tbuckley/cabot-search huggingface dataset:
Code of conduct for personnel involved in whole-genome sequencing.
Authors: Eva C. Winkler, Hanno Glimm, Klaus Tanner, Christof V. Kalle
Journal: Journal of Clinical Oncology (2014)

e22193 Background: In cancer research, whole genome sequencing is promising and widely used in order to understand the molecular basis of tumor growth and to develop targeted therapies. However, genomic research also raises ethical questions about the handling of incidental findings, confidentiality and sharing of genetic data and the informed consent process. Methods: We developed specific recommendations for each of the ethically controversial issues and integrated them into a institution wide code of conduct. This code of conduct is informed by the interdisciplinary EURAT Project in Heidelberg which aims at an ethically and legally informed practice for bio-based genomic research. Results: The code includes the following specific recommendations. We tailor informed consent process to the needs of our patients. Hence, patient preferences for the return of incidental findings should be registered during the informed consent discussion. We will re-contact patients for offering participation in clinical trials or for returning validated cancer-related results depending on the stated preferences of the patient. We do not actively search for non-cancer related mutations in individual patients’ non-cancerous genome. We institutionalize and consult with a Returnable Result Committee if a result leaves the diagnostic context of the study. The germ-line row data will be stored disconnected from networks that are accessible via the Internet. Conclusions: A thorough informed consent process and this code of conduct are elements of a best-practice guideline and should inform the conduct of all employees at our center concerned with the handling of sensible genetic data. These recommendations can be used to inform and stimulate policy development at other centers as well.
Chromatin dynamics meet cancer: Chromatin protein PC4 in genome organization and breast cancer manifestation.
Authors: K. S. Gopinath, Sujata Kumari, Sindhura Gopinath, Akshay Bhat, Tapas Kumar Kundu, Shivananda Swamy
Journal: Journal of Clinical Oncology (2014)

e22073 Background: Multifunctional chromatin proteins play important roles in the regulation of chromatin dynamics and thereby the fine tune the underlying gene expression and repair. Human Positive transcriptional co-activator 4, PC4, is a highly abundant multifunctional nuclear protein involved in several cellular functions which include chromatin compaction/organization, transcriptional co-activation and DNA repair. Methods: Originally discovered as a positive transcriptional co-activator, PC4 was found to be a p53 responsive gene. PC4 interact with p53 and positively regulates p53 function, nearly qualifying it also as tumor suppressor. Remarkably, it was discovered that, PC4 is a bonafied component of chromatin and possesses a histone interaction ability which is essential for its chromatin compaction function. Silencing of PC4 by means of siRNA as well as lentivirus mediated stable knockdown, dramatically alters the transcription activation related epigenetic marks and thereby a huge array of genes.PC4 knockdown cells show remarkable defects in cell cycle, genome size, and also in nuclear architecture, which resembles highly progressive cancerous cells. Results: Significantly, it was found that PC4 is down regulated in all types of Breast Cancer samples collected across the globe. The cause and functional consequences of this down regulation of PC4 is being investigated. Conclusions: The present work signifies involvement of chromatin associated nonhistone protein in cancer manifestation and can be interpreted as contribution of the abnormal chromatin in the cancer manifestation.
A translational phase 2 study of cabozantinib in men with metastatic castration resistant prostate cancer with visceral metastases with characterization of circulating tumor cells and large oncosomes.
Authors: Edwin M. Posadas, Mourad Tighgohart, YI-TSUNG LU, Dolores Di Vizio, David M. J. Hoffman, Leland Green, Margarit Sievert, Amy Oppenheim, Nancy P. Moldawer, Beatrice Knudsen, Michael Freeman, Neil Bhowmick, Andre Rogatko, Hsian-Rong Tseng, Leland WK Chung, Robert A. Figlin
Journal: Journal of Clinical Oncology (2014)

e16080 Background: Cabozantinib (XL184) is a potent multi-targeted tyrosine kinase inhibitor (TKI) that is under active investigation in several malignancies including prostate cancer (PC). The mechanism of action in PC has not been well characterized at this time. While considerable attention has been given to the impact of this agent on Tc-bone scans, less is known about its activity in men with visceral metastases. Methods: This study was designed as a single arm phase 2 study of cabozantinib 60 mg daily for men with visceral disease. The primary endpoint of this study is clinical benefit rate at 12 weeks (CBR12) which included stable disease and radiographic response. PSA was not used as an endpoint. Beyond standard clinical assessments, blood and urine were collected for circulating tumor cell (CTC) assessments using CellSearch (CS) and NanoVelcro (NV) chips and large oncosome selection. Biopsies before treatment and at progression are being collected when possible. Circulating tumor cell RNA and large oncosome content were profiled at baseline and 2 weeks for all patients. Results: Eight patients have been treated of the anticipated 40 patient cohort. 13% had pulmonary metastatic lesion; 88% had hepatic metastases; 88% had concurrent osseous metastases. CBR12 was 80% at the time of this report. Discordant responses were noted between visceral metastases and bone scans. Grade 3 toxicities included hypertension, hand-foot syndrome, GGT, and diarrhea. CTC numbers by NV and CS declined within 2 weeks and increased at progression. Updated results of CTC and oncosome analysis will be presented including alterations in MET and SChLAP1expression. Conclusions: Cabozantinib is a TKI with activity in PC even in men with visceral metastasis who are typically considered to have more aggressive disease. The activity in the viscera appears to be lower than that seen in osseous metastases. Further understanding of the biology of cabozantinib based on CTC, oncosomes, and tissue studies will refine our use of this active agent. Clinical trial information: NCT01834651.
Outcome of childhood acute lymphoblastic leukemia: A single center experience from India.
Authors: Rajat Sharma, Yogi Raj Chopra, Mohammed Ramzaan, Satyendra Katewa, Satya Prakash Yadav
Journal: Journal of Clinical Oncology (2014)

e21001 Background: Outcome reports of childhood acute lymphoblastic leukemia (ALL) are lacking from India. Here we report a single centre experience. Methods: Outcome data of children diagnosed with ALL over a period of 7yrs (Jan 2006-Dec 2013) was analyzed retrospectively. Results: A total of 61 (53 B-cell, 8 T-cell) patients were evaluated. Mean age at presentation was 7.2 yrs (1 to 18 yrs). Male to Female ratio was 2:1.National Cancer Institute risk stratification was standard in 35, high 23 and very high in 3 patients. 35 were treated on BFM 95 protocol and 26 on UK ALL XI protocol. Cytogenetic analysis was possible only in 40 children. Twenty had normal cytogenetics, 14 hyperdiploidy (13 B cells, one T cell) and 6 had pseudodiploidy (B cell ALL). Molecular analysis was positive for BCR-ABL in 5, TEL-AML in 5 and MLL rearrangement in 1. Eight abandoned therapy. Of the remaining 53 patients 49 are alive with a mean follow up of 35.2 months. Of these 37 have completed treatment and 12 are on various phases of treatment. Ten children relapsed at median of 34 months (12 to 57 months). Relapsed were very early in 4, early in 2 and late in 4. All relapses except one were in high or very high risk (BCR-ABL) category. All were treated on BFM-REZ-96 relapse protocol. Due to cost constraints and non availability of donors, only 3 relapsed patients underwent allogeneic bone marrow transplant and are alive, 4 are still on chemotherapy, 2 died and one abandoned therapy. For the entire cohort of 61 patients event free survival is 65% and overall survival (OS) is 83% at 35.2 months of mean follow up. Conclusions: Our results are encouraging despite lesser prevalence of tel-aml in our cohort. Barriers like treatment abandonment are yet to be overcome.
Recurrence and survival analysis of robotic versus traditional laparoscopic staging of endometrial cancer in a Medicare population.
Authors: Joshua Garrett Cohen, BJ Rimel, Christie Y Jeon
Journal: Journal of Clinical Oncology (2014)

e16544 Background: Uterine cancer is the most common gynecologic malignancy in the United States. Prospective evidence exists which supports the use of traditional laparoscopic staging in the management of uterine cancer. With the advent of robotic surgery, many surgeons have transitioned to use of this technology. There is a paucity of data comparing outcomes between robotic and traditional laparoscopic staging. Our objective was to compare rates of disease recurrence and survival in patients with endometrial cancer who undergo robotic staging versus standard laparoscopy. Methods: We employed data from the linked SEER registry and Medicare Claims database to extract data on the method and timing of laparoscopic hysterectomy in patients with endometrial cancer from September 2008, when a Medicare bill for robotic laparoscopy was first claimed. Patients were retrospectively followed until December 2010. We examined the association of robotic laparoscopy with recurrence and survival employing Cox regression, adjusting for age, race, stage, grade, chemotherapy, and radiation. Results: Of 894 patients, 446 (50%) and 448 (50%) received traditional and robotic laparoscopy, respectively. 562 (63%) were aged 65-74, 273 (31%) were aged 75-84, and 59 (6.6%) were aged ≥85; those who underwent received robotic surgery were more likely to be in 65-74 age group (p<0.02). The majority (89%) was white and there was no difference in race by method of laparoscopy. Stage I, II, III, and IV disease were found in 75%, 5.8%, 15%, and 1.5% of women respectively, while 3.6% had an unknown stage. Median follow-up time was 17.6 months (interquartile range, 13.7, 21.8) for the robotic group and 18.9 months (interquartile range, 14.3, 22.8) for the traditional laparoscopic group. In multivariable analysis, there were no significant differences in tumor recurrence or survival when comparing robotic to traditional laparoscopic staging: HR 0.99 (95% CI, 0.71-1.37) and 1.62 (95% CI, 0.90-2.91). Conclusions: In this cohort of elderly patients, robotic surgery in the initial surgical management of endometrial cancer has equivalent tumor recurrence rates and overall survival compared to traditional laparoscopy.
Biosimilar G-CSF Versus Originator G-CSF for Autologous Peripheral Blood Stem Cell Mobilization: A Comparative Analysis of Mobilization and Engraftment
Authors: Julie Stakiw, Waleed Sabry, Mohamed Elemary, Mark J. Bosch, Pat Danyluk, Vibhuti Aggarwal, Prosanta Mondal
Journal: Blood (2018)
Free-radical processes in multifocal colon cancer tissue.
Authors: Michail L. Maleyko, Elena Frantsiyants, Yuri Gevorkyan, Ekaterina Komarova, Andrey Dashkov, Vladimir A. Dontsov
Journal: Journal of Clinical Oncology (2014)

e14636 Background: Dissonance in the cascade of natural antioxidant enzymes results in abnormalities in the normal disposal of reactive oxygen species (hydroxyl anion radical, responsible for heterogeneity of tumor tissue, in particular), changes in transcription factors controlling apoptosis processes. As tumor emergence and growth are connected to changes in cell programs, studies of balance in system “lipid peroxidation-antioxidants” in neoplasm tissue are relevant. Methods: Free-radical processes in tumor and intact tissue taken during the operation from 90 patients with solitary, synchronous and metachronous colon cancer aged 30-87 years were analyzed. All the patients had adenocarcinoma (G2 mostly). Results: Content of conjugated dienes in multifocal colon cancer tumor tissue was increased by 2,6 times in solitary cancer, 2,5 times in synchronous cancer, 1,6 times in metachronous cancer. MDA level was decreased on average by 2,3 times in all cases. It was accompanied by decreased content of antioxidant vitamins in tumor tissue. Thus, vitamine A level in solitary, synchronous and metachronous colon cancer was decreased by 31,3%, 45,5%, 26,7% respectively, vitamine E level – by 20%, 24,3%, 33,3% respectively. Level of sulfhydryl groups in tumor tissue was higher than that in intact tissue by 1,8 times in solitary cancer, 2,2 times in synchronous cancer, 1,4 times in metachronous cancer. SOD activity was increased on average by 1,4 times in colon cancer tissue in all cases. GPO activity was not changed in solitary and synchronous cancer, decreased by 2,7 times in metachronous cancer. Catalase activity was increased in all tissue samples. SOD/GPO coefficient increased in tumor tissue by 1,5 times in solitary and synchronous cancer, by 3,3 times in metachronous cancer. Conclusions: A marked repression of free-radical processes and indicators of both units of antioxidant defense was detected in colon tumor tissue in solitary and metachronous cancer, so these types of tumor growth can be supposed to be the most aggressive.
Primary Care Interventions to Promote Breastfeeding: U.S. Preventive Services Task Force Recommendation Statement
Authors: Ned Calonge, Diana B. Petitti, Thomas G. DeWitt, Allen Dietrich, Kimberly D. Gregory, Russell Harris, George Isham, Michael L. LeFevre, Rosanne Leipzig, Carol Loveland-Cherry, Lucy N. Marion, Virginia A. Moyer, Judith K. Ockene, George F. Sawaya, Barbara P. Yawn
Journal: Annals of Internal Medicine (2008)

Description: Update of a 2003 U.S. Preventive Services Task Force (USPSTF) recommendation on counseling to promote breastfeeding. Methods: The USPSTF evaluated the results of a systematic review, conducted by the Tufts-New England Medical Center Evidence-based Practice Center, of literature published since January 2007 on primary care–initiated, –conducted, or –referable activities to promote and support breastfeeding. Recommendation: The USPSTF recommends interventions during pregnancy and after birth to promote and support breastfeeding (Grade B recommendation).
Patient-relevant symptoms and impacts of chronic lymphocytic leukemia: Evidence from online social networks-based qualitative research with treated and “watch and wait” patients.
Authors: Kelly P McCarrier, Scott Bull, Kristina F Simacek, Matthew Wolfe, Renee F Pierson, Sarah Fleming, David Cella, Margaret Rothman
Journal: Journal of Clinical Oncology (2014)

e17692 Background: We sought to identify patient-reported disease symptoms and concerns relevant to patients with Chronic Lymphocytic Leukemia (CLL) who have experienced treatment versus watch and wait. Methods: Adults with CLL participating as members of the PatientsLikeMe online patient community were invited to complete a web-based survey about their experiences with the condition. Respondents were grouped by treatment status, and descriptors such as CLL stage, performance status, and demographic characteristics were collected. Open-ended survey questions elicited descriptions of CLL symptoms, impacts, and treatment-related perceptions. Survey responses were coded for qualitative content analysis using Atlas.ti. Results: Survey responses from 50 members of the PatientsLikeMe CLL community were coded for content analysis. The mean age of respondents was 60.5 years; 54.0% were female; 96% were White. When surveyed, 20% of respondents were receiving current treatment, 16% had received previous treatment, and 64% were under “watch and wait” (WW) for their CLL. The majority of patients (78.0%) reported experiencing at least 1 symptom and 17% of patients reported their symptoms required them to be in bed for up to 50% of their waking day. Among 50 patients, 369 descriptions of CLL symptoms were coded. The five most frequently-expressed disease symptoms were the same between the two subgroups, but each symptom was more prevalent among treated patients. These key symptoms included fatigue (expressed by 25% of WW and 67% of treated patients), tiredness (34% vs. 55%), night sweats (34% vs. 44%), swollen lymph nodes (31% vs. 33%) and pain (19% vs. 33%). Conversely, the most frequently-expressed impact of CLL, worry and fear was more prevalent among WW (69%) than treated (61%) patients. Conclusions: Results identify little difference in the set of key CLL symptoms experienced by WW and treated patients, but suggest a higher symptom burden among treated patients. Emotional effects (e.g., worry, fear, depression) are the most frequently-expressed impacts of CLL, and appear to be particularly relevant to WW patients.
A community hospital experience on the outcome of patients with different genetic variant epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC).
Authors: Sukesh Manthri, Bruno R. Bastos
Journal: Journal of Clinical Oncology (2014)

e19099 Background: The era of molecular medicine for NSCLC has arrived. However, this is creating unique challenges for the community oncologist. Many centers routinely perform molecular profiling on all advanced non-squamous NSCLC. However, in the community setting, only approximately 60% of these patients have their tumor analyzed. In addition, clinical knowledge on the behavior of different EGFR genotypes is subpar. Our data shows the experience of a community based hospital in the diagnosis of EGFR mutant NSCLC and their outcomes based on genetic variants. Methods: An institutional database of a total of 269 patients with NSCLC was reviewed in an IRB approved fashion. Patients with advanced NSCLC harboring EGFR mutation were selected for analysis. We calculated the prevalence of different EGFR variants and analyzed their frequency and outcomes among different races in our cohort. Results: We identified 229 patients with non-squamous NSCLC (85% of total NSCLC cases). A total of 81 patients (84%) with stage IV non-squamous NSCLC had EGFR molecular test performed. A total of 38 patients (16%) with non-squamous NSCLC harbored an EGFR mutation, 60% were woman. The prevalence of exon 18, 19, 20 and 21 were 7.8%, 44.7%, 5.2%, and 31.5%. Four patients (10.5%) had double mutations. The most common mutation in Hispanics was at exon 19 (50%), in African-Americans exon 19 (83%) and in Caucasians exon 19 and exon 21 each with 34 %.All of our patients with advanced non-squamous NSCLC harboring EGFR mutation received Erlotinib.Our only patient with exon 20 mutation treated with Erlotinib experienced no response; however our patient with combined exon 20 and exon 18 mutations had complete response to Erlotinib. Conclusions: Our community practice data on the prevalence of different EGFR genotypes in NSCLC mirrors historical data. We were able to analyze 84% of all our stage IV non-squamous NSCLC samples for EGFR mutation. Exon 19 is the most common found genotype across all ethnicity groups. This data suggests that the diagnosis of patients with EGFR mutant advanced NSCLC at the community practice level is feasible and comparable with published academic data.
The impact of pharmacological and non‐pharmacological interventions to improve physical health outcomes in people with schizophrenia: a meta‐review of meta‐analyses of randomized controlled trials
Authors: Davy Vancampfort, Joseph Firth, Christoph U. Correll, Marco Solmi, Dan Siskind, Marc De Hert, Rebekah Carney, Ai Koyanagi, André F. Carvalho, Fiona Gaughran, Brendon Stubbs
Journal: World Psychiatry (2019)

We summarized and compared meta‐analyses of pharmacological and non‐pharmacological interventions targeting physical health outcomes among people with schizophrenia spectrum disorders. Major databases were searched until June 1, 2018. Of 3,709 search engine hits, 27 meta‐analyses were included, representing 128 meta‐analyzed trials and 47,231 study participants. While meta‐analyses were generally of adequate or high quality, meta‐analyzed studies were less so. The most effective weight reduction interventions were individual lifestyle counseling (standardized mean difference, SMD=–0.98) and exercise interventions (SMD=–0.96), followed by psychoeducation (SMD=–0.77), aripiprazole augmentation (SMD=–0.73), topiramate (SMD=–0.72), d‐fenfluramine (SMD=–0.54) and metformin (SMD=–0.53). Regarding waist circumference reduction, aripiprazole augmentation (SMD=–1.10) and topiramate (SMD=–0.69) demonstrated the best evidence, followed by dietary interventions (SMD=–0.39). Dietary interventions were the only to significantly improve (diastolic) blood pressure (SMD=–0.39). Switching from olanzapine to quetiapine or aripiprazole (SMD=–0.71) and metformin (SMD=–0.65) demonstrated best efficacy for reducing glucose levels, followed by glucagon‐like peptide‐1 receptor agonists (SMD=–0.39), dietary interventions (SMD=–0.37) and aripiprazole augmentation (SMD=–0.34), whereas insulin resistance improved the most with metformin (SMD=–0.75) and rosiglitazone (SMD=–0.44). Topiramate had the greatest efficacy for triglycerides (SMD=–0.68) and low‐density lipoprotein (LDL)‐cholesterol (SMD=–0.80), whereas metformin had the greatest beneficial effects on total cholesterol (SMD=–0.51) and high‐density lipoprotein (HDL)‐cholesterol (SMD=0.45). Lifestyle interventions yielded small effects for triglycerides, total cholesterol and LDL‐cholesterol (SMD=–0.35 to –0.37). Only exercise interventions increased exercise capacity (SMD=1.81). Despite frequent physical comorbidities and premature mortality mainly due to these increased physical health risks, the current evidence for pharmacological and non‐pharmacological interventions in people with schizophrenia to prevent and treat these conditions is still limited and more larger trials are urgently needed.