tbuckley/cabot-search huggingface dataset:
Sex Differences in Prognosis for Children With Acute Lymphoblastic Leukemia
Authors: Ching-Hon Pui, James M. Boyett, Mary V. Relling, Patricia L. Harrison, Gaston K. Rivera, Frederick G. Behm, John T. Sandlund, Raul C. Ribeiro, Jeffrey E. Rubnitz, Amar Gajjar, William E. Evans
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Whether recent improvements in the treatment of childhood acute lymphoblastic leukemia (ALL) have nullified the adverse prognosis associated with male sex remains unclear. Therefore, we analyzed the survival experience and presenting clinical and laboratory features of boys and girls with newly diagnosed ALL who were treated at our institution over the past three decades. PATIENTS AND METHODS: One thousand one hundred fifty-one boys and 904 girls were treated in 13 consecutive Total Therapy studies between 1962 and 1994. An overview analysis was used to investigate the impact of sex on overall and event-free survival, both for the entire cohort and for subgroups defined by treatment era and blast-cell immunophenotype. Stratified analyses were performed to adjust for treatment protocol and known risk factors, and in the modern treatment era, for protocol, immunophenotype, and the DNA content of leukemic cells (ie, DNA index). The pharmacokinetics of methotrexate, teniposide, and cytarabine, as well as the thiopurine methyltransferase activity of erythrocytes, were compared between boys and girls treated on a single protocol. RESULTS: Compared with girls, boys were more likely to have T-cell ALL (20.9% v 10.7%, P &lt; .001) and seemed less likely to have a favorable DNA index (17.8% v 25.1%, P = .072). There were no other statistically significant differences between the two sexes with respect to presenting features, including leukemic-cell genetic abnormalities, nor were there significant sex differences in the pharmacokinetics of methotrexate, teniposide, or cytarabine or in erythrocyte thiopurine methyltransferase activity. Girls clearly fared better than boys (P &lt; .001) on protocols used during the early era of treatment (10-year event-free survival ± 1 SE, 43.1% ± 2.1% v 31.5% ± 1.7%). Although prognosis improved for both sexes in the modern era, the difference in outcome between girls and boys persisted (P = .025) (10-year event-free survival, 73.4% ± 3.7% v 63.5% ± 4.0%). However, stratification of modern-era patients by protocol, immunophenotype, and DNA index mitigated statistical evidence of a sex difference in overall survival (P = .263) and event-free survival (P = .124). CONCLUSION: Although boys and girls alike have benefited from improvements in ALL therapy, these gains have not completely eliminated the sex difference in prognosis that has persisted since the early 1960s. The apparent difference in outcome is partially explained by differences between boys and girls in the distributions of ALL immunophenotype and DNA index.
Vascular endothelial growth factor polymorphisms and clinical outcome in colorectal cancer patients treated with irinotecan-based chemotherapy and bevacizumab in the first-line setting.
Authors: A. Koutras, A. Antonacopoulou, F. Fostira, E. C. Briasoulis, I. Sgouros, A. Koumarianou, N. Xiros, C. Christodoulou, G. Fountzilas, H. Kalofonos
Journal: Journal of Clinical Oncology (2010)

3587 Background: Currently, no definitive biomarkers have been identified to predict outcome with the use of bevacizumab (Bev) in cancer patients.The aim of this study was to evaluate the association of vascular endothelial growth factor (VEGF) genotype with efficacy in a randomized phase III trial. This study compared two standard chemotherapy regimens (FOLFIRI versus XELIRI) combined with Bev, as first-line chemotherapy for metastatic colorectal cancer. Methods: DNA was extracted from blood samples of patients participating in the trial. Two hundred nine samples out of 285 enrolled patients were available (106 in the FOLFIRI- Bev and 103 in the XELIRI-Bev arm). Genotyping was performed for selected single nucleotide polymorphisms (SNPs) (VEGF-634, -936, -1154, and -2578). All candidate genotypes were evaluated for associations with response rate (RR), progression-free survival (PFS) and overall survival (OS). Results: There were no significant differences between the distribution of polymorphisms in the treatment groups. The VEGF-2578 CC genotype was associated with an inferior median OS when compared with AA (HR = 1.953; 95% CI: 1.153 to 3.310; p = 0.013) and CA (HR = 1.627; 95% CI: 1.078 to 2.453; p = 0.02). Patients with the VEGF-1154 GG genotype also demonstrated a significantly worse median OS compared with those with GA (HR = 1.681; 95% CI: 1.140 to 2.479; p = 0.009) or with the alternate genotypes (GA and AA) combined (HR = 1.665; 95% CI: 1.160 to 2.391; p = 0.006). The VEGF-1154 GA genotype was associated with marginally significant superior PFS compared with AA (HR = 0.608; 95% CI: 0.373 to 0.990; p = 0.046). The aforementioned effects did not change when adjusting for treatment group. There were no other significant associations between genotypes and clinical outcome for the other VEGF SNPs evaluated. Moreover, there was no genotyping effect observed for response rate. Conclusions: Our results support an association between VEGF genotype and survival when using irinotecan-based chemotherapy combined with Bev in metastatic colorectal cancer patients. Our findings however, need to be validated in larger prospective cohorts. No significant financial relationships to disclose.
1382 LONG-TERM EFFECTS OF TAFAMIDIS - A NEW THERAPEUTIC OPTION FOR PATIENTS WITH TRANSTHYRETIN FAMILIAL AMYLOID POLYNEUROPATHY (TTR-FAP)
Authors: T. Coelho, L. Maia, A. Martins da Silva, M. Waddington Cruz, V. Plante-Bordeneuve, O.B. Suhr, I. Conceicao, H. Schmidt, P. Trigo, J. Packman, M. Harnett, D.R. Grogan
Journal: Journal of Hepatology (2012)
Association of Gestational Diabetes Mellitus With Left Ventricular Structure and Function: The CARDIA Study
Authors: Duke Appiah, Pamela J. Schreiner, Erica P. Gunderson, Suma H. Konety, David R. Jacobs, Chike C. Nwabuo, Imo A. Ebong, Hilary K. Whitham, David C. Goff, Joao A. Lima, Ivy A. Ku, Samuel S. Gidding
Journal: Diabetes Care (2016)

OBJECTIVE Gestational diabetes mellitus (GDM) predicts incident cardiovascular disease (CVD). However, mechanisms linking GDM to CVD beyond intervening incident diabetes are not well understood. We examined the relation of GDM with echocardiographic parameters of left ventricular (LV) structure and function, which are important predictors of future CVD risk. RESEARCH DESIGN AND METHODS We studied 609 women (43% black) from the Coronary Artery Risk Development in Young Adults (CARDIA) study who delivered one or more births during follow-up and had echocardiograms in 1990–1991 (mean age 28.8 years) and 2010–2011. RESULTS During the 20-year follow-up, 965 births were reported, with GDM developing in 64 women (10.5%). In linear regression models adjusted for sociodemographic factors, BMI, physical activity, parity, smoking, use of oral contraceptives, alcohol intake, family history of coronary heart disease, systolic blood pressure, and lipid levels, women with GDM had impaired longitudinal peak strain (−15.0 vs. −15.7%, P = 0.025), circumferential peak strain (−14.8 vs. −15.6%, P = 0.028), lateral e′ wave velocity (11.0 vs. 11.8 cm/s, P = 0.012), and septal e′ wave velocity (8.6 vs. 9.3 cm/s, P = 0.015) in 2010–2011 and a greater 20-year increase in LV mass indexed to body surface area (14.3 vs. 6.0 g/m2, P = 0.006) compared with women with non-GDM pregnancies. Further adjustment for incident type 2 diabetes after pregnancy did not attenuate these associations. CONCLUSIONS Pregnancy complicated by GDM is independently associated with increased LV mass and impaired LV relaxation and systolic function. Implementation of postpartum cardiovascular health interventions in women with a history of GDM may offer an additional opportunity to reduce future CVD risk.
Immune correlates in a Phase II clinical trial with ipilimumab in combination with finite androgen deprivation therapy in patients with metastatic non-castrate prostate cancer
Authors: Sumit K Subudhi, Ana Aparicio, Jianjun Gao, Amado Zurita, Araujo John, Christopher Logothetis, Brinda Rao, Luis Vence, James Allison, Ryan O Emerson, Erik Yusko, Marissa Vignali, Harlan Robins, Jing Jing Sun, Padmanee Sharma
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Ipilimumab is an immunotherapy that blocks the function of an immune checkpoint, cytotoxic T-lymphocyte antigen 4 (CTLA-4), and promotes durable anti-tumor responses in a subset of patients. We hypothesized that ipilimumab could be added to androgen deprivation therapy (ADT) as
Phase III randomized study of vinorelbine (V), gemcitabine (G) followed by docetaxel (D) (VGD) versus paclitaxel (P) and carboplatin (C) (PC) in patients (pts) with advanced non-small cell lung cancer (NSCLC) (Japan Multinational Trial Organization LC00–03)
Authors: M. Kawahara, M. Ogawara, Y. Nishiwaki, K. Kubota, K. Komuta, K. Minato, Y. Fujita, H. Origasa, M. Fukushima, K. Furuse
Journal: Journal of Clinical Oncology (2006)

7013 Background: Our phase II study of non-platinum VGD for advanced NSCLC demonstrated excellent results with the median survival time (MST) of 15.7 mos and a 1-year survival rate of 59% (Brit J Cancer 88:42,2003). A phase III trial was performed to determine the survival benefit of VGD compared with PC for advanced NSCLC as a Japan-SWOG Lung Cancer Common Arm Trial. Methods: Between Mar 2001 and Apr 2005, 401 chemo-naïve NSCLC pts with Stage IIIB with pleural effusion or Stage IV without brain metastasis, who had ECOG PS 0–1, were randomized to VGD; V 25 mg/m 2 iv and G 1000 mg/m 2 iv, days 1, 8, every 21 days for 3 cycles followed by D 60 mg/m 2 iv, d1, every 21 days for 3 cycles or PC; C AUC=6 iv and P 225 mg/m 2 iv, day 1, every 21 days for 6 cycles. The primary endpoint was overall survival (OS). For a two-sided test at the 5% level of significance and power of 85%, the number of pts required to detect a 40% difference in MST was 400. Results: 393 pts (196 VGD, 197 PC) were evaluable for response, OS and toxicity. Baseline demographics were balanced (VGD vs PC): median age 65 yrs(both arms);male(74 vs 69%); PS 0 40%(both arms);Stage IIIB (17 vs 18%); Ad/Sq (66%/23% vs 76%/15%). There were 238 deaths with a median follow-up of 23 mos. 49% in VGD and 29% in PC arm completed 6 cycles (p=0.00005). Response rates in arms VGD/PC were 23% vs 36% (p= 0.008). There were no significant differences in progression free survival, OS, 1- and 2-yr survivals between VGD and PC arms: 5.9 vs 6.0 mos (p=0.95, Log rank), 13.1 vs 13.8 mos (MST, p=0.28, Log rank), 55.6 vs 55.5%, and 27.6 vs 31.8%. Grade 3/4 toxicities in arms VGD/PC were: neutropenia (G4) (30 vs 54%, p&lt;0.00001), thrombocytopenia (4 vs 6%), febrile neutropenia (20 vs 19%), neuropathy (2 vs 21%, p&lt;0.00001), pulmonary (9 vs 2%, p=0.0006). There were 2 treatment-related deaths (pneumonitis) in VGD arm. Conclusions: Non-platinum triplet chemotherapy had comparable activity in pts with advanced NSCLC. The VGD had significantly less myelosuppression, but more pulmonary toxicity than PC. No significant financial relationships to disclose.
Chemotherapy of Endodermal Sinus Tumour (Yolk Sac Tumour) of the Ovary: Preliminary Communication
Authors: E Wiltshaw, R Stuart-Harris, G H Barker, N F C Gowing, S Raju
Journal: Journal of the Royal Society of Medicine (1982)

Eight patients presenting with endodermal sinus tumour of the ovary have been treated with combination chemotherapy using cisplatin, bleomycin and vinblastine (PVB). Complete remission occurred in 7 out of 8 cases, all of whom are alive and well 3 to 33 months later. These preliminary results are compared with our own past experience and recent reports in the literature. It is concluded that the PVB regimen is probably as effective in female germ cell tumours as it is in testicular teratoma.
Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment
Authors: Gerhard Zugmaier, Nicola Gökbuget, Matthias Klinger, Andreas Viardot, Matthias Stelljes, Svenja Neumann, Heinz-A. Horst, Reinhard Marks, Christoph Faul, Helmut Diedrich, Albrecht Reichle, Monika Brüggemann, Chris Holland, Margit Schmidt, Hermann Einsele, Ralf C. Bargou, Max S. Topp
Journal: Blood (2015)
The use of malignant serosal fluid as a tumor vaccine in patients with advance malignancies
Authors: Suresh Katakkar
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts After getting approval from IRB 15 patients were treated with the vaccine prepared from their own malignant serosal fluid. This study was done 1990. These were patients who had all conventional chemotherapy and have failed and had progressive disease. The serosal fluid was heat
Received dose-intensity: a randomized trial of weekly chemotherapy with and without granulocyte colony-stimulating factor in small-cell lung cancer.
Authors: D W Miles, O Fogarty, C M Ash, R M Rudd, C W Trask, S G Spiro, W M Gregory, J A Ledermann, R L Souhami, P G Harper
Journal: Journal of Clinical Oncology (1994)

PURPOSE A prospective randomized trial to determine if granulocyte colony-stimulating factor (G-CSF) could increase the received dose-intensity (RDI) of weekly chemotherapy in patients with small-cell lung cancer (SCLC). PATIENTS AND METHODS Forty patients with SCLC with good prognostic features (all patients with limited disease [LD], and extensive-disease [ED] patients with Eastern Cooperative Oncology Group [ECOG] 0 or 1 and plasma alkaline phosphatase levels &lt; 1.5 times the upper limit of normal) were randomized to receive weekly chemotherapy with or without G-CSF. G-CSF (5 micrograms/kg) was self-administered subcutaneously on days when chemotherapy was not given. Chemotherapy consisted of cisplatin 50 mg/m2 intravenously (IV) on day 1 and etoposide 75 mg/m2 IV on days 1 and 2 alternating weekly with ifosfamide 2 g/m2 IV (with mesna) and doxorubicin 25 mg/m2 on day 1, for a total of 12 courses. Dose modifications (dose reductions and treatment delays) were made according to defined hematologic criteria. RESULTS Dose reductions were made at some point during treatment in 12 of 17 patients in the control arm and in 11 of 23 patients in the G-CSF arm (P = .20). The proportion of patients experiencing dose reductions due to leukopenia was significantly higher in the control arm (nine of 17) compared with the G-CSF arm (four of 23, P &lt; .04). Cycle delays due to leukopenia were similar in both arms of the study. The RDI was 82% of projected in the control arm (95% confidence interval [CI], 79% to 84%) and 84% in patients receiving G-CSF (95% CI, 82% to 87%) (P value not significant). CONCLUSION In this randomized trial, G-CSF significantly decreased dose reductions due to neutropenia. However, administration of G-CSF did not decrease dose reductions or treatment delays to a level that would allow an increase in received dose-intensity. Nonhematologic toxicities such as increased creatinine concentration also prevented an increase in the RDI in the G-CSF arm.
The acquired immune deficiency syndrome (AIDS) and suicidal behavior in alcohol-dependent homosexual men
Authors: D K Flavin, J E Franklin, R J Frances
Journal: American Journal of Psychiatry (1986)

Three alcohol-dependent homosexual men with suicidal ideation and behavior consciously attempted to contract the acquired immune deficiency syndrome (AIDS) as a means of committing suicide. The authors briefly examine the interrelationship among alcoholism and substance abuse, homosexuality, suicidal behavior, and AIDS; implications for the substance abuse treatment setting are noted. Early diagnosis and treatment of depression and substance abuse in homosexual men or parenteral drug abusers may prevent the spread of AIDS and reduce hidden suicidal potential.
Abstract 14726: Sortilin 1 is a Novel Inducer of Vascular Calcification via a Phosphate-Dependent Mechanism
Authors: Claudia Goettsch, Masanori Aikawa, Sasha Singh, Manabu Shibasaki, Elena Aikawa
Journal: Circulation (2012)

Background. Vascular calcification is a prominent feature of chronic inflammatory disorders such as chronic renal disease (CRD) and atherosclerosis, and has no medical therapies. Human genome wide ...
Abstract #LB-257: Immunohistochemical detection of tyrosine phosphatase SHP-1 predicts outcome after radical prostatectomy for localized prostate cancer
Authors: Helena Tassidis, Leon Brokken, David Ulmert, Roy Ehrnström, Karin Jirström, Anders Bjartell, Pirkko Härkönen, Anette Gjörloff Wingren
Journal: Cancer Research (2009)

The protein tyrosine kinase (PTK) receptors and cytosolic signalling proteins as well as the protein tyrosine phosphatases (PTP) have important roles in regulation of growth and function of the benign and malignant prostate gland. Here we studied the expression levels and functions of the protein tyrosine phosphatase SHP-1 in prostate cancer cell lines and in benign and malignant human prostatic tissues. We found that SHP-1 is expressed at a high level in LNCaP prostate cancer cells compared to PC-3 cells. Silencing of SHP-1 expression with siRNA in LNCaP cells led to an increased rate of proliferation as measured by thymidine incorporation, whereas in PC3 cells in which SHP1 was overexpressed by transient transfection proliferation rate was decreased. We also examined SHP-1 expression in prostate cancer by immunohistochemical staining of tissue microarrays comprising tumor specimens from 122 prostate cancer patients. We found an inverse correlation between SHP-1 staining intensity and the time to biochemical recurrence as measured by a rise in the serum level of prostate-specific antigen (PSA) in prostate cancer patients. In conclusion, our results suggest that a low level of SHP-1 expression in prostate cancer cells is associated with high proliferation rate and with an increased risk of biochemical recurrence after radical prostatectomy for localized prostate cancer.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-257.
Pemetrexed—Limitation of toxicity through supplementation treatment
Authors: A. Kehely, C. C. Smith, A. Czarnecki
Journal: Journal of Clinical Oncology (2008)

19104 Background: In clinical development of pemetrexed, an association was identified with febrile neutropenia and mucositis and elevated levels of homocysteine and methylmalonic acid, markers of deficiencies of folate and vitamin B12 respectively. Since the end of 1999 supplementation with these vitamins became mandatory. This analysis assesses the impact on pemetrexed’s toxicity profile. Methods: Serious adverse event (SAE) reports for pemetrexed arising from clinical trial (CT) and spontaneous sources were retrieved from the Lilly safety database. The proportion of possibly related SAEs arising from the MedDRA Blood and Gastrointestinal Disorders (GI) System Organ Classes (SOCs) was compared for two time periods: pre and post supplementation. Agranulocytosis, cytopenia, leukopenia and thrombocytopenia and several GI terms were of special interest. Results: Although there was an increase CT exposure post supplementation of 10 fold, this resulted in only a 4.7 fold (388 to 2235) in the number of possibly related SAEs cases. Pre supplementation 84.8% of SAEs originated from the Blood and GI disorders SOCs falling to 67.3% post supplementation (p<0.001). Significant reductions were also seen within individual SOCs: Blood (49.5 to 43.0%, p=0.015), GI (26.5 to 12.9%, p<0.001) and events associated with severe toxicity when experienced at high grade: diarrhoea (17.8 to 7.9%, p<0.001), vomiting (26.0% to 13.9%, p<0.001), neutropenia (36.6 to 12.8%, p<0.001) and thrombocytopenia (16.5 to 10.1%, p<0.001). For spontaneously reported cases, reporting rates were generally lower compared with the supplemented CT period (49.7% vs 67.3%, p<0.001) largely due to relative under-reporting in the Blood SOC (39.8% vs 54.4%, p<0.001) with use of the single term pancytopenia; there was no difference in reporting rates in the GI SOC (9.9% vs 12.9%, p=0.055). Conclusions: A sustained reduction in relative reporting rates of serious haematological and GI AEs has been seen since the introduction of vitamin supplementation. The safety profile of pemetrexed improved significantly with the introduction of risk minimisation measures in CTs and subsequently everyday use. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly Eli Lilly
Health-related quality of life in the general Norwegian population assessed by the European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire: the QLQ=C30 (+ 3).
Authors: M J Hjermstad, P M Fayers, K Bjordal, S Kaasa
Journal: Journal of Clinical Oncology (1998)

PURPOSE To obtain reference data on health-related quality of life (HRQOL) for the functional and symptom scales and single items of the European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire (EORTC QLQ-C30 [+ 3]) in a representative sample of the Norwegian general population. PATIENTS AND METHODS A randomly selected sample of 3,000 people from the Norwegian population, aged 18 to 93 years, who represent geographic diversity, took part in this postal survey. The EORTC QLQ-C30 (+ 3) and a questionnaire about demographic data and health were sent by mail. A new questionnaire package was sent as a reminder after 3 weeks. RESULTS The survey yielded a high response rate with 1,965 of 2,892 eligible persons responding (68%). There was a low amount of missing data (1.8%). Internal consistency was highly satisfactory and yielded Cronbach's alpha coefficients greater than 0.70 for all but two functional scales and one symptom scale. The sensitivity of the questionnaire was shown by the excellent discrimination between age and sex groups. Clinical validity was shown by the distinct differences according to age and sociodemographic characteristics. Women reported lower functional status and global quality of life (mean scale scores from 71.7 to 91.0) than men (mean scale scores from 75.4 to 94.4), and also more symptoms and problems. This was remarkably consistent across age groups, as was a decline in functional status with an increase in age. CONCLUSION This is the first study that presented reference data from the EORTC QLQ-C30 (+ 3) in a sample from a general population and seems to provide valid measures of HRQOL within different age groups. The results may serve as a guideline for clinicians when interpreting HRQOL in their own groups of patients, and contributes to a better understanding of the significance of mean scores and their clinical relevance.