tbuckley/cabot-search huggingface dataset:
Suicidality in patients with pure and depressive mania
Authors: S C Dilsaver, Y W Chen, A C Swann, A M Shoaib, K J Krajewski
Journal: American Journal of Psychiatry (1994)

A previous comprehensive literature review indicated that suicide accounted for 18.9% of the deaths of 9,389 individuals with manic-depressive illness. The literature associates these deaths with the depressed phase of the disease. This study was designed to determine the rate and severity of suicidality among patients with pure and depressive mania.The patients were 93 persons who met the Research Diagnostic Criteria (RDC) for bipolar I disorder (N = 75) or schizoaffective disorder (N = 18). All met the RDC for primary mania and the DSM-III-R criteria for bipolar disorder, manic or mixed. Patients with depressive mania met the RDC for mania and major depressive disorder concurrently. Severity of current suicidality was measured by using the Schedule for Affective Disorders and Schizophrenia suicide subscale. Differences in the mean suicidality scores between any two groups were assessed with the Kruskal-Wallis test. Relationships of age, gender, type of affective illness (bipolar I versus schizoaffective disorder), psychosis, race, and mania subtype to suicidality were assessed by using multivariate logistic regression analysis.One (2.0%) of the 49 patients with pure mania was suicidal. In contrast, 24 (54.5%) of the 44 patients with depressive mania were suicidal. This difference was highly significant. Gender and psychosis were not related to suicidality. African-Americans were less likely to be suicidal than Caucasians. Subtype of mania had the strongest relationship to suicidality.A subgroup of manic patients are severely suicidal. Presentation in the manic state is an indication for careful assessment of depressive symptoms and suicidality.
Safety of pemetrexed according to the duration of vitamin B12 and folic acid supplementation prior to the first dose of pemetrexed
Authors: Yasumasa Tsuda, Atsushi Kitamura, Naoki Nishimura, Nao Yagi, Shinji Takayama, Kouhei Okafuji, Yutaka Tomishima, Torahiko Jinta, Keiko Koyama, Sachiko Ohde, Kazumi Gotoh, Naohiko Chohnabayashi
Journal: European Respiratory Journal (2014)

Objective: Administration of vitamin B12 and folic acid 7 days prior to the administration of the first dose of pemetrexed is recommended. However, vitamin supplementation is rarely initiated less than 7 days prior to the first dose of pemetrexed. Therefore, we analyzed the safety of vitamin supplementation less than 7 days prior to the first dose of pemetrexed.   Methods: Patients with nonsquamous non-small-cell lung cancer were classified into 2 groups according to the duration of vitamin supplementation prior to the first dose of pemetrexed: group A received vitamin supplementation for more than 7 days, group B received vitamin supplementation for less than 7 days. We analyzed the adverse effects such as myelosuppression, rash, and diarrhea after 1 cycle of pemetrexed therapy.   Results: A total of 73 patients were administered pemetrexed; 41 patients were men and 32 were women with a median age of 64 years (range, 43–86 years). A total of 59 patients were classified into group A and 14 into group B; 32 patients were administered pemetrexed as a first-line treatment. Neutropenia of Grade 3 or more occurred in 3/52(5.8%) patients in group A and 2/14(14.3%) patients in group B (p = 0.29). There were no significant differences in the rate of occurrence of neutropenia, rash, or diarrhea.   Conclusion: In this retrospective study, we determined that it was safe to administer pemetrexed if vitamin supplementation had been initiated for less than 7 days prior to the first dose of pemetrexed.
Clinical outcomes and predictive factors in patients with liver metastasis from breast cancer treated with gemcitabine and cisplatin (GC) salvage regimen
Authors: L. Araujo, O. Metzger Filho, C. A. Gomes, M. V. Moitinho, A. M. Silva, F. M. Carcano, H. Noronha Júnior
Journal: Journal of Clinical Oncology (2009)

e17568 Background: Liver metastasis (mets) from breast cancer is typically associated with poor prognosis. GC is a good option, since patients (pts) have often failed anthracycline and taxane therapy and liver dysfunction may preclude these regimens. Methods: Retrospective study designed to evaluate the clinical outcomes and predictive factors in pts with metastatic breast cancer treated with GC, with special interest for liver mets. Results: From 2004 to 2007, 56 pts were treated with GC. Median age was 52.1 years, 33 pts had PS 0–1, 26 were hormone receptor (HR) negative, 32 had been treated with 3 or more chemotherapy (CT) regimens and 34 had liver mets. The median overall survival (OS) was 7,1 mo (95% CI; 4.3–9.7), the progression free survival was 3.3 mo (95% CI; 2.2–5.5) and the clinical response rate was 25%. OS was 4.0 mo (95% CI; 2.3–8.9) for pts with liver mets and 9.7 mo (95% CI; 6.9–12.9) for pts without liver mets (p = 0.03). No factor showed correlation with OS in pts with liver mets, including age &lt; 45 years (median OS [95% CI]: 2.8 mo [1.8–11.5] versus 4.5 mo [2.5–8.9]; p = 0.74), PS 0–1 (median OS [95% CI]: 7.3 mo [2.5–11.5] versus 2.8 mo [0.8–9.7]; p = 0.55), HR positivity (median OS [95% CI]: 7.3 mo [2.0–11.5] versus 5.9 mo [1.9–9.7]; p = 0.87), bilirubin level ≥ 5 times the superior limit of the normality (median OS [95% CI]: 5.9 mo [0.5–16.7] versus 4.5 mo [2.5–9.7]; p = 0.45), progression free interval after the previous CT ≤ 1 mo (median OS [95% CI]: 4.0 mo [2.0–9.7] versus 7.1 mo [2.5–14.7]; p = 0.93) and previous treatment with ≥ 3 CT regimens (median OS [95% CI]: 7.3 mo [1.0–11.0] versus 4.0 mo [2.0–9.7]; p = 0.93). Conclusions: These data is in accordance with the literature concerning the dismal prognosis in liver mets from breast cancer and the clinical activity of GC. We could not define predictive factors in this cohort, which was probably due to the relatively small number of pts. No significant financial relationships to disclose.
A prospective study to evaluate the role of gene expression profiles (GEP) in predicting clinical outcome of patients (pts) receiving preoperative chemotherapy for oesophagogastric (OG) cancer
Authors: S. Rao, D. Cunningham, M. Benson, R. Te Poele, L. Welsh, N. Starling, A. Norman, C. Saffery, P. Workman, P. Clarke
Journal: Journal of Clinical Oncology (2007)

4501 Background: Whilst preoperative chemotherapy has demonstrated survival benefit for pts with potentially resectable OG cancer it is not possible to predict the benefit for an individual pt. This study was designed to prospectively correlate GEP with clinical outcome. Methods: Eligible pts were deemed to have resectable disease after staging CT, EUS, and laparoscopy as indicated &amp; following discussion at the multidisciplinary team meeting. All pts received neoadjuvant platinum &amp; fluoropyrimidine based chemotherapy &amp; clinical data were entered prospectively onto a study specific database. GEP were produced from total RNA isolated from snap frozen pre treatment tumour biopsies obtained at baseline endoscopy. Labelled cDNA was hybridised versus a universal human reference using an in house c DNA array of 22,000 clones. Results: Of the pts with adequate follow up accrued between 2002–2005, 35 met the quality control measures for the arrays. Median age=66 yrs (47–83); male=32, female=3; tumour subsites: oesophagus=23, oesophago-gastric junction (OGJ)=12; adenocarcinoma=35; T stage: T 2=3, T3=30, T4=2; N stage: N0=12, N1=23; performance status 0=7, 1=28. Median follow up=938 days. Median overall survival (OS) = 570 days. Prognostic groups were designated according to the median OS (days) of the group: good &gt; median and poor &lt; median. Supervised hierarchical clustering of normalised data revealed significantly differentially expressed genes based on OS (p&lt;0.01) with 2 distinct clusters: a poor outcome group: N= 17 (2yr OS 17.6%) [95% CI: 4.3–38.3], a good outcome group: N=18 (2 yr OS 55%) [95% CI: 30.5–74.8]. Of the differentially expressed genes, those involved in receptor tyrosine kinase signalling &amp; cell growth were amongst the most significantly affected pathways. Conclusions: This novel technique using GEP in tumour biopsies has successfully identified groups of tumours with distinct gene expression profiles that correlate with survival. The approach warrants further validation in a larger cohort. It could facilitate the development of tailored treatment according to individual tumour biology in OG cancer. No significant financial relationships to disclose.
First results of the EORTC-GELA H9 randomized trials: the H9-F trial (comparing 3 radiation dose levels) and H9-U trial (comparing 3 chemotherapy schemes) in patients with favorable or unfavorable early stage Hodgkin’s lymphoma (HL)
Authors: E. M. Noordijk, J. Thomas, C. Fermé, M. B. van ’t Veer, P. Brice, M. Diviné, F. Morschhauser, P. Carde, H. Eghbali, M. Henry-Amar
Journal: Journal of Clinical Oncology (2005)

6505 Background: EORTC and GELA aim at reducing acute and late side effects of treatment in early stages HL, without jeopardizing high event-free survival (EFS) and overall survival (OS) rates already achieved. Methods: From October 1998 to May 2004, 1591 patients with stage I-II HL were enrolled into 2 trials based on 4 prognostic factors: age, symptoms, number of involved areas, MT-ratio. The H9-F trial compared 36 Gy involved field radiotherapy (IF-RT) vs 20 Gy IF-RT vs no RT in patients in complete remission (CR(u)) after 6 cycles of EBVP. The H9-U trial compared 6 cycles of ABVD vs 4 cycles of ABVD vs 4 cycles of BEACOPP baseline, followed by 30 Gy IF-RT in all arms, in patients with unfavorable clinical features. Results: In the H9-F trial, of the 783 patients enrolled, 619 (79%) achieved a CR(u) and were randomized. Inclusion of patients in the no-RT arm was stopped in May 2002, because stopping rules were met (ie. > 20% of events). Inclusion in the other 2 arms continued until May 2004. After a median follow-up of 33 months, the 4-year EFS rates were 87% in the 36 Gy and 84% in the 20 Gy arm; it was 70% in the 0 Gy arm (p<0.001). The 4-year OS rate was 98% in all 3 arms. Until September 2002, 808 patients were randomized in the H9-U trial. The 4-year EFS rates were 94%, 89% and 91% in the 3 arms, respectively (p=0.23) and the 4-year OS rates 96%, 95% and 93% (p=0.89). Chemotherapy-related toxicity (measured by antibiotics, transfusions, hospitalization, S.A.E.) was higher with BEACOPP compared to ABVD. Conclusions: In favorable HL patients who achieve CR(u) after 6 cycles of EBVP, omission of IF-RT leads to an unacceptable failure rate; in contrast, an IF-RT dose reduced to 20 Gy provides equivalent early results as an IF-RT dose of 36 Gy. In unfavorable HL patients, similar early EFS rates are observed when the number of ABVD cycles is reduced from 6 to 4. BEACOPP is not more efficient but more toxic. No significant financial relationships to disclose.
The impact of dietary patterns on cancer recurrence and survival in patients with stage III colon cancer: Findings from CALGB 89803
Authors: J. A. Meyerhardt, D. Niedzwiecki, D. Hollis, L. Saltz, W. Willett, R. J. Mayer, C. S. Fuchs
Journal: Journal of Clinical Oncology (2007)

4019 Background: Dietary factors have been associated with the risk of developing colon cancer; the influence of diet on pts with established disease is unknown. Methods: We conducted a prospective observational study of 1,009 patients with stage III colon cancer enrolled in a phase III adjuvant chemotherapy trial. Patients reported on dietary intake using a food frequency questionnaire during and 6 months after adjuvant chemotherapy. We identified two major dietary patterns, prudent and Western, by factor analysis. The prudent pattern was characterized by higher intake of fruits, vegetables, poultry and fish; the Western pattern by higher intake of red meat, fat, refined grains and desserts. Since there was no difference in efficacy between the 2 treatments, data for all pts were combined and analyzed according to quintiles of each dietary pattern. Patients were followed for cancer recurrence or death. Results: A higher intake of a Western pattern diet after cancer diagnosis was associated with a significantly worsened disease-free survival (DFS). After adjustment for gender, age, T and N stage, body mass index, physical activity level, weight change, baseline performance status, and treatment arm, patients in the highest quintile of Western pattern diet intake experienced a hazard ratio for DFS of 3.15 (95% confidence interval [CI], 1.76–5.63; p trend = &lt;0.0001), compared to those in the lowest quintile. Western pattern diet was associated with a similar detriment in recurrence-free survival (adjusted p trend = 0.001) and overall survival (adjusted p trend = 0.0002). In contrast, prudent pattern diet did not significantly influence cancer recurrence or mortality. Conclusions: Higher intake of a Western pattern diet may increase the risk of recurrence and mortality among patients with stage III colon cancer patients treated with surgery and adjuvant chemotherapy. Further studies are needed to delineate which components of such a diet are most influential. [Table: see text] No significant financial relationships to disclose.
Evaluation of the false-negative rate of standardized and quantitative measurement of estrogen receptor (ER) in tissue using AQUA technology
Authors: M. D. Gustavson, A. Welsh, C. Jones, J. Mayotte, J. Tu, J. Hopkins, D. Rimm, J. Christiansen
Journal: Journal of Clinical Oncology (2009)

567 Background: The discovery of an astoundingly high false negative rate for estrogen receptor (ER) testing in Canada has raised questions about the accuracy and reproducibility of ER testing. One solution would be the introduction of a standardized and reproducible diagnostic test that is easily adaptable in the clinical setting. Here, we have tested the AQUA method of quantitative immunofluorescence for the standardized and reproducible quantification of ER protein expression in tissue. Methods: Quantitative Western blotting was used in conjunction with AQUA analysis to create standard curves for assessment of absolute ER protein concentration in tissue (n = 118). We used standard scoring methods and AQUA analysis to quantify ER protein expression in a large cohort of breast cancer samples (n =669). Results: Using a series of standard curves, we determined that the range of the ER AQUA assay is between 100 pg/μg and 1500 pg/μg total protein. ER protein concentration in breast cancer samples showed an expected unimodal distribution for quantitative assessment of ER. Reproducibility studies of AQUA analysis demonstrated significant instrument-to-instrument (laboratory-to-laboratory) reproducibility for 3 instruments across the range of AQUA scores (average %CV = 1.34; R 2 &gt;0.99; ANOVA p = 0.67). The same cases were then read and classified by 3 pathologists using the Allred scoring system. Although their concordance is similar to that seen in the literature (Kappa = 0.81, 0.88, and 0.89), pathologist concordance rate is lower than for that observed with AQUA analysis (Kappa = 0.95, 0.96, and 0.97). Importantly, 9.0% of cases showed a change of diagnosis (positive/negative) across 3 pathologists whereas only 2.8% of cases changed classification using AQUA analysis. Additionally, misclassified cases occurred across the entire range of Allred scores, but were restricted to a narrow region defined by the cut-point for AQUA scoring. Conclusions: We have demonstrated that AQUA technology can provide for the standardized and reproducible quantification of ER with a 3 fold reduction in misclassification. This approach has the potential to decrease the problem of false negative tests for ER. [Table: see text]
Abstract 2330: Activation of cancer stem cells by oncogenic K-Ras requires activated Wnt/β-catenin signaling
Authors: Byoung-San Moon, Kug Hwa Lee, Kyounghwa Koo, Kang-Yell Choi
Journal: Cancer Research (2015)

Abstract Adenomatous polyposis coli (APC) loss-of-function mutations and K-Ras gain-of-function mutations are common abnormalities that occur during the initiation and intermediate adenoma stages of colorectal tumorigenesis, respectively. However, little is known about the role of these mutations in the regulation of cancer stem cells (CSCs) associated with colorectal cancer (CRC) tumorigenesis. We analyzed tissue from CRC patients (n = 49) and observed an association between K-Ras mutations and CSC activation during colorectal tumorigenesis. The oncogenic K-Ras mutations enhanced stemness of CRC cells carrying an APC mutation, as shown by comparisons of sphere formation, transforming potential, and differentiation in vitro and tumor-forming capacity in vivo between isogenic APC mutated CRC cells harboring either wild-type or mutant K-Ras. Moreover, the activation of CSC by K-Ras mutations in CRC required an additional APC mutation, as revealed by the induction of CD44, CD133, and CD166 in intestinal tumor tissues of APCMin/+/K-RasLA2 double-mutant mice, but not in K-RasLA2 mice. Overall, the progression and metastasis of CRC induced by K-Ras mutation occurs by initial activation of CSC by APC loss and further activation of Wnt/β-catenin signaling and subsequent activation of Ras-ERK signaling. Citation Format: Byoung-San Moon, Kug Hwa Lee, Kyounghwa Koo, Kang-Yell Choi. Activation of cancer stem cells by oncogenic K-Ras requires activated Wnt/β-catenin signaling. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2330. doi:10.1158/1538-7445.AM2015-2330
Use of PET SUV for primary tumor to predict outcome in locally advanced esophageal cancer treated with trimodality therapy
Authors: G. M. Videtic, H. M. Macley, C. Reddy, D. J. Adelstein, T. W. Rice, J. P. Saxton, N. Venigalla, S. Srinivas
Journal: Journal of Clinical Oncology (2009)

e15559 Background: To assess the value of the primary tumor's SUVmax (PT-SUVmax) from the staging FDG-PET as a predictor of clinical and pathologic outcomes in patients undergoing trimodality therapy for locally advanced esophageal cancer. Methods: A retrospective chart review was conducted on patients with T3/4 and/or node positive esophageal carcinoma treated at the Cleveland Clinic between 7/1/03 and 5/31/06. All patients were managed with an institutional regimen consisting of preoperative radiotherapy [30 Gy @ 1.5 Gy twice daily over two weeks] with concurrent cisplatin and 5-fluorouracil during the first week. Following resection, an identical postoperative course of concurrent chemoradiotherapy (CRT) was delivered. Pretreatment patient and tumor characteristics including PT-SUVmax were analyzed with respect to response and survival. Results: 141 patients completed preoperative CRT: 125 (88.7%) were male, median age was 60 years, 73.8% had adenocarcinoma, 79.4% had N1 disease, 81.6% underwent surgery and 63.8% completed the full regimen. Median follow-up was 17.2 months [range 0.7–75.1]. Median PT-SUVmax was 9.43 [range 0 to 47.7]. Increasing clinical stage was associated with increasing PT-SUVmaxs: for cT2 vs. cT3 and cN0 vs. cN1, PT-SUVmax cutoffs were 8 (p=0.03) and 11 (p=0.02), respectively. Median (MST) and 5-year overall survivals were 20.7 months and 27.4%, respectively. A PT-SUVmax of &lt; vs. &gt; 7 was a significant predictor for T downstaging (p=0.0502) and N downstaging (p=0.0467). A PT-SUVmax cutoff of 7.6 was associated with a significant difference in MST, at 29.1 and 13.0 months for PT-SUVmax&lt; 7.6 and &gt;7.6, respectively (p=0.0158, HR=1.82, 95%CI=1.19–2.94). On multivariate analysis, PT-SUVmax was the only significant factor associated with survival (p=0.0.314, HR=1.71, 95%CI=1.05–2.79). Conclusions: The pretreatment SUVmax of a primary esophageal cancer appears to correlate with clinical stage, pathologic response to therapy and survival. This finding could play a role in the design of clinical trials and in adapting treatment strategies. No significant financial relationships to disclose.
Smoking rates in pregnant women one year before and after the Irish workplace smoke-free policy: A widening gap?
Authors: Z Kabir, H McAvoy, U Reulbach, L Clancy
Journal: European Respiratory Journal (2011)

Objectives:  To examine smoking rates during pregnancy among Irish mothers across selected socio-economic and demographic maternal characteristics one year before and after the Irish workplace smoke-free policy introduced in March 2004.   Methods:  Individual-level data on mothers9 with singleton live-births were analyzed for the years 2003 [n=7,593] and 2005 [n=7,648] in a Dublin university teaching hospital. Smokers were classified as current smokers and are self-reported. Age-standardized smoking rates for the two main sub-groups of employment status (working vs. not working) were estimated across maternal age, ethnicity and marital status based on the 2002 Census, as the standard. Relative Index of Inequality (RII), with 95% CI, in age-standardized smoking rates was computed (comparing not working with working mothers) for each calendar year.   Results:  Overall, there was a 12% significant decline in crude smoking rates from 23.4% [in 2003] to 20.6% [in 2005]. RII in age-standardized smoking rates for 2003 was 0.65 (0.50-0.81) and increased to 0.79 (0.62-0.96) in 2005 (widened relatively by 22%) when comparing pregnant mothers not working with those working separately for each of the two calendar years.   Conclusions:  Smoking rates in unemployed pregnant mothers remain high in Ireland, despite a significant decline one year after the comprehensive smoke-free policy. The disparity in smoking rates observed between employed and unemployed women has widened by 22%. Tobacco control and smoking cessation approaches must develop successful approaches to targeting unemployed women in pregnancy if social inequalities in birth outcomes and women9s health are to be tackled.