tbuckley/cabot-search huggingface dataset:
Abstract 11170: Obesity and Prognosis of Patients on Hemodialysis and After Renal Transplantation
Authors: jose De Lima, Luis Henrique W Gowdak, Flavio J de Paula, Henrique C Muela, Luiz A Bortolotto
Journal: Circulation (2014)

Introduction:  Obesity is not associated with CV events and death and may even be protective in patients on hemodialysis (HD), contrary to observations in the general population. The reason for this apparent paradox is unknown, but necessarily involves chronic uremia.   Methods:  We examined the impact of obesity (BMI > 30 Kg/m2) on prognosis in a cohort of 1696 HD patients on the waiting list for renal transplantation (TX) (54.4 ± 10.7 yo, 68% Whites, 61% males, 42% diabetics, 29% smokers, 33% dyslipidemic, 42% with associated CVD) before and after TX. TX was performed in 439 patients (26%). End-points were coronary events (MI, unstable angina and sudden death) and death by any cause.   Results:  There were 357 patients with obesity (21%). Mean BMI were 32.7 ± 2.6 and 23.8 ± 3.0 for obese and non-obese, respectively. Obese patients on HD were older (55.9 ± 9.2 v 54.2 ± 11) and had an increased prevalence of diabetes (54% v 40%), dyslipidemia (49% v 30%), altered myocardial scan (38% v 31%), previous MI (16% v 10%) and coronary intervention (11% v 7%), higher total-cholesterol (186 ± 52 v 169 ± 47) and triglycerides (219 ± 167 v 144 ± 91). Obese TX patients had more dyslipidemia (46% v 31%), more individuals with angina (23% v 14%) and MI (18% v 5%), increased total-cholesterol (185 ± 56 v 172 ± 48) and triglycerides (237 ± 190 v 149 ± 100). P values were    Conclusion:  Obese HD patients had more risk factors and ischemic heart disease but these characteristics did not interfere with prognosis. However, after TX, obesity predicted early coronary events and death. The results suggest that obese CKD patients may be somehow protected against the consequences of myocardial ischemia while on dialysis but protection is lost right after TX. This fact must be considered when selecting patients for TX.
Final analysis of a phase IB/randomized phase II study of gemcitabine (G) plus placebo (P) or vismodegib (V), a hedgehog (Hh) pathway inhibitor, in patients (pts) with metastatic pancreatic cancer (PC): A University of Chicago phase II consortium study.
Authors: Daniel Virgil Thomas Catenacci, Nathan Bahary, Sreenivasa R. Nattam, Robert de Wilton Marsh, James Alfred Wallace, Lakshmi Rajdev, Deirdre Jill Cohen, Bethany G. Sleckman, Heinz-Josef Lenz, Patrick J. Stiff, Sachdev P. Thomas, Peng Xu, Les Henderson, Margit Naomi Horiba, Michael Vannier, Theodore Karrison, Walter Michael Stadler, Hedy Lee Kindler
Journal: Journal of Clinical Oncology (2013)

4012 Background: Sonic Hh (SHh), the ligand for the Hh pathway, is over-expressed in &gt;80% of PC. V had activity in preclinical murine PC models leading to increased tumor perfusion, enhanced tumor delivery of G, and an improvement in survival. Methods: We conducted a placebo-controlled, phase IB/randomized phase II trial of GV or GP. Eligible pts, KPS 80-100, had untreated metastatic PC, or had completed adjuvant therapy &gt; 6 months (mo) prior. Primary endpoint: progression-free survival (PFS). Correlatives: serial SHh serum levels; serial perfusion CT imaging. All pts received G 1000mg/m 2 over 30 minutes, days (D) 1, 8, 15, Q28D. A lead-in phase IB was performed. Pts, stratified by KPS (80 v 90/100), and disease status (newly diagnosed/recurrent), were randomized to V (150 mg PO daily) or P. For pts on P, cross-over was allowed at progression. Assuming a mPFS of 3.5 months for GP and 5.7 months for GV (HR=0.61), a sample size of 106 subjects (53 per group) provided 85% power to detect this difference, using a one-sided test at the 0.10 significance level. Results: No safety issues were identified in 7 pts enrolled in the phase IB study. The phase II study enrolled 106 evaluable pts (V/P 53/53) at 13 sites 2/10-6/12. Pt characteristics: median age 65/64 (range 52-82/39-83); KPS (% pts) 80: 38/30; 90: 26/38; 100: 36/32; newly diagnosed 91%/91%; recurrent: 9%/9%. Grade 3/4 toxicity (V/P, % pts, &gt;5% in either arm): neutropenia 32/28; lymphopenia 4/15; thrombocytopenia 9/11; anemia 9/23; hyponatremia 4/15; fatigue 13/8; hyperglycemia 23/19; elevated ALT 13/9; hyperbilirubinemia 11/6; nausea 11/11. Response (%): CR 0/2, PR 8/11, SD 51/38. mPFS: 4.0/2.5 mo (95% CI: 2.5-5.3/1.9-3.8; HR 0.81 [0.54-1.21], p=0.30). 22 pts (42%) on GP crossed over to GV at progression. mOS: 6.9/6.1 mo (95% CI:5.8-8.0/5.0-8.0, HR 1.04, [0.69-1.58], p=0.84). Updated laboratory/radiological correlatives will be presented. Conclusions: Toxicity between the groups was similar. The addition of V to G in an unselected cohort does not improve response, PFS, or OS in pts with metastatic PC. Funding NCI N01-CM-62201. Clinical trial information: NCT01064622.
Abstract 11006: Pathological Mechanism of LV Out-flow Obstruction in Hypertrophic Cardiomyopathy: Insights From Cardiac Magnetic Resonance Analysis
Authors: Takashi Nakamura, Yoshitaka Iwanaga, Masakazu Yasuda, Tomoyuki Ikeda, Hanako Morooka, Shunichi Miyazaki
Journal: Circulation (2013)

Background:  Myocardial fibrosis is frequently observed and may be associated with the prognosis in patients with hypertrophic cardiomyopathy (HCM). However, with regard to pathologic basis, the difference between HCM patients with and without LV outflow-tract (LVOT) obstruction remains unclear. Therefore, we sought to determine the different characteristics between hypertrophic obstructive cardiomyopathy (HOCM) and hypertrophic nonobstructive cardiomyopathy (HNCM) using delayed-enhancement cardiac magnetic resonance (DE-CMR).   Methods:  Fifty-three HCM patients receiving regular outpatient treatment underwent CMR (cine and DE imaging). HOCM was defined as LVOT pressure gradient>30 mmHg at rest. LV mass and fibrosis mass was calculated and the distribution/pattern was analyzed using 17 segment model.   Results:  In total patients, mean maximal wall thickness was 20.3 ± 3.2mm and any DE was observed in 45 (85%) patients. There were no significant differences in clinical characteristics including clinical cardiac events between HOCM (n=13) and HNCM (n=40) patients. Plasma BNP level was only significantly higher in patients with HOCM compared to HNCM (p   Conclusions:  In HCM patients, a significant inverse association was observed between LVOT obstruction and myocardial fibrosis in basal septum by DE-CMR. Local hypertrophy without fibrosis in LVOT may explain the pathological mechanism of LVOT obstruction.
Association of gene expression profile and survival among patients with head and neck carcinoma treated with cisplatin and 5-fluorouracil induction chemotherapy
Authors: F. C. Holsinger, S. Temam, D. Bui, Y. Zhang, F. Janot, K. R. Coombes, L. Mao
Journal: Journal of Clinical Oncology (2008)

6012 Background: Induction chemotherapy prior to chemoradiation is associated with improved overall survial for patients with head and neck cancer. We hypothesize that there is a gene-expression profile associated with survival in patients treated with PF induction chemotherapy. Methods: 30 patients with locally advanced (T3–4) laryngopharyngeal carcinoma squamous cell carcinoma were treated in a prospective organ preservation trial with induction chemotherapy with 5-FU and CDDP. Pre-treatment fresh frozen tumor biopsies were obtained prospectively under an IRB-approved protocol from the Institut Gustave-Roussy (Villejuif, France) between 2000 and 2003. For each patient, total RNA was extracted from cells using the RNeasy Kit. Quality control was performed using the Agilent BioAnalyzer 2100 and spectrophotometry to determine concentration. RNA was labeled and used for hybridization with the Affymetrix GeneChip U133Plus 2.0 Array, which contains 54,675 probe sets representing more than 46,000 transcripts derived from the entire human genome. Expression data from these arrays were then analyzed using DNA-Chip Analyzer software (dChip). Quantile normalization was then performed across all 29 samples, using only the PM signals with specified probe sequences. Using the R software environment and the BioConductor package, two-sided sample t-tests were used to compare both OC and LP primary SCC. Results: Results of the p-values were modeled by the beta-uniform mixture (BUM) model. Using false discovery rate (FDR) =10% (correspond p=0.001), and the average fold-change ≥2.5, as cutoff; we identified 204 genes that were differentially expressed between patients alive at 5-years following treatment and those not. Conclusions: We present a discovery set of 19 genes identified from oligonucleotide microarray experiments using patient samples to predict overall survival to platin-based chemotherapy. Future validation of this discovery set should be performed using separate patient samples from an independent data set in a prospective clinical trial. No significant financial relationships to disclose.
Clinicopathologic significance of p53, hypoxia-inducible factor 1 alfa, and vascular endothelial growth factor expression in colorectal cancer.
Authors: H. Kwon, S. Kim, S. Oh, S. Lee, K. Kwon, J. H. Lee, H. Choi, K. Park, M. Roh, H. Kim
Journal: Journal of Clinical Oncology (2010)

3609 Background: Hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) are correlated with angiogenesis and involved in tumor growth and metastases. P53 gene mutation is well established pathways in carcinogenesis and related to angiogenesis. The aim of this study was to evaluate the prognostic significances of the expressions of p53, HIF- 1α, and VEGF in colorectal cancer. Methods: The tumor tissues of 311 patients with colorectal carcinoma that underwent potentially curative resection were investigated immunohistochemically using monoclonal antibodies against p53, HIF-1α, and VEGF. Clinical information and disease-free survival and overall survival were evaluated with respect to the expressions of p53, HIF-1α, and VEGF. Results: Median follow-up duration was 48 months, and median patient age was 60 ± 11 years (range 22-82). Positivity rates of p53, HIF-1α, and VEGF were 42.4%, 63.0%, and 56.6%, respectively. HIF-1α expression in tumor tissue was found to be significantly correlated with the expression of VEGF (p = 0.040), and depth of invasion (p = 0.019). Positive relationships were found between the expressions VEGF and vascular invasion (p = 0.037), and CEA (p = 0.005), p53 expression was related to vascular invasion (p = 0.011), and CEA (p = 0.026). Univariate analysis showed that stage (p < 0.001), vascular invasion (p < 0.001), CEA (p < 0.001), and HIF-1α expression (P = 0.033) were associated with disease free survival. Stage (p < 0.001), vascular invasion (p = 0.010), CEA (p < 0.001), histological grade (p = 0.038), and HIF-1α expression (p = 0.001) were significant variables affecting overall survival. Multivariate analysis showed that stage and CEA were independently associated with disease free survival (p = 0.006, p < 0.001, respectively), and overall survival (p = 0.001, p = 0.003, respectively). HIF- 1α was independently associated with a poor overall survival (p = 0.002), however, p53 and VEGF were not found to be related to prognosis. Conclusions: HIF-1α expression in tumor tissue is associated with angiogenesis and a poor overall survival in colorectal cancer patients. No significant financial relationships to disclose.
Nimustine plus teniposide in recurrent glioblastoma
Authors: M. Glas, T. Hundsberger, M. Stuplich, D. Wiewrodt, D. Kurzwelly, B. Nguyen-Huu, K. Rasch, U. Herrlinger
Journal: Journal of Clinical Oncology (2008)

13018 Background: There is no established standard chemotherapy for recurrent glioblastoma (GBM). In a previous trial (NOA-01), the combination of nimustine and teniposide showed efficacy in previously untreated GBM. After temozolomide has been established as the standard for primary therapy of GBM, nimustin and teniposide is now been used as a second or third line chemotherapy for recurrent GBM. However, there are no data on toxicity and efficacy of this regimen in recurrent GBM. Methods: In two neurooncological centers, all patients with recurrent glioblastoma who had received nimustine (90 mg/m2, day 1/42) and tenoposide (45–60 mg/m2, days 1–3/42) chemotherapy were analyzed retrospectively for progression-free survival, overall survival and toxicity. Results: Thirty-five patients, median age 51 years (range 25–71), all of them pretreated with temozolomide were identified. The rate of progression-free patients at 6 months after initiation of therapy was 29%. The median overall survival after initiation of nimustine/teniposide was 7 months and 14% of patients survived 1 year or longer after diagnosis of recurrent disease. Grade 4 hematotoxicity according to the common terminology criteria for adverse events (CTCAE v 3.0) was observed in 12/35 patients (34%) and in 12/83 chemotherapy cycles (14%). No high-grade non-hematological toxicity was observed. Conclusions: These data support the efficacy of nimustine and teniposide combination chemotherapy in recurrent GBM. Nimustine and teniposide combination therapy is associated with a comparably high rate of high-grade hematotoxicity. No significant financial relationships to disclose.
Live birth and adverse birth outcomes in women with ulcerative colitis and Crohn's disease receiving assisted reproduction: a 20-year nationwide cohort study
Authors: B M Nørgård, P V Larsen, J Fedder, P S de Silva, M D Larsen, S Friedman
Journal: Gut (2016)

<h3>Objective</h3> To examine the chance of live births and adverse birth outcomes in women with ulcerative colitis (UC) and Crohn9s disease (CD) compared with women without inflammatory bowel disease (IBD) who have undergone assisted reproductive technology (ART) treatments. <h3>Methods</h3> This was a nationwide cohort study based on Danish health registries, comprising all women with an embryo transfer during 1 January 1994 through 2013. The cohorts comprised 1360 ART treatments in 432 women with UC, 554 ART treatments in 182 women with CD and 148 540 treatments in 52 489 women without IBD. Our primary outcome was live births per ART treatment cycle. We controlled for multiple covariates in the analyses. Our secondary outcomes were adverse birth outcomes. <h3>Results</h3> The chance of a live birth for each embryo transfer was significantly reduced in ART treatments in women with UC (OR=0.73, 95% CI 0.58 to 0.92), but not significantly reduced in the full model of ART treatments in women with CD (OR=0.77, 95% CI 0.52 to 1.14). Surgery for CD before ART treatment significantly reduced the chance of live birth for each embryo transfer (OR=0.51, 95% CI 0.29 to 0.91). In children conceived through ART treatment by women with UC, the OR of preterm birth was 5.29 (95% CI 2.41 to 11.63) in analyses including singletons and multiple births; restricted to singletons the OR was 1.80, 95% CI 0.49 to 6.62. <h3>Conclusions</h3> Our results suggest that women with UC and CD receiving ART treatments cannot expect the same success for each embryo transfer as other infertile women. Women with CD may seek to initiate ART treatment before needing CD surgery. Increased prenatal observation in UC pregnancies after ART should be considered.
EORTC Study 26041–22041: Phase I/II study on concomitant and adjuvant temozolomide (TMZ) and radiotherapy (RT) with or without PTK787/ZK222584 (PTK/ZK) in newly diagnosed glioblastoma—Results of a phase I trial
Authors: A. A. Brandes, R. Stupp, P. Hau, S. Sleijfer, D. Lacombe, T. Gorlia, H. Yun, A. Tosoni, R. Mirimanoff, M. J. van den Bent
Journal: Journal of Clinical Oncology (2007)

2026 Background: VEGF is an essential mediator of angiogenesis. PTK/ZK is an orally available tyrosine kinase inhibitor of all known VEGF receptors. The EORTC has initiated a randomized phase I/II study in which PTK/ZK is being investigated in combination with standard RT and concomitant TMZ. The results of the safety and dose-finding run-in of the triple combination are reported here. Methods: Escalating doses of PTK/ZK QD continuously (using classical 3+3 design) and concomitant RT (60 Gy) and TMZ (75 mg/m 2 /day) during 6–7 weeks were to be administered. During the adjuvant/maintenance part, PTK/ZK was prescribed at a fixed standard dose of 750mg bid until progression. Dose limiting toxicities (DLT) were defined as &gt;G3 toxicity occurring during RT + 2 weeks. Results: 18 GBM pts (M/F: 11/7, median age: 53 years, PS 0/1) have been enrolled and complete data for 15 pts are currently available. DL1 (500 mg): 4 pts; no DLT; DL2 (1000 mg): 6 pts: 1 DLT: G3, liver enzyme (ALAT) elevation and hyponatremia DL3 (1250 mg); 8 pts: 3 DLTs: G3 hepatic toxicity (2 pts) and G3 platelets and G4 neutrophil (1 pt). In a 4th patient a G3 diarrhea and hepatic DLT leading to PTK/ZK interruption was doubtful therefore it was decided to extend DL3. Frequently observed possibly related non-dose limiting drug adverse events of all grades included: abdominal pain/cramping (2 pts), ALAT/ASAT elevation (10 pts), creatinine elevation (2 pts), allergic reaction (2 pts), constipation (4 pts), diarrhea (5 pts), fatigue (11 pts), hypertension (6 pts), nausea (8 pts), vomiting (3 pts), and weight loss (4 pts). All toxicities were reversible. Conclusions: MTD has been reached at 1250 mg and the recommended dose of PTK/ZK in combination with RT and TMZ is 1000 mg/day. A randomized 3-arm phase II will start accrual in January 2007. Patients will receive standard TMZ/RT alone or with PTK/ZK starting at the beginning of radiotherapy or at the beginning of adjuvant therapy 4 weeks after the end of radiotherapy. [Table: see text]
Adjuvant radiochemotherapy (RTx/CTx) using 5-FU/Folinic acid (FA) /cisplatin (DDP) ± paclitaxel (P) and radiation in patients (pts) with completely (R0) resected high-risk gastric cancer (UICC stages II-IV (M0): An extended phase II study of the AIO/ARO/ACO
Authors: C. Bokemeyer, C. Kollmannsberger, W. Budach, M. Stahl, N. Schleucher, T. Hehr, H.-J. Wilke, U. Vanhoefer, J. Schleicher, L. Kanz
Journal: Journal of Clinical Oncology (2004)

4036 Background: The US-Intergroup study 0116 has demonstrated a significant survival benefit for pts receiving adjuvant Rtx/CTx following complete resection of gastric cancer. The current study evaluates the feasibility, toxicity and efficacy of a novel adjuvant combined modality treatment strategy containing a 3–4-drug chemotherapy regimen (CTx) plus 5-FU-based RTx/CTx. Patients and methods: Between 12/2000 and 10/2003 96 pts were included. Treatment consisted of 2 cycles of FA 500 mg/m2 (2h) / 5-FU 2000 mg/m2 (24h) once weekly for 6 consecutive weeks, P 175 mg/m2 (3h) weeks 1 and 4 and DDP 50 mg/m2 (1h) weeks 2 and 5 or 2 cycles of FA 500 mg/m2 (2h) / 5-FU 2000 mg/m2 (24h) once weekly for 6 consecutive weeks with DDP 50 mg/m2 (1h) weeks 1,3,5. The applied regimen was individually chosen by each center. Radiation therapy with 45 Gy plus concomitantly applied 5-FU 225mg/m2/24h was scheduled in between the 2 cycles. Pts with completely resected adenocarcinoma of the stomach including a systematic D1 or D2 lymph node dissection (LND) were eligible. Results: Treatment: FA/5-FU/P/DDP 44 pts; FA/5-FU/DDP 52 pts. Pts characteristics: median age: 52 years [25–69]; extended/total/subtotal gastrectomy 38%/49%/13%; D1/D2 LND 31%/69%, stage distribution: UICC stage II 36%, IIIA 25%, IIIB 18%, IV(M0) 21%. Toxicity CTC III/IV: granulocytopenia 42%, neutropenic infection 4%; anorexia 13%; diarrhea 8%, nausea/vomiting 10%; early death 1 pt due to pneumocystis carinii pneumonia; study discontinuation 19 pts (11x toxicity, 6x personal reasons, 2x tumor progression). Median follow-up for all pts is 12 months [3–22]. 18% of pts have relapsed and 82% of pts are alive without tumor recurrence. Projected 2-year progression-free survival is 61% [95% CI: 42%–80%]. Conclusions: These novel RTx/CTx regimens appear feasible and safe with acceptable toxicity indicating that DDp can be safely added to 5-FU/FA and that even a 3-drug regimen is a feasible treatment option for adjuvant radiochemotherapy in gastric cancer patients. No significant financial relationships to disclose.
A phase II study using multi-fractionation of paclitaxel and cisplatin by twice weekly schedule, plus weekly 24-hour infusion of high-dose 5-fluorouacil and leucovorin (twice weekly TP-HDFL) in the treatment of metastatic or recurrent esophageal cancer: The final report
Authors: C.-C. Lin, C.-H. Hsu, K.-H. Yeh, C. Hsu, Y.-C. Tsai, W.-L. Hsu, A.-L. Cheng
Journal: Journal of Clinical Oncology (2005)

4078 Background: Multi-fraction of paclitaxel (T) has been shown to reduce acute toxicity and improve therapeutic index in patients with advanced esophageal cancers. We designed a novel protocol by using a twice-weekly schedule for T and cisplatin (P), plus a weekly 24-hour infusional schedule for 5-fluorouracil (F). Methods: This regimen was composed of paclitaxel 35mg/m2 IV on days 1, 4, 8, 11; cisplatin 20 mg/m2 IV on days 2, 5, 9, 12; and 5-FU 2,000 mg/m2 and leucovorin 300 mg/m2, 24-hour IVF, on days 5, 12; repeated every 28 days. Between Feb 2001 and Nov 2004, a total of 40 patients (M: F = 38: 1) with a median age of 51 (range 38–73) years were enrolled. There were 22 patients with de novo metastatic esophageal cancer, 16 with recurrent disease, and 2 with bulky locally advanced disease. Among 16 patients with recurrent disease, 10 had been treated with pre-operative chemoradiotherapy (CRT) and another 6 with definitive CRT alone. Eighteen of them had exposed to cisplatin, 17 to 5-FU, and 3 to paclitaxel. Results: They received a total of 179 courses of twice weekly TP-HDFL, with an average of 4.5 courses/patient (range 1–9). All of the patients were eligible for evaluation of toxicity. Grade 3/4 leukopenia and neutropenia occurred in 30.7% and 38.5% of treatment cycles, respectively. One patient died of invasive fungal infection. Grade 3/4 diarrhea was seen in 14.0% of treatment cycles. Other non-hematologic toxicities were generally mild. Among 39 patients evaluable for tumor response, 3 CR, 13 PR, and 13 SD were seen. The response rate was 42.1% (95% C.I.: 33%–51%). The median progression-free survival was 6.4 months. The median survival for the whole group of 40 patients was 11.6 months (range: 1–44.3+ months). Conclusions: We conclude that twice weekly TP-HDFL protocol is active in patients with advanced esophageal cancers. No significant financial relationships to disclose.