tbuckley/cabot-search huggingface dataset:
Preoperative bevacizumab may impair liver hypertrophy of the future remnant liver after a portal vein occlusion in patients undergoing major resections of colorectal liver metastasis
Authors: B. Aussilhou, S. Faivre, D. Lepillé, C. Le Tourneau, V. Vilgrain, V. Paradis, J. Belghiti
Journal: Journal of Clinical Oncology (2008)

4081 Background: Preoperative chemotherapy containing bevacizumab may increase surgical morbidity in patients undergoing major hepatic resections for colorectal liver metastasis (CRLM). In this exploratory study, we investigated whether bevacizumab may impair hepatic hypertrophy of the future remnant liver (FRL) after portal vein occlusion (PVO) before major hepatectomy for CRLM. Methods: Patients underwent 4–6 cycles of FOLFOX/FOLFIRI (chemotherapy) with or without bevacizumab, followed >4 weeks later by PVO (embolization or vein ligation) prior to surgical resection of CRLM. Liver hypertrophy was measured prior and 4 weeks after PVO by volumetric C-scan. Results: A total of 39 patients are currently evaluable for analysis including 12 patients who received bevacizumab (bev+) and 27 patients treated with chemotherapy only (bev-). In patients treated with bevacizumab, the median age was 59 (ranging 39–76) and the mean number of cycles of bevacizumab was 11 (ranging 2–36). Bevacizumab infusions were interrupted 4–34 weeks before the PVO procedure. Before PVO, FRL volumes were similar in bev+ (498 cm3) and bev- (511 cm3, p=NS) groups. The increase of the FRL volume was significantly lower in the bev+ group (570 cm3) as compared to the bev- group (667 cm3) 4 weeks after PVO (p<0.031). The hypertrophy rate was also significantly lower in the bev+ group (17%) as compared to the bev- group (40%, p<0.05). No or low rate of liver regeneration (<10%) was observed in 5 (42%) patients in the bev+ group as compared to 4 (15%) in the bev- group (p=0.034). These 5 patients without hypertrophy (bev+) were older (63 vs. 52) and received 17 cycles of bevacizumab (vs. 4). Only one patient in the bev+ group (8%) had severe chemo induced histological lesions as compared to 6 patients (22%) in the bev- group. Conclusion: This study strongly suggests that bevacizumab reduces the hypertrophy of the FRL induced by PVO. Absence of hypertrophy after PVO was especially observed in older patients, after more than 4 cycles of bevacizumab and not related to histological lesions. No significant financial relationships to disclose.
Prognostic factors by histologic subtype in stage IV non-small cell lung cancer (NSCLC): A population-based survival analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Program (1988–2003)
Authors: K. Cetin, D. S. Ettinger, Y. Hei, C. D. O'Malley
Journal: Journal of Clinical Oncology (2009)

11053 Background: Representing roughly 85% of all lung cancers, NSCLC is frequently diagnosed at an advanced stage and has a poor prognosis. To better understand the prognostic importance of select patient and tumor characteristics in late-stage disease, we examined survival in patients diagnosed with stage IV NSCLC. Methods: Data from SEER were used to study 53,319 patients with stage IV NSCLC diagnosed between 1988 and 2003, with follow-up through 2005. The distribution of cases according to time period of diagnosis and select patient and tumor characteristics was described for each histologic subtype (squamous; adenocarcinoma (bronchioloalveolar adenocarcinoma (BAC), non-BAC); large cell; and other/unknown). Kaplan-Meier and multivariate Cox proportional hazard models were used to examine the influence of these variables on overall survival by histologic subtype. Results: Most recent period of diagnosis (1998–2003 versus 1988–1992) conferred a survival advantage across histologic subtypes, independent of gender, age, ethnicity/race, tumor grade, and uptake of surgery/radiation. This was especially pronounced for those diagnosed with large cell tumors (adjusted hazard ratio (aHR): 0.76, 95% confidence interval (CI): 0.71–0.82). Similarly, females survived longer than males across histologic groups, particularly for those with BAC tumors (aHR: 0.77, 95% CI: 0.66–0.89). Increasing age was associated with reduced survival in all histologic subtypes except BAC, where prognosis was poorest in the youngest age group. The influence of ethnicity/race also varied with histology: compared to Whites, American Indians/Alaskan Natives with squamous tumors and Blacks with large cell tumors had a poorer prognosis, whereas Asians/Pacific Islanders with either non-BAC or large cell tumors demonstrated superior survival. Conclusions: Survival among stage IV NSCLC patients improved over the study period, which may reflect the use of third generation chemotherapy as well as better supportive care. Nonetheless, lung cancer remains a deadly disease, and the prognostic effect of demographic factors varies with histologic subtype. [Table: see text]
A phase III random assignment trial comparing percutaneous hepatic perfusion with melphalan (PHP-mel) to standard of care for patients with hepatic metastases from metastatic ocular or cutaneous melanoma.
Authors: J. F. Pingpank, M. S. Hughes, H. R. Alexander, M. B. Faries, J. S. Zager, R. Royal, E. D. Whitman, C. W. Nutting, G. P. Siskin, S. S. Agarwala
Journal: Journal of Clinical Oncology (2010)

LBA8512 Background: Patients with hepatic metastases from primary melanoma have a median survival between 6 and 9 months. Few treatment strategies provide a meaningful impact on outcome. This report examines the efficacy of a minimally invasive regional therapy with melphalan (MEL) in patients with hepatic metastases from malignant melanoma. Methods: Between February 2006 and October 2009, 93 patients (M:F; 45:48) were accrued to a phase III, random-assignment trial comparing percutaneous hepatic perfusion (PHP-mel) (n=44) to standard of care (BAC) (n=49). This represents 100% of a planned 92 patient accrual. The primary endpoint was hepatic progression-free survival (H-PFS). Crossover to PHP-mel therapy was permitted at hepatic progression. Secondary endpoints included assessment of response rate (RR), duration of response (RES), and overall survival (OS) after PHP. A planned PHP treatment regimen included 4 to 6 PHP procedures at 28 to 35 day intervals. MEL (3.0 mg/kg) was delivered via the hepatic artery in a 30-minute hepatic artery infusion via a percutaneously placed catheter with hepatic venous hemofiltration using a retrohepatic, double balloon catheter (Delcath Systems, Inc.) and paired hemofiltration cartridges. Patients randomized to BAC were offered treatment considered to be the best alternative regimen by the treating physician. Staging evaluations were performed at baseline and then at 6 to 8 week intervals post baseline. All responses represent investigator-based results and were evaluated via standard RECIST criteria. Intent to treat based survival analysis was via the Kaplan-Meier method, with a 2-sided p&lt; 0.05 defining significance. Results: Median H-PFS was 245 days (CI:136, 267) for PHP-mel vs. 49 days (CI:43, 68) for BAC (p&lt;0.001). Overall response rate was 34.1 % (15/44) (CI: 20.5, 49.9) for PHP (15/44) vs. 2.0 % (1/49) (CI: 0.1, 10.9) for BAC (p&lt;0.001). Upon hepatic progression, crossover to PHP occurred in 27 patients (55%) randomized to BAC. Conclusions: For patients with metastatic melanoma to the liver, H-PFS is significantly improved with PHP-mel versus best available care. [Table: see text]
Vitamin D deficiency and TB disease phenotype
Authors: Manish Pareek, John Innes, Saranya Sridhar, Lisa Grass, David Connell, Gerrit Woltmann, Martin Wiselka, Adrian R Martineau, Onn Min Kon, Martin Dedicoat, Ajit Lalvani
Journal: Thorax (2015)

<h3>Background</h3> Extrapulmonary TB is increasingly common, yet the determinants of the wide clinical spectrum of TB are poorly understood. <h3>Methods</h3> We examined surveillance data (Birmingham, UK: 1980–2009 and USA Centers for Disease Control: 1993–2008) to identify demographic factors associated with extrapulmonary TB. We then directly tested association of these factors and serum 25-hydroxycholecalciferol (25(OH)D) concentration with extrapulmonary TB by multivariable analysis in a separate UK cohort. <h3>Results</h3> Data were available for 10 152 and 277 013 TB cases for Birmingham and US, respectively. Local-born individuals of white ethnicity had a lower proportion of extrapulmonary disease when compared with local-born non-whites (p&lt;0.0001); both groups had a lower proportion of extrapulmonary disease when compared with foreign-born non-whites (p&lt;0.0001). In a separate UK cohort (n=462), individuals with extrapulmonary TB had lower mean serum 25(OH)D concentration than those with pulmonary TB (11.4 vs 15.2 nmol/L, respectively, p=0.0001). On multivariable analysis, vitamin D deficiency was strongly associated with extrapulmonary TB independently of ethnicity, gender and other factors. Doubling in serum 25(OH)D concentration conferred substantially reduced risk of extrapulmonary disease (OR 0.55, 95% CI 0.41 to 0.73). <h3>Conclusions</h3> We identify vitamin D deficiency as a probable risk factor for extrapulmonary dissemination in TB, which may account for the associations of dark-skinned ethnicity and female gender with extrapulmonary disease. Our findings implicate vitamin D status in <i>Mycobacterium tuberculosis</i> containment in vivo and, given the high prevalence of deficiency, may inform development of novel TB prevention strategies.
Antitumor activity of YM155, a novel survivin suppressant, in combination with docetaxel against malignant melanoma cells.
Authors: N. Kaneko, K. Yamanaka, A. Kita, M. Nakata, H. Koutoku, M. Sasamata
Journal: Journal of Clinical Oncology (2010)

e13621 Background: YM155 is a novel survivin suppressant which shows potent antiproliferative activity against a wide range of cancer cells. In this study, we evaluated the therapeutic potential of YM155 alone, and in combination with docetaxel (TXT) against human malignant melanoma (MM) cells. Methods: Antiproliferative effect of YM155 was evaluated by sulforhodamine B assay. Intracellular mRNA and protein levels of apoptosis related biomarkers, cell viability and caspase 3/7 activity were evaluated after the treatment with survivin siRNA or YM155±TXT. The in vivo antitumor activities were evaluated in A375 and SK-MEL-5 human MM cell xenografted nude mice model. Results: YM155 showed potent in vitro antiproliferative activity against human MM cells with GI50 values ranging from 1.2 to 297 nM, regardless of BRAF, p53, N-Ras and K-Ras mutation status. YM155 suppressed survivin expression, leading to cell growth inhibition and apoptosis induction in the same way as survivin siRNA did. In SK-MEL-5 cells, YM155 significantly enhanced TXT induced cell growth inhibition, caspase 3/7 activity and apoptosis. The survivin protein was increased by the treatment of TXT and completely suppressed in YM155-TXT combination. In the human MM xenograft models, continuous infusion of YM155 induced tumor regression without body weight loss. Concomitant administration of YM155 (2 mg/kg/day) and TXT (20 mg/kg/day) showed more significant antitumor activities than the administration of each single agent, including complete regression without exacerbation of body weight loss. Conclusions: YM155 potentiates the efficacy of TXT against MM in vitro and in vivo, by down regulating TXT-induced survivin expression. These results provide a rationale for YM155-TXT combination against MM. Further clinical investigation of YM155-TXT combination for the treatment of MM is worthwhile. No significant financial relationships to disclose.
High BAALC expression associates with other molecular prognostic markers, poor outcome and a distinct gene expression signature in cytogenetically normal acute myeloid leukemia (CN AML): A Cancer and Leukemia Group B (CALGB) study
Authors: C. Langer, A. S. Ruppert, M. D. Radmacher, S. P. Whitman, P. Paschka, C. D. Baldus, K. Mrózek, J. E. Kolitz, G. Marcucci, C. D. Bloomfield
Journal: Journal of Clinical Oncology (2007)

7013 Background: High BAALC expression predicts poor outcome in CN AML patients (pts). Yet, little is known about BAALC's function or its relation to other prognostic markers. We evaluated BAALC expression in the context of molecular markers and clinical outcome in 172 de novo CN AML adults, aged &lt;60 years (y) treated on similar CALGB protocols (9621 and 19808). Methods: BAALC expression was measured by quantitative real-time RT-PCR in pretreatment blood samples. Pts were grouped as high (n=86) or low BAALC (n=86) expressers using the median expression value, by protocol, as a cutoff. Gene expression profiling (Affymetrix U133 plus 2.0 GeneChip) was performed on high (n=26) and low (n=24) pts. Results: BAALC expression was associated with several molecular markers ( Table ). Complete remission (CR) rate was lower in high BAALC pts (79% v 90%), for whom achieving CR was almost 4 times less likely than for low BAALC pts (P=.02; odds ratio=0.27), after adjusting for age (P=.004), ERG expression (P=.05) and white blood cell count (WBC; P=.04). With a median follow-up of 4.3 y, high BAALC pts had shorter overall survival (OS) (P=.002; 3-y OS: 42% v 59%). In a multivariable model, high BAALC provided further adverse prognostic information (P=.06; hazard ratio=1.66) independent of FLT3 ITD (P&lt;.001), WBC (P=.007) and NPM1 (P=.02). A gene expression signature was identified consisting of 312 probe sets differentially expressed (P&lt;.001) between BAALC groups. High BAALC was associated with overexpression of, among other genes, PROM1, CD34 and KIT indicating a less differentiated phenotype in these pts. Conclusions: Although associated with other prognostic markers, high BAALC expression independently predicts outcome and is associated with a distinct gene expression profile, potentially identifying new therapeutic targets in this pt subset. No significant financial relationships to disclose. [Table: see text]
Enzyme-linked immunoabsorbent assay-detected p53 protein accumulation: a prognostic factor in a large breast cancer cohort.
Authors: M A Levesque, H Yu, G M Clark, E P Diamandis
Journal: Journal of Clinical Oncology (1998)

PURPOSE This study was designed to evaluate whether patients with an unfavorable breast cancer prognosis could be identified by p53 protein overexpression detected by a quantitative enzyme-linked immunoabsorbent assay (ELISA). PATIENTS AND METHODS Extracts from 998 breast carcinomas were assayed for p53 protein by an ELISA that used both DO-1 monoclonal and CM-1 polyclonal antibodies. Relative risks (RRs) for cancer relapse and death after 6 years of follow-up for patients with p53-positive tumors based on different dichotomization criteria were determined by multivariate Cox regression, adjusted for patient age, tumor size, S-phase fraction, estrogen (ER) and progesterone (PR) receptor concentrations, DNA ploidy, and lymph node metastases. Disease-free (DFS) and overall (OS) survival probabilities of p53-positive and p53-negative groups, using a median cutoff, were also estimated by the Kaplan-Meier method and the log-rank test. These analyses were performed for all patients and for subgroups defined by ER status, node status, and primary postoperative treatment. RESULTS Univariate analysis showed that p53 concentrations that exceeded the median indicated significantly increased risks for relapse (P &lt; .01) and death (P = .02). Multivariate analyses confirmed these observations (RR = 1.40; P = .02 for DFS and RR = 1.50; P &lt; .01 for OS) and showed trends for increasing risks for relapse (P = .02) and death (P = .06) when p53 was considered as a four-level categoric variable, and identified p53 positivity as a significant predictor of outcome in node-positive patients (RR = 1.67; P &lt; .01 and RR = 2.10; P &lt; .01 for DFS and OS, respectively), ER-positive patients (RR = 1.45; P = .02 and RR = 1.50; P = .01 for DFS and OS, respectively), and in patients treated with chemotherapy (RR = 1.73; P = .04 for relapse and RR = 2.04; P = .03 for death). CONCLUSION Assessment of p53 overexpression by ELISA, easily incorporated into the routine biochemical work-up of breast tumors, may be an independent predictor of reduced survival of breast cancer patients.
Arresting the Inflammatory Drive of Chronic Lymphocytic Leukemia with Ibrutinib
Authors: Pavan Bachireddy, Catherine J. Wu
Journal: Clinical Cancer Research (2016)

The clinical success of agents targeting the B-cell receptor signaling pathway in chronic lymphocytic leukemia (CLL) may also derive from disrupting the CLL microenvironment. Investigation of the immunomodulatory effects of these agents illuminates the unique immunobiology of CLL and highlights potential targets for dismantling the chronic inflammatory drive. See related article by Niemann et al., p. 1572.
Pharmacokinetics (PK) study of sphingosomal vincristine (SV) in patients with metastatic melanoma (MM)
Authors: A. Y. Bedikian, A. Vardeleon, T. Smith
Journal: Journal of Clinical Oncology (2004)

2038 Background: SV is a formulation of vincristine sulfate (VCR) encapsulated in sphingomyelin/cholesterol liposomes. In preclinical studies, sphingosomal encapsulation prolonged the circulation half-life of total vincristine, increased drug accumulation at the tumor, and improved anticancer activity compared to VCR. Methods: We evaluated the PK of total (encapsulated and released) and released vincristine and urinary excretion of vincristine in patients with stage IV metastatic melanoma. SV 2.0 mg/m2 IV over 1 h was given every 2 weeks. Blood samples were collected from 0 to 97 hours at cycles 1 & 3, and at predose in cycles 2 & 4. Urine samples were collected from 0 to 96 hours at cycle 1. Results: 12 patients with median age 58, Zubrod-PS of ≤ 2, and median number of 2 prior chemo/immunotherapies were enrolled. Median number of SV cycles given was 4. After VSLI infusion, total plasma vincristine concentrations remained relatively constant for 3 to 12 hours. Following this delay, two-thirds of the patients displayed a range of apparent biexponential profiles with a relatively rapid clearance phase (t1/2λ0 2.2 ± 0.9 h) followed by a slower phase (t1/2λ1 12.1 ± 4.1 h). The rapid clearance phase was not present in the other one-third of patients, who exhibited apparent monoexponential concentration declines (t1/2λ1 12.0 ± 5.9 h). Patients with monoexponential profiles had slower total clearance (Cl) (131 versus 445 mL/h), higher AUC0-inf (36890 versus 10221 h•ng/mL), and longer MRT0-inf (22.7 versus 6.2 h) than patients with biexponential profiles. The Vss values were similar between both profiles (mean 2650 mL). Released VCR was undetectable in 95% of samples. PK profiles were similar between cycles 1 and 3. Less than 8% of the VSLI dose excreted in the urine. One PR and 2 SD were seen. Adverse events were similar to VCR with Grade 1 or 2 neurologic and gastrointestinal events predominantly seen. There were no treatment associated deaths. Conclusions: Longer circulation half-life and higher AUC of total vincristine were achieved with SV compared to VCR. SV was well tolerated and showed promising antitumor activity against metastatic melanoma. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration INEX Pharmaceuticals Inc.
Detection of bed-exit events using a new wireless bed monitoring assistance
Authors: Marie Bruyneel, Walter Libert, Vincent Ninane
Journal: European Respiratory Journal (2011)

Objectives:  To assess the capability of using Heasys, an innovative wireless bed monitoring assistance that records body movements, presence and temperature, in the detection of bed-exit events and body position changes at night.   Design:  Descriptive study.   Settings:  Sleep laboratory for patient9s recording and home for healthy volunteers.   Participants:  Twelve patients referred for suspicion or treatment of sleep disordered breathing and 5 healthy subjects.   Measurements:  Complete polysomnography was recorded during one night in patients and during two nights in healthy volunteers. Heasys sheet was placed under the fitted bed sheet to allow concomitant recording. During the second night, healthy subjects were asked to get out of bed at least 2 times for a minimal duration of 3 minutes.   Results:  Heasys allowed the detection of all bed-exit events in patients and volunteers (sensitivity: 100%, and specificity: 85%). When bed-exit events were defined by the lack of the presence signal combined with absence of motion and a dip in temperature, sensitivity and specificity of Heasys were 92 and 100%. In patients and volunteers, Heasys detected body position changes recorded by polysomnography respectively in 84 and 98% of the cases. Additional recorded motions were mainly related to leg movements or arousals.   Conclusion:  In this small feasibility study, we can conclude that Heasys is an effective innovative device allowing bed-exit events detection in adult patients and healthy volunteers.
Phase II study of irinotecan (CPT-11) alone in patients (pts) with metastatic pancreatic cancer
Authors: A. Funakoshi, T. Okusaka, H. Ishii, A. Sawaki, S. Ohkawa, O. Ishikawa, S. Saitoh
Journal: Journal of Clinical Oncology (2004)

4102 Purpose: The objective of this study was to determine the efficacy and safety of CPT-11 monotherapy in pts with metastatic pancreatic cancer. The influence of biliary drainage on the pharmacokinetics of CPT-11 was also investigated. Patients and Methods: Chemotherapy naive pts with metastatic pancreatic cancer who fulfilled the following criteria were registered: measurable metastatic disease, KPS≥50, age<75, ANC≥2000, Hgb≥10, Plts≥100K, AST&ALT≤2.5X nl, t-bili≤2.0, adequate organ function, and written informed consent. CPT-11 (100 mg/m2 as a 90-minute infusion) was administered on days 1, 8, and 15 every 4 weeks. Results: Forty pts were enrolled between Aug. 2001 and Nov. 2002, and 37 pts were evaluable for efficacy and safety. Their characteristics were: M/F 25/12; median age 59 years (41–74); median KPS 90 (100–70); and 2 pts with biliary drainage. Median number of courses administered was 2 (1–10). Ten pts (27%) showed a partial response (PR) using bi-dimensional criteria, while assessment using RECIST criteria indicated 8 PRs (28%) in 29 pts. Neutropenia, diarrhea, and vomiting were the common adverse events, as in other studies of CPT-11 monotherapy. The median survival time was 7.3 months. One pt was died of sepsis due to neutropenia and diarrhea induced by CPT-11. Other serious adverse events (SAE) were neutropenia and thrombocytopenia. Obstructive jaundice, elevated bilirubin and gastric variceal bleeding also occurred as drug unrelated SAE. Seven pts (including 2 with biliary drainage) were used to assess pharmacokinetics. The AUC of CPT-11 was similar between pts with or without biliary drainage, but the metabolites (SN-38, APC, and SN-38 glucuronide) showed larger AUCs in the pts with drainage. Conclusions: CPT-11 monotherapy is effective for metastatic pancreatic cancer. No significant financial relationships to disclose.
Response to Letter Regarding Article, “Anti-inflammatory and Antiatherogenic Effects of the Inflammasome NLRP3 Inhibitor Arglabin in ApoE2.Ki Mice Fed a High-Fat Diet”
Authors: Amna Abderrazak, Dominique Couchie, Dler Faieeq Darweesh Mahmood, Rima Elhage, Cécile Vindis, Muriel Laffargue, Véronique Matéo, Berthold Büchele, Monica Rubio Ayala, Menna El Gaafary, Tatiana Syrovets, Mohamed-Naceur Slimane, Bertrand Friguet, Tamas Fulop, Thomas Simmet, Khadija El Hadri, Mustapha Rouis
Journal: Circulation (2015)