tbuckley/cabot-search huggingface dataset:
Randomized trial of quality-of-life measurement in oncology practice: Do oncologists need to know?
Authors: G. Velikova, S. Sheppard, L. Campbell, A. Smith, N. Awad, P. Selby, J. Brown
Journal: Journal of Clinical Oncology (2008)

9586 Background: Previous randomised trial suggested that regular measurement of quality of life (QOL) during chemotherapy may have a positive impact on patient wellbeing, even when the data was not provided to physicians (Velikova et al. J Clin Oncol 2004, 22:714). The trial design allowed for possible contamination effect on physicians behaviour, as patients were randomized, but physicians saw both patients with and without QOL information. This subsequent randomized study was designed to replicate previous trial without contamination effect, evaluating the impact of questionnaire completion only, without feedback and training of oncologists. Methods: Cancer patients on chemotherapy were randomized to: intervention-completion of EORTC QLQ-C30 and Hospital Anxiety and Depression Scale on touch-screen computers before 3 consecutive clinic visits, without providing scores to oncologists; and Control group-standard care. Outcome measures were doctor-patient communication (measured by content analysis of recorded consultations) and patient wellbeing (measured by FACT-G questionnaire). Results: 502 patients from 3 hospitals were approached, 145 (29%) declined, 356 were randomized, 236 completed the study. No significant impact on doctor-patient communication was found, apart from an increased discussion of appetite in the intervention group (51% of encounters vs 40% in control group, p=0.015). Patients completing the questionnaires showed a small, but statistically significant deterioration in their wellbeing in comparison with the control group (mean change FACT-G score -3.3 in intervention group vs 0.99 in control, p=0.047) in a regression analysis controlling for baseline FACT-G, age, gender, diagnosis, performance status, response to treatment. Conclusions: This trial did not confirm previous findings of positive effect on patient care from regular QOL measurement during chemotherapy and suggested a small negative effect, when the information is not provided to oncologists. It appears that the QOL intervention could only work if both patients and physicians participate in eliciting relevant issues. Training physicians how to engage and use QOL information in clinical practice should be the focus of future work. No significant financial relationships to disclose.
First-line gefitinib therapy for elder advanced non-small cell lung cancer patients with epidermal growth factor receptor mutations: Multicenter phase II trial (NEJ 003 study).
Authors: Y. Minegishi, M. Maemondo, S. Okinaga, N. Morikawa, A. Inoue, K. Kobayashi, M. Harada, K. Hagiwara, T. Nukiwa, A. Gemma
Journal: Journal of Clinical Oncology (2010)

7561 Background: First line treatment by gefitinib for NSCLC patients with EGFR mutations has been validated by us (NEJ 002 Study) and WJTOG3405. In these studies, patients with ages less than 75 years were enrolled. Namely, there has been no data of the first-line gefitinib for elderly patients with EGFR mutations. The purpose of this study was to investigate the efficacy and the feasibility of gefitinib for chemotherapy-naïve patients of 75 years or older advanced non-small cell lung cancer (NSCLC) harboring the epidermal growth factor receptor (EGFR) mutations. Methods: Chemotherapy-naïve patients of 75 years of age or older with advanced NSCLC, Eastern Cooperative Oncology Group performance status 0-1, adequate organ function who had EGFR mutations examined by peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp (PNA-LNA PCR Clamp) method were enrolled and receive 250 mg/day of gefitinib alone. Results: Between January 2008 and May 2009, 31 patients were enrolled, of whom all patients were eligible. Median age (range) was 80 (75-87) years. Twenty five patients were female (81%) and 30 patients had adenocarcinoma (97%). Overall response rate was 74% (95% CI, 58% to 91%), and the disease control rate was 90%. The median progression-free survival was 13.6 months. The most common adverse events were rash, liver dysfunction and diarrhea. One treatment related death by interstitial lung disease was observed. Conclusions: This is the first report indicating that gefitinib first-line therapy could achieve a high efficacy with acceptable toxicity in advanced NSCLC patients with EGFR mutations who are 75 years of age or older. Updated data including overall survival will be presented in the conference. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca, Chugai Pharma, Lilly, Novartis Research fund for translational researcch
Association of Lipopolysaccharide-Binding Protein With Aging-Related Adiposity Change and Prediabetes Among African Ancestry Men
Authors: Curtis M. Tilves, Joseph M. Zmuda, Allison L. Kuipers, Cara S. Nestlerode, Rhobert W. Evans, Clareann H. Bunker, Alan L. Patrick, Iva Miljkovic
Journal: Diabetes Care (2015)

Cross-sectional studies suggest that lipopolysaccharide-binding protein (LBP) may be associated with obesity and metabolic disorders. However, prospective studies examining LBP are lacking. This prospective study investigated the association between LBP and metabolic abnormalities in 580 African ancestry men (mean age, 59.1 ± 10.5 years).We measured fasting serum LBP at baseline. Changes in adiposity and glucose homeostasis as well as case subjects with new type 2 diabetes and impaired fasting glucose (IFG) were assessed at a follow-up visit ~6 years later. Baseline LBP values were tested across quartiles for linear trend with metabolic measures. Multivariable logistic regression was used to determine the odds of new cases of IFG or diabetes per 1-SD greater baseline LBP.LBP was significantly associated with baseline BMI, waist circumference, whole-body and trunk fat, skeletal muscle density, fasting serum insulin, and HOMA-insulin resistance (IR) (all P < 0.01). Greater baseline LBP was significantly associated with longitudinal increases in the percentage of trunk fat (P = 0.025) and HOMA-IR (P = 0.034), but only borderline so with a decrease in skeletal muscle density (P = 0.057). In men with normal glucose, baseline LBP was associated with increased odds of having IFG at follow-up after adjustment for age, baseline trunk fat, and lifestyle factors (odds ratio per 1-SD LBP: 1.51; 95% CI 1.02-2.21). This association was attenuated after additional adjustment for change in trunk fat (P = 0.067).LBP may be a marker of prediabetes. Some of this association appears to be mediated through increased central and ectopic skeletal muscle adiposity.
Subgroup Efficacy in Patients Receiving Intralesional Rose Bengal to All Existing Melanoma in Phase Ii Study Pv-10-Mm-02
Authors: S. Agarwala, J.F. Thompson, B.M. Smithers, M. Ross, C.R. Scoggins, B.J. Coventry, S.J. Neuhaus, D.R. Minor, J.M. Singer, E. Wachter
Journal: Annals of Oncology (2014)
A retrospective study of adolescents' visits to a general hospital psychiatric emergency service
Authors: J R Hillard, M Slomowitz, L S Levi
Journal: American Journal of Psychiatry (1987)

Characteristics of 100 visits by adolescents (less than 18 years old) to a psychiatric emergency service were examined and compared with those of 100 visits by adults. Adolescents were less likely than adults to receive diagnoses of psychosis and personality disorder but more likely to receive diagnoses of adjustment and conduct disorders, were less likely to have had previous psychiatric treatment but equally likely (40%) to be in current treatment, and required more time to evaluate. Self-destructive ideation or behavior was present in 40% of the adolescents. Nearly all visits were judged to have represented genuine emergencies.
Expression of estrogen receptors alfa and beta (ERa and ERb) in hereditary breast cancer
Authors: M. Litwiniuk, J. Breborowicz, V. Filas, J. Moczko, D. Godlewski, M. Stawicka, R. Kaleta
Journal: Journal of Clinical Oncology (2005)

550 Background: Breast cancers (BC) in women carrying mutations in BRCA1 gene are more frequently estrogen receptor negative than the nonhereditary BC. However, tamoxifen has been found to have a protective effect in preventing contralateral tumors in BRCA1 mutation carriers. The identification of the second human estrogen receptor, ERβ, raised a question of its role in hereditary breast cancer. Patients and Methods: Formalin-fixed, paraffin embedded breast cancer tissues from 46 patients with mutations in BRCA1 gene were used in this study. A mutation analysis was carried out by a multiplex PCR assay. Only 3 common founder mutations in Poland in the BRCA1: 5382insC, 4153 delA, C61G were tested. Immunostaining for ERα, ERβ and PgR (progesterone receptor) was performed using monoclonal antibodies against ERα, PgR (DakoCytomation), and against ERβ (CHEMICON). The EnVision detection system was applied. The study population comprised a control group of 65 BC patients operated successively in 2002. The data were analyzed using a nonparametric Fisher-Freeman-Halton test; the statistical significance was considered when p<0,05. Results: BRCA1 mutation carriers were more likely to have ERα-negative BC than those in the control group. Only 17% of BRCA1-related cancers were ERα-positive compared with 58% in the control group (p=0,0001). The expression of ERβ protein was observed in 37% of BRCA1-related tumors. The expression of ERβ protein in ERα-negative tumors was twice as frequent in the BRCA1-related group. This was particularly striking at the age ≥ 50 where 33% of BRCA1 mutation bearing patients were exclusively ERβ positive vs. 13% in the control group. The results obtained in a similar analysis for patients below 50 showed 25% and 16%, respectively. The expression of PgR was observed in 17% of BRCA1-related BC and in 68% of tumors in the control group. Conclusions: In BRCA1-associated tumors the expression of ERβ was higher than the expression of ERα. This may, in part, explain the protective effect of tamoxifen in preventing contralateral tumors in BRCA1 mutation carriers. Testing patients with BRCA1 mutation for the presence of both ERα and ERβ may help to identify those who might benefit from endocrine therapy. No significant financial relationships to disclose.
Abstract 9954: 5-Lipoxygenase Inhibitor VIA-2291 (Atreleuton) Intake Improves Left Ventricular Ejection Fraction in Patients with Recent Acute Coronary Syndrome
Authors: Reuben J Ram, Vahid Nabavi Larijani, Sachidanand Prabhu, Christopher Dialing, Armand Ardestani, Nina Ram, Naser Ahmadi, Reda Ibrahim, Josephine Pressacco, Jean-Claude Tardif, Matthew J Budoff
Journal: Circulation (2012)

Background: Previous studies have shown coronary artery syndrome can result in left ventricular myocardial remodeling (LVMR); and progressive LVMR after infarction could lead to decline in ejection fraction. In this study we evaluated the effect of a potent and selective 5-Lipoxygenase inhibitor, VIA-2291, on Left Ventricular Ejection Fraction (LVEF) in patients with recent Acute Coronary Syndrome (ACS) on top of standard medical therapy. Methods: This is a double blinded: placebo controlled: dose ranging: randomized: multicenter trial (clinicaltrials.gov NCT00358826 ) of 56 individuals with recent ACS who were recruited and followed for 24 weeks in an imaging substudy. Subjects were randomized to four study arms including: 25 mg, 50 mg, and 100 mg of VIA-2291 as well as placebo. LVEF and Stroke Volume (SV) were measured post-hoc by contrast enhanced Cardiac Computed Tomographic Angiography on GE Advantage Windows 4.4 Workstations (GE Healthcare, Milwaukee, WI). Result: There were no major differences between traditional cardiovascular risk factors among the 4 randomized study arms. LVEF improved dramatically in subjects who had taken VIA-2291 vs. placebo: 1.8±8.4 vs. -3.0±9.3 (p=0.0001). Similarly SV improved significantly with VIA-2291 vs. placebo: 3.9±15.9 vs. -4.8±17.2 (p=0.0001). VIA-2291 demonstrated a dose dependent effect on LVEF and SV with largest benefit achieved with the highest dose of the drug (100mg) vs. Placebo; LVEF and SV: 2.64±6.06 and 4.65±14.01, p=0.0001, respectively (Figure 1). Of note, the placebo group was shown to have a decrease in LVEF and SV -3.1±9.3 and -4.8±17.2, respectively, which can be attributed to post-ACS myocardial-remodeling. Conclusion: The addition of VIA-2291 to standard of care medical regimen is able to improve ejection fraction dramatically in patient with recent coronary artery syndrome over a 6 month follow-up period. Benefits of VIA-2291 are dose dependent.
Long-term outcome of phase II study of biweekly dose-dense AC followed by weekly paclitaxel and carboplatin and trastuzumab (TC ± H) based on HER2 status in large and inflammatory breast cancer (BC).
Authors: R. S. Mehta, T. Schubbert, D. Jackson
Journal: Journal of Clinical Oncology (2010)

680 Background: We reported high pathologic complete response (pCR) with TC±H as salvage or consolidative treatment following anthracyclines in a pilot and a confirmatory phase II trial (SABCS2004-ASCO 2009). Methods: 47 of 48 enrolled women with BC received weekly TC for 9-12 weeks, and concurrent 12-16 weekly H (if HER2–positive) following 2-4 cycles of dose-dense AC. The clinical response, pCR rates and early survival outcomes were reported previously. Results: In 35 patients (pts) with stage II-III BC, higher pCR rates occurred in pts with HER2-positive tumors (80% vs. 32% for HER2-negative tumors; p > 0 .008), with ER–negative tumors (94% vs. 16% for ER-positive tumors; p < 0.0001), or with triple-negative tumors (100% vs. 13% ER-positive and HER2-negative tumors; p > 0.001); at a median of 54 months postoperatively, recurrence-free survival (RFS) was 94%, and distant RFS (DRFS) was 97%, and at a median of 60 months from diagnosis, overall survival (OS) was 97% (95% CI 91-100). In 15 pts with HER2-positive BC, RFS and OS is 100%, versus 90% and 95%, respectively in 20 with HER2- negative BC (log-rank p > 0.22 and 0.39). For comparison, in 13 pts with stage II-III BC in the pilot study, RFS, DRFS and OS were 77% (includes contra-lateral BRCA-associated primary), 85%, and 92% at median of 80 months. At five years, combining pilot and phase-II data (n=48), RFS and OS is similar at 96% for 22 patients with HER2-positive and 26 with HER2-negative breast cancer (p > 0.91). Importantly, of 22 HER2-positive patients, only 2 completed ≥ 6 months of trastuzumab. Though 5 pts with metastasis achieved pCR, RFS and OS at 5 years is 8% and 25% in phase II study (n > 12) and 0% in the pilot study (n > 4). Conclusions: Despite inclusion of inflammatory BC, neoadjuvant weekly carboplatin and paclitaxel with trastuzumab (in HER2-postive) following response-adjusted dose-dense anthracyclines achieves high long-term survival in patients with HER2-positive and HER2-negative BC. Moreover, RFS and OS in HER2-positive are similar to that in HER2-negative BC, despite use of short course of trastuzumab. Long-term survival in metastatic setting remains dismal. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Berlex
Preoperative cetuximab and radiation (XRT) for patients (pts) with surgically resectable esophageal and gastroesophageal junction (GEJ) carcinomas: A pilot study from the Hoosier Oncology Group and the University of Texas Southwestern
Authors: A. K. Agarwala, N. Hanna, A. McCollum, N. Bechar, M. DiMaio, M. Yu, Y. Tong, C. R. Becerra, H. Choy
Journal: Journal of Clinical Oncology (2009)

4557 Background: Pre-operative chemoradiotherapy (CRT) followed by surgical resection is a standard treatment option for pts with resectable esophageal or GE junction (GEJ) carcinomas (CA). Cetuximab, when combined with XRT is effective treatment for locally advanced cancers of the head and neck. We conducted this study to evaluate this regimen in pts with esophageal and GEJ CA. Methods: This is a single arm, open label pilot study combining cetuximab with XRT for pts with resectable esophageal and GEJ CA. The primary objective is to determine the pathologic complete response rate (pCR) (null hypothesis: p=0.20; alternative hypothesis: p=0.35) and determine the feasibility and toxicity of this regimen when given prior to esophagectomy. Key eligibility criteria are: squamous cell (SC)or adenoCA of the esophagus or GEJ, ECOG PS 0–2, clinical stage II -IVa, and eligible for esophagectomy. Pts received a loading dose of cetuximab at 400mg/m2 2 weeks prior to XRT, then weekly at 250 mg/m2 starting one week prior to XRT until completion of 50.4 Gy XRT. After satisfactory recovery, pts had esophagectomy. Results: Patient characteristics (n=40): median age 65 years (range, 54–82); 92% male; PS 0/1 63%/32%; esophageal/GEJ 65%/35%; adenoCA/SC 78%/22%; 36 pts have completed cetuximab and radiation and 26 pts have undergone esophagectomy. Of the 26 pts that have undergone esophagectomy, 13 obtained a pCR. 5/13 SC had pCR and 8/13 adenoCA had pCR. 10 pts did not undergo surgery for various reasons including disease progression (n=7), AE unrelated to treatment (n=2), and personal decision to forgo esophagectomy (n=1). 4 patients are still completing cetuximab/XRT. The most common G3 adverse event was rash (56%). Other G3 toxicities were infrequent and included dysphagia (6%), infection (6%), and GI bleed (3%). There have been no treatment or surgery related deaths. Conclusions: Cetuximab and XRT results in pCR's in pts with esophageal and GEJ CA (rate of pCR 13/36), including patients with either SC or adenoCA histologies. G3/4 toxicities, including dysphagia were generally uncommon. Further study of this combination prior to esophagectomy is warranted. [Table: see text]
Phase II study of erlotinib in chemo-naive women with advanced pulmonary adenocarcinoma
Authors: D. Jackman, N. I. Lindeman, J. Lucca, L. K. Morse, M. S. Rabin, J. P. Marcoux, M. Huberman, B. E. Johnson, P. A. Janne
Journal: Journal of Clinical Oncology (2007)

7591 Background: Erlotinib is associated with a survival benefit over placebo for pts with advanced NSCLC who had received 1–2 prior regimens. Its role as initial therapy in clinically defined subgroups or in pts prospectively tested for EGFR mutations is less clear. Methods: Chemotherapy-naive women with adenocarcinoma, stage IIIB/IV, PS 0–1, who had formerly or never smoked, were enrolled and treated with erlotinib 150 mg PO daily, until the time of disease progression or unacceptable toxicity. Response rate was the primary endpoint. Secondary endpoints included overall survival, progression-free survival and toxicity. Tumor tissue adequate for genomic analysis was mandated and prospectively collected for determination of EGFR and KRAS mutations by direct sequencing. Results: From 11/04 to 10/06, 40 women were treated. Demographics: median age 65 yrs (range 36–87); 38 white, 1 black, 1 Asian; 30% PS 0, 70% PS 1; 20% BAC or adenoCA w/ predominant BAC features, 80% adenoCA w/o BAC features; smoking status: 63% former, 37% never. Toxicity: Rash (95%; 30% grade 3) and diarrhea (73%; 10% grade 3) were the most common toxicities. 50% of pts developed toxicity of grade 3 or greater. 5 pts were discontinued due to toxicity, with 2 deaths that were possibly treatment-related: 1 DIC, 1 hepatic failure. There were also two pts with PE (one fatal). Response: CR 0, PR 12 (30%), SD 11 (28%), and PD 10 (25%), 7 not evaluable. To date, 27 patients have progressed, with 14 deaths. Median PFS was 5.6 months; median overall survival has not yet been reached and exceeds 23 months. Of 32 patients sequenced for EGFR to date, there were 9 exon 19 deletions, 3 L858R mutations, and 1 exon 20 insertion. For the 12 pts prospectively determined to have classic EGFR mutations, RR was 75% (9 PR, 2 SD, 1 not evaluable). Of 15 pts w/ wild-type EGFR, only 1 response (7%) was achieved. The pt w/ the exon 20 insertion developed PD. Of 28 pts evaluated to date for KRAS, 6 KRAS mutations were found, w/ no responses in this group (2 PD, 4 SD). Conclusions: Preliminary results suggest that first-line erlotinib monotherapy may be a useful treatment strategy for women with adenocarcinoma and a limited smoking history. Response rate is particularly impressive for those subjects prospectively found to have an EGFR mutation, and poor for those with KRAS mutations. No significant financial relationships to disclose.
Abstract 19687: The Signaling Pathway for Aldosterone-induced Mitochondrial Production of Superoxide Anion in the Myocardium
Authors: Irene L Ennis, Claudia Caldiz, Maria C Villa-Abrille, Patricio E Morgan, Gladys E Chiappe de Cingolani, Horacio E Cingolani
Journal: Circulation (2012)

Mineralocorticoid receptor (MR) antagonists decrease morbidity and mortality in heart failure patients for whom oxidative stress is common; however, the underlying mechanism of MR-antagonist protection is unclear. Because aldosterone stimulates reactive oxygen species production, we explored in rat myocardium the effect of aldosterone on O2[[Unable to Display Character: &amp;#729;]] production and the intracellular pathway involved. Aldosterone dose-dependently stimulated O2[[Unable to Display Character: &amp;#729;]] production. At 10 nmol/L, aldosterone increased O2[[Unable to Display Character: &amp;#729;]] to 165±8.8 % of control, an effect prevented by the MR antagonists, eplerenone and spironolactone (107±7.8 and 103±5.3 %, respectively), and by inhibition of EGF receptor (EGFR) with AG1478 (105±8.0%), implicating EGFR transactivation in this pathway. Similar results were obtained silencing MR expression by direct intramyocardial injection of a lentivirus coding for a siRNA against the MR. The aldosterone effect was mimicked by the mKATP channel opener diazoxide but blocked by preventing its opening with 5-HD and glibenclamide, implicating the mitochondria as the O2[[Unable to Display Character: &amp;#729;]] source. Inhibiting the respiratory chain with rotenone also cancelled aldosterone-induced O2[[Unable to Display Character: &amp;#729;]] production. In addition, the aldosterone effect depended on NADPH oxidase and phosphoinositide 3-kinase activation, as apocynin and wortmannin respectively inhibited it. EGF (0.1µg/mL) similarly increased O2[[Unable to Display Character: &amp;#729;]], although in this case MR antagonists had no effect, suggesting that EGFR transactivation occurred downstream from MR. The results allow us to propose that a decrease in oxidative stress may be one of the mechanisms contributing to the beneficial effects of MR antagonists in heart failure.