tbuckley/cabot-search huggingface dataset:
A phase 2 study of an allogeneic GM-CSF gene-transduced prostate cancer cell line vaccine in patients with metastatic hormone-refractory prostate cancer (HRPC)
Authors: E. Small, C. Higano, D. Smith, J. Corman, A. Centeno, C. Steidle, M. Gittelman, G. Hudes, N. Sacks, J. Simons
Journal: Journal of Clinical Oncology (2004)

4565 Background A prior phase 2 study of allogeneic prostate carcinoma cell lines (PC-3 and LNCaP) genetically modified to secrete GM-CSF in 34 metastatic HRPC patients (pts) yielded a median survival of 26 months (Proc ASCO, Vol. 21:183a, 2002). The vaccine was re-engineered to secrete higher levels of GM-CSF, and this GVAX prostate cancer vaccine has been evaluated in a study designed to optimize the dose for phase 3 trials. Methods 80 metastatic HRPC pts were treated for 24 weeks in a dose-escalation trial. Doses (in millions of cells) included 200 monthly (low), 200 bi-weekly (medium), and 500 prime/300 boost bi-weekly (high). Vaccine specific antigenic protein antibodies were measured by Western blot of vaccine lysates against pts sera collected at baseline, Wk 12 and Wk 24. Type I Carboxy-terminal telopeptide (ICTP), a biologic marker useful for monitoring osteoclast activity in metastatic prostate cancer, was assayed at the same time points. PSA was collected at each treatment visit. Results 80 pts enrolled and completed treatment, and have been followed for a median of 5.4 months with no dose-limiting toxicities observed. 6/19 (32%) of pts in the high dose group showed PSA declines following repeat vaccinations. In addition, stable or decreasing ICTP levels occurred in 34/55 (62%) pts tested including all dose groups. The proportion of pts generating an antibody response to at least one cell line at Wk 12 increased with dose, with 87% of pts demonstrating an immune response in the high dose group compared with 72% and 40% in the medium and low dose groups (p=0.001, Kendall's Tau-b). Conclusions GVAX prostate cancer vaccine demonstrates immunogenicity and clinical activity in metastatic HRPC pts which appears to be dose-dependent. Stable or decreasing ICTP levels suggest osteoclast inhibition. Phase 3 trials are planned with the high dose that generated PSA declines and the optimal immunologic response rate. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cell Genesys Cell Genesys Mentor; Oncura
Vorinostat in combination with gemcitabine and cisplatinum in patients with advanced non-small cell lung cancer (NSCLC): A Phase I dose-escalation study
Authors: J. Trédaniel, R. Descourt, D. Moro-Sibilot, J. Misset, E. Gachard, J. Garcia-Vargas, E. Roben, G. Zalcman
Journal: Journal of Clinical Oncology (2009)

8049 Background: Preclinical data indicate that vorinostat, a histone deacetylase inhibitor, enhances the efficacy of gemcitabine and platinum chemotherapy agents. This study investigated the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of vorinostat plus gemcitabine and a platinum agent in patients (pts) with advanced NSCLC. Methods: Eligible pts (aged ≥18 years; stage IIIB/IV NSCLC, ECOG performance status ≤1, no prior systemic chemotherapy [except adjuvant]) were sequentially enrolled on escalating doses of vorinostat plus gemcitabine and a platinum agent (standard 3+3 design) for ≤6 cycles ( Table ). Carboplatin regimens were to be investigated if dose levels 1 or 2 exceeded the MTD. Results: 28 pts enrolled to date (M/F: 22/6; median age: [range] 55 [34–70] years; 20 chemonaïve) at 5 dose levels ( Table ). Two pts had DLTs: elevated creatinine leading to cisplatin dose reduction (dose level 2) and febrile neutropenia (dose level 5) ( Table ). Dose level 5 was achieved without reaching the MTD; however, based on clinical tolerability, dose level 4 was chosen as the recommended dose (RD). 24 pts had adverse events (AEs): 86% mild/moderate, 53% not considered treatment-related. The most common drug-related Grade 3/4 AEs were thrombocytopenia (19 events) and neutropenia (14 events). Serious AEs occurred in 15 pts, and 5 deaths occurred (1 ‘probably‘ and 4 ‘definitely not‘ treatment-related). Of 19 evaluable pts at 5 dose levels, 9 (47%) had a partial response, 8 stable disease, and 2 disease progression ( Table ). Updated results of pts treated at the RD in an expansion cohort will be presented. Conclusions: These phase I data suggest that vorinostat can be administered with standard doses of gemcitabine and cisplatin and the combination is active in the initial treatment of metastatic NSCLC: randomized trials are needed to determine whether addition of vorinostat improves outcomes in such pts. [Table: see text] [Table: see text]
CCL2 expression in ovarian carcinoma is associated with chemotherapy response and survival but not with the -2518 A/A polymorphism
Authors: A. Nickles Fader, S. A. Vaziri, N. Rasool, P. Elson, P. W. Faber, C. Biscotti, L. Rojas-Espaillat, P. G. Rose, J. Belinson, R. Ganapathi
Journal: Journal of Clinical Oncology (2008)

16509 Background: CCL2, a macrophage chemoattractant, is expressed in normal human ovarian epithelium but down-regulated in ovarian adenocarcinomas. The purpose of this study was to determine the association between quantitative expression of CCL2 with chemotherapy response and clinical outcome in ovarian cancer (OC) patients (pts) as well as its association with a known polymorphism (-2518 A/A) in the CCL2 promoter region. Methods: Solid or ascitic tumor cells from pts with advanced papillary serous OC were obtained at the time of primary surgery or neoadjuvant chemotherapy. RT-PCR with PCR-based amplification of the CCL2 promoter region containing the -2518 A/A polymorphism (PM) was performed on samples of genomic DNA from blood and tumor. The PM frequency was compared to the genotype frequency in control patients with renal cell carcinoma (RCC). Chemoresponse was correlated with genotype and CCL2 expression. Sensitive (S) tumors = complete response and no disease recurrence/progression 6 months after treatment. Resistant tumors (R) = progression or recurrence ≤6 months after treatment. Results: Sixty nine pt specimens were analyzed. The incidence of the PM in blood and matched tumor was 65 and 70%, respectively, a frequency significantly higher than that previously reported (∼50%) in population-based studies on CCL2 polymorphisms and higher than that in the RCC group (54%, p =0.02). 46/69 patients had clinical follow up (f/u) data available (median f/u = 36 months). RT-PCR analysis demonstrated that CCL2 was significantly down-regulated in the R versus the S tumors (p<0.001). Sensitivity was 89%. Lack of CCL2 mRNA expression correlated inversely with progression free survival (PFS, p=0.05) and overall survival (OS, p=0.01). Expression of the PM was not predictive of response or survival. On multivariate analysis, only debulking status and CCL2 expression were predictive of PFS and OS. Conclusions: Decreased expression of CCL2 is associated with poorer chemoresponse and survival. Although the CCL2 promoter-region PM -2518 A/A is commonly expressed in women with ovarian carcinoma, it is not predictive of PFS or OS. Further studies are needed to characterize the relationship between this PM, expression of CCL2 and clinical outcomes. No significant financial relationships to disclose.
Scientific misconduct in cancer clinical trials.
Authors: E J Emanuel, W B Patterson
Journal: Journal of Clinical Oncology (1998)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1998.16.10.3433 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9779723 Scientific misconduct in cancer clinical trials. E J EmanuelxE J EmanuelSearch for articles by this author , W B PattersonxW B PattersonSearch for articles by this author Show More Dana-Farber Cancer Institute, Boston, MA 02115-6084, USA. [email protected] https://doi.org/10.1200/JCO.1998.16.10.3433 First Page PDF © 1998 by American Society of Clinical OncologyKeywords: Biomedical and Behavioral Research... Show All
Predictors that influence contralateral prophylactic mastectomy election among women with ductal carcinoma in situ who tested negative for a <i>BRCA</i> mutation.
Authors: Nisreen Elsayegh, Heather Y. Lin, Angelica M. Gutierrez-Barrera, Jessica Profato, Jennifer Keating Litton, Henry Mark Kuerer, Gabriel N. Hortobagyi, Banu Arun
Journal: Journal of Clinical Oncology (2014)

42 Background: Patients with ductal carcinoma in situ (DCIS) are at increased risk for developing contralateral breast cancer (CBC). Consequently, more women with DCIS are electing to undergo contralateral prophylactic mastectomy (CPM). We previously reported a 27% CPM rate among patients with DCIS who were evaluated for BRCA genetic testing (positive, negative, not tested). In this specific cohort, we further evaluated factors associated with CPM in patients with DCIS who tested negative for a BRCA mutation. Specifically, we aimed to identify differences within BRCA-negative patients who underwent CPM and those who did not. Methods: This retrospective study from a prospective registry included 100 women with DCIS referred for genetic counseling between 2003 and 2011. Patient characteristics included: age, marital and educational status, tumor markers, nuclear grade, family history of breast cancer (BC) and ovarian cancer (OC), race, Ashkenazi Jewish ancestry, and BRCA results. Univariate and multivariate logistic regression analyses were used to determine predictive factors associated with CPM election. Results: Of 100 BRCA-negative patients, 31 (31%) underwent CPM. Univariate analysis revealed patients who had a first-degree relative with OC were more likely to elect CPM that those who did not (p = 0.0278). Patients who had a family history of OC (53.3%) were more likely to choose CPM than those with no family history (p = 0.0425). Married patients were more likely to elect CPM than those who were not married (p = 0.0235). In multivariate analysis, married patients were more likely to elect CPM than those who were not married (OR = 4.367; 95% CI, 1.198-15.924; p = 0.0255). Conclusions: The CPM rate among patients with DCIS who tested negative for a BRCA mutation is high. Factors associated with increased rate of CPM among this group include a family history of OC and being married. Further studies are needed to evaluate patients' perceptions of CBC risk and their role in the likelihood of CPM choice.
A randomized controlled trial (RCT) of <sup>18</sup>F-fluorodeoxyglucose (FDG) positron emission tomography (PET) versus conventional imaging (CI) in staging potentially resectable non-small cell lung cancer (NSCLC)
Authors: D. Maziak, G. E. Darling, R. I. Inculet, K. Gulenchyn, A. A. Driedger, Y. C. Ung, J. D. Miller, T. Koru-Sengul, W. K. Evans, M. N. Levine
Journal: Journal of Clinical Oncology (2008)

7502 Background: Patients with early-stage NSCLC who undergo surgery have the highest survival among patients with NSCLC. Preoperative imaging tests are critical in defining which patients are surgical candidates. PET/CT imaging may identify patients with more advanced disease not evident by CI and thereby avoid inappropriate surgery. Previous RCTs of CI plus PET/CT versus CI alone in the staging of early-stage NSCLC have produced conflicting results. Methods: Eligible patients had histological or cytological proof of NSCLC, clinical stage I, II, or IIIA based on chest X-ray and CT thorax, and a tumor considered to be technically resectable. Consenting patients were randomized to CI (CT abdomen including liver and adrenals, bone scan and cranial imaging) or PET/CT plus cranial imaging. Patients were stratified by stage (I/II vs. IIIA) and enrolling center. The primary endpoint was the percentage of patients correctly upstaged who avoided stage inappropriate surgery. The planned sample size, based on an alpha = 0.05 two-tailed, beta = 0.10 and an absolute difference of 15%, was approximately 146 patients per study arm. Allowing 10% for losses to follow-up, a total of approximately 322 patients was required. Results: 337 patients were randomized from 8 centers in Ontario between July 2004 and August 2007: 167 in the CI arm and 170 in the PET/CT arm. Seventeen patients (10 on CI and 7 on PET/CT) were excluded from the analysis for protocol violations. The mean age of participants was 66 years and 50% were male. Twenty-three (14%) of 163 patients in the PET/CT arm were correctly upstaged and avoided inappropriate surgery compared to 11 (7%) of 157 in the CI group, Fisher's exact p=0.046. The difference in proportions is 7% with 95% confidence interval, 0.03% to14%. Conclusions: Preoperative staging with PET/CT and cranial imaging identifies more precisely those patients with mediastinal and extrathoracic disease, thereby sparing some patients from stage inappropriate surgery when compared to conventional preoperative staging. Importantly, our trial shows that PET/CT can replace CI in staging early-stage NSCLC. No significant financial relationships to disclose.
Abstract 20435: Myocardial Mechanics of the Systemic Right Ventricle in Hypoplastic Left Heart Syndrome Through the Perinatal Transition
Authors: Santokh S Dhillon, Akiko Hirose, Nee S Khoo, Lindsay Mills, Timothy Colen, Winne Savard, Po Yin Cheung, Lisa Hornberger
Journal: Circulation (2014)

Background: Rapid changes occur in myocardial loading during the transition from the fetal to postnatal circulation. In healthy neonates, the LV output almost doubles within hours of delivery but decreases to levels slightly higher than the fetal LV output within the first few days. In contrast, we have found in Hypoplastic left heart syndrome (HLHS) the combined cardiac output (CO) is initially similar to that of the late gestation fetus with a gradual but progressive increase occurring within the first 3-5 days. We sought to define the functional changes of the systemic right ventricle (RV) during the perinatal transition in the neonate with HLHS. Methods: We prospectively recruited 11 pregnancies with fetal HLHS. Echocardiograms were performed in late gestation and at 4 -12, 20-24, 44-48 hours (hrs) and 3-5 days after birth. Hemodynamics including stroke volume (SV), heart rate (HR), CO, blood pressure (BP), and RV size and fractional area change (FAC) were measured. High frame rate images were used fo...
P08 People with diabetes have a higher risk of death from liver disease compared to the general population
Authors: J Parkes
Journal: Gut (2010)

Introduction  The association between liver disease and diabetes has been described, but less information is available regarding mortality from liver disease among people with diabetes from a population perspective.  Aim  To compare mortality from liver disease among people with prevalent diabetes in 2001 and incident diabetes between 2001 and 2007 with that of the general population of Scotland.  Method  We used a population-based diabetes register derived from primary and secondary care electronic records linked to death records to compare mortality from liver disease among people with prevalent diabetes in 2001 and incident diabetes between 2001 and 2007 with that among the general population of Scotland for people of 35–84 years for the period 2001–2007. There were just over 1 million person years of data for people with diabetes and almost 20 million person years of data for the general population. Mortality rates were estimated for liver disease as underlying (primary) cause of death on death certificates using conventional ICD-10 codes including those for hepatocellular carcinoma (HCC). Standardised mortality ratios (SMRs) were estimated adjusting for age, sex and quintile of an area-based measure of socio-economic status, the Scottish Index of Multiple Deprivation 2006 using the population of Scotland in 2004 as the standard.  Results  There were 1267 and 10 100 records that mentioned liver disease as the primary underlying cause of death in the diabetes and general populations, giving crude mortality rates of 122.4 and 50.9/100 000 person years, respectively. The major single cause of liver-related death was alcoholic liver disease which accounted for 38% and 63% of liver disease deaths among people with diabetes and the general population respectively, with HCC accounting for 24% and 9% of liver disease deaths in these populations. SMRs (95% CI) for underlying (primary) cause of death for people with diabetes compared to the general population were 169 (160–178) for all liver disease, 116 (106–126) for alcoholic liver disease and 318 (283–356) for HCC. SMRs were similar for any mention of liver disease on death certificate. SMRs for women with diabetes were higher than men. Further analyses will stratify by type of diabetes.  Conclusion  Analysis of a very large population based data set has shown that people with diabetes have a raised mortality rate from liver disease compared to the general population. Management of people with diabetes should include strategies to reduce risk of liver disease.
With modern imaging techniques, is staging laparotomy necessary in pediatric Hodgkin's disease? A Pediatric Oncology Group study.
Authors: N P Mendenhall, A B Cantor, J L Williams, J L Ternberg, M A Weiner, F H Kung, R B Marcus, C R Ferree, B G Leventhal
Journal: Journal of Clinical Oncology (1993)

PURPOSE To determine whether the information gained from staging laparotomy can be predicted by imaging and/or clinical factors in children with Hodgkin's disease. PATIENTS AND METHODS Between 1986 and 1991, 216 consecutive pediatric patients with Hodgkin's disease underwent laparotomy and were treated on two concurrent protocols in a multiinstitutional cooperative group. All patients had computed tomography (CT) of the chest, abdomen, and pelvis. Clinical factors studied included sedimentation rate, B symptoms, histology, number and location of involved sites, sex, mediastinal involvement, and age. Pretreatment CTs were centrally reviewed in 88 cases for the presence and size of both supradiaphragmatic and infradiaphragmatic lymph nodes, intrinsic spleen lesions, and splenic size. Models were generated that were predictive of any abdominal disease, splenic involvement, extensive splenic involvement, and upstaging at the laparotomy. False-positive and false-negative rates were calculated. RESULTS For the end point of any abdominal disease, a model based on B symptoms, histology, sedimentation rate, and number and location of involved sites was highly significant (P &lt; .0001). However, the success in predicting abdominal disease in an individual patient was limited: false-negative rate, 26%; false-positive rate, 32%. Highly significant models based on clinical factors and/or radiographic findings were also generated to predict splenic involvement, extensive splenic involvement, and upstaging with laparotomy, but they also had high false-positive and false-negative rates. CONCLUSION Laparotomy findings cannot be predicted accurately in the majority of patients based on knowledge of CT findings and clinical factors.
How much can patients, with low Karnofsky performance status and advanced non-small cell lung cancer, benefit from cisplatin-based chemotherapy? A retrospective analysis of a phase III randomised trial
Authors: M. Paesmans, J. Lafitte, T. Berghmans, J. Lecomte, C. Alexopoulos, O. Van Cutsem, V. Giner, A. Efremidis, M. Berchier, J. Sculier
Journal: Journal of Clinical Oncology (2007)

19516 Background: Performance status (PS) is a strong independent prognostic factor for survival in patients with advanced non- small cell lung cancer and administration of platinum-based chemotherapy (CT) in patients with poor PS is associated to more severe toxicity. Our purpose was to determine whether poor PS patients (ie those registered with a performance index of 60–70 on the Karnofsky scale) could benefit from CT in terms of clinical improvement defined as reaching, during CT, a PS of at least 80 on the same scale (ECOG PS 0 or 1). Methods: Retrospective analysis of a randomised trial performed in advanced NSCLC where 485 patients received three courses of GIP (gemcitabine + ifosfamide + cisplatin) induction CT, in order to determine the potential clinical benefit of conventional cisplatin-based CT in patients with poor PS defined as 60–70 on the Karnofsky scale. Results: 387 (80%) patients had good PS (Karnofsky 80–100) and 98 (20%) poor PS. Response rates were respectively 38 and 28% (p=0.06), no independent predictive value for PS was found using response to CT as endpoint. Clinical improvement was observed in 25% (95% CI : 15%-38%) of the poor PS patients (respectively 38%, 20% and 14% in case of response, no change and progression, p=0.05). Nine additional patients improved from 60 to 70 during induction CT. Improvement occurred earlier in responders (rates of patients with improvement were 12% after 1 course, 31% after 2 courses and 38% after 3 courses compared to 3%, 5% and 17% in the non responders). Survival of patients with poor PS was significantly worse but survival of responders was similar, whatever initial poor or good PS (logrank test after landmark, p=0.47, HR=1.18, 95%CI: 0.76–1.84 for poor responders). If non fatal toxicity was relatively similar as well as dose intensity delivered after 3 CT courses, there were more toxic deaths (including vascular and cardiac fatalities) in poor PS patients (2.1% versus 9.2%; p=0.002). Conclusions: Although toxicity is increased, combination chemotherapy is associated with clinical improvement in a non negligible rate of patients with poor PS in case of advanced NSCLC. No significant financial relationships to disclose.
Withdrawn: OCTN2-mediated active targeting L-carnitine modified PLGA based nanoparticles for enhanced oral paclitaxel delivery
Authors: Jin Sun, Longfa Kou, Qing Yao, Zhonggui He
Journal: Asian Journal of Pharmaceutical Sciences (2015)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.