% (between 2012 and 2015) and the reported reasons for lack of data availability have changed in recent years. <h3>Conclusions</h3> IPD meta-analyses are considered to be the "gold standard" for the synthesis of data from clinical research studies; however, only 25% of published IPD meta-analyses have had access to all IPD.
John Stuart Morris
Authors: Huw Morris
Journal: BMJ (2017)

John Stuart Morris was born in Merthyr Tydfil. He qualified from the Welsh National School of Medicine in 1963. At medical school he met Lucy, who became his wife. After junior hospital posts in Llandough Hospital he pursued a career in gastroenterology and general medicine. He worked on bile acid metabolism with A E Read at the University of Bristol, gaining an MD in 1974. Between 1971 and 1974 he was lecturer in medicine in the liver unit at the Royal Free Hospital, working with Sheila Sherlock, continuing …
“Lung sparing growth”: is the lung not affected by malnutrition?
Authors: Insa Korten, Jakob Usemann, Philipp Latzin
Journal: European Respiratory Journal (2017)

Malnutrition is a major cause of mortality and morbidity in developing countries [1]. It has been reported to play a role in different acute and chronic disease conditions [2–4], including respiratory diseases and lung development [5, 6]. Starting in utero , maternal malnutrition during pregnancy may influence postnatal lung function directly ( e.g. through decreased alveolar number), or indirectly ( e.g. through intrauterine growth retardation, prematurity or low birth weight) [7]. There is clear evidence of detrimental effects of vitamin A deficiency in pregnancy on lung function in childhood [8]. Early postnatal malnutrition was associated with several adverse pulmonary effects and lung injury in animal models, e.g. decreased lung protein and DNA synthesis in the lungs [9], whereas breastfeeding and balanced nutrition is thought to be protective [10, 11]. Furthermore, Vitamin D and C deficiency have been reported to cause deficits in lung function and structure [12, 13]. To summarise, malnutrition potentially influences respiratory health and lung function on multiple levels. "Lung sparing growth": intriguing hypothesis to explain why the lung is not affected by severe acute malnutrition <http://ow.ly/9V5d309M1ho>
Phase 1 trial of gemcitabine/nab-paclitaxel in combination with the autophagy inhibitor hydroxychloroquine in previously untreated patients with metastatic pancreatic adenocarcinoma.
Authors: Mark H. O'Hara, Maryann Gallagher, Ursina R. Teitelbaum, Bruce J. Giantonio, Nevena Damjanov, Arturo Loaiza-Bonilla, Ravi K. Amaravadi, Daniel F Heitjan, Irina Vasilevskaya, Daniel D. Von Hoff, Ramesh K Ramanathan, Dan Laheru, Ana De Jesus-Acosta, Victor E Velculescu, Peter J. O'Dwyer
Journal: Journal of Clinical Oncology (2015)

e15213 Background: Autophagy is important for sustained growth of pancreatic cancer (PDAC) human cell lines and xenograft models. Inhibition of autophagy with drugs such as chloroquine results in tumor growth retardation and increased survival in preclinical models. Hydroxychloroquine (HCQ), an antimalarial drug that inhibits autophagy, has acceptable toxicity at maximal doses in cancer patients (pts). We performed a phase 1/2 study of HCQ in combination with gemcitabine/nab-paclitaxel in patients with metastatic PDAC and here we report the initial phase 1 results. Methods: We enrolled 24 pts with untreated stage IV PDAC - 17M/7F, median age 65 – at three sites (Penn, JHU, TGEN). Two dose levels of HCQ were investigated: 400mg (7 pts) and 600mg (17 pts) BID. Results: The most common adverse events (AEs) were fatigue, nausea, anorexia, and neuropathy. Grade 4 toxicities, including elevated glucose, AST/ALT, and Tbili (1 each), sepsis (2), nausea (1), neutropenia (1), pneumothorax (1), bowel obstruction (1), and limb ischemia (1), were not thought to be related to the addition of HCQ, and therefore not dose-limiting. One pt died of respiratory failure unrelated to treatment. One pt (1st cohort) and 9 pts (2ndcohort) withdrew from the study prior to completion of 2 cycles due to AEs (3), clinical progression (3), pt decision (3), and poor compliance (1) and were included only in the AE assessment. Of 14 evaluable pts by RECIST v1.1, 50% had partial response, 36% had stable disease, and 14% had progressive disease. The median number of cycles was 7.5 (2-17) and median PFS 6.4 months (1.2–15.5 months). TP53 mutation status was obtained on tumor biopsies. We completed Western blot analysis of LC3B-II, a protein that is increased in autophagosome vesicles, showing an increase in LC3B-II expression in PMNs after the start of therapy, suggesting inhibition of autophagy. Conclusions: Full doses of gemcitabine/nab-paclitaxel are well tolerated in combination with HCQ 600mg BID and there is pharmacodynamic evidence of autophagy inhibition with this combination. Enrollment in the randomized phase 2 study with HCQ 600mg BID is proceeding. Clinical trial information: NCT01506973.
Erratum: Inactivation of nuclear factor κB by soy isoflavone genistein contributes to increased apoptosis induced by chemotherapeutic agents in human cancer cells (Cancer Research (August 1, 2005) 65 (6934-6942))
Authors: Y. Li, F. Ahmed, S. Air, P. A. Philip, O. Kucuk, F. H. Sarkar
Journal: Cancer Research (2005)
Tolerance to chemotherapy and /or radiotherapy (Ch/Rxt) in older breast cancer patients
Authors: N. G. Pilnik, C. R. Lazaris, O. G. Mareca, S. Breier, M. M. Nasetta, M. A. Ibero, H. L. Montrull, D. J. Carri
Journal: Journal of Clinical Oncology (2004)

8281 Background: Older women have a high risk of developing breast cancer. They are also more likely to present multiple, comorbid conditions.Besides, age affects the pharmacokinetics of antineoplasic agents and increases the susceptibility to complications. Methods: 103 breast cancer pts, mean age 72, underwent Ch and /or Rxt after diagnosis. Pts selection was conducted using General Geriatric Assessment:18 pts had Basic Activities of Daily Living ( BADL) score A; 47 B; 36 C; 1 D; and 1 E. Based on Instrumental Activity Daily Living (IADL ) the pts had scores 2 (1pt); 4(1pt); 6 (36pts); 7 (47 pts); 8 (18pts). Pfeiffer's questionnaire was used for Cognitive status. Forty four pts had St II;32 St III, and 27 St IV. Pts were divided in two groups: I 65–69 yrs (37) and II > 70 yrs(66). Comorbidities studied were: hypertension, diabetes, arrhythmia, coronary disease and digestive disease. All pts had adequate cardiac, hepatic, renal and bone marrow functions. Toxicities were evaluated following the WHO criteria and studied according to age, comorbidities,BADL and IADL scores and the use of more than 3 drugs apart from Ch. Statistical analysis: Chi Square Pearson, Irwin-Fisher exact tests,odds ratio and Kaplan Meier tables were used. Results: The most common toxicities were leukopenia: 71,7 %, anemia 71 %, digestive 59,5%, and infection 39,6%. There was no correlation between age and the most frequent toxicities, BADL and IADL scores. No relation between both age groups and comorbidities was found. There was no association between age and toxicity grade, irrespective of toxicity type. Low and mild toxicities did not affect survival, but high toxicities did. We found improvement of QoL when symptoms and BADL were analyzed (p=0.0001, p= 0.0001). Conclusions: 1-Toxicities in both age groups allowed us to continue the treatment in most patients. 2- Ch/Rt in older breast cancer pts with controlled comorbidities is feasible. No significant financial relationships to disclose.
Structuring supplemental materials in support of reproducibility
Authors: Dov Greenbaum, Joel Rozowsky, Victoria Stodden, Mark Gerstein
Journal: Genome biology (2017)

Supplements are increasingly important to the scientific record, particularly in genomics. However, they are often underutilized. Optimally, supplements should make results findable, accessible, interoperable, and reusable (i.e., "FAIR"). Moreover, properly off-loading to them the data and detail in a paper could make the main text more readable. We propose a hierarchical organization for supplements, with some parts paralleling and "shadowing" the main text and other elements branching off from it, and we suggest a specific formatting to make this structure explicit. Furthermore, sections of the supplement could be presented in multiple scientific "dialects", including machine-readable and lay-friendly formats.
Gene-expression profile of colorectal adenocarcinoma tissues identified by gene microarray analysis
Authors: F. Franceschi, L. Fini, A. Manno, E. Carloni, M. A. Zocco, S. Di Caro, A. Picciocchi, C. Coco, G. Gasbarrini, A. Gasbarrini
Journal: Journal of Clinical Oncology (2004)

3651 Background: Several genes are differentially expressed during the multistep process of colorectal carcinogenesis. The human U133A array (Affymetrix) provides a representation of 22.000 genes. Aim of the study was to identify the gene expression of colorectal adenocarcinoma tissues compared to the normal mucosa. Methods: RNA was extracted from 3 samples of moderately differentiated sporadic rectal adenocarcinoma and 3 samples of normal rectal mucosa obtained from the same patients and hybridized against the human U133A array set. Gene expression of tumoral tissues and normal samples was compared; a minimum of 3 times fold differential expression among the same genes in neoplastic and normal samples was considered as significant. Real-time PCR (Roche, Manheim) using the same RNA was also performed on a pool of either up- or down-regulated randomly-selected genes to validate the results. Results: Approximately 550 genes showed a significant differential expression in adenocarcinomas compared to normal mucosa. 537 genes were upregulated while 13 genes were downregulated in neoplastic tissues. The up-regulated genes included angiogenic factors (VEGF, PD-ECGF, EGF), markers of proliferation (PCNA), tumoral markers (CEA, ACE), genes involved in chemotherapy activity (Farnesyl-transferase, Topoisomerase-1) and several other genes of unclear function. The down-regulated genes included transcription factors (SPIB), adhesion molecules (Desmin), anti-oxidant (GPX3) and other genes of unclear activity. RT-PCR confirmed the results obtained by the microarray analysis.Conclusions: Colorectal cancer tissues show a different gene expression compared to the normal mucosa. This differential expression includes several known genes involved in cell growth, angiogenesis, transcription and proliferation as well as other genes of unclear activity, which have never previously been associated with cancer. The identification of a panel of genes specifically expressed in neoplastic tisssues may provide a new tool for the molecular diagnosis of colorectal cancer and furnish new molecular targets for innovative therapeutical strategies. No significant financial relationships to disclose.