tbuckley/cabot-search huggingface dataset:
Induction chemotherapy (IC) docetaxel (T), cisplatin (P), 5-fluorouracil (F) (TPF), or TP followed by concomitant boost radiotherapy (R) with or without cetuximab (E) for functional organ preservation (FOP) of resectable laryngeal and hypopharyngeal cancer (LHSCC): First results of the phase II randomized DeLOS-II study.
Authors: Andreas Dietz, Michael Flentje, Rudolf Hagen, Ulrike Bockmuehl, Oliver Koelbl, Volker Schilling, Georg Maschmeyer, Ursula Schroeder, Christian Sittel, Martin Goerner, Thomas Lenarz, Jens Peter Klussmann, Orlando Guntinas-Lichius, Claudia Rudack, Sabine Reinisch, Thomas Foerg, Martin Westhofen, Hans Juergen Welkoborsky, Dirk Esser, Ulrich Keilholz
Journal: Journal of Clinical Oncology (2014)

6016^ Background: The DeLOS-II trial is a German multicenter randomized phase II trial (IIT) investigating IC with or without cetuximab for patients with LHSCC, followed by R assessing FOP. Methods: Previously untreated patients (pts) with resectable stage III/IV LHSCC indicated for total laryngectomy were randomized to three cycles (TP both 75 mg/m² day 1 and F 750 mg/m²/day on days 1-5) without (arm A) or with (arm B) standard dose of cetuximab for 16 weeks. In case of non-response after the first cycle, the study therapy was terminated and salvage laryngectomy was performed. Three cycles of IC were followed by R (69.6Gy). In this first analysis, we report rates of 6-months survival with functional larynx (FOP). Secondary endpoints included feasibility and toxicity. Results: 180 pts were randomized (7/2007-9/2012), 174 fulfilled ITT criteria (85.1% male, 49.4% larynx, 87.4% T3/4N2bc, equally distributed both arms). Due to 4 therapy related deaths among the first 64 pts (3 arm A, 1 B), F was omitted from IC in 2/2009. Interim analysis for response and toxicity of 126 pts in 2011 showed no efficacy differences between TPF vs TP and no more treatment related deaths. Overall, in arm A 31 pts received TPF and 55 TP, in arm B 31 TPFE and 57 TPE IC. 66.7% of pts received complete IC (4.0% two cycles; 29.3% one cycle). Dose reduction (>10%) mainly due to toxicity occurred in 27.9% arm A and 98.9% B (30.7% T, 31.8% P, 18.2% F, 98.9% E). Main early toxicity grade 3/4 was hematotoxicity (81.4% in A, 85.2% B). Early response (CR, PR) after first cycle in arm A was 67.4% (95%-CI: 56.5-77.2) and in arm B 77.3% (67.1-85.5; p=0.15). 126 pts were early responders and suitable for the complete IC and R protocol. Overall response in this group was CR/PR 81.0/8.6% in A, 77.9/5.9% in B. Endpoint (loss of FOP, death) was reached in 31.4% vs. 17.0%, favoring arm B (HR 0.502 [0.267-0.944]; p=0.0289). Conclusions: IC with TPFE/TPE was feasible and more effective compared to TPF/TP for Larynx preservation. TPE was less toxic and similarly effective as TPFE. Clinical trial information: NCT00508664.
Abstract P125: Reverse Causality of the Relationship Between Dietary Cholesterol and Serum Low Density Lipoprotein Cholesterol Associated With Education and Employment: the INTERLIPID Study
Authors: Yukiko Okami, Hirotsugu Ueshima, Yasuyuki Nakamura, Nagako Okuda, Hideaki Nakagawa, Kiyomi Sakata, Shigeyuki Saitoh, Akira Okayama, Katsushi Yoshita, Naoko Miyagawa, Sohel R Choudhury, Queenie Chan, Paul Elliott, Jeremiah Stamler, Katsuyuki Miura
Journal: Circulation (2017)

Introduction: The upper limit of recommended dietary cholesterol has been abolished recently from guidelines in Japan and US even though high intake is known to increase serum cholesterol levels. Reverse causality has been involved, reflecting availability of widespread information with consequent lifestyle modifications among knowledgeable people. People with higher serum cholesterol are more likely to modify diet than those with lower serum cholesterol, especially among more educated; if enough people do this, dietary cholesterol will not relate to serum cholesterol or will relate inversely. Hypothesis: We assessed the hypothesis that lifestyle modifications separately by those with high education level and employment status reverse the positive relationship between dietary cholesterol and serum low density lipoprotein cholesterol (LDL-C); therefore, the positive relationship between dietary cholesterol and LDL-C would prevail after adjustment for education level and employment status. Methods: A population-based, random sample, cross-sectional study (INTERLIPID) which was an ancillary study of the International Study of Macronutrients and Blood Pressure (INTERMAP), conducted a survey between 1996 and 1999. Among 1,145 Japanese individuals ages 40-59 years, 106 were excluded because of special diets, use of lipid lowering drugs, hormone replacement, and missing data, leaving 1,039 individuals (533 men and 506 women). Dietary cholesterol was assessed from four 24-h dietary recalls and LDL-C was measured by enzymatic methods on an auto-analyzer. A standard questionnaire inquired about years of education and employment status. Results: Linear regression analysis revealed an inverse association between dietary cholesterol and LDL-C in men (coefficient, -0.04 [95%CI, -0.08 to -0.01]), no significant association when adjusted for education and its interaction term with dietary cholesterol in men (coefficient, 0.05 [95%CI, -0.03 to 0.14]), and a significant positive relation when adjusted for employment and its interaction term in men (coefficient, 0.13 [95%CI, 0.01 to 0.26]). With adjustment for education and employment and their interactions, a significant positive relation was recorded again in men (coefficient, 0.16 [95%CI, 0.03 to 0.29]). These relationships were not observed in women. Conclusions: In Japanese men, education, employment, and their interaction terms with dietary cholesterol reversed an observed inverse relationship between dietary cholesterol and LDL-C. A positive relation prevailed between dietary cholesterol and LDL-C after adjustment for education level and employment status.
Real-World Data of Immune Tolerance Induction Using rFVIIIFc in Subjects With Severe Hemophilia A With Inhibitors at High Risk for ITI Failure
Authors: Manuel Carcao, Amy Shapiro, Nina Hwang, Steven Pipe, Sanjay Ahuja, Kenneth Lieuw, Janice Staber, Haowei Linda Sun, Hilda Ding, Michael Wang, Macgregor Steele, Elisa Tsao, Jing Feng, Zahra Al-Khateeb, Jennifer Dumont, Nisha Jain
Journal: Blood (2018)
Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk
Authors: Iris E. Jansen, Jeanne E. Savage, Kyoko Watanabe, Julien Bryois, Dylan M. Williams, Stacy Steinberg, Julia Sealock, Ida K. Karlsson, Sara Hägg, Lavinia Athanasiu, Nicola Voyle, Petroula Proitsi, Aree Witoelar, Sven Stringer, Dag Aarsland, Ina S. Almdahl, Fred Andersen, Sverre Bergh, Francesco Bettella, Sigurbjorn Bjornsson, Anne Brækhus, Geir Bråthen, Christiaan de Leeuw, Rahul S. Desikan, Srdjan Djurovic, Logan Dumitrescu, Tormod Fladby, Timothy J. Hohman, Palmi V. Jonsson, Steven J. Kiddle, Arvid Rongve, Ingvild Saltvedt, Sigrid B. Sando, Geir Selbæk, Maryam Shoai, Nathan G. Skene, Jon Snaedal, Eystein Stordal, Ingun D. Ulstein, Yunpeng Wang, Linda R. White, John Hardy, Jens Hjerling-Leffler, Patrick F. Sullivan, Wiesje M. van der Flier, Richard Dobson, Lea K. Davis, Hreinn Stefansson, Kari Stefansson, Nancy L. Pedersen, Stephan Ripke, Ole A. Andreassen, Danielle Posthuma
Journal: Nature Genetics (2019)
The impact of dose reduction on survival for colon cancer patients treated with adjuvant FOLFOX.
Authors: Fahad Ibnshamsah, Jacob C. Easaw
Journal: Journal of Clinical Oncology (2014)

e14576 Background: Dose reduction (DR) is common during oxaliplatin based treatment for stage III colon cancer. In this study we evaluated the impact of DR of adjuvant FOLFOX chemotherapy on disease free survival (DFS) and overall survival (OS). We also investigated the causes of DR in these patients and evaluated their specific impact on survival. Methods: A multi-center retrospective study was conducted. Patients were included if they had pathologically confirmed and resected stage II or III colon cancer treated with at least one cycle of adjuvant FOLFOX. Chemotherapy dose was calculated using relative dose intensity (RDI). Clinical outcomes were correlated with RDI. Results: One hundred thirty patients treated in Alberta cancer centers between February 2006 and December 2010 were included. The mean age was 60 years, 55% were male and 92% had stage III disease. The incidence of DR was 34% and 55% for 5FU and oxaliplatin, respectively. Median RDI was 0.87 and 0.77 for 5FU and oxaliplatin, respectively. Neuropathy was identified in 105 patients (81%) and was a cause of DR in 40 patients (31%). OS was significantly higher for patients who had neuropathy-related DR (n=40) OS:65.0 months (60.5 , 69.5), compared to patients who had no neuropathy-related DR (n=90) OS:57.2 months (52.7 ,61.7), p-value=0.029. This improvement in OS was only observed in neuropathy patients but DR of any cause did not impact OS (OS 60.5 months for patients with DR versus 54.7 months with no DR, p= 0.10). There was no significant difference in DFS in DR patients (52.5 months) compared to (45.2 month) in patients with no DR, p-value=0.11. Conclusions: Dose reduction of any cause did not impact clinical outcomes of patients treated with adjuvant FOLFOX chemotherapy for resected colon cancer. However, neuropathy induced dose reduction was associated with improved survival in patients treated with adjuvant FOLFOX chemotherapy.
Disruption of the Rbm38-eIF4E Complex with a Synthetic Peptide Pep8 Increases p53 Expression
Authors: Christopher A. Lucchesi, Jin Zhang, Buyong Ma, Mingyi Chen, Xinbin Chen
Journal: Cancer Research (2018)

Abstract Rbm38 is a p53 target and an RNA-binding protein known to suppress p53 translation by preventing eukaryotic translation initiation factor 4E (eIF4E) from binding to p53 mRNA. In this study, we show that synthetic peptides corresponding to the binding interface between Rbm38 and eIF4E, including an 8 amino acid peptide (Pep8) derived from Rbm38, are effective in relieving Rbm38-mediated repression of p53. Molecular simulations showed that Ser-6 in Pep8 forms a hydrogen bond with Asp-202 in eIF4E. Substitution of Ser-6 with Lys, but not with Asp, enhanced the ability of Pep8 to inhibit the Rbm38-eIF4E complex. Importantly, Pep8 alone or together with a low dose of doxorubicin potently induced p53 expression and suppressed colony and tumor sphere formation and xenograft tumors in Rbm38- and p53-dependent manners. Together, we conclude that modulating the Rbm38-eIF4E complex may be explored as a therapeutic strategy for cancers that carry wild-type p53. Significance: Disruption of the Rbm38-eIF4E complex via synthetic peptides induces wild-type p53 expression, suppresses tumor growth and progression, and may serve as a novel cancer therapeutic strategy.
Low health literacy and its correlates among allogeneic bone marrow transplant recipients.
Authors: Natalie Susan Bezler, Anna Malyak, Dongjing Guo, Wendy B. London, Jennifer W. Mack, Steven Joffe
Journal: Journal of Clinical Oncology (2014)

e17565 Background: Health literacy is the degree to which individuals can understand basic health information to make medical decisions and to access needed services. Low health literacy, which affects 36% of the US population, has been linked to poor outcomes in chronic diseases such as diabetes and asthma. To our knowledge, no studies have investigated health literacy in a bone marrow transplant (BMT) setting, where patients require complex outpatient self-care. Methods: Participants were recruited from the BMT units of Brigham and Women’s Hospital and Boston Children’s Hospital. English- and Spanish-speaking patients admitted for a first allogeneic BMT were eligible. For minor patients, the child’s primary caregiving parent was eligible. Health literacy was measured using the Newest Vital Sign (NVS) and the Short Test of Functional Health Literacy in Adults (STOFHLA). Demographic information (age, gender, race, ethnicity, and education) was collected, along with psychosocial measures, including the Medical Outcomes Study Social Support Survey, Perceived Stress Scale, Multidimensional Health Locus of Control Scale, General Self-Efficacy Scale, and Hospital Anxiety and Depression Scale. Instruments were administered in English or Spanish. Results: 186 individuals (169 adult patients, 17 parents of pediatric patients) of a planned 188 have been enrolled to date, representing 69% of those approached. Forty-nine (26%) demonstrated low health literacy on either the NVS or STOFHLA, including 2 identified by both measures and 47 identified by the NVS alone. In bivariate analyses, participants who had lower levels of education (p=0.008) were more likely to demonstrate low health literacy. Health literacy did not differ significantly by any other sociodemographic or psychosocial variables measured. Conclusions: Low health literacy is prevalent among adult patients and parents of patients undergoing BMT. This may have implications for patients’ outcomes, given complex self-care expectations after transplant. In our population, the NVS appeared more sensitive than the STOFHLA in detecting low health literacy, likely due to inclusion of numeracy assessments.
Monitoring next-generation sequencing (NGS) workflows in oncology research using AcroMetrix sequencing controls.
Authors: Nakul Nataraj, Kara Norman, Aron Lau, Mona D Shahbazian
Journal: Journal of Clinical Oncology (2014)

e22101 Background: Reproducible control materials that mimic tissue specimens help assess the performance of NGS test procedures. For FFPE samples, controls such as plasmids, genomic DNA, and cell lines lack the ability to monitor the entire sample preparation workflow. The AcroMetrix MultiMix FFPE Controls, in contrast, encompass all steps of the process from deparaffinization through variant calling. Methods: The FFPE Controls include sections from eight cancer cell lines. Cells were mixed with a proprietary polymer and solidified within a mold to form a synthetic tissue. The tissue was then treated with formalin, dehydrated with alcohol, cleared with SafeClear, embedded in paraffin, and sectioned at 10 microns. For testing, each control was extracted using the QIAGEN QIAamp DNA FFPE Tissue protocol. Libraries were prepared using the Ion AmpliSeq Cancer Hotspot Panel v2. Templates were generated using the Ion PGM Template OT2 200 Kit and sequenced with the Ion Torrent Personal Genome Machine. Results: The entire process of extraction, library preparation, template generation, sequencing, and variant calling was performed independently at least three times on each control. The lists of variants for each control were compared to determine the subset of calls that was consistent across multiple runs. Each control had variants present in 10-16 genes, including 12-26 variants at 30-100% frequencies. In good quality runs, low frequency variants dropped out intermittently indicating a context-specific limit of detection. In poorly performing runs, selective drop outs were observed in mutations across a wide range of frequencies (up to 50%). Conclusions: In conclusion, the AcroMetrix MultiMix FFPE controls mimic FFPE tissue samples and allow oncology research labs performing NGS to assess and monitor their entire workflow from extraction to result. Routine use of these FFPE Controls would enable laboratories to identify possible variations between lots of assay reagents and operators and assist in identifying increases in random or systematic errors in testing systems. Disclaimers: All products and platforms are for Research Use Only.Not for use in diagnostic procedures.
<i>CYP2D6 </i>genotyping in an Argentinean population.
Authors: Maria Florencia Gosso, Melisa Del federico, Analia Seravalle, Maria Sonia Baquedano, Fabian Fay
Journal: Journal of Clinical Oncology (2014)

e13543 Background: The polymorphic CYP2D6 gene shows a high degree of interindividual and interethnic variability that influences its expression and function. CYP2D6 polymorphism influences the metabolism of tamoxifen and the analgesic response to product opioids (codeine, tramadol and oxycodone). Given the limited availability of data regarding the alleles and genotypes in Argentina, where Native American founder effects and the multiracial demography of immigration are predicted to result in high genetic variation, this study aimed to determine CYP2D6alleles and their frequencies in this population. Methods: 56 unrelated Argentinean subjects were screened using a CYP2D6specific long range PCR with sequencing platform. Results: We detected a total of 26 known single nucleotide polymorphisms; and gene duplication or multiplication (CYP2D6*1xN) in 2/112 alleles. The deleterious variants 100C>T, 1846G>A y 2988G>A were found in 25/112, 25/112 and 4/112 alleles, respectively. The identified alleles are derived from 5 mayor alleles, namely the wild type CYP2D6*1, the functional CYP2D6*2 and CYP2D6*35 alleles, the null allele CYP2D6*4 and the reduced-activity allele CYP2D6*41 with a frequency of 46/112, 10/112, 6/112, 42/112 and 6/112, respectively. CYP2D6 gene deletions (CYP2D6*5) were not found. Conclusions: To our knowledge, this study is the first resequencing analysis of CYP2D6 gene in Argentinean population, providing information about genetic diversity relevant in the development of pharmacogenomics in this region.
Connectome-Based Prediction of Cocaine Abstinence
Authors: Sarah W. Yip, Dustin Scheinost, Marc N. Potenza, Kathleen M. Carroll
Journal: American Journal of Psychiatry (2019)

The authors sought to identify a brain-based predictor of cocaine abstinence by using connectome-based predictive modeling (CPM), a recently developed machine learning approach. CPM is a predictive tool and a method of identifying networks that underlie specific behaviors ("neural fingerprints").Fifty-three individuals participated in neuroimaging protocols at the start of treatment for cocaine use disorder, and again at the end of 12 weeks of treatment. CPM with leave-one-out cross-validation was conducted to identify pretreatment networks that predicted abstinence (percent cocaine-negative urine samples during treatment). Networks were applied to posttreatment functional MRI data to assess changes over time and ability to predict abstinence during follow-up. The predictive ability of identified networks was then tested in a separate, heterogeneous sample of individuals who underwent scanning before treatment for cocaine use disorder (N=45).CPM predicted abstinence during treatment, as indicated by a significant correspondence between predicted and actual abstinence values (r=0.42, df=52). Identified networks included connections within and between canonical networks implicated in cognitive/executive control (frontoparietal, medial frontal) and in reward responsiveness (subcortical, salience, motor/sensory). Connectivity strength did not change with treatment, and strength at posttreatment assessment also significantly predicted abstinence during follow-up (r=0.34, df=39). Network strength in the independent sample predicted treatment response with 64% accuracy by itself and 71% accuracy when combined with baseline cocaine use.These data demonstrate that individual differences in large-scale neural networks contribute to variability in treatment outcomes for cocaine use disorder, and they identify specific abstinence networks that may be targeted in novel interventions.
Abstract #5000: Detection of micro-dissemination of cancer cells by testing for progastrin-releasing peptide expression in the peripheral blood of SCLC patients
Authors: Hideharu Kimura, Kazuo Kasahara
Journal: Cancer Research (2009)

BACKGROUND: Dissemination of cancer cells in peripheral blood has a strong negative impact on patient survival. Some groups have reported using the reverse transcriptase polymerase chain reaction (RT-PCR) of progastrin-releasing peptide (proGRP) as a specific marker to detect micro-dissemination of small-cell lung cancer (SCLC) cells in peripheral blood. We evaluated the correlation between the presence of micro-disseminated cancer cells in SCLC patients\#8217; blood and their clinical manifestations, including stage in the form of limited disease (LD) and extensive disease (ED), response to therapy, and survival. METHODS: Disseminated cancer cells were detected among the peripheral blood mononuclear cells in blood specimens from SCLC patients treated with chemotherapy alone and SCLC patients treated with a combination of chemotherapy and radiotherapy. A blood specimen was collected at 3 points: before the start of treatment, 4 weeks after the 1st cycle of 1st line chemotherapy, and after the completion of 1st line chemotherapy. Control specimens were collected from non-small cell lung cancer patients and healthy individuals. Expression of proGRP was investigated by real-time RT-PCR. RESULTS: Expression of proGRP in peripheral blood was detected in about half of the SCLC patients. The rate of expressions in ED was higher than in LD, and the rates of expression in both LD and ED decreased after treatment. No expression was detected in the NSCLC and in healthy controls. CONCLUSIONS: It was possible to detect disseminated cancer cells in SCLC patients by RT-PCR analysis for expression of proGRP. Expression of proGRP may be related to disease extent and prognosis.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5000.
Is computerized tomography (CT) sufficient without bone scan (BS) for routine, asymptomatic breast cancer (BC) staging?
Authors: Jill Rene Tichy, Mark Raymond Waddle, Allison Mary Deal, Jessica Lavery, Lisa A. Carey, Hyman Bernard Muss, Nisha Mehta
Journal: Journal of Clinical Oncology (2014)

e17547 Background: Redundant use of imaging modalities for staging is not cost effective. This study characterizes the utility of staging BS coupled with CT chest/abdomen/pelvis in detection of asymptomatic BC bone metastasis (BM), the most common site of distant disease. Methods: Eligible patients had clinical/pathological stage I-III asymptomatic BC diagnosed between 2010-2013 who underwent staging BS and CT < 6 weeks apart. Radiographic discordance in BM detection was defined by at least indeterminate findings on either BS or CT bone windows with the other read as normal, provided that the area of BS abnormality was imaged by CT. Discordant scans were independently reviewed by a dedicated musculoskeletal radiologist. Fisher’s Exact and Wilcoxon sum rank tests evaluated the association of discordance and clinical characteristics. Results: Among 124 patients, the median age was 53 (24, 87) years, median tumor size 3.45 cm (<1.0, 20.0) and 82 (67%) ≥ 1 positive lymph node. Clinical subsets included: HR+/HER2- (67, 54%), HR-/HER2- (35, 28%), and HER2+ (22, 18%). Median follow-up was 2.2 years. 102 (82.3%) were radiologically concordant for BM evaluation with 93 (75.0%) negative and 9 (7.3%) positive. There were 22 (17.7%) radiologically discordant cases; 13 patients underwent follow-up for BM with 1 biopsy confirmation. Of 11 (8.9%) CT+/BS- patients, 9 are alive without disease, 1 died with BM, and 1 was lost to follow-up. Of 11 (8.9%) BS+/CT- patients, 8 are alive without disease, 1 died with visceral-only metastases, 1 died with visceral+BM, and 1 was lost to follow-up with confirmed BM. Skull-only metastases were suspected by BS in 2 cases; 1 died with visceral+BM. There was no association of any patient or tumor characteristic with measured discordance (all p-values ≥ 0.07). Expert review of 22 discordant cases yielded 9 confirmed discordant results. Conclusions: There were no cases of isolated clinically significant BM outside CT bone windows. Of discordant cases, the majority had negative follow-up imaging for BM. BS routinely coupled with CT chest/abdomen/ pelvis contributed additional information regarding BM in fewer than 10% of cases, and may be unnecessary for routine staging in asymptomatic BC.