tbuckley/cabot-search huggingface dataset:
Phase II randomized trial of neoadjuvant (NA) chemotherapy (CT) with or without bevacizumab (Bev) in advanced epithelial ovarian cancer (EOC) (GEICO 1205/NOVA TRIAL).
Authors: Yolanda García, Ana De Juan, Cesar Mendiola, Pilar Barretina-Ginesta, Laura Vidal, Ana Santaballa, Isabel Bover, Marta Gil-Martin, Aránzazu Manzano, M Jesus Rubio, Margarita Romeo, Alfonso Gomez de Liaño, Elena García-Martínez, Antonio Gonzalez-Martin
Journal: Journal of Clinical Oncology (2015)

5531 Background: First-line carboplatin(C)-paclitaxel(P) and Bev has proved to be an active combination after primary debulking surgery and improved overall survival in suboptimal resected advanced EOC patients (pts). However, the role of Bev in the NA setting has not been well defined yet. Methods: We performed a phase II randomized open label multicentric study in 66 pts with high grade serous or endometroid EOC, FIGO stage III-IV, ECOG 0-2, considered unresectable in whom NA CT and interval debulking surgery (IDS) were planned. Main exclusion criteria were intestinal occlusion and contraindication for Bev therapy. Pts were randomized to four courses of triweekly C AUC 6 and P 175 mg/m2 iv alone or with at least 3 courses of bev 15 mg/kg i.v. every 3 w. in experimental arm. The primary endpoint was the complete macroscopic response rate at the time of IDS. Secondary objectives were safety, surgical feasibility, optimal surgery rate, RECIST 1.1 and GCIG response rate. Biomarker analysis were performed in pre and post biopsies. All pts received 3 additional courses of CT and Bev after IDS followed by maintenance Bev up to complete 15 month. Results: We report the preliminary data of 64 pts. Clinical pts characteristics were well balanced with median age 59.9 y.o and a 34.4% stage IV. No differences in the primary endpoint were found (1/32 Control Arm and 0/32 Bev Arm) but there was a higher rate of surgical feasibility in the Bev Arm (64 vs 88%). Optimal surgery rate also favored the Bev arm (77.7 vs 86.4%) and there wasn't any patient deemed unresectable at the time of surgery in the Bev arm (2 vs 0). None of these figures were statistically significant difference. There were lower rates of serious adverse events (grade 3-4) in bev arm (40.6 vs 18.8%, p = 0.055). Three Bev related adverse events of special interest were observed in 3 pts (1 G3 entero-vaginal fistulae, 1 surgical dehiscence, 1 deep venous thrombosis). Conclusions: Our preliminary data have shown that NA bev seems feasible and could improve the surgical outcomes in advanced EOC considered initially unresectable. Updated clinical and translational data will be provided. Clinical trial information: NCT01847677.
Abstract 225: The Protective Role of Mitral Valve Surgery on Right Ventricular Reverse Remodeling
Authors: Julia Grapsa, Dimosthenis Pandis, Prakash P Punjabi, Petros Nihoyannopoulos
Journal: Circulation (2009)

Objectives: Mitral valve surgery is known to benefit left ventricular reverse remodeling. The aim of this study was the follow up of right ventricular remodeling with real time three dimensional echocardiography of patients undergoing mitral valve surgery. Methods: 31 patients with severe mitral regurgitation who underwent mitral valve surgery constituted the study cohort. All patients had a baseline and a 6-month follow up scan with two and real time three-dimensional echocardiography. Right ventricular (RV) volumes (end-diastolic: EDV, end-systolic: ESV, stroke volume: SV), function (ejection fraction: EF) and mass (M) were measured with the method of summation of disks. Results had a normal distribution and they were expressed as mean ± standard deviation (SD). Systematic differences in measurements were assessed with Student t-test. Analysis was performed with SPSS 13.0 and a p value of <0.05 was considered significant. Results: Mean age was 52.6±14.8 years and 19 patients (61.3%) were women. 24 patie...
Outcomes of Unilateral Cataracts in Infants and Toddlers 7 to 24 Months of Age
Authors: Erick D. Bothun, M. Edward Wilson, Elias I. Traboulsi, Nancy N. Diehl, David A. Plager, Deborah K. Vanderveen, Sharon F. Freedman, Kimberly G. Yen, Natalie C. Weil, Allison R. Loh, David Morrison, Jill S. Anderson, Scott R. Lambert, Scott Lambert, Amy Hutchinson, Stephen Christiansen, Erick Bothun, Ed Wilson, Elias Traboulsi, David Plager, Daniel Neely, Deborah Vanderveen, Ed Buckley, Sharon Freedman, David Wallace, Kimberly Yen, David Wheeler, David Morrison
Journal: Ophthalmology (2019)
What's hot that the other lot got
Authors: Piers Dixey
Journal: Thorax (2019)

Despite clear evidence of safety of titrated oxygen therapy in critical illness, patients are frequently treated in the initial presentation with high inspired oxygen fractions (FiO2). The Hyper2S trial, design to assess the role of hyperoxia (FiO2 1.0 vs titrated FiO2 for SpO2 88–95% in first 24 hours) and hypertonic saline in the management of septic shock was stopped early due to high mortality in the hyperoxia group. Demiselle et al ( Ann Int Care 2018;8:90) report a post hoc analysis of patients from the Hyper2S trial selected by the sepsis-3 criteria (septic shock requiring vasopressor support despite adequate fluid resuscitation with a lactaemia; >2 mmol/L). Three hundred and ninety-seven out of 442 patients had available lactate levels with 230 of those patients meeting the sepsis-3 definition (122 normoxia, 108 hyperoxia). As expected, patients with lactaemia were more unwell (higher Sequential OrganFailure Assessment core and Simplified Acute Physiology Score II, with more need for organ support) than those without lactaemia. There was a numerically higher mortality at 28 days in hyperoxia compared with normoxia patients (57% vs 44%), with hyperoxia demonstrating a significant impact on mortality in the multivariate analysis at both 28 (HR 1.79, 95% CI 1.21 to 2.63, p<0.003) and 90 (HR 1.57, 95% CI 1.09 to 2.28, p=0.016) days. The results …
Personalized first-line chemotherapy for advanced colorectal cancer using the collagen gel droplet-embedded culture drug sensitivity test.
Authors: Takumi Ochiai, Kazuhiko Nishimura, Tomoo Watanabe, Masayuki Kitajima, Akinori Nakatani, Tsuyoshi Sato, Kennji Kishine, Isao Nagaoka, Shunji Futagawa
Journal: Journal of Clinical Oncology (2015)

e14523 Background: The most effective regimen should be selected as first-line chemotherapy for colorectal cancer (CRC) patients since disease progression, adverse events, or even high medical costs can preclude second-line treatment. We proposed the importance of assessing tumor cell drug sensitivity (ASCO 2010 #3582). In this study, we explored personalized first-line chemotherapy for CRC based on the collagen gel droplet-embedded culture drug sensitivity test (CD-DST). Methods: Between Mar. 2008 and Oct. 2014, we obtained tumor specimens from 100 CRC patients without preoperative chemotherapy. CD-DST was performed and the growth inhibition rate (IR) was determined by incubation for 24 h with 5-FU and l-OHP (6.0 and 3.0 μg/ml, respectively) and 5-FU and SN-38 (6.0 and 0.2 μg/ml, respectively). The cumulative distribution of IR values under each condition was evaluated on the basis that the clinical response to FOLFOX and FOLFIRI is equivalent. Patients were divided into 4 cohorts, which were FOLFOX and FOLFIRI responders (dual responders), FOLFOX responders, FOLFIRI responders, and poor responders. Since only FOLFOX and FOLFIRI are currently available, the patients were divided into 3 cohorts: FOLFOX recommended, FOLFIRI recommended, and both regimens recommended. First-line regimens were selected by the attending physician. The Kaplan-Meier method was used for analysis of overall survival. Results: There were 36 patients with unresectable CRC with chemotherapy, and personalization of first-line chemotherapy was possible in 100 patients. In 4 cohorts, the median survival time (MST) of dual responders (n = 18) and poor responders (n = 15) was 1,128 and 433 days, respectively. In 3 cohorts, FOLFOX was recommended, FOLFIRI was recommended, and both regimens were recommended in 19, 15, and 2 patients, respectively. In first-line treatment, the MST was 960 days in 25 patients with recommended regimen and 419 days in 11patients without recommended regimen (p = 0.05). For poor responders, the corresponding MST values were 810 and 244 days (p = 0.014). Conclusions: Personalizingfirst-line therapy with the CD-DST may improve the survival time of patients with unresectable CRC.
CSF pharmacokinetics of high-dose pulsatile tyrosine kinase therapy in brain cancer patients.
Authors: Sandeep C. Pingle, Tiffany Juarez, Marlon G. Saria, Santosh Kesari
Journal: Journal of Clinical Oncology (2015)

e13032 Background: Previous studies have shown improvement in patients with leptomeningeal metastases from non-small cell lung cancer (NSCLC) following high-dose gefitinib therapy. Based on these data, we explored the effect of high-dose erlotinib, another epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) on clinical response and CNS penetration in brain cancer. Methods: Patients were treated with an alternate dosing regimen of erlotinib after receiving prior standard dosing erlotinib for either glioma or NSCLC with brain metastases. Blood and cerebrospinal fluid (CSF) samples were collected at various time points. Results: CSF concentrations of erlotinib were generally 2% that of plasma concentration. Among the five patients examined, concentrations of erlotinib reached up to 131nM in the CSF when high dose erlotinib was administered at 600 to 1200 mg every four to six days. Additionally, drug clearance was decreased with an increased dosing regimen. The area under the curve (AUC) estimations showed a 24% increase in the CSF versus only a 2% increase in the plasma following an increase from 150 mg to 600 mg of erlotinib. In addition, we conducted detailed analyses of the activity of different kinases in CSF samples following erlotinib therapy. These findings further validated our hypothesis by demonstrating a functional effect of erlotinib therapy in inhibiting kinase activity in CSF samples. Conclusions: Our data in five patients receiving erlotinib therapy for primary and metastatic CNS disease suggests that high-dose erlotinib administered as a pulse dose every four to six days increases the drug concentrations and residence time in the CSF. In addition, our data provides evidence of effect on CSF pharmacodynamics. In spite of variations among the patients, higher dosing regimens of erlotinib may provide enhanced CNS penetration.
Relation between clinicopathological findings and PD-1 or PD-L1 status in non-clear cell renal cell carcinoma by a multicenter study.
Authors: Hiroaki Matsumoto, Kazuhiro Nagao, Masahiro Samoto, Junichi Mori, Kosuke Shimizu, Ryo Inoue, Yoshiaki Yamamoto, Seiji Yano, Hiroshi Hirata, Tomoyuki Shimabukuro, Hideyasu Matsuyama
Journal: Journal of Clinical Oncology (2019)

654 Background: We investigated correlation of their pathological findings and their prognostic factors in non-clear cell renal cell carcinoma (ncRCC) diagnosed by both regional pathology (RP) and central pathology (CP) in multicenter study. Methods: In January 2005 to December 2014, 140 cases of ncRCC diagnosed by radical or partial nephrectomy were assessed. We assessed their pathological diagnosis by one central pathologist using the 2016 WHO classification tumor of the kidney. We assessed the correlation between clinical parameters or pathological findings and their prognosis. Then, we performed immunohistochemical analysis using PD-1 related antibody in ncRCC. Results: Median follow up was 32.7 months (1-134). Median age was 66 years, 99 males and 41 females. Pathological stage was pT1a: 58, pT1b: 30, pT2a: 17, pT2b: 6, pT3a: 21, pT3b: 2, pT4: 3 cases, respectively. In RP, histology was papillary (PAP): 60 (42.9%), chromophobe (CHR): 49 (35.0%), containing with sarcomatoid components (SAR): 14 (10.0%) and other histology: 17 (12.1%) cases, respectively. The tumors evaluable by CP were 127 cases, PAP: 52 (40.9%), CHR: 31 (24.4%), SAR: 20 (15.7%) and other histology: 24 cases (18.8%), respectively. The overall concordance rate was 59.5% between RP and CP. In multivariate analysis, SAR was extremely poor prognosis in ncRCC. The high neutrophil lymphocyte ratio (NLR) and at high CRP value were also poor prognostic factors. So, we stratified three risk groups using three factors, namely NLR, CRP and SAR. In overall survival, there were significant prognostic differences within three groups (p = 0.0014). In immunohistochemistry, PD-1 or PD-L1 expression correlated with poor overall, cancer specific and recurrence free survival in ncRCC. In multivariate analysis, PD-L1 expression was most significant prognostic factor for ncRCC. Conclusions: These results suggest that Risk stratification by three risk factors is useful prognostic model and the expression of PD-1 and PD-L1 may be a useful prognostic factor in ncRCC.
Real world treatment patterns and healthcare resource utilization (HRU) among chronic lymphocytic leukemia (CLL) patients by regimen.
Authors: Stacey DaCosta Byfield, Stephanie Korrer, Lorie Ellis, Brad Schenkel
Journal: Journal of Clinical Oncology (2015)

e18043 Background: Few studies examine HRU of CLL, the most common hematologic malignancy in adults. This study describes HRU by the most common regimens among CLL patients (pts). Methods: A retrospective study using a large, national US claims database from 1/2007-10/2013 was conducted. Adult CLL pts (≥2 claims for CLL) with ≥1 claim for systemic anti-cancer therapy (SACT) were identified; first SACT claim date was the index date. Pts had to have a CLL diagnosis within 3 months (m) prior to the index date and be continuously enrolled (CE) in the health plan for 24m pre- and ≥6m post-index date. Pregnant pts and those with SACT in the pre-index period were excluded. A line of therapy (LOT) started with the first SACT; regimens included all agents received in the 1st 60 days. LOTs ended at the earliest of, start of a new drug, ≥60-day gap in receipt of initial regimen drugs, death or CE end. All-cause HRU was examined by regimen. Results: There were 946 CLL pts identified. Mean age was 68 yrs, 63% were male and by insurance type, 41% were Medicare Advantage vs. 59% commercially insured. During the 1st LOT, 96% and 78% of pts had ≥1 office or hospital outpatient visit with mean per patient per month (PPPM) visits of 4.3 (standard deviation, SD=2.8) and 2.2 (SD=2.8), respectively. 31% and 25% had ≥1 ER visit or inpatient stay with mean PPPM visits of 0.2 (SD=0.4) and 0.1 (SD=0.3), respectively. Mean PPPM count of inpatient stay days was 1.4 (SD=8.0). In 1st LOT, the top 3 regimens accounted for 56% of pts: FCR: fludarabine, cyclophosphamide, rituximab (19%); R: rituximab (19%); BR: bendamustine, rituximab (18%). During the study period, 318 pts (34%) started a 2ndLOT. The top 3 LOT2 regimens accounted for 52% of pts: R (30%); BR (14%); chlorambucil (8%). Conclusions: HRU of CLL pts varied by initial regimen received. Future studies should examine influences of regimen choice and whether regimen choice is associated with differences in outcomes. HRU in 1st LOT FCR N=183 R N=180 BR N=169 Office visit % 98 96 98 PPPM^ 5.1 (2.8) 3.9 (2.3) 4.2(2.6) Hospital outpatient visits % 83 67 83 PPPM^ 2.3 (2.6) 1.9 (2.9) 2.4 (3.0) ER visits % 32 21 37 PPPM^ 0.1 (0.3) 0.2 (0.5) 0.2 (0.3) Inpatient stays % 25 15 33 PPPM^ 0.1 (0.2) 0.1 (0.2) 0.1 (0.3) ^mean (SD)
Abstract 18494: WNT Mediated Regulation Signals IN Chamber-Specific Neonatal Heart Maturation and Disease
Authors: Marlin Touma, Xuedong Kang, Yan Zhao, Ashley Cass, Reshma Biniwale, Xinshu Xiao, Brian Reemtsen, Yibin Wang
Journal: Circulation (2015)

Background: Chamber-specific and temporally orchestrated perinatal cardiac growth and maturation is critical to functional adaptation of heart to the dramatic changes in hemodynamic load and nutrient environment, and perturbation of this process may have major implications in congenital heart defects (CHDs). However, the responsible molecular regulatory mechanisms are still poorly understood. Objective: To determine the factors that control chamber specificity of neonatal heart growth during perinatal maturation Methods: Total transcriptome was analyzed from deep RNA-seq in male newborn mouse (C57BL) left ventricle (LV) and right ventricle (RV) at postnatal day 0, 3 and 7. Functional validation was performed in Neonatal Rat Ventricular Myocytes (NRVMs) and intact neonatal mice. Results: Chamber specific- regulation of cell cycle genes was correlated with chamber specific- expression of the non-canonical Wnt11. Exogenous expression of Wnt11 induced maturation markers and suppressed cell cycle genes in myocytes. In contrast, targeted Wnt11 inhibition induced myocyte proliferation associated with upregulated cell cycle genes both in cultured NRVMs and in the intact heart. Notably, Wnt inhibition also significantly enhanced β-catenin phosphorylation without impacting JNK, PKCα, or p38- activities. Remarkably, both Wnt mediated signals and cell cycle markers were altered in heart samples from infants cyanotic CHDs. Furthermore, hypoxia exposure suppressed Wnt11 and induced cell cycle genes in cultured cardiomyocytes. Conclusions: Differential expression of Wnt11 and downstream cell cycle genes are novel molecular basis for chamber specific maturation. Wnt11 mediated-signaling has potential impact on cyanotic CHDs. Differential role of Wnt signaling in chamber specific post-natal heart maturation can lead to potential chamber-specific diagnoses and therapies for congenital heart diseases.
Abstract P388: Socioeconomic and Demographic Status and Perceived Health Risk of E-cigarettes Among Youth--Results From a National Survey
Authors: Thanh-Huyen T Vu, Allison Groom, Joy L Hart, Hy Tran, Robyn L Landry, Jennie Z Ma, Kandi L Walker, Aida L Giachello, Anshula Kesh, Thomas J Payne, Rose M Robertson
Journal: Circulation (2019)

Background: The prevalence of e-cigarette use among youth is on the rise and may be associated with adolescents’ limited knowledge of the health effects of these products. We examined how demographics and socioeconomic status (SES) are correlated with the perceived health risks of e-cigarettes among youth. Methods: Data from a national online survey of youth aged 13-18 in 2017, weighted to be representative of the overall U.S. population in age, sex, race, ethnicity, and region were analyzed. Differences in perceived health risks of nicotine and other chemicals provided by vaping were addressed with respect to the demographics and SES of the participants, taking into account their e-cigarette use status. Results: Among 3,174 participants, 56.5% were female, 19.3% Hispanics and 14.7% non-Hispanic Blacks. Indicators of low SES [family receiving public assistance (PA) or participating in free school lunch program] were seen in 50.2%. With adjustment for e-cigarette use status in multivariable regression models, perceived health risks from the contents of e-cigarettes differed by gender, age, place of residence, and SES status. For example, the odds of perceiving harm from nicotine in e-cigarette products was 1.6 times higher in girls than in boys; the same odds was lower by 27% for those in families receiving government PA compared to those in families that did not. A parent’s education level also significantly influenced their child’s perception of the harm of the contents of e-cigarette products ( see Figure ). Conclusions: For youth, the perceived health risks of nicotine, toxins or chemicals in e-cigarette products were significantly different by age, gender, race/ethnicity, and SES. The findings may have relevance for developing communications and education strategies targeting specific youth audiences, especially those in vulnerable groups. These strategies could improve awareness among youth concerning the health effects of e-cigarettes, helping to prevent or reduce e-cigarette use.
Treatment duration and survival time: Does only the last line matter?
Authors: Daisuke Goto, Nader Hanna, Brian S. Seal, Ebere Onukwugha, C. Daniel Mullins
Journal: Journal of Clinical Oncology (2015)

e17695 Background: An increasing number of metastatic colon cancer (mCC) patients today receive multiple lines of chemotherapy as new chemotherapy agents and biologics have become available following the FDA’s approvals in the late 1990s and early 2000s. Although evidence shows that new therapeutic regimens, as well as second and subsequent lines of treatment (Tx) prolong patients’ survival, whether Tx duration is correlated with survival time is unclear. In our study, we used real world practice data to investigate correlations between Tx duration and survival time among elderly mCC patients. Methods: We examined 4,222 mCC patients in the SEER-Medicare database who were diagnosed between 2006 and 2009 and had 1 or 2 Tx lines of chemotherapy and/or biologics. The Cox hazard model with time varying covariates was used to estimate patients’ survival after the termination of the first and second (if applicable) line of Tx. Our primary endpoint of interest was all-cause mortality. Patients were followed until the end of 2010, and 474 patients were truncated. In addition to Tx duration, we used demographic and clinical variables as covariates; including age, sex, marital status, Charlson Comorbidity Index, and dose reduction during Tx. We conducted sensitivity analysis using a generalized gamma model. Results: Statistically significant positive correlations exist between duration of the last line of Tx and survival time (measured from the end of the treatment) among patients with 1 and 2 lines of Tx (N = 2631 and 1591, respectively). The adjusted hazard ratios between patients in the lowest and highest quartiles of the last Tx duration were 0.52 (95% CI = 0.46 - 0.61) and 0.73 (95% CI = 0.62 - 0.88) on day 90 for patients with 1 and 2 Tx lines, respectively. In contrast, no significant correlation was found between the duration of the first line Tx and survival time among patients with 2 Tx lines. These results were consistent across the Cox and gamma models. Conclusions: Our results indicate that duration of Tx before the last line is not predictive of survival time of mCC patients, but the duration of the last line is predictive of survival time. Thus, the prognosis of elderly patients who proceed to an additional line of Tx cannot be predicted by length of prior Tx.