Is progression-free survival a more relevant endpoint than overall survival in first-line HR+/HER2− metastatic breast cancer?

Directory of Open Access Journals (Sweden)

Forsythe A

2018-05-01

Full Text Available Anna Forsythe,1 David Chandiwana,2 Janina Barth,3 Marroon Thabane,4 Johan Baeck,5 Anastasiya Shor,1 Gabriel Tremblay6 1Health Technology Assessment Evidence, Purple Squirrel Economics, New York, NY, USA; 2Global Value and Access, Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 3German Market Access, Novartis Pharma GmbH, Nuremberg, Germany; 4Health Policy and Patient Access, Novartis Pharmaceuticals Incorporated, Dorval, QC, Canada; 5Global Medical Affairs (Oncology Business Unit, Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 6Health Economics, Purple Squirrel Economics, New York, NY, USA Background: Hormone receptor-positive (HR+, human epidermal growth factor receptor 2- negative (HER2−, metastatic breast cancer (MBC accounts for 73% of all MBCs. Endocrine therapy (ET is the basis of first-line (1L therapy for patients with HR+/HER2− MBC. Novel therapies have demonstrated improvements in progression-free survival (PFS compared to ET. The clinical relevance of PFS is being debated, as there is no proven direct correlation with overall survival (OS benefit to date. We reviewed studies of HR+/HER2− MBC to assess PFS and other factors that influence OS and treatment response, and health-related quality of life (HRQoL. Methods: The Embase®, Medline®, and Cochrane databases were systematically searched to identify studies in adult women with HR+/HER2− MBC, published between January 2006 and January 2017, and written in English. Phase II and III randomized controlled trials (RCTs, observational, and retrospective studies were included. Results: Seventy-nine RCTs were identified: 58 (73% in the 1L+ setting and 21 (27% in second-line or greater settings. PFS hazard ratios (HRs were reported in 61 (77% studies; 31 (39% reported significant PFS improvements. OS was reported in 44 (41% studies; 12 (15% reported significant OS improvements. Significant improvements in both PFS and OS were reported in only 6 (8% studies

Missing data and censoring in the analysis of progression-free survival in oncology clinical trials.

Science.gov (United States)

Denne, J S; Stone, A M; Bailey-Iacona, R; Chen, T-T

2013-01-01

Progression-free survival (PFS) is increasingly used as a primary endpoint in oncology clinical trials. However, trial conduct is often such that PFS data on some patients may be partially missing either due to incomplete follow-up for progression, or due to data that may be collected but confounded by patients stopping randomized therapy or starting alternative therapy prior to progression. Regulatory guidance on how to handle these patients in the analysis and whether to censor these patients differs between agencies. We present results of a reanalysis of 28 Phase III trials from 12 companies or institutions performed by the Pharmaceutical Research and Manufacturers Association-sponsored PFS Expert Team. We show that analyses not adhering to the intention-to-treat principle tend to give hazard ratio estimates further from unity and describe several factors associated with this shift. We present illustrative simulations to support these findings and provide recommendations for the analysis of PFS.

Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis.

Science.gov (United States)

Yardley, Denise A; Noguchi, Shinzaburo; Pritchard, Kathleen I; Burris, Howard A; Baselga, José; Gnant, Michael; Hortobagyi, Gabriel N; Campone, Mario; Pistilli, Barbara; Piccart, Martine; Melichar, Bohuslav; Petrakova, Katarina; Arena, Francis P; Erdkamp, Frans; Harb, Wael A; Feng, Wentao; Cahana, Ayelet; Taran, Tetiana; Lebwohl, David; Rugo, Hope S

2013-10-01

Effective treatments for hormone-receptor-positive (HR(+)) breast cancer (BC) following relapse/progression on nonsteroidal aromatase inhibitor (NSAI) therapy are needed. Initial Breast Cancer Trials of OraL EveROlimus-2 (BOLERO-2) trial data demonstrated that everolimus and exemestane significantly prolonged progression-free survival (PFS) versus placebo plus exemestane alone in this patient population. BOLERO-2 is a phase 3, double-blind, randomized, international trial comparing everolimus (10 mg/day) plus exemestane (25 mg/day) versus placebo plus exemestane in postmenopausal women with HR(+) advanced BC with recurrence/progression during or after NSAIs. The primary endpoint was PFS by local investigator review, and was confirmed by independent central radiology review. Overall survival, response rate, and clinical benefit rate were secondary endpoints. Final study results with median 18-month follow-up show that median PFS remained significantly longer with everolimus plus exemestane versus placebo plus exemestane [investigator review: 7.8 versus 3.2 months, respectively; hazard ratio = 0.45 (95% confidence interval 0.38-0.54); log-rank P NSAIs. These results further support the use of everolimus plus exemestane in this patient population. ClinicalTrials.gov #NCT00863655.

Association between time to disease progression end points and overall survival in patients with neuroendocrine tumors

Directory of Open Access Journals (Sweden)

Singh S

2014-08-01

Full Text Available Simron Singh,1 Xufang Wang,2 Calvin HL Law1 1Sunnybrook Odette Cancer Center, University of Toronto, Toronto, ON, Canada; 2Novartis Oncology, Florham Park, NJ, USA Abstract: Overall survival can be difficult to determine for slowly progressing malignancies, such as neuroendocrine tumors. We investigated whether time to disease progression is positively associated with overall survival in patients with such tumors. A literature review identified 22 clinical trials in patients with neuroendocrine tumors that reported survival probabilities for both time to disease progression (progression-free survival and time to progression and overall survival. Associations between median time to disease progression and median overall survival and between treatment effects on time to disease progression and treatment effects on overall survival were analyzed using weighted least-squares regression. Median time to disease progression was significantly associated with median overall survival (coefficient 0.595; P=0.022. In the seven randomized studies identified, the risk reduction for time to disease progression was positively associated with the risk reduction for overall survival (coefficient on −ln[HR] 0.151; 95% confidence interval −0.843, 1.145; P=0.713. The significant association between median time to disease progression and median overall survival supports the assertion that time to disease progression is an alternative end point to overall survival in patients with neuroendocrine tumors. An apparent albeit not significant trend correlates treatment effects on time to disease progression and treatment effects on overall survival. Informal surveys of physicians’ perceptions are consistent with these concepts, although additional randomized trials are needed. Keywords: neuroendocrine tumors, progression-free survival, disease progression, mortality

Association of drug transporter expression with mortality and progression-free survival in stage IV head and neck squamous cell carcinoma.

Directory of Open Access Journals (Sweden)

Rolf Warta

Full Text Available Drug transporters such as P-glycoprotein (ABCB1 have been associated with chemotherapy resistance and are considered unfavorable prognostic factors for survival of cancer patients. Analyzing mRNA expression levels of a subset of drug transporters by quantitative reverse transcription polymerase chain reaction (qRT-PCR or protein expression by tissue microarray (TMA in tumor samples of therapy naïve stage IV head and neck squamous cell carcinoma (HNSCC (qRT-PCR, n = 40; TMA, n = 61, this in situ study re-examined the significance of transporter expression for progression-free survival (PFS and overall survival (OS. Data from The Cancer Genome Atlas database was used to externally validate the respective findings (n = 317. In general, HNSCC tended to lower expression of drug transporters compared to normal epithelium. High ABCB1 mRNA tumor expression was associated with both favorable progression-free survival (PFS, p = 0.0357 and overall survival (OS, p = 0.0535. Similar results were obtained for the mRNA of ABCC1 (MRP1, multidrug resistance-associated protein 1; PFS, p = 0.0183; OS, p = 0.038. In contrast, protein expression of ATP7b (copper transporter ATP7b, mRNA expression of ABCG2 (BCRP, breast cancer resistance protein, ABCC2 (MRP2, and SLC31A1 (hCTR1, human copper transporter 1 did not correlate with survival. Cluster analysis however revealed that simultaneous high expression of SLC31A1, ABCC2, and ABCG2 indicates poor survival of HNSCC patients. In conclusion, this study militates against the intuitive dogma where high expression of drug efflux transporters indicates poor survival, but demonstrates that expression of single drug transporters might indicate even improved survival. Prospectively, combined analysis of the 'transportome' should rather be performed as it likely unravels meaningful data on the impact of drug transporters on survival of patients with HNSCC.

Being treated in higher volume hospitals leads to longer progression-free survival for epithelial ovarian carcinoma patients in the Rhone-Alpes region of France

OpenAIRE

Huguet, Marius; Perrier, Lionel; Bally, Olivia; Benayoun, David; De Saint Hilaire, Pierre; Beal Ardisson, Dominique; Morelle, Magali; Havet, Nathalie; Joutard, Xavier; Meeus, Pierre; Gabelle, Philippe; Provençal, Jocelyne; Chauleur, Céline; Glehen, Olivier; Charreton, Amandine

2018-01-01

Background To investigate the relationship between hospital volume activities and the survival for Epithelial Ovarian Carcinoma (EOC) patients in France. Methods This retrospective study using prospectively implemented databases was conducted on an exhaustive cohort of 267 patients undergoing first-line therapy during 2012 in the Rhone-Alpes Region of France. We compared Progression-Free Survival for Epithelial Ovarian Carcinoma patients receiving first-line therapy in high- (i.e. ≥ 12 cases/...

Individual Patient Data Analysis of Progression-Free Survival Versus Overall Survival As a First-Line End Point for Metastatic Colorectal Cancer in Modern Randomized Trials: Findings From the Analysis and Research in Cancers of the Digestive System Database

NARCIS (Netherlands)

Shi, Qian; de Gramont, Aimery; Grothey, Axel; Zalcberg, John; Chibaudel, Benoist; Schmoll, Hans-Joachim; Seymour, Matthew T.; Adams, Richard; Saltz, Leonard; Goldberg, Richard M.; Punt, Cornelis J. A.; Douillard, Jean-Yves; Hoff, Paulo M.; Hecht, Joel Randolph; Hurwitz, Herbert; Díaz-Rubio, Eduardo; Porschen, Rainer; Tebbutt, Niall C.; Fuchs, Charles; Souglakos, John; Falcone, Alfredo; Tournigand, Christophe; Kabbinavar, Fairooz F.; Heinemann, Volker; van Cutsem, Eric; Bokemeyer, Carsten; Buyse, Marc; Sargent, Daniel J.

2015-01-01

Purpose Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Methods Individual

How to Deal with Interval-Censored Data Practically while Assessing the Progression-Free Survival: A Step-by-Step Guide Using SAS and R Software.

Science.gov (United States)

Dugué, Audrey Emmanuelle; Pulido, Marina; Chabaud, Sylvie; Belin, Lisa; Gal, Jocelyn

2016-12-01

We describe how to estimate progression-free survival while dealing with interval-censored data in the setting of clinical trials in oncology. Three procedures with SAS and R statistical software are described: one allowing for a nonparametric maximum likelihood estimation of the survival curve using the EM-ICM (Expectation and Maximization-Iterative Convex Minorant) algorithm as described by Wellner and Zhan in 1997; a sensitivity analysis procedure in which the progression time is assigned (i) at the midpoint, (ii) at the upper limit (reflecting the standard analysis when the progression time is assigned at the first radiologic exam showing progressive disease), or (iii) at the lower limit of the censoring interval; and finally, two multiple imputations are described considering a uniform or the nonparametric maximum likelihood estimation (NPMLE) distribution. Clin Cancer Res; 22(23); 5629-35. ©2016 AACR. ©2016 American Association for Cancer Research.

Correlation of hedgehog signal activation with chemoradiotherapy sensitivity and survival in esophageal squamous cell carcinomas

International Nuclear Information System (INIS)

Zhu Weiguo; You Zhenbin; Li Tao; Yu Changhua; Tao Guangzhou; Hu Mingli; Chen Xiaofei

2011-01-01

The objective of this study was to investigate the significance of hedgehog signaling pathway in chemoradiotherapy sensitivity and its effect on the prognosis of esophageal squamous cell carcinoma. In the present study, we used the method of immunohistochemistry to examine the expression status of two hedgehog components, PTCH1 and glioma-associated oncogene GLI-1, in 100 pre-treated biopsy specimens of esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy. We find that high levels of PTCH1 and GLI-1 were detected in 76.0 and 72.0% of esophageal squamous cell carcinoma, respectively. Significant associations of high PTCH1 and GLI-1 expression with large tumor size (both P=0.01), locoregional progression (P=0.001 and 0.003, respectively) and the lack of complete response to chemoradiotherapy (P=0.008 and 0.01, respectively) were observed. Univariate analysis revealed that high PTCH1 and GLI-1 expression was associated with poor locoregional progression-free survival, distant progression-free survival and overall survival. Furthermore, esophageal squamous cell carcinoma patients with high PTCH1 and GLI-1 expression have the shorter survival time than the subgroups with negative and low PTCH1 and GLI-1 expression. In multivariate analysis, PTCH1 and GLI-1 expression status were both evaluated as independent prognostic factors for locoregional progression-free survival, distant progression-free survival and overall survival. These findings suggest an important role for the activation of hedgehog signaling in esophageal squamous cell carcinoma progression and that PTCH1 and GLI-1 expression may be significantly associated with esophageal squamous cell carcinoma resistance to chemoradiotherapy. (author)

CX3CR1 is a modifying gene of survival and progression in amyotrophic lateral sclerosis.

Directory of Open Access Journals (Sweden)

Alan Lopez-Lopez

Full Text Available The objective of this study was to investigate the association of functional variants of the human CX3CR1 gene (Fractalkine receptor with the risk of Amyotrophic Lateral Sclerosis (ALS, the survival and the progression rate of the disease symptoms in a Spanish ALS cohort. 187 ALS patients (142 sporadic [sALS] and 45 familial and 378 controls were recruited. We investigated CX3CR1 V249I (rs3732379 and T280M (rs3732378 genotypes and their haplotypes as predictors of survival, the progression rate of the symptoms (as measured by ALSFRS-R and FVC decline and the risk of suffering ALS disease. The results indicated that sALS patients with CX3CR1 249I/I or 249V/I genotypes presented a shorter survival time (42.27 ± 4.90 than patients with 249V/V genotype (67.65 ± 7.42; diff -25.49 months 95%CI [-42.79,-8.18]; p = 0.004; adj-p = 0.018. The survival time was shorter in sALS patients with spinal topography and CX3CR1 249I alleles (diff =  -29.78 months; 95%CI [-49.42,-10.14]; p = 0.003. The same effects were also observed in the spinal sALS patients with 249I-280M haplotype (diff =  -27.02 months; 95%CI [-49.57, -4.48]; p = 0.019. In the sALS group, the CX3CR1 249I variant was associated with a faster progression of the disease symptoms (OR = 2.58; 95IC% [1.32, 5.07]; p = 0.006; adj-p = 0.027. There was no evidence for association of these two CX3CR1 variants with ALS disease risk. The association evidenced herein is clinically relevant and indicates that CX3CR1 could be a disease-modifying gene in sALS. The progression rate of the disease's symptoms and the survival time is affected in patients with one or two copies of the CX3CR1 249I allele. The CX3CR1 is the most potent ALS survival genetic factor reported to date. These results reinforce the role of the immune system in ALS pathogenesis.

Apparent diffusion coefficient histogram metrics correlate with survival in diffuse intrinsic pontine glioma: a report from the Pediatric Brain Tumor Consortium

Science.gov (United States)

Poussaint, Tina Young; Vajapeyam, Sridhar; Ricci, Kelsey I.; Panigrahy, Ashok; Kocak, Mehmet; Kun, Larry E.; Boyett, James M.; Pollack, Ian F.; Fouladi, Maryam

2016-01-01

Background Diffuse intrinsic pontine glioma (DIPG) is associated with poor survival regardless of therapy. We used volumetric apparent diffusion coefficient (ADC) histogram metrics to determine associations with progression-free survival (PFS) and overall survival (OS) at baseline and after radiation therapy (RT). Methods Baseline and post-RT quantitative ADC histograms were generated from fluid-attenuated inversion recovery (FLAIR) images and enhancement regions of interest. Metrics assessed included number of peaks (ie, unimodal or bimodal), mean and median ADC, standard deviation, mode, skewness, and kurtosis. Results Based on FLAIR images, the majority of tumors had unimodal peaks with significantly shorter average survival. Pre-RT FLAIR mean, mode, and median values were significantly associated with decreased risk of progression; higher pre-RT ADC values had longer PFS on average. Pre-RT FLAIR skewness and standard deviation were significantly associated with increased risk of progression; higher pre-RT FLAIR skewness and standard deviation had shorter PFS. Nonenhancing tumors at baseline showed higher ADC FLAIR mean values, lower kurtosis, and higher PFS. For enhancing tumors at baseline, bimodal enhancement histograms had much worse PFS and OS than unimodal cases and significantly lower mean peak values. Enhancement in tumors only after RT led to significantly shorter PFS and OS than in patients with baseline or no baseline enhancement. Conclusions ADC histogram metrics in DIPG demonstrate significant correlations between diffusion metrics and survival, with lower diffusion values (increased cellularity), increased skewness, and enhancement associated with shorter survival, requiring future investigations in large DIPG clinical trials. PMID:26487690

Surrogacy of progression-free survival (PFS) for overall survival (OS) in esophageal cancer trials with preoperative therapy: Literature-based meta-analysis.

Science.gov (United States)

Kataoka, K; Nakamura, K; Mizusawa, J; Kato, K; Eba, J; Katayama, H; Shibata, T; Fukuda, H

2017-10-01

There have been no reports evaluating progression-free survival (PFS) as a surrogate endpoint in resectable esophageal cancer. This study was conducted to evaluate the trial level correlations between PFS and overall survival (OS) in resectable esophageal cancer with preoperative therapy and to explore the potential benefit of PFS as a surrogate endpoint for OS. A systematic literature search of randomized trials with preoperative chemotherapy or preoperative chemoradiotherapy for esophageal cancer reported from January 1990 to September 2014 was conducted using PubMed and the Cochrane Library. Weighted linear regression using sample size of each trial as a weight was used to estimate coefficient of determination (R 2 ) within PFS and OS. The primary analysis included trials in which the HR for both PFS and OS was reported. The sensitivity analysis included trials in which either HR or median survival time of PFS and OS was reported. In the sensitivity analysis, HR was estimated from the median survival time of PFS and OS, assuming exponential distribution. Of 614 articles, 10 trials were selected for the primary analysis and 15 for the sensitivity analysis. The primary analysis did not show a correlation between treatment effects on PFS and OS (R 2 0.283, 95% CI [0.00-0.90]). The sensitivity analysis did not show an association between PFS and OS (R 2 0.084, 95% CI [0.00-0.70]). Although the number of randomized controlled trials evaluating preoperative therapy for esophageal cancer is limited at the moment, PFS is not suitable for primary endpoint as a surrogate endpoint for OS. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Denosumab and bone metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer: exploratory analyses by baseline prostate-specific antigen doubling time.

Science.gov (United States)

Smith, Matthew R; Saad, Fred; Oudard, Stephane; Shore, Neal; Fizazi, Karim; Sieber, Paul; Tombal, Bertrand; Damiao, Ronaldo; Marx, Gavin; Miller, Kurt; Van Veldhuizen, Peter; Morote, Juan; Ye, Zhishen; Dansey, Roger; Goessl, Carsten

2013-10-20

Denosumab, an anti-RANK ligand monoclonal antibody, significantly increases bone metastasis-free survival (BMFS; hazard ratio [HR], 0.85; P = .028) and delays time to first bone metastasis in men with nonmetastatic castration-resistant prostate cancer (CRPC) and baseline prostate-specific antigen (PSA) ≥ 8.0 ng/mL and/or PSA doubling time (PSADT) ≤ 10.0 months. To identify men at greatest risk for bone metastasis or death, we evaluated relationships between PSA and PSADT with BMFS in the placebo group and the efficacy and safety of denosumab in men with PSADT ≤ 10, ≤ 6, and ≤ 4 months. A total of 1,432 men with nonmetastatic CRPC were randomly assigned 1:1 to monthly subcutaneous denosumab 120 mg or placebo. Enrollment began February 2006; primary analysis cutoff was July 2010, when approximately 660 men were anticipated to have developed bone metastases or died. In the placebo group, shorter BMFS was observed as PSADT decreased below 8 months. In analyses by shorter baseline PSADT, denosumab consistently increased BMFS by a median of 6.0, 7.2, and 7.5 months among men with PSADT ≤ 10 (HR, 0.84; P = .042), ≤ 6 (HR, 0.77; P = .006), and ≤ 4 months (HR, 0.71; P = .004), respectively. Denosumab also consistently increased time to bone metastasis by PSADT subset. No difference in survival was observed between treatment groups for the overall study population or PSADT subsets. Patients with shorter PSADT are at greater risk for bone metastasis or death. Denosumab consistently improves BMFS in men with shorter PSADT and seems to have the greatest treatment effects in men at high risk for progression.

Perioperative blood transfusion: does it influence survival and cancer progression in metastatic spine tumor surgery?

Science.gov (United States)

Zaw, Aye Sandar; Kantharajanna, Shashidhar B; Maharajan, Karthikeyan; Tan, Barry; Vellayappan, Balamurugan; Kumar, Naresh

2017-02-01

Despite advances in surgical techniques for spinal metastases, there is often substantial blood loss, resulting in patients requiring blood transfusion during the perioperative period. Allogeneic blood transfusion (ABT) has been the main replenishment method for lost blood. However, the impact of ABT on cancer-related outcomes has been controversial in various studies. We aimed to evaluate the influence of perioperative ABT on disease progression and survival in patients undergoing metastatic spinal tumor surgery (MSTS). We conducted a retrospective study that included 247 patients who underwent MSTS at a single tertiary institution between 2005 and 2014. The impact of using perioperative ABT (either exposure to or quantities of transfusion) on disease progression and survival was assessed using Cox regression analyses while adjusting for potential confounding variables. Of 247 patients, 133 (54%) received ABT. The overall median number of blood units transfused was 2 (range, 0-10 units). Neither blood transfusion exposure nor quantities of transfusion were associated with overall survival (hazard ratio [HR], 1.15 [p = 0.35] and 1.10 [p = 0.11], respectively) and progression-free survival (HR, 0.87 [p = 0.18] and 0.98 [p = 0.11], respectively). The factors that influenced overall survival were primary tumor type and preoperative Eastern Cooperative Oncology Group performance status, whereas primary tumor type was the only factor that had an impact on progression-free survival. This is the first study providing evidence that disease progression and survival in patients who undergo MSTS are less likely to be influenced by perioperative ABT. The worst oncologic outcomes are more likely to be caused by the clinical circumstances necessitating blood transfusion, but not transfusion itself. However, because ABT can have a propensity toward developing postoperative infections, including surgical site infection, the use of patient blood management

Hypermetabolism in ALS is associated with greater functional decline and shorter survival.

Science.gov (United States)

Steyn, Frederik J; Ioannides, Zara A; van Eijk, Ruben P A; Heggie, Susan; Thorpe, Kathryn A; Ceslis, Amelia; Heshmat, Saman; Henders, Anjali K; Wray, Naomi R; van den Berg, Leonard H; Henderson, Robert D; McCombe, Pamela A; Ngo, Shyuan T

2018-04-29

To determine the prevalence of hypermetabolism, relative to body composition, in amyotrophic lateral sclerosis (ALS) and its relationship with clinical features of disease and survival. Fifty-eight patients with clinically definite or probable ALS as defined by El Escorial criteria, and 58 age and sex-matched control participants underwent assessment of energy expenditure. Our primary outcome was the prevalence of hypermetabolism in cases and controls. Longitudinal changes in clinical parameters between hypermetabolic and normometabolic patients with ALS were determined for up to 12 months following metabolic assessment. Survival was monitored over a 30-month period following metabolic assessment. Hypermetabolism was more prevalent in patients with ALS than controls (41% vs 12%, adjusted OR=5.4; pALS. Mean lower motor neuron score (SD) was greater in hypermetabolic patients when compared with normometabolic patients (4 (0.3) vs 3 (0.7); p=0.04). In the 12 months following metabolic assessment, there was a greater change in Revised ALS Functional Rating Scale score in hypermetabolic patients when compared with normometabolic patients (-0.68 points/month vs -0.39 points/month; p=0.01). Hypermetabolism was inversely associated with survival. Overall, hypermetabolism increased the risk of death during follow-up to 220% (HR 3.2, 95% CI 1.1 to 9.4, p=0.03). Hypermetabolic patients with ALS have a greater level of lower motor neuron involvement, faster rate of functional decline and shorter survival. The metabolic index could be important for informing prognosis in ALS. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Rituximab-containing reduced-intensity conditioning improves progression-free survival following allogeneic transplantation in B cell non-Hodgkin lymphoma

Directory of Open Access Journals (Sweden)

Narendranath Epperla

2017-06-01

Full Text Available Abstract Background In B cell non-Hodgkin lymphoma (B-NHL, rituximab-containing reduced-intensity conditioning regimens (R-RIC have been shown to provide favorable outcomes in single-arm studies; however, large multicenter studies comparing R-RIC and non-rituximab-containing reduced-intensity conditioning regimens (nonR-RIC have not been performed. Using the CIBMTR database, we report the outcomes of R-RIC versus nonR-RIC regimens in B-NHL. Methods We evaluated 1401 adult B-NHL patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT who received nonR-RIC (n = 1022 or R-RIC (n = 379 regimens. Graft-versus-host disease (GVHD prophylaxis was limited to calcineurin inhibitor-based approaches. Results Median follow-up of survivors in the R-RIC and nonR-RIC groups was 47 and 37 months, respectively. On multivariate analysis, no difference was seen between the R-RIC and nonR-RIC cohorts in terms of acute GVHD grade II–IV (RR = 1.14, 95%CI = 0.83–1.56, p = 0.43 or grade III–IV (RR = 1.16, 95%CI = 0.72–1.89, p = 0.54, chronic GVHD (RR = 1.15, 95%CI = 0.92–1.46, p = 0.22, non-relapse mortality (RR = 0.90; 95%CI = 0.67–1.22; p = 0.51, relapse/progression (RR = 0.79; 95%CI = 0.63–1.01; p = 0.055, and mortality (RR = 0.84, 95%CI = 0.69–1.02, p = 0.08 risk. However, R-RIC was associated with a significantly improved progression-free survival (RR = 0.76; 95%CI 0.62–0.92; p = 0.006. On subgroup analysis, mortality benefit was noted in the R-RIC group patients not receiving busulfan-based RIC (RR = 0.76; 95%CI = 0.60–0.96; p = 0.02 and with the use of a higher cumulative rituximab dose (RR = 0.43; 95%CI = 0.21–0.90; p = 0.02. Conclusion Our analysis shows that inclusion of rituximab in RIC regimens improves progression-free survival in patients with B cell NHL. These data supports the use of R-RIC in B

Denosumab and Bone Metastasis–Free Survival in Men With Nonmetastatic Castration-Resistant Prostate Cancer: Exploratory Analyses by Baseline Prostate-Specific Antigen Doubling Time

Science.gov (United States)

Smith, Matthew R.; Saad, Fred; Oudard, Stephane; Shore, Neal; Fizazi, Karim; Sieber, Paul; Tombal, Bertrand; Damiao, Ronaldo; Marx, Gavin; Miller, Kurt; Van Veldhuizen, Peter; Morote, Juan; Ye, Zhishen; Dansey, Roger; Goessl, Carsten

2013-01-01

Purpose Denosumab, an anti–RANK ligand monoclonal antibody, significantly increases bone metastasis–free survival (BMFS; hazard ratio [HR], 0.85; P = .028) and delays time to first bone metastasis in men with nonmetastatic castration-resistant prostate cancer (CRPC) and baseline prostate-specific antigen (PSA) ≥ 8.0 ng/mL and/or PSA doubling time (PSADT) ≤ 10.0 months. To identify men at greatest risk for bone metastasis or death, we evaluated relationships between PSA and PSADT with BMFS in the placebo group and the efficacy and safety of denosumab in men with PSADT ≤ 10, ≤ 6, and ≤ 4 months. Patients and Methods A total of 1,432 men with nonmetastatic CRPC were randomly assigned 1:1 to monthly subcutaneous denosumab 120 mg or placebo. Enrollment began February 2006; primary analysis cutoff was July 2010, when approximately 660 men were anticipated to have developed bone metastases or died. Results In the placebo group, shorter BMFS was observed as PSADT decreased below 8 months. In analyses by shorter baseline PSADT, denosumab consistently increased BMFS by a median of 6.0, 7.2, and 7.5 months among men with PSADT ≤ 10 (HR, 0.84; P = .042), ≤ 6 (HR, 0.77; P = .006), and ≤ 4 months (HR, 0.71; P = .004), respectively. Denosumab also consistently increased time to bone metastasis by PSADT subset. No difference in survival was observed between treatment groups for the overall study population or PSADT subsets. Conclusion Patients with shorter PSADT are at greater risk for bone metastasis or death. Denosumab consistently improves BMFS in men with shorter PSADT and seems to have the greatest treatment effects in men at high risk for progression. PMID:24043751

Survival after failure of first-line chemotherapy in advanced gastric cancer patients: differences between Japan and the rest of the world.

Science.gov (United States)

Takashima, Atsuo; Iizumi, Sakura; Boku, Narikazu

2017-07-01

In this review, we focus on post-progression survival after first-line chemotherapy of advanced gastric cancer, and particularly the differences between Japan and the rest of the world. We reviewed 15 recent phase III trials of which 4 were solely recruited from Japanese and 11 from rest of the world. The patient characteristics age, performance status, previous gastrectomy and the number of metastatic sites were similar in Japan and rest of the world. However, the diffuse histological type was more common in Japan. While overall survival was longer in Japan (10.5-14.1 vs. 7.9-12.2 months), progression-free survival tended to be shorter in Japan (3.6-6.0 vs. 3.1-7.4 months). Post-progression survival calculated as the difference between median overall survival and progression-free survival was clearly longer in Japan (6.9-8.6 vs. 2.4-6.2 months). The proportion of patients receiving second-line chemotherapy (%2nd-CX) was quite different in Japan and rest of the world (69-85% vs. 11-59%). Correlations between %2nd-CX and post-progression survival were strong (Spearman's rank correlation coefficient; ρ = 0.86, P < 0.001). Correlations between %2nd-CX and ratio of post-progression survival to total overall survival were also strong (ρ = 0.84, P < 0.001). Because a survival benefit of second-CX was documented in several phase III trials, it can be concluded that higher %2nd-CX partly contributed to extended post-progression survival. However, considering that second-CX increased survival only by ~1.5 months at median, other factors such as third-line chemotherapy may have some influences to prolonged post-progression survival. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Simulation and comparison of progression-free survival among patients with non-squamous non-small-cell lung cancer receiving sequential therapy.

Science.gov (United States)

Walzer, Stefan; Chouaid, Christos; Lister, Johanna; Gultyaev, Dmitry; Vergnenegre, Alain; de Marinis, Filippo; Meng, Jie; de Castro Carpeno, Javier; Crott, Ralph; Kleman, Martin; Ngoh, Charles

2015-01-01

In recent years, the treatment landscape in advanced non-squamous non-small-cell lung cancer (nsNSCLC) has changed. New therapies (e.g., bevacizumab indicated in first line) have become available and other therapies (e.g., pemetrexed in first line and second line) moved into earlier lines in the treatment paradigm. While there has been an expansion of the available treatment options, it is still a key research question which therapy sequence results in the best survival outcomes for patients with nsNSCLC. A therapy-sequencing disease model that approximates treatment outcomes in up to five lines of treatment was developed for patients with nsNSCLC. The primary source of data for progression-free survival (PFS) and time to death was published pivotal trial data. All patients were treatment-naïve and in the PFS state, received first-line treatment with either bevacizumab-based therapy or doublet chemotherapy (including the option of pemetrexed + cisplatin). Patients would then progress to a subsequent line of therapy, remain in PFS or die. In case of progression, it was assumed that each survivor would receive a subsequent line of therapy, based on EMA licensed therapies. Weibull distribution curves were fitted to the data. All bevacizumab-based first-line therapy sequences analyzed achieved total PFS of around 15 months. Bevacizumab + carboplatin + paclitaxel (first line) → pemetrexed (second line) → erlotinib (third line) → docetaxel (fourth line) resulted in total mean PFS time of 15.7 months, for instance. Sequences with pemetrexed in combination with cisplatin in first line achieved total PFS times between 12.6 and 12.8 months with a slightly higher total PFS time achieved when assuming pemetrexed continuation therapy in maintenance after pemetrexed + cisplatin in first-line induction. Overall survival results followed the same trend as PFS. The model suggests that treatment-sequencing strategies starting with a bevacizumab-based combination in first line

Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma.

Science.gov (United States)

Avet-Loiseau, Hervé; Fonseca, Rafael; Siegel, David; Dimopoulos, Meletios A; Špička, Ivan; Masszi, Tamás; Hájek, Roman; Rosiñol, Laura; Goranova-Marinova, Vesselina; Mihaylov, Georgi; Maisnar, Vladimír; Mateos, Maria-Victoria; Wang, Michael; Niesvizky, Ruben; Oriol, Albert; Jakubowiak, Andrzej; Minarik, Jiri; Palumbo, Antonio; Bensinger, William; Kukreti, Vishal; Ben-Yehuda, Dina; Stewart, A Keith; Obreja, Mihaela; Moreau, Philippe

2016-09-01

The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n = 48; Rd, n = 52) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standard-risk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01080391. © 2016 by The American Society of Hematology.

Active smoking may negatively affect response rate, progression-free survival, and overall survival of patients with metastatic renal cell carcinoma treated with sunitinib.

Science.gov (United States)

Keizman, Daniel; Gottfried, Maya; Ish-Shalom, Maya; Maimon, Natalie; Peer, Avivit; Neumann, Avivit; Hammers, Hans; Eisenberger, Mario A; Sinibaldi, Victoria; Pili, Roberto; Hayat, Henry; Kovel, Svetlana; Sella, Avishay; Boursi, Ben; Weitzen, Rony; Mermershtain, Wilmosh; Rouvinov, Keren; Berger, Raanan; Carducci, Michael A

2014-01-01

Obesity, smoking, hypertension, and diabetes are risk factors for renal cell carcinoma development. Their presence has been associated with a worse outcome in various cancers. We sought to determine their association with outcome of sunitinib treatment in metastatic renal cell carcinoma (mRCC). An international multicenter retrospective study of sunitinib-treated mRCC patients was performed. Multivariate analyses were performed to determine the association between outcome and the pretreatment status of smoking, body mass index, hypertension, diabetes, and other known prognostic factors. Between 2004 and 2013, 278 mRCC patients were treated with sunitinib: 59 were active smokers, 67 were obese, 73 were diabetic, and 165 had pretreatment hypertension. Median progression-free survival (PFS) was 9 months, and overall survival (OS) was 22 months. Factors associated with PFS were smoking status (past and active smokers: hazard ratio [HR]: 1.17, p = .39; never smokers: HR: 2.94, p non-clear cell histology (HR: 1.62, p = .011), pretreatment neutrophil-to-lymphocyte ratio >3 (HR: 3.51, p smoking status (past and active smokers: HR: 1.25, p = .29; never smokers: HR: 2.7, p 3 (HR: 2.95, p smoking may negatively affect the PFS and OS of sunitinib-treated mRCC. Clinicians should consider advising patients to quit smoking at initiation of sunitinib treatment for mRCC.

The prosurvival activity of ascites against TRAIL is associated with a shorter disease-free interval in patients with ovarian cancer

Directory of Open Access Journals (Sweden)

Lane Denis

2010-01-01

associated with shorter disease-free interval. Conclusions The prosurvival activity of ascites against TRAIL is associated with shorter disease-free interval, which may be explained, at least in part, by ascites-induced cisplatin/paclitaxel resistance. Our findings suggest that ascites may contain prosurvival factors that protect against TRAIL and chemotherapy and consequently affect disease progression.

ATM/RB1 mutations predict shorter overall survival in urothelial cancer.

Science.gov (United States)

Yin, Ming; Grivas, Petros; Emamekhoo, Hamid; Mendiratta, Prateek; Ali, Siraj; Hsu, JoAnn; Vasekar, Monali; Drabick, Joseph J; Pal, Sumanta; Joshi, Monika

2018-03-30

Mutations of DNA repair genes, e.g. ATM/RB1 , are frequently found in urothelial cancer (UC) and have been associated with better response to cisplatin-based chemotherapy. Further external validation of the prognostic value of ATM/RB1 mutations in UC can inform clinical decision making and trial designs. In the discovery dataset, ATM/RB1 mutations were present in 24% of patients and were associated with shorter OS (adjusted HR 2.67, 95% CI, 1.45-4.92, p = 0.002). There was a higher mutation load in patients carrying ATM/RB1 mutations (median mutation load: 6.7 versus 5.5 per Mb, p = 0.072). In the validation dataset, ATM/RB1 mutations were present in 22.2% of patients and were non-significantly associated with shorter OS (adjusted HR 1.87, 95% CI, 0.97-3.59, p = 0.06) and higher mutation load (median mutation load: 8.1 versus 7.2 per Mb, p = 0.126). Exome sequencing data of 130 bladder UC patients from The Cancer Genome Atlas (TCGA) dataset were analyzed as a discovery cohort to determine the prognostic value of ATM/RB1 mutations. Results were validated in an independent cohort of 81 advanced UC patients. Cox proportional hazard regression analysis was performed to calculate the hazard ratio (HR) and 95% confidence interval (CI) to compare overall survival (OS). ATM/RB1 mutations may be a biomarker of poor prognosis in unselected UC patients and may correlate with higher mutational load. Further studies are required to determine factors that can further stratify prognosis and evaluate predictive role of ATM/RB1 mutation status to immunotherapy and platinum-based chemotherapy.

Interstitial lung abnormalities in treatment-naïve advanced non-small-cell lung cancer patients are associated with shorter survival

Energy Technology Data Exchange (ETDEWEB)

Nishino, Mizuki, E-mail: Mizuki_Nishino@DFCI.HARVARD.EDU [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215 (United States); Cardarella, Stephanie [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States); Dahlberg, Suzanne E. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215 (United States); Araki, Tetsuro [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Lydon, Christine; Jackman, David M.; Rabin, Michael S. [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States); Hatabu, Hiroto [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Johnson, Bruce E. [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States)

2015-05-15

Highlights: • Interstitial lung abnormalities were present in 14% of stage IV NSCLC patients. • ILA was more common in older patients with heavier smoking history. • ILA was associated with shorter survival after adjusting for smoking and therapy. • ILA could be an additional independent marker for survival in advanced NSCLC. - Abstract: Objective: Interstitial lung diseases are associated with increased risk of lung cancer. The prevalence of ILA at diagnosis of advanced non-small-cell lung cancer (NSCLC) and its impact on overall survival (OS) remain to be investigated. Materials and method: The study included 120 treatment-naïve stage IV NSCLC patients (53 males, 67 females). ILA was scored on CT prior to any systemic therapy using a 4-point scale [0 = no evidence of ILA, 1 = equivocal for ILA, 2 = suspicious for ILA, 3 = ILA] by a sequential reading method previously reported. ILA scores of 2 or 3 indicated the presence of ILA. Results: ILA was present in 17 patients (14%) with advanced NSCLC prior to any treatment (score3: n = 2, score2: n = 15). These 17 patients were significantly older (median age: 69 vs. 63, p = 0.04) and had a heavier smoking history (median: 40 vs. 15.5 pack-year, p = 0.003) than those with ILA score 0 or 1. Higher ILA scores were associated with shorter OS (p = 0.001). Median OS of the 17 patients with ILA was 7.2 months [95%CI: 2.9–9.4] compared to 14.8 months [95%CI: 11.1–18.4] in patients with ILA score 0 or 1 (p = 0.002). In a multivariate model, the presence of ILA remained significant for increased risk for death (HR = 2.09, p = 0.028) after adjusting for first-line systemic therapy (chemotherapy, p < 0.001; TKI, p < 0.001; each compared to no therapy) and pack years of smoking (p = 0.40). Conclusion: Radiographic ILA was present in 14% of treatment-naïve advanced NSCLC patients. Higher ILA scores were associated with shorter OS, indicating that ILA could be a marker of shorter survival in advanced NSCLC.

Pretreatment F-18 FDG PET/CT Parameters to Evaluate Progression-Free Survival in Gastric Cancer

Energy Technology Data Exchange (ETDEWEB)

Kim, Jeonghun; Lim, Seok Tae; Na, Chang Ju; Han, Yeonhee; Kim, Chanyoung; Jeong, Hwanjeong; Sohn, Myunghee [Chonbuk National Univ., Jeonju (Korea, Republic of)

2014-03-15

We performed this study to evaluate the predictive value of pretreatment F-18 FDG PET/CT for progression-free survival (PFS) in patients with gastric cancer. Of 321 patients with a diagnosis of gastric cancer, we retrospectively enrolled 97 patients (men:women = 61:36, age 59.8±13.2 years), who underwent pretreatment F-18 fluoro-2-deoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) from January 2009 to December 2009. Maximum standardized uptake value (SUVmax) was measured for each case with detectable primary lesions. In the remaining non-detectable cases, SUVmax was measured from the corresponding site seen on gastroduodenoscopy for analysis. In subgroup analysis, metabolic tumor volume (MTV) was measured in 50 patients with clearly distinguishable primary lesions. SUVmax, stage, depth of tumor invasion and presence of lymph node metastasis were analyzed in terms of PFS. Receiver operating characteristic (ROC) curves were used to find optimal cutoff values of SUVmax and MTV for disease progression. The relationship between SUVmax, MTV and PFS was analyzed using the Kaplan-Meier with log-rank test and Cox's proportional hazard regression methods. Of 97 patients, 15 (15.5 %) had disease progression. The mean follow-up duration was 29.6±10.2 months. The mean PFS of low SUVmax group (≤5.74) was significantly longer than that of the high SUVmax group (>5.74) (30.9±8.0 vs 24.3±13.6 months, p =0.008). In univariate analysis, stage (I vs II, III, IV), depth of tumor invasion (T1 vs T2, T3, T4), presence of lymph node metastasis and SUVmax (>5.74 vs ≤5.74) were significantly associated with recurrence. In multivariate analysis, high SUVmax (>5.74) was the only poor prognostic factor for PFS (p =0.002, HR 11.03, 95% CI 2.48.49.05). Subgroup multivariate analysis revealed that high MTV (>16.42) was the only poor prognostic factor for PFS (p =0.034, HR 3.59, 95 % CI 1.10.11.71). In gastric cancer, SUVmax measured by pretreatment F-18

Impact of tumour volume on prediction of progression-free survival in sinonasal cancer

International Nuclear Information System (INIS)

Hennersdorf, Florian; Mauz, Paul-Stefan; Adam, Patrick; Welz, Stefan; Sievert, Anne; Ernemann, Ulrike; Bisdas, Sotirios

2015-01-01

The present study aimed to analyse potential prognostic factors, with emphasis on tumour volume, in determining progression free survival (PFS) for malignancies of the nasal cavity and the paranasal sinuses. Retrospective analysis of 106 patients with primary sinonasal malignancies treated and followed-up between March 2006 and October 2012. Possible predictive parameters for PFS were entered into univariate and multivariate Cox regression analysis. Kaplan-Meier curve analysis included age, sex, baseline tumour volume (based on MR imaging), histology type, TNM stage and prognostic groups according to the American Joint Committee on Cancer (AJCC) classification. Receiver operating characteristic (ROC) curve analysis concerning the predictive value of tumour volume for recurrence was also conducted. The main histological subgroup consisted of epithelial tumours (77%). The majority of the patients (68%) showed advanced tumour burden (AJCC stage III–IV). Lymph node involvement was present in 18 cases. The mean tumour volume was 26.6 ± 21.2 cm 3 . The median PFS for all patients was 24.9 months (range: 2.5–84.5 months). The ROC curve analysis for the tumour volume showed 58.1% sensitivity and 75.4% specificity for predicting recurrence. Tumour volume, AJCC staging, T- and N- stage were significant predictors in the univariate analysis. Positive lymph node status and tumour volume remained significant and independent predictors in the multivariate analysis. Radiological tumour volume proofed to be a statistically reliable predictor of PFS. In the multivariate analysis, T-, N- and overall AJCC staging did not show significant prognostic value

Meta-analysis of single-arm survival studies: a distribution-free approach for estimating summary survival curves with random effects.

Science.gov (United States)

Combescure, Christophe; Foucher, Yohann; Jackson, Daniel

2014-07-10

In epidemiologic studies and clinical trials with time-dependent outcome (for instance death or disease progression), survival curves are used to describe the risk of the event over time. In meta-analyses of studies reporting a survival curve, the most informative finding is a summary survival curve. In this paper, we propose a method to obtain a distribution-free summary survival curve by expanding the product-limit estimator of survival for aggregated survival data. The extension of DerSimonian and Laird's methodology for multiple outcomes is applied to account for the between-study heterogeneity. Statistics I(2)  and H(2) are used to quantify the impact of the heterogeneity in the published survival curves. A statistical test for between-strata comparison is proposed, with the aim to explore study-level factors potentially associated with survival. The performance of the proposed approach is evaluated in a simulation study. Our approach is also applied to synthesize the survival of untreated patients with hepatocellular carcinoma from aggregate data of 27 studies and synthesize the graft survival of kidney transplant recipients from individual data from six hospitals. Copyright © 2014 John Wiley & Sons, Ltd.

Post progression survival in glioblastoma: where are we?

Science.gov (United States)

Franceschi, Enrico; Ermani, Mario; Bartolini, Stefania; Bartolotti, Marco; Poggi, Rosalba; Tallini, Giovanni; Marucci, Gianluca; Fioravanti, Antonio; Tosoni, Alicia; Agati, Raffaele; Bacci, Antonella; Pozzati, Eugenio; Morandi, Luca; Balestrini, Damiano; Ghimenton, Claudio; Crisi, Girolamo; Brandes, Alba A

2015-01-01

The optimal end point for phase II studies for recurrent glioblastoma (GBM) is unclear and a matter of debate. Moreover, data about post-progression survival (PPS) after the first disease progression in GBM patients treated according to EORTC 26981/22981/NCIC CE.3 trial are limited. The aim of this study was to evaluate the PPS in GBM patients. The analysis was made with a database on 1,006 GBM patients followed prospectively between 06/2005 and 06/2010. Eligibility criteria for the study were: age ≥ 18 years; PS: 0-2; chemotherapy given at disease progression after RT/TMZ. 232 patients (mean age 52 years, range 18-77 years) were enrolled. The median PFS following second line chemotherapy (PFS2) was 2.5 months (95 % CI 2.1-2.9) and the rate of patients free of progression at 6 months (PFS2-6 mo), was 21.6 % (95 % CI 16.3-26.9 %). The median PPS was 8.6 months (95 % CI 7.4-9.8), PPS rates were: PPS-6: 66 % (95 % CI 60.3-72.9 %), PPS-9: 48.2 % (95 % CI 41.5-54.9 %) and PPS-12: 31.7 % (95 % CI 25.2-38.2 %). PPS in unselected patients treated with alkylating agents is about 8 months. PPS rates could be of interest as an end point in future studies in recurrent GBM.

Adding Erlotinib to Chemoradiation Improves Overall Survival but Not Progression-Free Survival in Stage III Non-Small Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Komaki, Ritsuko, E-mail: rkomaki@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K.; Wei, Xiong [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Blumenschein, George R. [Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tang, Ximing [Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lee, J. Jack [Department of Biostatatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Welsh, James W. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wistuba, Ignacio I. [Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liu, Diane D. [Department of Biostatatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hong, Waun Ki [Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2015-06-01

Purpose: To test, in a single-arm, prospective, phase 2 trial, whether adding the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to concurrent chemoradiotherapy for previously untreated, locally advanced, inoperable non-small cell lung cancer would improve survival and disease control without increasing toxicity. Methods and Materials: Forty-eight patients with previously untreated non-small cell lung cancer received intensity modulated radiation therapy (63 Gy/35 fractions) on Monday through Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin area under the curve [AUC] = 2) on Mondays, for 7 weeks. All patients also received the EGFR tyrosine kinase inhibitor erlotinib (150 mg orally 1/d) on Tuesday-Sunday for 7 weeks, followed by consolidation paclitaxel–carboplatin. The primary endpoint was time to progression; secondary endpoints were overall survival (OS), toxicity, response, and disease control and whether any endpoint differed by EGFR mutation status. Results: Of 46 patients evaluable for response, 40 were former or never-smokers, and 41 were evaluable for EGFR mutations (37 wild-type [WT] and 4 mutated [all adenocarcinoma]). Median time to progression was 14.0 months and did not differ by EGFR status. Toxicity was acceptable (no grade 5, 1 grade 4, 11 grade 3). Twelve patients (26%) had complete responses (10 WT, 2 mutated), 27 (59%) partial (21 WT, 2 mutated, 4 unknown), and 7 (15%) none (6 WT, 2 mutated, 1 unknown) (P=.610). At 37.0 months' follow-up (range, 3.6-76.5 months) for all patients, median OS time was 36.5 months, and 1-, 2-, and 5-year OS rates were 82.6%, 67.4%, and 35.9%, respectively; none differed by mutation status. Twelve patients had no progression, and 34 had local and/or distant failure. Eleven of 27 distant failures were in the brain (7 WT, 3 mutated, 1 unknown). Conclusions: Toxicity and OS were promising, but time to progression did not meet expectations. The prevalence of

c-MET Overexpression in Colorectal Cancer: A Poor Prognostic Factor for Survival.

Science.gov (United States)

Lee, Su Jin; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Park, Young Suk; Kim, Seung Tae

2018-03-02

Increased mesenchymal-epithelial transition factor gene (c-MET) expression in several human malignancies is related to increased tumor progression and is a new potential drug target for several types of cancers. In the present study, we investigated the incidence of c-MET overexpression and its prognostic significance in patients with colorectal cancer (CRC). We retrospectively reviewed the data from 255 stage IV CRC patients who had results from a c-MET immunohistochemical test at Samsung Medical Center. We explored the relationships between c-MET overexpression and clinicopathological features and survival. Primary tumor sites were 67 right-sided colon, 98 left-sided colon, and 90 rectum. Forty-two patients (16.7%) had poorly differentiated or mucinous carcinoma. Among the 255 patients, 39 (15.3%) exhibited c-MET overexpression. There was no significant difference in the prevalence of c-MET overexpression according to primary site, histologic differentiation, molecular markers, or metastatic sites. In a comparison of the tumor response to first-line chemotherapy according to the level of c-MET expression, we found no significant difference in either partial response or disease control rate. In the survival analysis, patients with c-MET overexpression had significantly shorter overall survival (39 vs. 27 months; P = .018) and progression-free survival (PFS) during bevacizumab treatment (10 vs. 7 months; P = .024). c-MET overexpression, which was detected in 39 CRC patients (15.3%) irrespective of primary sites or molecular markers, indicated a poor survival prognosis and predicted shorter PFS during bevacizumab treatment in patients with CRC. Further studies are warranted to elucidate the value of c-MET-targeted therapy in CRC patients. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Stomatin-like protein 2 is overexpressed in epithelial ovarian cancer and predicts poor patient survival

International Nuclear Information System (INIS)

Sun, Fei; Ding, Wen; He, Jie-Hua; Wang, Xiao-Jing; Ma, Ze-Biao; Li, Yan-Fang

2015-01-01

Stomatin-like protein 2 (SLP-2, also known as STOML2) is a stomatin homologue of uncertain function. SLP-2 overexpression has been suggested to be associated with cancer progression, resulting in adverse clinical outcomes in patients. Our study aim to investigate SLP-2 expression in epithelial ovarian cancer cells and its correlation with patient survival. SLP-2 mRNA and protein expression levels were analysed in five epithelial ovarian cancer cell lines and normal ovarian epithelial cells using real-time PCR and western blotting analysis. SLP-2 expression was investigated in eight matched-pair samples of epithelial ovarian cancer and adjacent noncancerous tissues from the same patients. Using immunohistochemistry, we examined the protein expression of paraffin-embedded specimens from 140 patients with epithelial ovarian cancer, 20 cases with borderline ovarian tumours, 20 cases with benign ovarian tumours, and 20 cases with normal ovarian tissues. Statistical analyses were applied to evaluate the clinicopathological significance of SLP-2 expression. SLP-2 mRNA and protein expression levels were significantly up-regulated in epithelial ovarian cancer cell lines and cancer tissues compared with normal ovarian epithelial cells and adjacent noncancerous ovarian tissues. Immunohistochemistry analysis revealed that the relative overexpression of SLP-2 was detected in 73.6 % (103/140) of the epithelial ovarian cancer specimens, 45.0 % (9/20) of the borderline ovarian specimens, 30.0 % (6/20) of the benign ovarian specimens and none of the normal ovarian specimens. SLP-2 protein expression in epithelial ovarian cancer was significantly correlated with the tumour stage (P < 0.001). Epithelial ovarian cancer patients with higher SLP-2 protein expression levels had shorter progress free survival and overall survival times compared to patients with lower SLP-2 protein expression levels. Multivariate analyses showed that SLP-2 expression levels were an independent prognostic

Radiographic Progression-Free Survival as a Clinically Meaningful End Point in Metastatic Castration-Resistant Prostate Cancer: The PREVAIL Randomized Clinical Trial.

Science.gov (United States)

Rathkopf, Dana E; Beer, Tomasz M; Loriot, Yohann; Higano, Celestia S; Armstrong, Andrew J; Sternberg, Cora N; de Bono, Johann S; Tombal, Bertrand; Parli, Teresa; Bhattacharya, Suman; Phung, De; Krivoshik, Andrew; Scher, Howard I; Morris, Michael J

2018-05-01

Drug development for metastatic castration-resistant prostate cancer has been limited by a lack of clinically relevant trial end points short of overall survival (OS). Radiographic progression-free survival (rPFS) as defined by the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) is a candidate end point that represents a clinically meaningful benefit to patients. To demonstrate the robustness of the PCWG2 definition and to examine the relationship between rPFS and OS. PREVAIL was a phase 3, randomized, double-blind, placebo-controlled multinational study that enrolled 1717 chemotherapy-naive men with metastatic castration-resistant prostate cancer from September 2010 through September 2012. The data were analyzed in November 2016. Patients were randomized 1:1 to enzalutamide 160 mg or placebo until confirmed radiographic disease progression or a skeletal-related event and initiation of either cytotoxic chemotherapy or an investigational agent for prostate cancer treatment. Sensitivity analyses (SAs) of investigator-assessed rPFS were performed using the final rPFS data cutoff (May 6, 2012; 439 events; SA1) and the interim OS data cutoff (September 16, 2013; 540 events; SA2). Additional SAs using investigator-assessed rPFS from the final rPFS data cutoff assessed the impact of skeletal-related events (SA3), clinical progression (SA4), a confirmatory scan for soft-tissue disease progression (SA5), and all deaths regardless of time after study drug discontinuation (SA6). Correlations between investigator-assessed rPFS (SA2) and OS were calculated using Spearman ρ and Kendall τ via Clayton copula. In the 1717 men (mean age, 72.0 [range, 43.0-93.0] years in enzalutamide arm and 71.0 [range, 42.0-93.0] years in placebo arm), enzalutamide significantly reduced risk of radiographic progression or death in all SAs, with hazard ratios of 0.22 (SA1; 95% CI, 0.18-0.27), 0.31 (SA2; 95% CI, 0.27-0.35), 0.21 (SA3; 95% CI, 0.18-0.26), 0.21 (SA4; 95% CI, 0.17-0.26), 0

Development of anti-drug antibodies is associated with shortened survival in patients with metastatic melanoma treated with ipilimumab

DEFF Research Database (Denmark)

Kverneland, Anders H.; Enevold, Christian; Donia, Marco

2018-01-01

significantly with a shorter OS (p = 0.01) and PFS (p = 0.02). Eight patients (26%) were ADA-positive at either timepoint. ADA positivity correlated significantly with a shorter OS (p = 0.03) with a hazard ratio (HR) of 3.0 (95% CI: 1.2-7.8). Four of 8 ADA-positive patients (50%) discontinued therapy before......Introduction: Checkpoint inhibitors, including the CTLA-4 blocking antibody ipilimumab, have become the new standard therapy for many metastatic cancers. Development of anti-drug antibodies (ADAs) after treatment with other biopharmaceuticals has been thoroughly described, but the induction of ADAs...... for serum levels of ipilimumab and ADAs to ipilimumab at baseline, and before the 2nd and 4th infusion using an in-house bead-based assay. The results were correlated with progression-free survival (PFS) and overall survival (OS). Results: Low serum levels of ipilimumab before the 2nd infusion correlated...

When Progressive Disease Does Not Mean Treatment Failure: Reconsidering the Criteria for Progression

Science.gov (United States)

2012-01-01

Although progression-based endpoints, such as progression-free survival, are often key clinical trial endpoints for anticancer agents, the clinical meaning of “objective progression” is much less certain. As scrutiny of progression-based endpoints in clinical trials increases, it should be remembered that the Response Evaluation Criteria In Solid Tumors (RECIST) progression criteria were not developed as a surrogate for survival. Now that progression-free survival has come to be an increasingly important trial endpoint, the criteria that define progression deserve critical evaluation to determine whether alternate definitions of progression might facilitate the development of stronger surrogate endpoints and more meaningful trial results. In this commentary, we review the genesis of the criteria for progression, highlight recent data that question their value as a marker of treatment failure, and advocate for several research strategies that could lay the groundwork for a clinically validated definition of disease progression in solid tumor oncology. PMID:22927506

The prediction of progression-free and overall survival in women with an advanced stage of epithelial ovarian carcinoma.

Science.gov (United States)

Gerestein, C G; Eijkemans, M J C; de Jong, D; van der Burg, M E L; Dykgraaf, R H M; Kooi, G S; Baalbergen, A; Burger, C W; Ansink, A C

2009-02-01

Prognosis in women with ovarian cancer mainly depends on International Federation of Gynecology and Obstetrics stage and the ability to perform optimal cytoreductive surgery. Since ovarian cancer has a heterogeneous presentation and clinical course, predicting progression-free survival (PFS) and overall survival (OS) in the individual patient is difficult. The objective of this study was to determine predictors of PFS and OS in women with advanced stage epithelial ovarian cancer (EOC) after primary cytoreductive surgery and first-line platinum-based chemotherapy. Retrospective observational study. Two teaching hospitals and one university hospital in the south-western part of the Netherlands. Women with advanced stage EOC. All women who underwent primary cytoreductive surgery for advanced stage EOC followed by first-line platinum-based chemotherapy between January 1998 and October 2004 were identified. To investigate independent predictors of PFS and OS, a Cox' proportional hazard model was used. Nomograms were generated with the identified predictive parameters. The primary outcome measure was OS and the secondary outcome measures were response and PFS. A total of 118 women entered the study protocol. Median PFS and OS were 15 and 44 months, respectively. Preoperative platelet count (P = 0.007), and residual disease statistic of 0.63. Predictive parameters for OS were preoperative haemoglobin serum concentration (P = 0.012), preoperative platelet counts (P = 0.031) and residual disease statistic of 0.67. PFS could be predicted by postoperative residual disease and preoperative platelet counts, whereas residual disease, preoperative platelet counts and preoperative haemoglobin serum concentration were predictive for OS. The proposed nomograms need to be externally validated.

Prognostic factors for progression-free and overall survival in advanced biliary tract cancer

DEFF Research Database (Denmark)

Bridgewater, J; Lopes, A; Wasan, H

2016-01-01

independently with outcome. This score was validated externally by receiver operating curve (ROC) analysis using the independent international dataset. RESULTS: A total of 410 patients were included from the ABC-02 study and 753 from the international dataset. An overall survival (OS) and progression......BACKGROUND: Biliary tract cancer is an uncommon cancer with a poor outcome. We assembled data from the National Cancer Research Institute (UK) ABC-02 study and 10 international studies to determine prognostic outcome characteristics for patients with advanced disease. METHODS: Multivariable...... biliary tract cancer derived from the ABC-02 study that are validated in an international dataset. Although these findings establish the benchmark for the prognostic evaluation of patients with ABC and confirm the value of longheld clinical observations, the ability of the model to correctly predict...

EG-09EPIGENETIC PROFILING REVEALS A CpG HYPERMETHYLATION PHENOTYPE (CIMP) ASSOCIATED WITH WORSE PROGRESSION-FREE SURVIVAL IN MENINGIOMA

Science.gov (United States)

Olar, Adriana; Wani, Khalida; Mansouri, Alireza; Zadeh, Gelareh; Wilson, Charmaine; DeMonte, Franco; Fuller, Gregory; Jones, David; Pfister, Stefan; von Deimling, Andreas; Sulman, Erik; Aldape, Kenneth

2014-01-01

BACKGROUND: Methylation profiling of solid tumors has revealed biologic subtypes, often with clinical implications. Methylation profiles of meningioma and their clinical implications are not well understood. METHODS: Ninety-two meningioma samples (n = 44 test set and n = 48 validation set) were profiled using the Illumina HumanMethylation450 BeadChip. Unsupervised clustering and analyses for recurrence-free survival (RFS) were performed. RESULTS: Unsupervised clustering of the test set using approximately 900 highly variable markers identified two clearly defined methylation subgroups. One of the groups (n = 19) showed global hypermethylation of a set of markers, analogous to CpG island methylator phenotype (CIMP). These findings were reproducible in the validation set, with 18/48 samples showing the CIMP-positive phenotype. Importantly, of 347 highly variable markers common to both the test and validation set analyses, 107 defined CIMP in the test set and 94 defined CIMP in the validation set, with an overlap of 83 markers between the two datasets. This number is much greater than expected by chance indicating reproducibly of the hypermethylated markers that define CIMP in meningioma. With respect to clinical correlation, the 37 CIMP-positive cases displayed significantly shorter RFS compared to the 55 non-CIMP cases (hazard ratio 2.9, p = 0.013). In an effort to develop a preliminary outcome predictor, a 155-marker subset correlated with RFS was identified in the test dataset. When interrogated in the validation dataset, this 155-marker subset showed a statistical trend (p < 0.1) towards distinguishing survival groups. CONCLUSIONS: This study defines the existence of a CIMP phenotype in meningioma, which involves a substantial proportion (37/92, 40%) of samples with clinical implications. Ongoing work will expand this cohort and examine identification of additional biologic differences (mutational and DNA copy number analysis) to further characterize the aberrant

Survival of Free and Encapsulated Human and Rat Islet Xenografts Transplanted into the Mouse Bone Marrow

Science.gov (United States)

Meier, Raphael P. H.; Seebach, Jörg D.; Morel, Philippe; Mahou, Redouan; Borot, Sophie; Giovannoni, Laurianne; Parnaud, Geraldine; Montanari, Elisa; Bosco, Domenico; Wandrey, Christine; Berney, Thierry; Bühler, Leo H.; Muller, Yannick D.

2014-01-01

Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow) and 10 days (kidney capsule). Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation. PMID:24625569

Survival of free and encapsulated human and rat islet xenografts transplanted into the mouse bone marrow.

Directory of Open Access Journals (Sweden)

Raphael P H Meier

Full Text Available Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow and 10 days (kidney capsule. Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation.

Individual patient data analysis of progression-free survival versus overall survival as a first-line end point for metastatic colorectal cancer in modern randomized trials: findings from the analysis and research in cancers of the digestive system database.

Science.gov (United States)

Shi, Qian; de Gramont, Aimery; Grothey, Axel; Zalcberg, John; Chibaudel, Benoist; Schmoll, Hans-Joachim; Seymour, Matthew T; Adams, Richard; Saltz, Leonard; Goldberg, Richard M; Punt, Cornelis J A; Douillard, Jean-Yves; Hoff, Paulo M; Hecht, Joel Randolph; Hurwitz, Herbert; Díaz-Rubio, Eduardo; Porschen, Rainer; Tebbutt, Niall C; Fuchs, Charles; Souglakos, John; Falcone, Alfredo; Tournigand, Christophe; Kabbinavar, Fairooz F; Heinemann, Volker; Van Cutsem, Eric; Bokemeyer, Carsten; Buyse, Marc; Sargent, Daniel J

2015-01-01

Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti-epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R(2) statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models. Forty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R(2), 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy. In modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents. © 2014 by American Society of Clinical Oncology.

Free Testosterone During Androgen Deprivation Therapy Predicts Castration-Resistant Progression Better Than Total Testosterone.

Science.gov (United States)

Regis, Lucas; Planas, Jacques; Carles, Joan; Maldonado, Xavier; Comas, Inma; Ferrer, Roser; Morote, Juan

2017-01-01

The optimal degree of testosterone suppression in patients with prostate cancer undergoing androgen deprivation therapy remains in question. Furthermore, serum free testosterone, which is the active form of testosterone, seems to correlate with intraprostatic testosterone. Here we compared free and total serum testosterone as predictors of survival free of castration resistance. Total testosterone (chemiluminescent assay, lower sensitivity 10 ng/dl) and free testosterone (analogue-ligand radioimmunoassay, lower sensitivity 0.05 pg/ml) were determined at 6 months of LHRH agonist treatment in a prospective cohort of 126 patients with prostate cancer. During a mean follow-up of 67 months (9-120), 75 (59.5%) events of castration-resistant progression were identified. Multivariate analysis and survival analysis according to total testosterone cutoffs of 50, 32, and 20 ng/dl, and free testosterone cutoffs of 1.7, 1.1, and 0.7 pg/ml were performed. Metastatic spread was the most powerful predictor of castration resistance, HR: 2.09 (95%CI: 1.18-3.72), P = 0.012. Gleason score, baseline PSA and PSA at 6 months were also independents predictors, but not free and total testosterone. Stratified analysis was conducted on the basis of the status of metastatic diseases and free testosterone was found to be an independent predictor of survival free of castration resistance in the subgroup of patients without metastasis, HR: 2.12 (95%CI: 1.16-3.85), P = 0.014. The lowest threshold of free testosterone which showed significant differences was 1.7 pg/ml, P = 0.003. Free testosterone at 6 months of LHRH agonist treatment seems to be a better surrogate than total testosterone to predict castration resistance in no metastatic prostate cancer patients. Prostate 77:114-120, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Histologic progression in non-hodgkin's lymphoma

International Nuclear Information System (INIS)

Hubbard, S.M.; Chabner, B.A.; DeVita, V.T. Jr.; Simon, R.; Berard, C.W.; Jones, R.B.; Garvin, A.J.; Canellos, G.P.; Osborne, C.K.; Young, R.C.

1982-01-01

The clinical course and biopsy specimens from 515 consecutive non-Hodgkin's lymphoma patients was evaluated retrospectively in an attempt to determine the clinical importance of documented changes in histology over time. Two-hundred and five of these patients has an initial diagnosis of nodular lymphoma and were reviewed for this anaysis. Sixty-three underwent a repeat biopsy greater than 6 mo after initial diagnosis. In 23 patients, these repeat biopsies revealed a change in histology to a diffuse pattern and/or a change to a larger ''histiocytic'' cell type, while repeat biopsies for the other 40 (63%) disclosd persistence of a nodular pattern and no clear change in basic cell type. Progression from nodular lymphoma to diffuse histiocytic, mixed, or undifferentiated types of lymphomas of Rappaport was found in repeate biopsies obtained from 19 patients (30%). Prognosis for survival following a biopsy that demonstrated histologic change was related to the histology demonstrated at the most recent biopsy and to the response to subsequent drug treatment. Survival following repeat biopsy for these 19 patients was significantly shorter than for the 40 patients whose histology remained nodular (p < 0.001). However, attainment of a complete remission with intensive combination chemotherapy was associated with prolonged survival in eight patients and prolonged disease-free survival in one patient. Since prior treatment may compromise the ability to achieve a complete response to chemotherapy in patients with nodular lymphoma who develop an aggressive diffuse histology, the likelihood of histologic progression must be considered in the design of future clinical trials in nodular lymphoma. Histologic progression does not preclude attainment of a complete response to intensive chemotherapy

Combination of baseline metabolic tumour volume and early response on PET/CT improves progression-free survival prediction in DLBCL

Energy Technology Data Exchange (ETDEWEB)

Mikhaeel, N.G.; Smith, Daniel [Guy' s and St Thomas' NHS Foundation Trust, Department of Clinical Oncology, London (United Kingdom); Dunn, Joel T.; Phillips, Michael; Barrington, Sally F. [King' s College London, PET Imaging Centre at St Thomas' Hospital, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Moeller, Henrik [King' s College London, Department of Cancer Epidemiology and Population Health, London (United Kingdom); Fields, Paul A.; Wrench, David [Guy' s and St Thomas' NHS Foundation Trust, Department of Haematology, London (United Kingdom)

2016-07-15

The study objectives were to assess the prognostic value of quantitative PET and to test whether combining baseline metabolic tumour burden with early PET response could improve predictive power in DLBCL. A total of 147 patients with DLBCL underwent FDG-PET/CT scans before and after two cycles of RCHOP. Quantitative parameters including metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were measured, as well as the percentage change in these parameters. Cox regression analysis was used to test the relationship between progression-free survival (PFS) and the study variables. Receiver operator characteristics (ROC) analysis determined the optimal cut-off for quantitative variables, and Kaplan-Meier survival analysis was performed. The median follow-up was 3.8 years. As MTV and TLG measures correlated strongly, only MTV measures were used for multivariate analysis (MVA). Baseline MTV (MTV-0) was the only statistically significant predictor of PFS on MVA. The optimal cut-off for MTV-0 was 396 cm{sup 3}. A model combing MTV-0 and Deauville score (DS) separated the population into three distinct prognostic groups: good (MTV-0 < 400; 5-year PFS > 90 %), intermediate (MTV-0 ≥ 400+ DS1-3; 5-year PFS 58.5 %) and poor (MTV-0 ≥ 400+ DS4-5; 5-year PFS 29.7 %) MTV-0 is an important prognostic factor in DLBCL. Combining MTV-0 and early PET/CT response improves the predictive power of interim PET and defines a poor-prognosis group in whom most of the events occur. (orig.)

Prostate-Specific Antigen Persistence After Radical Prostatectomy as a Predictive Factor of Clinical Relapse-Free Survival and Overall Survival: 10-Year Data of the ARO 96-02 Trial

Energy Technology Data Exchange (ETDEWEB)

Wiegel, Thomas, E-mail: thomas.wiegel@uniklinik-ulm.de [Department of Radiation Oncology, University Hospital Ulm (Germany); Bartkowiak, Detlef; Bottke, Dirk; Thamm, Reinhard [Department of Radiation Oncology, University Hospital Ulm (Germany); Hinke, Axel [WiSP, Research Institute Pharma GmbH, Langenfeld (Germany); Stöckle, Michael [Department of Urology, University Hospital Homburg/Saar (Germany); Rübe, Christian [Department of Radiation Oncology, University Hospital Homburg/Saar (Germany); Semjonow, Axel [Department of Urology, University Hospital Münster (Germany); Wirth, Manfred [Department of Urology, University Hospital Dresden (Germany); Störkel, Stephan; Golz, Reinhard [Department of Pathology, HELIOS Hospital Wuppertal (Germany); Engenhart-Cabillic, Rita [Department of Radiation Oncology, University Hospital Giessen-Marburg (Germany); Hofmann, Rainer [Department of Urology, University Hospital Giessen-Marburg (Germany); Feldmann, Horst-Jürgen [Department of Radiation Oncology, General Hospital Fulda (Germany); Kälble, Tilman [Department of Urology, General Hospital Fulda (Germany); Siegmann, Alessandra; Hinkelbein, Wolfgang [Department of Radiation Oncology, University Hospital Berlin (Germany); Steiner, Ursula; Miller, Kurt [Department of Urology, University Hospital Berlin (Germany)

2015-02-01

Objective: The ARO 96-02 trial primarily compared wait-and-see (WS, arm A) with adjuvant radiation therapy (ART, arm B) in prostate cancer patients who achieved an undetectable prostate-specific antigen (PSA) after radical prostatectomy (RP). Here, we report the outcome with up to 12 years of follow-up of patients who retained a post-RP detectable PSA and received salvage radiation therapy (SRT, arm C). Methods and Materials: For the study, 388 patients with pT3-4pN0 prostate cancer with positive or negative surgical margins were recruited. After RP, 307 men achieved an undetectable PSA (arms A + B). In 78 patients the PSA remained above thresholds (median 0.6, range 0.05-5.6 ng/mL). Of the latter, 74 consented to receive 66 Gy to the prostate bed, and SRT was applied at a median of 86 days after RP. Clinical relapse-free survival, metastasis-free survival, and overall survival were determined by the Kaplan-Meier method. Results: Patients with persisting PSA after RP had higher preoperative PSA values, higher tumor stages, higher Gleason scores, and more positive surgical margins than did patients in arms A + B. For the 74 patients, the 10-year clinical relapse-free survival rate was 63%. Forty-three men had hormone therapy; 12 experienced distant metastases; 23 patients died. Compared with men who did achieve an undetectable PSA, the arm-C patients fared significantly worse, with a 10-year metastasis-free survival of 67% versus 83% and overall survival of 68% versus 84%, respectively. In Cox regression analysis, Gleason score ≥8 (hazard ratio [HR] 2.8), pT ≥ 3c (HR 2.4), and extraprostatic extension ≥2 mm (HR 3.6) were unfavorable risk factors of progression. Conclusions: A persisting PSA after prostatectomy seems to be an important prognosticator of clinical progression for pT3 tumors. It correlates with a higher rate of distant metastases and with worse overall survival. A larger prospective study is required to determine which patient subgroups

Overall survival and disease-free survival in endometrial cancer: prognostic factors in 276 patients

Directory of Open Access Journals (Sweden)

Tejerizo-García A

2013-09-01

Full Text Available Álvaro Tejerizo-García,1 Jesús S Jiménez-López,1 José L Muñoz-González,1 Sara Bartolomé-Sotillos,1 Laura Marqueta-Marqués,1 Gregorio López-González,1 José F Pérez-Regadera Gómez21Service of Obstetrics and Gynecology, 2Radiation Oncology Service, Hospital Universitario 12 de Octubre, Madrid, SpainObjective: The aim of the study reported here was to assess the disease-free survival and overall survival of patients with endometrial cancer and to determine independent factors affecting the prognosis.Materials and methods: This was a retrospective study of a single-center clinical series of 276 patients (mean age 64 years with histologically confirmed cancer of the corpus uteri. The standard treatments were extrafascial total hysterectomy and bilateral salpingo-oophorectomy with selective pelvic/para-aortic node dissection, according to risk for recurrence. Actuarial overall survival and disease-free survival were estimated according to the Kaplan–Meier method. Univariate and multivariate Cox proportional hazards analyses were used to assess the prognostic significance of the different variables.Results: The estimated median follow-up, determined using the inverse Kaplan–Meier method, was 45 months (95% confidence interval [CI] 41.2–48.8 for disease-free survival and 46 months (95% CI 43.0–49.0 for overall survival. The statistically significant variables affecting disease-free survival and overall survival were age, serous-papillary and clear-cell histological types, outer-half myometrial invasion, advanced International Federation of Gynecology and Obstetrics (FIGO stage, tumor grades G2 and G3, incomplete surgical resection, positive lymph nodes, lymphovascular space invasion, tumor remnants of >1 cm after surgery, and high-risk group. In the multivariate Cox regression model, predictors of tumor recurrence included advanced FIGO stage (hazard ratio [HR] 4.90, 95% CI 2.57–9.36, P < 0.001 and tumor grades G2 (HR 4.79, 95

Prespecified candidate biomarkers identify follicular lymphoma patients who achieved longer progression-free survival with bortezomib-rituximab versus rituximab.

Science.gov (United States)

Coiffier, Bertrand; Li, Weimin; Henitz, Erin D; Karkera, Jayaprakash D; Favis, Reyna; Gaffney, Dana; Shapiro, Alice; Theocharous, Panteli; Elsayed, Yusri A; van de Velde, Helgi; Schaffer, Michael E; Osmanov, Evgenii A; Hong, Xiaonan; Scheliga, Adriana; Mayer, Jiri; Offner, Fritz; Rule, Simon; Teixeira, Adriana; Romejko-Jarosinska, Joanna; de Vos, Sven; Crump, Michael; Shpilberg, Ofer; Zinzani, Pier Luigi; Cakana, Andrew; Esseltine, Dixie-Lee; Mulligan, George; Ricci, Deborah

2013-05-01

Identify subgroups of patients with relapsed/refractory follicular lymphoma deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase III LYM-3001 study. A total of 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary end point was PFS; this prespecified analysis of candidate protein biomarkers and genes was an exploratory objective. Archived tumor tissue and whole blood samples were collected at baseline. Immunohistochemistry and genetic analyses were completed for 4 proteins and 8 genes. In initial pairwise analyses, using individual single-nucleotide polymorphism genotypes, one biomarker pair (PSMB1 P11A C/G heterozygote, low CD68 expression) was associated with a significant PFS benefit with bortezomib-rituximab versus rituximab, controlling for multiple comparison corrections. The pair was analyzed under dominant, recessive, and additive genetic models, with significant association with PFS seen under the dominant model (G/G+C/G). In patients carrying this biomarker pair [PSMB1 P11A G allele, low CD68 expression (≤50 CD68-positive cells), population frequency: 43.6%], median PFS was 14.2 months with bortezomib-rituximab versus 9.1 months with rituximab (HR 0.47, P < 0.0001), and there was a significant overall survival benefit (HR 0.49, P = 0.0461). Response rates were higher and time to next antilymphoma therapy was longer in the bortezomib-rituximab group. In biomarker-negative patients, no significant efficacy differences were seen between treatment groups. Similar proportions of patients had high-risk features in the biomarker-positive and biomarker-negative subsets. Patients with PSMB1 P11A (G allele) and low CD68 expression seemed to have significantly longer PFS and greater clinical benefit with bortezomib-rituximab versus rituximab. ©2013 AACR.

A Retrospective Analysis of Precision Medicine Outcomes in Patients With Advanced Cancer Reveals Improved Progression-Free Survival Without Increased Health Care Costs.

Science.gov (United States)

Haslem, Derrick S; Van Norman, S Burke; Fulde, Gail; Knighton, Andrew J; Belnap, Tom; Butler, Allison M; Rhagunath, Sharanya; Newman, David; Gilbert, Heather; Tudor, Brian P; Lin, Karen; Stone, Gary R; Loughmiller, David L; Mishra, Pravin J; Srivastava, Rajendu; Ford, James M; Nadauld, Lincoln D

2017-02-01

The advent of genomic diagnostic technologies such as next-generation sequencing has recently enabled the use of genomic information to guide targeted treatment in patients with cancer, an approach known as precision medicine. However, clinical outcomes, including survival and the cost of health care associated with precision cancer medicine, have been challenging to measure and remain largely unreported. We conducted a matched cohort study of 72 patients with metastatic cancer of diverse subtypes in the setting of a large, integrated health care delivery system. We analyzed the outcomes of 36 patients who received genomic testing and targeted therapy (precision cancer medicine) between July 1, 2013, and January 31, 2015, compared with 36 historical control patients who received standard chemotherapy (n = 29) or best supportive care (n = 7). The average progression-free survival was 22.9 weeks for the precision medicine group and 12.0 weeks for the control group ( P = .002) with a hazard ratio of 0.47 (95% CI, 0.29 to 0.75) when matching on age, sex, histologic diagnosis, and previous lines of treatment. In a subset analysis of patients who received all care within the Intermountain Healthcare system (n = 44), per patient charges per week were $4,665 in the precision treatment group and $5,000 in the control group ( P = .126). These findings suggest that precision cancer medicine may improve survival for patients with refractory cancer without increasing health care costs. Although the results of this study warrant further validation, this precision medicine approach may be a viable option for patients with advanced cancer.

Factors influencing survival and recurrence-free intervals after treatment of primary breast cancer

International Nuclear Information System (INIS)

O'Higgins, N.; Brady, H.R.; Clark, C.G.

1984-01-01

A retrospective analysis of 739 patients with breast cancer is presented. Factors influencing overall survival, recurrence-free interval and survival after first recurrence are analysed and discussed. None of the factors was affected by age or menopausal status at the time of presentation. Overall survival and recurrence-free intervals varied significantly with tumour size, extent of nodal spread and tumour site. Medially situated tumours, large tumours and extensive nodal spread were associated with earlier first recurrence and poor prognosis. No difference in survival or recurrence-free interval was observed between different surgical operations. Although overall survival was longer in patients who received post-operative radiotherapy, no significant differences in survival or disease-free intervals were noted when patients were standardised for operation or tumour stage. Survival after local recurrence was longer than survival after distant metastases, although the time of onset of local and distant disease followed an identical pattern. These results suggest that the tumour characteristics of size, site and nodal spread are important determinants of survival and recurrence-free interval in primary breast cancer. Local recurrence should be regarded as a manifestation of systemic disease. (author)

Prognostic value of pre-treatment DCE-MRI parameters in predicting disease free and overall survival for breast cancer patients undergoing neoadjuvant chemotherapy

International Nuclear Information System (INIS)

Pickles, Martin D.; Manton, David J.; Lowry, Martin; Turnbull, Lindsay W.

2009-01-01

The purpose of this study was to investigate whether dynamic contrast enhanced MRI (DCE-MRI) data, both pharmacokinetic and empirical, can predict, prior to neoadjuvant chemotherapy, which patients are likely to have a shorter disease free survival (DFS) and overall survival (OS) interval following surgery. Traditional prognostic parameters were also included in the survival analysis. Consequently, a comparison of the prognostic value could be made between all the parameters studied. MR examinations were conducted on a 1.5 T system in 68 patients prior to the initiation of neoadjuvant chemotherapy. DCE-MRI consisted of a fast spoiled gradient echo sequence acquired over 35 phases with a mean temporal resolution of 11.3 s. Both pharmacokinetic and empirical parameters were derived from the DCE-MRI data. Kaplan-Meier survival plots were generated for each parameter and group comparisons were made utilising logrank tests. The results from the 54 patients entered into the univariate survival analysis demonstrated that traditional prognostic parameters (tumour grade, hormonal status and size), empirical parameters (maximum enhancement index, enhancement index at 30 s, area under the curve and initial slope) and adjuvant therapies demonstrated significant differences in survival intervals. Further multivariate Cox regression survival analysis revealed that empirical enhancement parameters contributed the greatest prediction of both DFS and OS in the resulting models. In conclusion, this study has demonstrated that in patients who exhibit high levels of perfusion and vessel permeability pre-treatment, evidenced by elevated empirical DCE-MRI parameters, a significantly lower disease free survival and overall survival can be expected.

Prognostic value of pre-treatment DCE-MRI parameters in predicting disease free and overall survival for breast cancer patients undergoing neoadjuvant chemotherapy

Energy Technology Data Exchange (ETDEWEB)

Pickles, Martin D. [Centre for Magnetic Resonance Investigations, Division of Cancer, Postgraduate Medical School, University of Hull, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ (United Kingdom)], E-mail: m.pickles@hull.ac.uk; Manton, David J. [Centre for Magnetic Resonance Investigations, Division of Cancer, Postgraduate Medical School, University of Hull, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ (United Kingdom)], E-mail: d.j.manton@hull.ac.uk; Lowry, Martin [Centre for Magnetic Resonance Investigations, Division of Cancer, Postgraduate Medical School, University of Hull, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ (United Kingdom)], E-mail: m.lowry@hull.ac.uk; Turnbull, Lindsay W. [Centre for Magnetic Resonance Investigations, Division of Cancer, Postgraduate Medical School, University of Hull, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ (United Kingdom)], E-mail: l.w.turnbull@hull.ac.uk

2009-09-15

The purpose of this study was to investigate whether dynamic contrast enhanced MRI (DCE-MRI) data, both pharmacokinetic and empirical, can predict, prior to neoadjuvant chemotherapy, which patients are likely to have a shorter disease free survival (DFS) and overall survival (OS) interval following surgery. Traditional prognostic parameters were also included in the survival analysis. Consequently, a comparison of the prognostic value could be made between all the parameters studied. MR examinations were conducted on a 1.5 T system in 68 patients prior to the initiation of neoadjuvant chemotherapy. DCE-MRI consisted of a fast spoiled gradient echo sequence acquired over 35 phases with a mean temporal resolution of 11.3 s. Both pharmacokinetic and empirical parameters were derived from the DCE-MRI data. Kaplan-Meier survival plots were generated for each parameter and group comparisons were made utilising logrank tests. The results from the 54 patients entered into the univariate survival analysis demonstrated that traditional prognostic parameters (tumour grade, hormonal status and size), empirical parameters (maximum enhancement index, enhancement index at 30 s, area under the curve and initial slope) and adjuvant therapies demonstrated significant differences in survival intervals. Further multivariate Cox regression survival analysis revealed that empirical enhancement parameters contributed the greatest prediction of both DFS and OS in the resulting models. In conclusion, this study has demonstrated that in patients who exhibit high levels of perfusion and vessel permeability pre-treatment, evidenced by elevated empirical DCE-MRI parameters, a significantly lower disease free survival and overall survival can be expected.

Androgen-deprivation therapy does not impact cause-specific or overall survival after permanent prostate brachytherapy

International Nuclear Information System (INIS)

Merrick, Gregory S.; Butler, Wayne M.; Wallner, Kent E.; Galbreath, Robert W.; Allen, Zachariah A. M.S.; Adamovich, Edward

2006-01-01

Purpose: To determine if androgen-deprivation therapy (ADT) has an impact on cause-specific, biochemical progression-free, or overall survival after prostate brachytherapy. Methods and Materials: From April 1995 through June 2002, 938 consecutive patients underwent brachytherapy for clinical Stage T1b to T3a (2002 AJCC) prostate cancer. All patients underwent brachytherapy more than 3 years before analysis. A total of 382 patients (40.7%) received ADT with a duration of 6 months or less in 277 and more than 6 months in 105. The median follow-up was 5.4 years. Multiple clinical, treatment, and dosimetric parameters were evaluated as predictors of cause-specific, biochemical progression-free, and overall survival. Results: The 10-year cause-specific, biochemical progression-free, and overall survival rates for the entire cohort were 96.4%, 95.9%, and 78.1%, respectively. Except for biochemical progression-free survival in high-risk patients, ADT did not statistically impact any of the three survival categories. A Cox linear-regression analysis demonstrated that Gleason score was the best predictor of cause-specific survival, whereas percent-positive biopsies, prostate volume, and risk group predicted for biochemical progression-free survival. Patient age and tobacco use were the strongest predictors of overall survival. One hundred two patients have died, with 80 of the deaths a result of cardiovascular disease (54) and second malignancies (26). To date, only 12 patients have died of metastatic prostate cancer. Conclusions: After brachytherapy, androgen-deprivation therapy did not have an impact on cause-specific or overall survival for any risk group; however, ADT had a beneficial effect on biochemical progression-free survival in high-risk patients. Cardiovascular disease and second malignancies far outweighed prostate cancer as competing causes of death

Pretreatment oral hygiene habits and survival of head and neck squamous cell carcinoma (HNSCC) patients.

Science.gov (United States)

Friemel, Juliane; Foraita, Ronja; Günther, Kathrin; Heibeck, Mathias; Günther, Frauke; Pflueger, Maren; Pohlabeln, Hermann; Behrens, Thomas; Bullerdiek, Jörn; Nimzyk, Rolf; Ahrens, Wolfgang

2016-03-11

The survival time of patients with head and neck squamous cell carcinoma (HNSCC) is related to health behavior, such as tobacco smoking and alcohol consumption. Poor oral health (OH), dental care (DC) and the frequent use of mouthwash have been shown to represent independent risk factors for head and neck cancerogenesis, but their impact on the survival of HNSCC patients has not been systematically investigated. Two hundred seventy-six incident HNSCC cases recruited for the ARCAGE study were followed through a period of 6-10 years. Interview-based information on wearing of dentures, gum bleeding, teeth brushing, use of floss and dentist visits were grouped into weighted composite scores, i.e. oral health (OH) and dental care (DH). Use of mouthwash was assessed as frequency per day. Also obtained were other types of health behavior, such as smoking, alcohol drinking and diet, appreciated as both confounding and study variables. Endpoints were progression-free survival, overall survival and tumor-specific survival. Prognostic values were estimated using Kaplan-Meier analysis and Cox proportional hazards regression models. A good dental care score, summarizing annual dental visits, daily teeth cleaning and use of floss was associated with longer overall survival time (p = .001). The results of the Cox regression models similarly suggested a higher risk of tumor progression and shortened overall survival in patients with poor dental care, but the results lost their statistical significance after other types of health behavior had been controlled for. Frequent use of mouthwash (≥ 2 times/day) significantly increased the risk of tumor-specific death (HR = 2.26; CI = 1.19-4.32). Alcohol consumption and tobacco smoking were dose-dependently associated with tumor progression and shorter overall survival. Frequent mouthwash use of ≥ 2 times/day seems to elevate the risk of tumor-specific death in HNSCC patients. Good dental care scores are associated with longer overall

Prognostic factors for survival after salvage total laryngectomy following radiotherapy or chemoradiation failure

DEFF Research Database (Denmark)

Wulff, N B; Andersen, E; Kristensen, C A

2017-01-01

with higher N classification and need for lymph node excision during salvage total laryngectomy along with use of frozen sections. The high number of patients with recurrence within 1 year after salvage total laryngectomy occurred although thorough and regular follow-up visits were performed.......OBJECTIVE: The primary aims were to determine the rates of and prognostic factors for overall survival, disease-specific survival and disease-free survival following salvage total laryngectomy. DESIGN: Retrospective longitudinal study. SETTING: Tertiary medical centres. PARTICIPANTS: A total of 142...... survival, disease-specific survival and disease-free survival were 37.7%, 54.9% and 55.3%, respectively. N classification at primary diagnosis, lymph node excision and postoperative complications within 1 year after salvage total laryngectomy were prognostic factors for shorter overall survival, disease...

Nation-Scale Adoption of Shorter Breast Radiation Therapy Schedules Can Increase Survival in Resource Constrained Economies: Results From a Markov Chain Analysis

Energy Technology Data Exchange (ETDEWEB)

Khan, Atif J., E-mail: atif.j.khan@rutgers.edu [Department of Radiation Oncology, Robert Wood Johnson Medical School/Cancer Institute of New Jersey, New Brunswick, New Jersey (United States); Rafique, Raza [Suleman Dawood School of Business, Lahore University of Management Sciences, Lahore (Pakistan); Zafar, Waleed [Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore (Pakistan); Shah, Chirag [Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio (United States); Haffty, Bruce G. [Department of Radiation Oncology, Robert Wood Johnson Medical School/Cancer Institute of New Jersey, New Brunswick, New Jersey (United States); Vicini, Frank [Michigan HealthCare Professionals, Farmington Hills, Michigan (United States); Jamshed, Arif [Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore (Pakistan); Zhao, Yao [Rutgers University School of Business, Newark, New Jersey (United States)

2017-02-01

Purpose: Hypofractionated whole breast irradiation and accelerated partial breast irradiation (APBI) offer women options for shorter courses of breast radiation therapy. The impact of these shorter schedules on the breast cancer populations of emerging economies with limited radiation therapy resources is unknown. We hypothesized that adoption of these schedules would improve throughput in the system and, by allowing more women access to life-saving treatments, improve patient survival within the system. Methods and Materials: We designed a Markov chain model to simulate the different health states that a postlumpectomy or postmastectomy patient could enter over the course of a 20-year follow-up period. Transition rates between health states were adapted from published data on recurrence rates. We used primary data from a tertiary care hospital in Lahore, Pakistan, to populate the model with proportional use of mastectomy versus breast conservation and to estimate the proportion of patients suitable for APBI. Sensitivity analyses on the use of APBI and relative efficacy of APBI were conducted to study the impact on the population. Results: The shorter schedule resulted in more women alive and more women remaining without evidence of disease (NED) compared with the conventional schedule, with an absolute difference of about 4% and 7% at 15 years, respectively. Among women who had lumpectomies, the chance of remaining alive and with an intact breast was 62% in the hypofractionation model and 54% in the conventional fractionation model. Conclusions: Increasing throughput in the system can result in improved survival, improved chances of remaining without evidence of disease, and improved chances of remaining alive with a breast. These findings are significant and suggest that adoption of hypofractionation in emerging economies is not simply a question of efficiency and cost but one of access to care and patient survivorship.

Nation-Scale Adoption of Shorter Breast Radiation Therapy Schedules Can Increase Survival in Resource Constrained Economies: Results From a Markov Chain Analysis

International Nuclear Information System (INIS)

Khan, Atif J.; Rafique, Raza; Zafar, Waleed; Shah, Chirag; Haffty, Bruce G.; Vicini, Frank; Jamshed, Arif; Zhao, Yao

2017-01-01

Purpose: Hypofractionated whole breast irradiation and accelerated partial breast irradiation (APBI) offer women options for shorter courses of breast radiation therapy. The impact of these shorter schedules on the breast cancer populations of emerging economies with limited radiation therapy resources is unknown. We hypothesized that adoption of these schedules would improve throughput in the system and, by allowing more women access to life-saving treatments, improve patient survival within the system. Methods and Materials: We designed a Markov chain model to simulate the different health states that a postlumpectomy or postmastectomy patient could enter over the course of a 20-year follow-up period. Transition rates between health states were adapted from published data on recurrence rates. We used primary data from a tertiary care hospital in Lahore, Pakistan, to populate the model with proportional use of mastectomy versus breast conservation and to estimate the proportion of patients suitable for APBI. Sensitivity analyses on the use of APBI and relative efficacy of APBI were conducted to study the impact on the population. Results: The shorter schedule resulted in more women alive and more women remaining without evidence of disease (NED) compared with the conventional schedule, with an absolute difference of about 4% and 7% at 15 years, respectively. Among women who had lumpectomies, the chance of remaining alive and with an intact breast was 62% in the hypofractionation model and 54% in the conventional fractionation model. Conclusions: Increasing throughput in the system can result in improved survival, improved chances of remaining without evidence of disease, and improved chances of remaining alive with a breast. These findings are significant and suggest that adoption of hypofractionation in emerging economies is not simply a question of efficiency and cost but one of access to care and patient survivorship.

Option A improved HIV-free infant survival and mother to child HIV transmission at 9-18 months in Zimbabwe.

Science.gov (United States)

Buzdugan, Raluca; Kang Dufour, Mi-Suk; McCoy, Sandra I; Watadzaushe, Constancia; Dirawo, Jeffrey; Mushavi, Angela; Mujuru, Hilda Angela; Mahomva, Agnes; Kangwende, Rugare Abigail; Hakobyan, Anna; Mugurungi, Owen; Cowan, Frances M; Padian, Nancy S

2016-06-19

We evaluated the impact of Option A on HIV-free infant survival and mother-to-child transmission (MTCT) in Zimbabwe. Serial cross-sectional community-based serosurveys. We analyzed serosurvey data collected in 2012 and 2014 among mother-infant pairs from catchment areas of 132 health facilities from five of 10 provinces in Zimbabwe. Eligible infants (alive or deceased) were born 9-18 months before each survey to mothers at least 16 years old. We randomly selected mother-infant pairs and conducted questionnaires, verbal autopsies, and collected blood samples. We estimated the HIV-free infant survival and MTCT rate within each catchment area and compared the 2012 and 2014 estimates using a paired t test and number of HIV infections averted because of the intervention. We analyzed 7249 mother-infant pairs with viable maternal specimens collected in 2012 and 8551 in 2014. The mean difference in the catchment area level MTCT between 2014 and 2012 was -5.2 percentage points (95% confidence interval = -8.1, -2.3, P Option A regimen. The association between HIV-free infant survival and duration of Option A implementation was NS at the multivariate level (P = 0.093). We found a substantial and statistically significant increase in HIV-free survival and decrease in MTCT among infants aged 9-18 months following Option A rollout in Zimbabwe. This is the only evaluation of Option A and shows the effectiveness of Option A and Zimbabwe's remarkable progress toward eMTCT.

The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer

Science.gov (United States)

Magnani, Luca; Patten, Darren K.; Nguyen, Van T.M.; Hong, Sung-Pil; Steel, Jennifer H.; Patel, Naina; Lombardo, Ylenia; Faronato, Monica; Gomes, Ana R.; Woodley, Laura; Page, Karen; Guttery, David; Primrose, Lindsay; Garcia, Daniel Fernandez; Shaw, Jacqui; Viola, Patrizia; Green, Andrew; Nolan, Christopher; Ellis, Ian O.; Rakha, Emad A.; Shousha, Sami; Lam, Eric W.-F.; Győrffy, Balázs; Lupien, Mathieu; Coombes, R. Charles

2015-01-01

Over 30% of ERα breast cancer patients develop relapses and progress to metastatic disease despite treatment with endocrine therapies. The pioneer factor PBX1 translates epigenetic cues and mediates estrogen induced ERα binding. Here we demonstrate that PBX1 plays a central role in regulating the ERα transcriptional response to epidermal growth factor (EGF) signaling. PBX1 regulates a subset of EGF-ERα genes highly expressed in aggressive breast tumours. Retrospective stratification of luminal patients using PBX1 protein levels in primary cancer further demonstrates that elevated PBX1 protein levels correlate with earlier metastatic progression. In agreement, PBX1 protein levels are significantly upregulated during metastatic progression in ERα-positive breast cancer patients. Finally we reveal that PBX1 upregulation in aggressive tumours is partly mediated by genomic amplification of the PBX1 locus. Correspondingly, ERα-positive breast cancer patients carrying PBX1 amplification are characterized by poor survival. Notably, we demonstrate that PBX1 amplification can be identified in tumor derived-circulating free DNA of ERα-positive metastatic patients. Metastatic patients with PBX1 amplification are also characterized by shorter relapse-free survival. Our data identifies PBX1 amplification as a functional hallmark of aggressive ERα-positive breast cancers. Mechanistically, PBX1 amplification impinges on several critical pathways associated with aggressive ERα-positive breast cancer. PMID:26215677

Multi-institutional Nomogram Predicting Survival Free From Salvage Whole Brain Radiation After Radiosurgery in Patients With Brain Metastases

International Nuclear Information System (INIS)

Gorovets, Daniel; Ayala-Peacock, Diandra; Tybor, David J.; Rava, Paul; Ebner, Daniel; Cielo, Deus; Norén, Georg; Wazer, David E.; Chan, Michael; Hepel, Jaroslaw T.

2017-01-01

Purpose: Optimal patient selection for stereotactic radiosurgery (SRS) as the initial treatment for brain metastases is complicated and controversial. This study aimed to develop a nomogram that predicts survival without salvage whole brain radiation therapy (WBRT) after upfront SRS. Methods and Materials: Multi-institutional data were analyzed from 895 patients with 2095 lesions treated with SRS without prior or planned WBRT. Cox proportional hazards regression model was used to identify independent pre-SRS predictors of WBRT-free survival, which were integrated to build a nomogram that was subjected to bootstrap validation. Results: Median WBRT-free survival was 8 months (range, 0.1-139 months). Significant independent predictors for inferior WBRT-free survival were age (hazard ratio [HR] 1.1 for each 10-year increase), HER2(−) breast cancer (HR 1.6 relative to other histologic features), colorectal cancer (HR 1.4 relative to other histologic features), increasing number of brain metastases (HR 1.09, 1.32, 1.37, and 1.87 for 2, 3, 4, and 5+ lesions, respectively), presence of neurologic symptoms (HR 1.26), progressive systemic disease (HR 1.35), and increasing extracranial disease burden (HR 1.31 for oligometastatic and HR 1.56 for widespread). Additionally, HER2(+) breast cancer (HR 0.81) and melanoma (HR 1.11) trended toward significance. The independently weighted hazard ratios were used to create a nomogram to display estimated probabilities of 6-month and 12-month WBRT-free survival with a corrected Harrell's C concordance statistic of 0.62. Conclusions: Our nomogram can be used at initial evaluation to help select patients best suited for upfront SRS for brain metastases while reducing expense and morbidity in patients who derive minimal or no benefit.

Multi-institutional Nomogram Predicting Survival Free From Salvage Whole Brain Radiation After Radiosurgery in Patients With Brain Metastases

Energy Technology Data Exchange (ETDEWEB)

Gorovets, Daniel [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Department of Radiation Oncology, Perlmutter Cancer Center, NYU School of Medicine, New York, New York (United States); Ayala-Peacock, Diandra [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Tybor, David J. [Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts (United States); Rava, Paul [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Department of Radiation Oncology, UMass Memorial Medical Center, University of Massachusetts School of Medicine, Worcester, Massachusetts (United States); Ebner, Daniel [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Cielo, Deus; Norén, Georg [Department of Neurosurgery, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Wazer, David E. [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Chan, Michael [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Hepel, Jaroslaw T., E-mail: jhepel@lifespan.org [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States)

2017-02-01

Purpose: Optimal patient selection for stereotactic radiosurgery (SRS) as the initial treatment for brain metastases is complicated and controversial. This study aimed to develop a nomogram that predicts survival without salvage whole brain radiation therapy (WBRT) after upfront SRS. Methods and Materials: Multi-institutional data were analyzed from 895 patients with 2095 lesions treated with SRS without prior or planned WBRT. Cox proportional hazards regression model was used to identify independent pre-SRS predictors of WBRT-free survival, which were integrated to build a nomogram that was subjected to bootstrap validation. Results: Median WBRT-free survival was 8 months (range, 0.1-139 months). Significant independent predictors for inferior WBRT-free survival were age (hazard ratio [HR] 1.1 for each 10-year increase), HER2(−) breast cancer (HR 1.6 relative to other histologic features), colorectal cancer (HR 1.4 relative to other histologic features), increasing number of brain metastases (HR 1.09, 1.32, 1.37, and 1.87 for 2, 3, 4, and 5+ lesions, respectively), presence of neurologic symptoms (HR 1.26), progressive systemic disease (HR 1.35), and increasing extracranial disease burden (HR 1.31 for oligometastatic and HR 1.56 for widespread). Additionally, HER2(+) breast cancer (HR 0.81) and melanoma (HR 1.11) trended toward significance. The independently weighted hazard ratios were used to create a nomogram to display estimated probabilities of 6-month and 12-month WBRT-free survival with a corrected Harrell's C concordance statistic of 0.62. Conclusions: Our nomogram can be used at initial evaluation to help select patients best suited for upfront SRS for brain metastases while reducing expense and morbidity in patients who derive minimal or no benefit.

Expression of nerve growth factor and heme oxygenase-1 predict poor survival of breast carcinoma patients

International Nuclear Information System (INIS)

Noh, Sang Jae; Chung, Myoung Ja; Moon, Woo Sung; Kang, Myoung Jae; Jang, Kyu Yun; Bae, Jun Sang; Jamiyandorj, Urangoo; Park, Ho Sung; Kwon, Keun Sang; Jung, Sung Hoo; Youn, Hyun Jo; Lee, Ho; Park, Byung-Hyun

2013-01-01

Nerve growth factor (NGF) is a neurotrophin and has been suggested to induce heme oxygenase-1 (HO1) expression. Although the role of HO1 in tumorigenesis remains controversial, recent evidence suggests NGF and HO1 as tumor-progressing factors. However, the correlative role of NGF and HO1 and their prognostic impact in breast carcinoma is unknown. We investigated the expression and prognostic significance of the expression of NGF and HO1 in 145 cases of breast carcinoma. Immunohistochemical expression of NGF and HO1 was observed in 31% and 49% of breast carcinoma, respectively. The expression of NGF and HO1 significantly associated with each other, and both have a significant association with histologic grade, HER2 expression, and latent distant metastasis. The expression of NGF and HO1 predicted shorter overall survival of breast carcinoma by univariate and multivariate analysis. NGF expression was an independent prognostic indicator for relapse-free survival by multivariate analysis. The combined expression pattern of NGF and HO1 was also an independent prognostic indicator of overall survival and relapse-free survival. The patients with tumors expressing NGF had the shortest survival and the patients with tumor, which did not express NGF or HO1 showed the longest survival time. This study has demonstrated that individual expression of NGF or HO1, and the combined NGF/HO1 expression pattern could be prognostic indicators for breast carcinoma patients

Human survivability of extreme impacts in free-fall.

Science.gov (United States)

1963-08-01

Human deceleration tolerances beyond the limits imposed by voluntary experimental methods were studied by means of intensive case histories of 137 individuals who have survived extremely abrupt impacts in accidental, suicidal, and homicidal free-fall...

Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

International Nuclear Information System (INIS)

Evers, Patrick; Lee, Percy P; DeMarco, John; Agazaryan, Nzhde; Sayre, James W; Selch, Michael; Pajonk, Frank

2010-01-01

Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs. 55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated. Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact. Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs

Maximum standard uptake value on pre-chemotherapeutic FDG-PET is a significant parameter for disease progression of newly diagnosed lymphoma

International Nuclear Information System (INIS)

Eo, Jae Seon; Lee, Won Woo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun

2005-01-01

F-18 FDG-PET is useful for detection and staging of lymphoma. We investigated the prognostic significance of maximum standard uptake (maxSUV) value of FDG-PET for newly diagnosed lymphoma patients before chemotherapy. Twenty-seven patients (male: female = 17: 10: age: 49±19 years) with newly diagnosed lymphoma were enrolled. Nine-teen patients suffered from B cell lymphoma, 6 Hodgkins disease and 2 T cell lymphoma. One patient was stage I, 9 stage II, 3 stage III, 1 stage IV and 13 others. All patients underwent FDG-PET before initiation of chemotherapy. MaxSUV values using lean body weight were obtained for main and largest lesion to represent maxSUV of the patients. The disease progression was defined as total change of the chemotherapeutic regimen or addition of new chemotherapeutic agent during follow up period. The observed period was 389±224 days. The value of maxSUV ranged from 3 to 18 (mean±SD = 10.6±4.4). The disease progressions occurred in 6 patients. Using Cox proportional-hazard regression analysis, maxSUV was identified as a significant parameter for the disease progression free survival (p=0.044). Kaplan-Meier survival curve analysis revealed that the group with higher maxSUV (=10.6, n=5) suffered from shorter disease progression free survival (median 299 days) than the group with lower maxSUV (<10.6, n = 22) (median 378 days, p=0.0146). We found that maxSUV on pre-chemotherapeutic F-18 FDG-PET for newly diagnosed lymphoma patients is a significant parameter for disease progression. Lymphoma patients can be stratified before initiation of chemotherapy in terms of disease progression by the value of maxSUV 10.6

Relapsed or Refractory Double-Expressor and Double-Hit Lymphomas Have Inferior Progression-Free Survival After Autologous Stem-Cell Transplantation.

Science.gov (United States)

Herrera, Alex F; Mei, Matthew; Low, Lawrence; Kim, Haesook T; Griffin, Gabriel K; Song, Joo Y; Merryman, Reid W; Bedell, Victoria; Pak, Christine; Sun, Heather; Paris, Tanya; Stiller, Tracey; Brown, Jennifer R; Budde, Lihua E; Chan, Wing C; Chen, Robert; Davids, Matthew S; Freedman, Arnold S; Fisher, David C; Jacobsen, Eric D; Jacobson, Caron A; LaCasce, Ann S; Murata-Collins, Joyce; Nademanee, Auayporn P; Palmer, Joycelynne M; Pihan, German A; Pillai, Raju; Popplewell, Leslie; Siddiqi, Tanya; Sohani, Aliyah R; Zain, Jasmine; Rosen, Steven T; Kwak, Larry W; Weinstock, David M; Forman, Stephen J; Weisenburger, Dennis D; Kim, Young; Rodig, Scott J; Krishnan, Amrita; Armand, Philippe

2017-01-01

Purpose Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL. Methods Patients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled. Immunohistochemistry for MYC, BCL2, and BCL6 and fluorescence in situ hybridization (FISH) for MYC were performed. In cases with MYC rearrangement or copy gain, FISH for BCL2 and BCL6 was also performed. Results A total of 117 patients were included; 44% had DEL and 10% had DHL. DEL and DHL were associated with inferior progression-free survival (PFS), and DHL was associated with poorer overall survival (OS). The 4-year PFS in patients with DEL compared with those with non-DEL was 48% versus 59% ( P = .049), and the 4-year OS was 56% versus 67% ( P = .10); 4-year PFS in patients with DHL compared with those with non-DHL was 28% versus 57% ( P = .013), and 4-year OS was 25% versus 61% ( P = .002). The few patients with concurrent DEL and DHL had a poor outcome (4-year PFS, 0%). In multivariable models, DEL and DHL were independently associated with inferior PFS, whereas DHL and partial response ( v complete response) at transplant were associated with inferior OS. Conclusion DEL and DHL are both associated with inferior outcomes after ASCT in patients with rel/ref DLBCL. Although ASCT remains a potentially curative approach, these patients, particularly those with DHL, are a high-risk subset who should be targeted for investigational strategies other than standard ASCT.

Consolidation chemotherapy improves progression-free survival in stage III small-cell lung cancer following concurrent chemoradiotherapy: a retrospective study

Directory of Open Access Journals (Sweden)

Chen XR

2016-09-01

Full Text Available Xin-Ru Chen,1,* Jian-Zhong Liang,2,* Shu-Xiang Ma,1 Wen-Feng Fang,1 Ning-Ning Zhou,1 Hai Liao,1 De-Lan Li,1 Li-Kun Chen1 1Department of Medical Oncology, 2Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: Concurrent chemoradiotherapy (CCRT is the standard treatment for limited-stage small-cell lung cancer (LD-SCLC. However, the efficacy of consolidation chemotherapy (CCT in LD-SCLC remains controversial despite several studies that were performed in the early years of CCT use. The aim of this study was to reevaluate the effectiveness and toxicities associated with CCT. Methods: This retrospective analysis evaluated 177 patients with stage IIIA and IIIB small-cell lung cancer (SCLC who underwent CCRT from January 2001 to December 2013 at Sun Yat-Sen University Cancer Center (SYSUCC. Overall survival (OS and progression-free survival (PFS were analyzed using Kaplan–Meier methods. Univariate and multivariate analyses were performed to analyze patient prognosis factors. Results: Among the 177 patients, 72 (41% received CCT and 105 (59% did not receive CCT. PFS was significantly better for patients in the CCT group compared to that for patients in the non-CCT group (median PFS: 17.0 vs 12.9 months, respectively, P=0.031, whereas the differences in OS were not statistically significant (median OS: 31.6 vs 24.8 months, respectively, P=0.118. The 3- and 5-year OS rates were 33.3% and 20.8% for patients in the CCT group and 27.6% and 6.7% for patients in the non-CCT group, respectively. Multivariate analysis revealed that having a pretreatment carcinoembryonic antigen level <5 ng/mL (P=0.035, having undergone prophylactic cranial irradiation (P<0.001, and having received CCT (P=0.002 could serve as favorable independent prognostic factors

A polymorphism of EGFR extracellular domain is associated with progression free-survival in metastatic colorectal cancer patients receiving cetuximab-based treatment

International Nuclear Information System (INIS)

Gonçalves, Anthony; Turrini, Olivier; Lelong, Bernard; Viens, Patrice; Borg, Jean-Paul; Birnbaum, Daniel; Olschwang, Sylviane; Viret, Frédéric; Esteyries, Séverine; Taylor-Smedra, Brynn; Lagarde, Arnaud; Ayadi, Mounay; Monges, Geneviève; Bertucci, François; Esterni, Benjamin; Delpero, Jean-Robert

2008-01-01

Cetuximab, a monoclonal antibody targeting Epidermal Growth Factor Receptor (EGFR), is currently used in metastatic colorectal cancer (mCRC), but predictive factors for therapeutic response are lacking. Mutational status of KRAS and EGFR, and EGFR copy number are potential determinants of cetuximab activity. We analyzed tumor tissues from 32 EGFR-positive mCRC patients receiving cetuximab/irinotecan combination and evaluable for treatment response. EGFR copy number was quantified by fluorescence in situ hybridization (FISH). KRAS exon 1 and EGFR exons coding for extracellular regions were sequenced. Nine patients experienced an objective response (partial response) and 23 were considered as nonresponders (12 with stable disease and 11 with progressive disease). There was no EGFR amplification found, but high polysomy was noted in 2 patients, both of which were cetuximab responders. No EGFR mutations were found but a variant of exon 13 (R521K) was observed in 12 patients, 11 of which achieved objective response or stable disease. Progression-free and overall survivals were significantly better in patients with this EGFR exon 13 variant. KRAS mutations were found in 14 cases. While there was a trend for an increased KRAS mutation frequency in nonresponder patients (12 mutations out of 23, 52%) as compared to responder patients (2 out of 9, 22%), authentic tumor response or long-term disease stabilization was found in KRAS mutated patients. This preliminary study suggests that: an increase in EGFR copy number may be associated with cetuximab response but is a rare event in CRC, KRAS mutations are associated with low response rate but do not preclude any cetuximab-based combination efficacy and EGFR exon 13 variant (R521K) may predict for cetuximab benefit

Telomere shortening and survival in free-living corvids

NARCIS (Netherlands)

Salomons, H.M.; Mulder, G.A.; Zande, L. van de; Haussmann, M.F.; Linskens, M.H.K.; Verhulst, S.

2009-01-01

Evidence accumulates that telomere shortening reflects lifestyle and predicts remaining lifespan, but little is known of telomere dynamics and their relation to survival under natural conditions. We present longitudinal telomere data in free-living jackdaws (Corvus monedula) and test hypotheses on

Use of common analgesic medications and ovarian cancer survival

DEFF Research Database (Denmark)

Dixon, Suzanne C; Nagle, Christina M; Wentzensen, Nicolas

2017-01-01

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with improved survival in some cancers, but evidence for ovarian cancer is limited. METHODS: Pooling individual-level data from 12 Ovarian Cancer Association Consortium studies, we evaluated the association between self......-reported, pre-diagnosis use of common analgesics and overall/progression-free/disease-specific survival among 7694 women with invasive epithelial ovarian cancer (4273 deaths). RESULTS: Regular analgesic use (at least once per week) was not associated with overall survival (pooled hazard ratios, pHRs (95......% confidence intervals): aspirin 0.96 (0.88-1.04); non-aspirin NSAIDs 0.97 (0.89-1.05); acetaminophen 1.01 (0.93-1.10)), nor with progression-free/disease-specific survival. There was however a survival advantage for users of any NSAIDs in studies clearly defining non-use as less than once per week (pHR=0...

ERCC1 Cys8092Ala and XRCC1 Arg399Gln polymorphisms predict progression-free survival after curative radiotherapy for nasopharyngeal carcinoma.

Directory of Open Access Journals (Sweden)

Hekun Jin

Full Text Available BACKGROUND: Single nucleotide polymorphisms (SNPs in DNA repair genes can alter gene expression and activity and affect response to cancer treatment and, correspondingly, survival. The present study was designed to evaluate the utility of the XRCC1 Arg399Gln and ERCC1 Cys8092Ala SNPs, measured in pretreatment biopsy samples, as predictors of response to radiotherapy in patients with non-metastatic nasopharyngeal carcinoma (NPC. MATERIALS AND METHODS: The study included 75 consecutive patients with stage II-IVA-B NPC. XRCC1 Arg399Glu and ERCC1 Cys8092Ala SNPs were identified from paraffin-embedded biopsy specimens via Sanger sequencing. Expression of p53 and pAkt protein was analyzed by immunohistochemical staining. Potential relationships between genetic polymorphisms and progression-free survival (PFS were analyzed by using a Cox proportional hazards model, the Kaplan-Meier method, and the log-rank test. RESULTS: Multivariate analysis showed that carriers of the ERCC1 8092 Ala/Ala genotype [hazard ratio (HR 1.882; 95% confidence interval (CI 1.031-3.438; P = 0.039] and heavy smokers (≥20 pack-years carrying the XRCC1 Arg/Arg genotype (HR 2.019; 95% CI 1.010-4.036; P = 0.047 had significantly lower PFS rates. Moreover, combined positive expression of p53 and pAkt led to significantly increased PFS in subgroups carrying the XRCC1 Gln allele (HR 7.057; 95% CI 2.073-24.021; P = 0.002 or the ERCC1 Cys allele (HR 2.568; 95% CI 1.056-6.248; P = 0.038. CONCLUSIONS: The ERCC1 Cys8092Ala polymorphism is an independent predictor of response to radiotherapy for NPC, and the XRCC1 Arg399Glu mutation combined with smoking status seems to predict PFS as well. Our results further suggest a possible correlation between these genetic polymorphisms and p53 protein status on survival.

Smoking may modify the association between neoadjuvant chemotherapy and survival from ovarian cancer.

Science.gov (United States)

Kelemen, Linda E; Warren, Graham W; Koziak, Jennifer M; Köbel, Martin; Steed, Helen

2016-01-01

Tobacco smoking by cancer patients is associated with increased mortality. Less is known of the impact of smoking on recurrence risk and interaction with chemotherapy treatment. We examined these associations in ovarian cancer. Patients were identified from the Alberta Cancer Registry between 1978 and 2010 and were oversampled for less-common histologic ovarian tumor types. Medical records were abstracted for 678 eligible patients on lifestyle, medical and cancer treatment, and review of pathology slides was performed for 605 patients. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazard models adjusted for age at diagnosis, race, stage and residual disease. Among patients receiving adjuvant chemotherapy (N=432), current smoking was significantly associated with shorter duration of overall (OS; HR, 8.56; 95% CI, 1.50-48.7) and progression-free (PFS; HR, 5.74; 95% CI, 1.05-31.4) survival from mucinous ovarian cancer only. There was no significant association between neoadjuvant chemotherapy and survival. However, among patients receiving neoadjuvant chemotherapy (N=44), current smokers had shorter PFS (HR, 4.32; 95% CI, 1.36-13.8; N=32 progressed/9 censored events) compared to never smokers, but the HRs were not statistically different across smoking categories (P interaction=0.87). Adverse associations were observed between smoking status and OS or PFS among patients with mucinous ovarian cancer receiving adjuvant chemotherapy. No significant effect was found from neoadjuvant chemotherapy on PFS overall; however, smoking may modify this association. Although needing replication, these findings suggest that patients may benefit from smoking cessation interventions prior to treatment with chemotherapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Cell cycle and aging, morphogenesis, and response to stimuli genes are individualized biomarkers of glioblastoma progression and survival

Directory of Open Access Journals (Sweden)

Southey Bruce R

2011-06-01

Full Text Available Abstract Background Glioblastoma is a complex multifactorial disorder that has swift and devastating consequences. Few genes have been consistently identified as prognostic biomarkers of glioblastoma survival. The goal of this study was to identify general and clinical-dependent biomarker genes and biological processes of three complementary events: lifetime, overall and progression-free glioblastoma survival. Methods A novel analytical strategy was developed to identify general associations between the biomarkers and glioblastoma, and associations that depend on cohort groups, such as race, gender, and therapy. Gene network inference, cross-validation and functional analyses further supported the identified biomarkers. Results A total of 61, 47 and 60 gene expression profiles were significantly associated with lifetime, overall, and progression-free survival, respectively. The vast majority of these genes have been previously reported to be associated with glioblastoma (35, 24, and 35 genes, respectively or with other cancers (10, 19, and 15 genes, respectively and the rest (16, 4, and 10 genes, respectively are novel associations. Pik3r1, E2f3, Akr1c3, Csf1, Jag2, Plcg1, Rpl37a, Sod2, Topors, Hras, Mdm2, Camk2g, Fstl1, Il13ra1, Mtap and Tp53 were associated with multiple survival events. Most genes (from 90 to 96% were associated with survival in a general or cohort-independent manner and thus the same trend is observed across all clinical levels studied. The most extreme associations between profiles and survival were observed for Syne1, Pdcd4, Ighg1, Tgfa, Pla2g7, and Paics. Several genes were found to have a cohort-dependent association with survival and these associations are the basis for individualized prognostic and gene-based therapies. C2, Egfr, Prkcb, Igf2bp3, and Gdf10 had gender-dependent associations; Sox10, Rps20, Rab31, and Vav3 had race-dependent associations; Chi3l1, Prkcb, Polr2d, and Apool had therapy-dependent associations

Lactate dehydrogenase predicts combined progression-free survival after sequential therapy with abiraterone and enzalutamide for patients with castration-resistant prostate cancer.

Science.gov (United States)

Mori, Keiichiro; Kimura, Takahiro; Onuma, Hajime; Kimura, Shoji; Yamamoto, Toshihiro; Sasaki, Hiroshi; Miki, Jun; Miki, Kenta; Egawa, Shin

2017-07-01

An array of clinical issues remains to be resolved for castration-resistant prostate cancer (CRPC), including the sequence of drug use and drug cross-resistance. At present, no clear guidelines are available for the optimal sequence of use of novel agents like androgen-receptor axis-targeted (ARAT) agents, particularly enzalutamide, and abiraterone. This study retrospectively analyzed a total of 69 patients with CRPC treated with sequential therapy using enzalutamide followed by abiraterone or vice versa. The primary outcome measure was the comparative combined progression-free survival (PFS) comprising symptomatic and/or radiographic PFS. Patients were also compared for total prostate-specific antigen (PSA)-PFS, overall survival (OS), and PSA response. The predictors of combined PFS and OS were analyzed with a backward-stepwise multivariate Cox model. Of the 69 patients, 46 received enzalutamide first, followed by abiraterone (E-A group), and 23 received abiraterone, followed by enzalutamide (A-E group). The two groups were not significantly different with regard to basic data, except for hemoglobin values. In a comparison with the E-A group, the A-E group was shown to be associated with better combined PFS in Kaplan-Meier analysis (P = 0.043). Similar results were obtained for total PSA-PFS (P = 0.049), while OS did not differ between groups (P = 0.62). Multivariate analysis demonstrated that pretreatment lactate dehydrogenase (LDH) values and age were significant predictors of longer combined PFS (P < 0.05). Likewise, multivariate analysis demonstrated that pretreatment hemoglobin values and performance status were significant predictors of longer OS (P < 0.05). The results of this study suggested the A-E sequence had longer combined PSA and total PSA-PFS compared to the E-A sequence in patients with CRPC. LDH values in sequential therapy may serve as a predictor of longer combined PFS. © 2017 Wiley Periodicals, Inc.

Option A Improved HIV-free Infant Survival and Mother to Child HIV Transmission at 9–18 Months in Zimbabwe

Science.gov (United States)

BUZDUGAN, Raluca; KANG DUFOUR, Mi-Suk; MCCOY, Sandra I; WATADZAUSHE, Constancia; DIRAWO, Jeffrey; MUSHAVI, Angela; MUJURU, Hilda Angela; MAHOMVA, Agnes; KANGWENDE, Rugare Abigail; HAKOBYAN, Anna; MUGURUNGI, Owen; COWAN, Frances M; PADIAN, Nancy S

2016-01-01

Objective We evaluated the impact of Option A on HIV-free infant survival and mother-to-child transmission (MTCT) in Zimbabwe. Design Serial cross-sectional community-based serosurveys. Methods We analyzed serosurvey data collected in 2012 and 2014 among mother-infant pairs from catchment areas (CAs) of 132 health facilities from 5 of 10 provinces in Zimbabwe. Eligible infants (alive or deceased) were born 9–18 months before each survey to mothers ≥16 years old. We randomly selected mother-infant pairs and conducted questionnaires, verbal autopsies and collected blood samples. We estimated: 1) the HIV-free infant survival and MTCT rate within each CA and compared the 2012 and 2014 estimates using a paired t-test, 2) number of HIV infections averted due to the intervention. Results We analyzed 7,249 mother-infant pairs with viable maternal specimens collected in 2012 and 8,551 in 2014. The mean difference in the CA-level MTCT between 2014 and 2012 was −5.2 percentage points (95% confidence interval (CI)=−8.1, −2.3, pOption A regimen. The association between HIV-free infant survival and duration of Option A implementation was not significant at the multivariate level (p=0.093). Conclusions We found a substantial and statistically significant increase in HIV-free survival and decrease in MTCT among infants aged 9–18 months following Option A rollout in Zimbabwe. This is the only impact evaluation of Option A and shows the effectiveness of Option A and Zimbabwe’s remarkable progress towards eMTCT. PMID:27058354

Expression of aurora kinase A is associated with metastasis-free survival in node-negative breast cancer patients

Directory of Open Access Journals (Sweden)

Siggelkow Wulf

2012-11-01

Full Text Available Abstract Background Inhibitors targeting the cell cycle-regulated aurora kinase A (AURKA are currently being developed. Here, we examine the prognostic impact of AURKA in node-negative breast cancer patients without adjuvant systemic therapy (n = 766. Methods AURKA was analyzed using microarray-based gene-expression data from three independent cohorts of node-negative breast cancer patients. In multivariate Cox analyses, the prognostic impact of age, histological grade, tumor size, estrogen receptor (ER, and HER2 were considered. Results Patients with higher AURKA expression had a shorter metastasis-free survival (MFS in the Mainz (HR 1.93; 95% CI 1.34 – 2.78; P Conclusions AURKA is associated with worse prognosis in estrogen receptor positive breast carcinomas. Patients with the highest AURKA expression (>75% percentile have a particularly bad prognosis and may profit from therapy with AURKA inhibitors.

Radical Nephrectomy for Primary Retroperitoneal Liposarcoma Near the Kidney has a Beneficial Effect on Disease-Free Survival.

Science.gov (United States)

Rhu, Jinsoo; Cho, Chan Woo; Lee, Kyo Won; Park, Hyojun; Park, Jae Berm; Choi, Yoon-La; Kim, Sung Joo

2018-01-01

The purpose of this study is to analyze the clinical impact of radical nephrectomy on retroperitoneal liposarcoma near the kidney. Data of patients who underwent surgery for unilateral primary retroperitoneal liposarcoma near the kidney were retrospectively collected. Patients were divided into four groups according to whether they underwent nephrectomy and combined resection of other organs. Kaplan-Meier survival analysis was used to estimate disease-free survival and overall survival. Multivariable Cox analysis was used to analyze factors related to disease-free survival and overall survival. Nephrectomy (HR = 0.260, CI = 0.078-0.873, p = 0.029) had a beneficial effect on disease-free survival, while interaction model of nephrectomy*other organ resection (HR = 4.655, CI = 1.767-12.263, p = 0.002) showed poor disease-free survival. Other organ resection was not related to disease-free survival (HR = 1.543, CI = 0.146-16.251, p = 0.718). Operation method (p = 0.007) and FNCLCC grade (p free survival. While combined organ resection without nephrectomy group (HR = 1.604, CI = 0.167-15.370, p = 0.682) and radical nephrectomy with combined organ resection group (HR = 1.309, CI = 0.448-3.825, p = 0.622) did not show significant difference in disease-free survival from the mass excision only group, radical nephrectomy without combined organ resection group (HR = 0.279, CI = 0.078-0.991, p = 0.048) showed superior disease-free survival. Radical nephrectomy of unilateral primary retroperitoneal liposarcoma near the kidney has a beneficial effect on disease-free survival.

The Role of the Neutrophil to Lymphocyte Ratio for Survival Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone

Directory of Open Access Journals (Sweden)

Martin Boegemann

2017-02-01

Full Text Available The purpose of this study was to examine the prognostic capability of baseline neutrophil-to-lymphocyte-ratio (NLR and NLR-change under Abiraterone in metastatic castration-resistant prostate cancer patients. The impact of baseline NLR and change after eight weeks of treatment on progression-free survival (PFS and overall survival (OS was analyzed using Kaplan-Meier-estimates and Cox-regression. 79 men with baseline NLR <5 and 17 with NLR >5 were analyzed. In baseline analysis of PFS NLR >5 was associated with non-significantly shorter median PFS (five versus 10 months (HR: 1.6 (95%CI:0.9–2.8; p = 0.11. After multivariate adjustment (MVA, ECOG > 0–1, baseline LDH>upper limit of normal (UNL and presence of visceral metastases were independent prognosticators. For OS, NLR >5 was associated with shorter survival (seven versus 19 months (HR: 2.3 (95%CI:1.3–4.0; p < 0.01. In MVA, ECOG > 0–1 and baseline LDH > UNL remained independent prognosticators. After 8 weeks of Abiraterone NLR-change to <5 prognosticated worse PFS (five versus 12 months (HR: 4.1 (95%CI:1.1–15.8; p = 0.04. MVA showed a trend towards worse PFS for NLR-change to <5 (p = 0.11. NLR-change to <5 led to non-significant shorter median OS (seven versus 16 months (HR: 2.3 (95%CI:0.7–7.1; p = 0.15. MVA showed non-significant difference for OS. We concluded baseline NLR <5 is associated with improved survival. In contrast, in patients with baseline NLR >5, NLR-change to <5 after eight weeks of Abiraterone was associated with worse survival and should be interpreted carefully.

Elevated HERV-K Expression in Soft Tissue Sarcoma Is Associated with Worsened Relapse-Free Survival.

Science.gov (United States)

Giebler, Maria; Staege, Martin S; Blauschmidt, Sindy; Ohm, Lea I; Kraus, Matthias; Würl, Peter; Taubert, Helge; Greither, Thomas

2018-01-01

A wide variety of endogenous retroviral sequences has been demonstrated in the human genome so far, divided into several different families according to the sequence homology to viral strains. While increased expression of human endogenous retrovirus (HERV) elements has already been linked to unfavorable prognosis in hepatocellular carcinoma, breast cancer, and ovarian carcinoma yet less is known about the impact of the expression of different HERV elements on sarcomagenesis in general as well as the outcome of soft tissue sarcoma (STS) patients. Therefore, in this study the association between expression of HERV-K and HERV-F and the clinicopathological characteristics in a cohort of STSs as well as the patients' prognosis was evaluated. HERV-K and HERV-F expression was assessed by quantitative real-time PCR in 120 patient specimens. HERV-K and HERV-F expression was significantly correlated ( r S = 0.5; p = 6.4 × 10 -9 ; Spearman's rank bivariate correlation). Also, tumor diameter exhibited a significant negative association to HERV-K and HERV-F expression. Levels of several hypoxia-related RNAs like HIF-1α and miR-210 showed a significant positive correlation with both HERV-K and HERV-F expression. Although in survival analyses no impact of HERV expression on disease-specific survival could be detected, patients with elevated HERV-K expression had a significantly shorter relapse-free survival ( p = 0.014, log-rank analysis). In conclusion, we provide evidence for the first time that the increased expression of HERV-K in tumors is associated with STS patients' prognosis.

Fontan fenestration closure and event-free survival.

Science.gov (United States)

Imielski, Bartlomiej R; Woods, Ronald K; Mussatto, Kathleen A; Cao, Yumei; Simpson, Pippa M; Tweddell, James S

2013-01-01

The purpose of the present study was to evaluate the association of open and closed Fontan fenestration status with event-free survival. All patients who underwent a fenestrated Fontan procedure at our institution from January 1994 through June 2007 were reviewed. Patient information was obtained from the medical records. The patients were assigned to 1 of 2 study groups, open or closed, according to their most recent fenestration status. Clinically relevant morbid events were tabulated, and Kaplan-Meier event analysis was used to create event-free probability curves with log-rank comparisons. A total of 161 patients were classified as open and 51 as closed. The median interval to an event was 1.1 years (interquartile range, 0.1-3.3 years) after the Fontan procedure. The median interval to closure was 1.2 years (interquartile range, 0.7-3.3 years). The median interval to an event was 1.5 years (interquartile range, 0.1-4.6 years) in the closed group and 1.1 years (interquartile range, 0.1-3.3 years) in the open group. Event-free probability analysis revealed no significant difference between the 2 groups (P = .15). The median follow-up arterial oxygen saturation was greater in the closed group (96.0%; interquartile range, 94.0%-97.0%) than in the open group (91.0%; interquartile range, 86.0%-95.0%; P < .0001). Fenestration closure was associated with greater arterial oxygen saturation but not greater event-free survival. The interval to an event was slightly less than the interval to fenestration closure, suggesting potential merit in the evaluation of earlier fenestration closure. Adoption of specific fenestration management guidelines might help improve the overall outcomes and enhance the quality of future studies. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Elevated CD147 expression is associated with shorter overall survival in non-small cell lung cancer.

Science.gov (United States)

Zhang, Xiaojun; Tian, Tian; Zhang, Xiaofeng; Liu, Changting; Fang, Xiangqun

2017-06-06

A number of studies have reported on the prognostic role of CD147 expression in non-small cell lung cancer (NSCLC); however, the results remain controversial. This study aims to investigate the impact of CD147 on the prognosis of NSCLC by means of a meta-analysis. A literature search was performed for relevant studies published before October 29, 2016. The hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated as effective measures. Sensitivity analysis and publication bias examination were also conducted. Ten eligible studies with a total of 1605 patients were included in this meta-analysis. CD147 overexpression was correlated with poor overall survival (OS) (HR=1.59, 95% CI=1.32-1.91, pCD147 expression was associated with the presence of lymph node metastasis (OR=2.31, 95% CI=1.74-3.07, pCD147 and sex, age, differentiation, or histology was found. No evidence of significant publication bias was identified. This meta-analysis revealed that overexpression of CD147 was associated with shorter OS, the presence of lymph node metastasis and advanced TNM stage in NSCLC. Therefore, CD147 could serve as a potential prognostic marker for NSCLC.

Summary curves for patients transplanted for chronic myeloid leukaemia salvaged by a donor lymphocyte infusion: the current leukaemia-free survival curve

DEFF Research Database (Denmark)

Klein, John P.; Keiding, Niels; Shu, Youyi

2000-01-01

CML, donor lymphocyte infusion, leukaemia-free survival, current leukaemia-free survival, statistical methods......CML, donor lymphocyte infusion, leukaemia-free survival, current leukaemia-free survival, statistical methods...

Treatment-related survival associations of claudin-2 expression in fibroblasts of colorectal cancer

DEFF Research Database (Denmark)

Mezheyeuski, Artur; Strell, Carina; Hrynchyk, Ina

2018-01-01

Claudin-2 is a trans-membrane protein—component of tight junctions in epithelial cells. Elevated claudin-2 expression has been reported in colorectal cancer (CRC). The aim of this study was to investigate the expression patterns of claudin-2 in human CRC samples and analyze its association...... with clinical characteristics and treatment outcome. TMAs of primary tumors from two cohorts of metastatic CRC (mCRC) were used. Claudin-2 IHC staining was evaluated in a semi-quantitative manner in different regions and cell types. Claudin-2 expression was also analyzed by immunofluorescence in primary...... cultures of human CRC cancer-associated fibroblasts (CAFs). Initial analyses identified previously unrecognized expression patterns of claudin-2 in CAFs of human CRC. Claudin-2 expression in CAFs of the invasive margin was associated with shorter progression-free survival. Subgroup analyses demonstrated...

The application of Gadopentate-Dimeneglumin has no impact on progression free and overall survival as well as renal function in patients with monoclonal plasma cell disorders if general precautions are taken

Energy Technology Data Exchange (ETDEWEB)

Hillengass, J. [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); German Cancer Research Center Heidelberg, Department of Radiology, Heidelberg (Germany); Stoll, J.; Wagner, B.; Goldschmidt, H. [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); Zechmann, C.M. [Rinecker Proton Therapy Center, Munich (Germany); Kunz, C.; Heiss, C. [German Cancer Research Center Heidelberg, Department of Biostatistics, Heidelberg (Germany); Sumkauskaite, M. [University of Heidelberg, Department of Radiology, Heidelberg (Germany); Moehler, T.M. [InVentiv Health Clinical, Wiesbaden (Germany); Schlemmer, H.P.; Delorme, S. [German Cancer Research Center Heidelberg, Department of Radiology, Heidelberg (Germany)

2014-10-31

The current analysis investigated the prognostic significance of gadopentetate dimeglumine on survival and renal function in patients with monoclonal plasma cell disorders. In this study 263 patients who had received gadopentetate dimeglumine within a prospective trial investigating dynamic contrast-enhanced magnetic resonance imaging (MRI) were compared with 335 patients who had undergone routine, unenhanced MRI. We found no significant prognostic impact of the application of contrast agent on progression-free survival in patients with either monoclonal gammopathy of undetermined significance, smouldering or symptomatic myeloma and no significant prognostic impact on overall survival in patients with symptomatic myeloma. Since renal impairment is a frequent complication of myeloma, and decreased renal function is associated with a higher risk of complications in patients receiving contrast agents, we evaluated the impact of contrast agent on renal function after 1 year. In the present analysis the only significant adverse impact on kidney function occurred in symptomatic myeloma patients who already had impaired renal parameters at baseline. Here, the renal function did not recover during therapy, whereas it did so in patients with normal or only slightly impaired renal function. If general recommendations are adhered to, gadopentetate dimeglumine can be safely applied in patients with monoclonal plasma cell disease. (orig.)

RUNX1 and RUNX3 protect against YAP-mediated EMT, stem-ness and shorter survival outcomes in breast cancer

Science.gov (United States)

Kulkarni, Madhura; Tan, Tuan Zea; Syed Sulaiman, Nurfarhanah Bte; Lamar, John M.; Bansal, Prashali; Cui, Jianzhou; Qiao, Yiting; Ito, Yoshiaki

2018-01-01

Hippo pathway target, YAP has emerged as an important player in solid tumor progression. Here, we identify RUNX1 and RUNX3 as novel negative regulators of oncogenic function of YAP in the context of breast cancer. RUNX proteins are one of the first transcription factors identified to interact with YAP. RUNX1 or RUNX3 expression abrogates YAP-mediated pro-tumorigenic properties of mammary epithelial cell lines in an interaction dependent manner. RUNX1 and RUNX3 inhibit YAP-mediated migration and stem-ness properties of mammary epithelial cell lines by co-regulating YAP-mediated gene expression. Analysis of whole genome expression profiles of breast cancer samples revealed significant co-relation between YAP–RUNX1/RUNX3 expression levels and survival outcomes of breast cancer patients. High RUNX1/RUNX3 expression proved protective towards YAP-dependent patient survival outcomes. High YAP in breast cancer patients’ expression profiles co-related with EMT and stem-ness gene signature enrichment. High RUNX1/RUNX3 expression along with high YAP reflected lower enrichment of EMT and stem-ness signatures. This antagonistic activity of RUNX1 and RUNX3 towards oncogenic function of YAP identified in mammary epithelial cells as well as in breast cancer expression profiles gives a novel mechanistic insight into oncogene–tumor suppressor interplay in the context of breast cancer progression. The novel interplay between YAP, RUNX1 and RUNX3 and its significance in breast cancer progression can serve as a prognostic tool to predict cancer recurrence. PMID:29581836

Protein Kinase CK2 Expression Predicts Relapse Survival in ERα Dependent Breast Cancer, and Modulates ERα Expression in Vitro

Directory of Open Access Journals (Sweden)

Marlon D. Williams

2015-12-01

Full Text Available The heterotetrameric protein kinase CK2 has been associated with oncogenic transformation, and our previous studies have shown that it may affect estrogenic signaling. Here, we investigate the role of the protein kinase CK2 in regulating ERα (estrogen receptor α signaling in breast cancer. We determined the correlation of CK2α expression with relapse free breast cancer patient survival utilizing Kaplan Meier Plotter (kmplot.com/analysis/ to mine breast cancer microarrays repositories. Patients were stratified according to ERα status, histological grade, and hormonal therapy. Luciferase reporter assays and flow cytometry were implemented to determine the impact of CK2 inhibition on ERE-mediated gene expression and expression of ERα protein. CK2α expression is associated with shorter relapse free survival among ERα (+ patients with grade 1 or 2 tumors, as well as among those patients receiving hormonal therapy. Biochemical inhibition of CK2 activity results in increased ER-transactivation as well as increased expression among ERα (+ and ERα (− breast cancer cell lines. These findings suggest that CK2 may contribute to estrogen-independent cell proliferation and breast tumor progression, and may potentially serve as a biomarker and pharmacological target in breast cancer.

Genomic variation in myeloma: design, content, and initial application of the Bank On A Cure SNP Panel to detect associations with progression-free survival

Directory of Open Access Journals (Sweden)

Fang Gang

2008-09-01

Full Text Available Abstract Background We have engaged in an international program designated the Bank On A Cure, which has established DNA banks from multiple cooperative and institutional clinical trials, and a platform for examining the association of genetic variations with disease risk and outcomes in multiple myeloma. We describe the development and content of a novel custom SNP panel that contains 3404 SNPs in 983 genes, representing cellular functions and pathways that may influence disease severity at diagnosis, toxicity, progression or other treatment outcomes. A systematic search of national databases was used to identify non-synonymous coding SNPs and SNPs within transcriptional regulatory regions. To explore SNP associations with PFS we compared SNP profiles of short term (less than 1 year, n = 70 versus long term progression-free survivors (greater than 3 years, n = 73 in two phase III clinical trials. Results Quality controls were established, demonstrating an accurate and robust screening panel for genetic variations, and some initial racial comparisons of allelic variation were done. A variety of analytical approaches, including machine learning tools for data mining and recursive partitioning analyses, demonstrated predictive value of the SNP panel in survival. While the entire SNP panel showed genotype predictive association with PFS, some SNP subsets were identified within drug response, cellular signaling and cell cycle genes. Conclusion A targeted gene approach was undertaken to develop an SNP panel that can test for associations with clinical outcomes in myeloma. The initial analysis provided some predictive power, demonstrating that genetic variations in the myeloma patient population may influence PFS.

High risk bladder cancer: current management and survival

Directory of Open Access Journals (Sweden)

Anna M. Leliveld

2011-04-01

Full Text Available PURPOSE: To evaluate the pattern of care in patients with high risk non muscle invasive bladder cancer (NMIBC in the Comprehensive Cancer Center North-Netherlands (CCCN and to assess factors associated with the choice of treatment, recurrence and progression free survival rates. MATERIALS AND METHODS: Retrospective analysis of 412 patients with newly diagnosed high risk NMIBC. Clinical, demographic and follow-up data were obtained from the CCCN Cancer Registry and a detailed medical record review. Uni and multivariate analysis was performed to identify factors related to choice of treatment and 5 year recurrence and progression free survival. RESULTS: 74/412 (18% patients with high risk NMIBC underwent a transurethral resection (TUR as single treatment. Adjuvant treatment after TUR was performed in 90.7% of the patients treated in teaching hospitals versus 71.8 % in non-teaching hospitals (p 80 years OR 0.1 p = 0.001 and treatment in non-teaching hospitals (OR 0.25; p < 0.001 were associated with less adjuvant treatment after TUR. Tumor recurrence occurred in 191/392 (49% and progression in 84 /392 (21.4% patients. The mean 5-years progression free survival was 71.6% (95% CI 65.5-76.8. CONCLUSION: In this pattern of care study in high risk NMIBC, 18% of the patients were treated with TUR as single treatment. Age and treatment in non-teaching hospitals were associated with less adjuvant treatment after TUR. None of the variables sex, age, comorbidity, hospital type, stage and year of treatment was associated with 5 year recurrence or progression rates.

High levels of microRNA-21 in the stroma of colorectal cancers predict short disease-free survival in stage II colon cancer patients

DEFF Research Database (Denmark)

Nielsen, Boye Schnack; Jørgensen, Stine; Fog, Jacob Ulrik

2011-01-01

Approximately 25% of all patients with stage II colorectal cancer will experience recurrent disease and subsequently die within 5 years. MicroRNA-21 (miR-21) is upregulated in several cancer types and has been associated with survival in colon cancer. In the present study we developed a robust...... in situ hybridization assay using high-affinity Locked Nucleic Acid (LNA) probes that specifically detect miR-21 in formalin-fixed paraffin embedded (FFPE) tissue samples. The expression of miR-21 was analyzed by in situ hybridization on 130 stage II colon and 67 stage II rectal cancer specimens. The mi...... relative to the nuclear density (TBR) obtained using a red nuclear stain. High TBR (and TB) estimates of miR-21 expression correlated significantly with shorter disease-free survival (p = 0.004, HR = 1.28, 95% CI: 1.06-1.55) in the stage II colon cancer patient group, whereas no significant correlation...

Preoperative radiation with concurrent chemotherapy for resectable rectal cancer: Effect of dose escalation on pathologic complete response, local recurrence-free survival, disease-free survival, and overall survival

International Nuclear Information System (INIS)

Wiltshire, Kirsty L.; Ward, Iain G.; Swallow, Carol; Oza, Amit M.; Cummings, Bernard; Pond, Gregory R.; Catton, Pamela; Kim, John; Ringash, Jolie; Wong, Chong S.; Wong, Rebecca; Siu, Lillian L.; Moore, Malcolm; Brierley, James

2006-01-01

Purpose: Three Phase II studies of preoperative radiotherapy and concurrent 5FU chemotherapy were undertaken. The primary endpoints were acute toxicity and pathologic complete response rate (pCR). Secondary endpoints were local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS). Methods and Materials: A total of 134 patients with adenocarcinoma of the rectum (clinical T3/T4 or N1/N2) were treated. The initial cohort received 40 Gy in 20 fractions, the second 46 Gy in 23 fractions, and the third 50 Gy in 25 fractions. 5FU (225 mg/m 2 /day) was given continuously throughout radiotherapy. A total of 121 patients underwent surgical resection. Results: Treatment was well tolerated. Grade 3/4 acute toxicity was observed in 13%, 4%, and 14% of patients in the 40 Gy, 46 Gy, and 50 Gy cohorts, respectively (p = 0.20). pCR was documented in 15%, 23%, and 33% of patients, respectively (p = 0.07). The 2-year actuarial LRFS was 72%, 90%, and 89% (p = 0.02); DFS was 62%, 84%, and 78% (p = 0.02); and OS was 72%, 94%, and 92%, respectively (p = 0.03). Conclusions: All treatment schedules were well tolerated. There was a trend toward increased pCR with higher doses. A statistically significant increase in LRFS, DFS, and OS was seen with radiation doses of 46 Gy and greater, but there was no difference between 46 Gy and 50 Gy

Areca nut is associated with younger age of diagnosis, poor chemoradiotherapy response, and shorter overall survival in esophageal squamous cell carcinoma.

Directory of Open Access Journals (Sweden)

Chang-Han Chen

Full Text Available Areca nut chewing is carcinogenic to humans. However, little is known about the impact of areca nut chewing on esophageal squamous cell carcinoma (ESCC.We retrospectively reviewed 286 ESCC patients who received surgery or preoperative chemoradiotherapy followed by surgery at our institution. Background characteristics including areca nut chewing history were analyzed. The 4-nitroquinoline 1-oxide (4-NQO-induced murine ESCC model was used to test the impact of arecoline, a main constituent of areca nut, on ESCC.Compared to patients without areca nut chewing history, patients with areca nut chewing history had overall a younger age of onset (Mean age: 56.75 versus 52.68 yrs, P<0.001 and significantly worse overall survival than those without areca nut chewing history (P = 0.026. Among patients who received surgery, the overall survival rates were not significantly different between those with or without areca nut chewing history. Among patients who received preoperative chemoradiotherapy followed by surgery, those with areca nut chewing history had a significantly lower pathologic complete response rate (P = 0.002 and lower overall survival rate (P = 0.002 than those without. In the murine ESCC model, the incidence of esophageal invasive squamous cell carcinoma was 40% in mice exposed to concomitant 4-NQO and arecoline treatment for 8 weeks and 6% in mice exposed to 4-NQO only for 8 weeks (P = 0.037.Our results indicate that areca nut chewing history is significantly associated with younger age of onset, poor response to chemoradiotherapy, and shorter overall survival in ESCC patients. Arecoline, a main constituent of areca nut, accelerates esophageal tumorigenesis in the 4-NQO-induced murine ESCC model.

Meta-analysis of CDKN2A methylation to find its role in prostate cancer development and progression, and also to find the effect of CDKN2A expression on disease-free survival (PRISMA).

Science.gov (United States)

Cao, Zipei; Wei, Lijuan; Zhu, Weizhi; Yao, Xuping

2018-03-01

), while CDKN2A expression was significantly associated with a poor disease-free survival (P < .01). CDKN2A methylation may not be significantly associated with the development, progression of PCa. Although CDKN2A expression had an unfavorable prognosis in disease-free survival. More studies are needed to confirm our results.

Refractory Graft-Versus-Host Disease-Free, Relapse-Free Survival as an Accurate and Easy-to-Calculate Endpoint to Assess the Long-Term Transplant Success.

Science.gov (United States)

Kawamura, Koji; Nakasone, Hideki; Kurosawa, Saiko; Yoshimura, Kazuki; Misaki, Yukiko; Gomyo, Ayumi; Hayakawa, Jin; Tamaki, Masaharu; Akahoshi, Yu; Kusuda, Machiko; Kameda, Kazuaki; Wada, Hidenori; Ishihara, Yuko; Sato, Miki; Terasako-Saito, Kiriko; Kikuchi, Misato; Kimura, Shun-Ichi; Tanihara, Aki; Kako, Shinichi; Kanamori, Heiwa; Mori, Takehiko; Takahashi, Satoshi; Taniguchi, Shuichi; Atsuta, Yoshiko; Kanda, Yoshinobu

2018-02-21

The aim of this study was to develop a new composite endpoint that accurately reflects the long-term success of allogeneic hematopoietic stem cell transplantation (allo-HSCT), as the conventional graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) overestimates the impact of GVHD. First, we validated current GRFS (cGRFS), which recently was proposed as a more accurate endpoint of long-term transplant success. cGRFS was defined as survival without disease relapse/progression or active chronic GVHD at a given time after allo-HSCT, calculated using 2 distinct methods: a linear combination of a Kaplan-Meier estimates approach and a multistate modelling approach. Next, we developed a new composite endpoint, refractory GRFS (rGRFS). rGRFS was calculated similarly to conventional GRFS treating grade III to IV acute GVHD, chronic GVHD requiring systemic treatment, and disease relapse/progression as events, except that GVHD that resolved and did not require systemic treatment at the last evaluation was excluded as an event in rGRFS. The 2 cGRFS curves obtained using 2 different approaches were superimposed and both were superior to that of conventional GRFS, reflecting the proportion of patients with resolved chronic GVHD. Finally, the curves of cGRFS and rGRFS overlapped after the first 2 years of post-transplant follow-up. These results suggest that cGRFS and rGRFS more accurately reflect transplant success than conventional GRFS. Especially, rGRFS can be more easily calculated than cGRFS and analyzed with widely used statistical approaches, whereas cGRFS more accurately represents the burden of GVHD-related morbidity in the first 2 years after transplantation. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Survival outcomes for oligometastasis in resected non-small cell lung cancer.

Science.gov (United States)

Shimada, Yoshihisa; Saji, Hisashi; Kakihana, Masatoshi; Kajiwara, Naohiro; Ohira, Tatsuo; Ikeda, Norihiko

2015-10-01

We investigated the factors associated with post-recurrence survival and the treatment for non-small-cell lung cancer patients with postoperative distant recurrence, especially oligometastasis. We reviewed the data of 272 patients with distant recurrence who underwent resection of non-small-cell lung cancer from January 2000 through December 2011. The type of distant recurrence was classified as oligometastasis (n = 76, 28%) or polymetastasis (n = 196, 72%). Forty-seven (62%) patients with oligometastasis received local therapy (surgery 5, radiotherapy 9, sequential local and systemic therapy 28, chemoradiotherapy 5). Multivariate analysis revealed older age, non-adenocarcinoma, shorter disease-free interval, no pulmonary metastasis, liver metastases, bone metastases, and polymetastasis had significant associations with unfavorable post-recurrence survival. Subgroup analysis of patients with oligometastasis showed histology and disease-free interval had a great impact on survival. Smoking history and histology were associated with survival in patients with lung oligometastasis, whereas systemic treatment and longer disease-free interval were related to increased post-recurrence survival in those with brain oligometastasis. This study showed that an oligometastatic state per se was a significant favorable factor. Optimization of personalized systemic treatment and adding local treatment are important in the management of patients with non-small-cell lung cancer and oligometastasis. © The Author(s) 2015.

Preirradiation PSA predicts biochemical disease-free survival in patients treated with postprostatectomy external beam irradiation

International Nuclear Information System (INIS)

Crane, Christopher H.; Rich, Tyvin A.; Read, Paul W.; Sanfilippo, Nicholas J.; Gillenwater, Jay Y.; Kelly, Maria D.

1997-01-01

Purpose: To assess the clinical outcome and prostate-specific antigen (PSA) response and to determine prognostic factors for biochemical disease-free survival in patients treated with external beam radiotherapy following radical prostatectomy without hormonal therapy. Methods and Materials: Forty-eight patients were treated after prostatectomy with radiotherapy between March, 1988 and December, 1993. Seven patients had undetectable PSA ( 2.7. Five-year actuarial biochemical disease-free survival values were 71, 48, and 0%, respectively, for the three groups. Biochemical disease-free survival was not affected by preoperative PSA level, clinical stage, Gleason's score, pathologic stage, surgical margins, presence of undetectable PSA after surgery, surgery to radiation interval, total dose, or presence of clinically suspicious local disease. Based on digital rectal exam, there were no local failures. Conclusion: Biochemical disease-free survival after postprostatectomy radiation is predicted by the PSA at the time of irradiation. Clinical local control is excellent, but distant failure remains a significant problem in this population. The addition of concomitant systemic therapy should be investigated in patients with PSA >2.7

[Research progress on free radicals in human body].

Science.gov (United States)

Wang, Q B; Xu, F P; Wei, C X; Peng, J; Dong, X D

2016-08-10

Free radicals are the intermediates of metabolism, widely exist in the human bodies. Under normal circumstances, the free radicals play an important role in the metabolic process on human body, cell signal pathway, gene regulation, induction of cell proliferation and apoptosis, so as to maintain the normal growth and development of human body and to inhibit the growth of bacteria, virus and cancer. However, when organic lesion occurs affected by external factors or when equilibrium of the free radicals is tipped in the human body, the free radicals will respond integratedly with lipids, protein or nucleic acid which may jeopardize the health of human bodies. This paper summarizes the research progress of the free radicals conducted in recent years, in relations to the perspective of the types, origins, test methods of the free radicals and their relationship with human's health. In addition, the possible mechanisms of environmental pollutants (such as polycyclic aromatic hydrocarbons) mediating oxidative stress and free radicals scavenging in the body were also summarized.

β2 -microglobulin normalization within 6 months of ibrutinib-based treatment is associated with superior progression-free survival in patients with chronic lymphocytic leukemia.

Science.gov (United States)

Thompson, Philip A; O'Brien, Susan M; Xiao, Lianchun; Wang, Xuemei; Burger, Jan A; Jain, Nitin; Ferrajoli, Alessandra; Estrov, Zeev; Keating, Michael J; Wierda, William G

2016-02-15

A high pretreatment β2 -microglobulin (B2M) level is associated with inferior survival outcomes in patients with chronic lymphocytic leukemia. However, to the authors' knowledge, the prognostic and predictive significance of changes in B2M during treatment have not been reported to date. The authors analyzed 83 patients treated with ibrutinib-based regimens (66 with recurrent/refractory disease) and 198 treatment-naive patients who were treated with combined fludarabine, cyclophosphamide, and rituximab (FCR) to characterize changes in B2M and their relationship with clinical outcomes. B2M rapidly decreased during treatment with ibrutinib; on multivariable analysis, patients who received FCR (odds ratio, 0.40; 95% confidence interval [95% CI], 0.18-0.90 [P = .027]) were less likely to have normalized B2M at 6 months than patients treated with ibrutinib. On univariable analysis, normalization of B2M was associated with superior progression-free survival (PFS) from the 6-month landmark in patients treated with ibrutinib-based regimens and FCR. On multivariable analysis, failure to achieve normalized B2M at 6 months of treatment was associated with inferior PFS (hazard ratio, 16.9; 95% CI, 1.3-220.0 [P = .031]) for patients treated with ibrutinib, after adjusting for the effects of baseline B2M, stage of disease, fludarabine-refractory disease, and del(17p). In contrast, in patients treated with FCR, negative minimal residual disease status in the bone marrow was the only variable found to be significantly associated with superior PFS (hazard ratio, 0.28; 95% CI, 0.12-0.67 [P = .004]). Normalization of B2M at 6 months in patients treated with ibrutinib was found to be a useful predictor of subsequent PFS and may assist in clinical decision-making. © 2015 American Cancer Society.

Analysis of Survival of Patients with Chronic Myeloid Leukemia Treated with Imatinib in the Last 15 Years in Lebanon.

Science.gov (United States)

Massoud, Marcel; Sakr, Riwa; Kerbage, Fouad; Makdissi, Joseph; Hawi, Jenny; Rached, Layale; Nasr, Fady; Chahine, Georges

2017-07-01

In the 2000s, the introduction of the tyrosine kinase inhibitor (TKI), imatinib, improved the survival outcomes of patients with chronic myeloid leukemia (CML). In Lebanon, we rapidly adopted this treatment strategy. To the best of our knowledge, this is the first study reporting the survival rates of Lebanese CML patients. We examined the rates of major molecular response (MMR) and complete cytogenetic response (CCyR) and analyzed the overall survival, progression-free survival, and event-free survival of CML patients treated with front-line imatinib in 3 university hospitals in Lebanon. We retrospectively reviewed the medical records of 46 patients diagnosed with CML and treated with front-line imatinib 400 mg/day from 2000 and followed up to 2015. In all patients, initially, 2 diagnostic tests were performed: cytogenetic analysis and qualitative molecular testing of the BCR-ABL transcript. The male-to-female sex ratio was 3:1. The median age at diagnosis was 49 years, and the mean age was 44.52 years. At diagnosis, 46 patients were in the chronic phase. All patients started imatinib 400 mg/day. Of the 46 patients, 35 had a typical karyotype, 8 an atypical karyotype, and 3 hypoploidism. The MMR rate at 18 months was 58.69%. The cumulative CCyR rate at 18 months of therapy with imatinib at the standard dose was 67.39%. The event-free survival rate was 75.86% and 74.14% at 5 and 8 years, respectively. The progression-free survival rate was 77.59% and 75.86% at 5 and 8 years, respectively. The overall survival rate was 98.27% and 98.27% at 5 and 8 years, respectively. Of the 46 patients, 12 developed disease progression and were salvaged by second-generation TKIs. These 12 patients were still alive with a MMR. In our study population, the achievement of a MMR and CCyR and overall survival, progression-free survival, and event-free survival were similar to previous published data. Reaching high survival rates with a first-generation TKI in a country with limited

Benefit from autologous stem cell transplantation in primary refractory myeloma? Different outcomes in progressive versus stable disease

Science.gov (United States)

Rosiñol, Laura; García-Sanz, Ramón; Lahuerta, Juan José; Hernández-García, Miguel; Granell, Miquel; de la Rubia, Javier; Oriol, Albert; Hernández-Ruiz, Belén; Rayón, Consuelo; Navarro, Isabel; García-Ruiz, Juan Carlos; Besalduch, Joan; Gardella, Santiago; Jiménez, Javier López; Díaz-Mediavilla, Joaquín; Alegre, Adrián; Miguel, Jesús San; Bladé, Joan

2012-01-01

Background Several studies of autologous stem cell transplantation in primary refractory myeloma have produced encouraging results. However, the outcome of primary refractory patients with stable disease has not been analyzed separately from the outcome of patients with progressive disease. Design and Methods In the Spanish Myeloma Group 2000 trial, 80 patients with primary refractory myeloma (49 with stable disease and 31 with progressive disease), i.e. who were refractory to initial chemotherapy, were scheduled for tandem transplants (double autologous transplant or a single autologous transplant followed by an allogeneic transplant). Patients with primary refractory disease included those who never achieved a minimal response (≥25% M-protein decrease) or better. Responses were assessed using the European Bone Marrow Transplant criteria. Results There were no significant differences in the rates of partial response or better between patients with stable or progressive disease. However, 38% of the patients with stable disease at the time of transplantation remained in a stable condition or achieved a minimal response after transplantation versus 7% in the group with progressive disease (P=0.0017) and the rate of early progression after transplantation was significantly higher among the group with progressive disease at the time of transplantation (22% versus 2%; P=0.0043). After a median follow-up of 6.6 years, the median survival after first transplant of the whole series was 2.3 years. Progression-free and overall survival from the first transplant were shorter in patients with progressive disease (0.6 versus 2.3 years, P=0.00004 and 1.1 versus 6 years, P=0.00002, respectively). Conclusions Our results show that patients with progressive refractory myeloma do not benefit from autologous transplantation, while patients with stable disease have an outcome comparable to those with chemosensitive disease. (ClinicalTrials.gov:NCT00560053) PMID:22058223

Research progress of free space coherent optical communication

Science.gov (United States)

Tan, Zhenkun; Ke, Xizheng

2018-02-01

This paper mainly introduces the research progress of free space coherent optical communication in Xi'an University of Technology. In recent years, the research on the outer modulation technology of the laser, free-space-to-fiber coupling technique, the design of transmitting and receiving optical antenna, adaptive optical technology with or without wave-front sensor, automatic polarization control technology, frequency stabilization technology, heterodyne detection technology and high speed signal processing technology. Based on the above related research, the digital signal modulation, transmission, detection and data recovery are realized by the heterodyne detection technology in the free space optical communication system, and finally the function of smooth viewing high-definition video is realized.

Elevated level of peripheral CD8(+)CD28(-) T lymphocytes are an independent predictor of progression-free survival in patients with metastatic breast cancer during the course of chemotherapy.

Science.gov (United States)

Song, Guohong; Wang, Xiaoli; Jia, Jun; Yuan, Yanhua; Wan, Fengling; Zhou, Xinna; Yang, Huabing; Ren, Jun; Gu, Jiezhun; Lyerly, Herbert Kim

2013-06-01

Suppression of cellular immunity resulting from tumorigenesis and/or therapy might promote cancer cells' growth, progression and invasion. Here, we explored whether T lymphocyte subtypes from peripheral blood of metastatic breast cancer (MBC) female patients could be used as alternative surrogate markers for cancer progress. Additionally, plasma levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IFN-γ, and transforming growth factor-β1 were quantitated from MBC and healthy volunteers. This study included 89 female MBC patients during the post-salvage chemotherapy follow-up and 50 age- and sex-matched healthy volunteers as control. The percentages of T lymphocyte subpopulations from peripheral blood and plasma levels of cytokines were measured. Both CD8(+)CD28(-) and CD4(+)CD25(+) were elevated in MBC patients compared to the control cohort (P < 0.05). In contrast, CD3(+) and CD8(+)CD28(+)cells were significantly lower in MBC patients (P < 0.0001, P = 0.045, respectively). MBC patients had elevated levels of immunosuppressive cytokines IL-6 and IL-10. Patients with elevated CD8(+)CD28(-) and CD4(+)CD25(+) cells showed increased levels of IL-6, and only patients with elevated CD8(+)CD28(-) had decreased interferon-γ. Univariate analysis indicated increased CD3(+)CD4(+) or CD8(+)CD28(+)correlated with prolonged progression-free survival (PFS), while elevated CD8(+)CD28(-)associated with shorten PFS. The percent of CD8(+)CD28(-) T lymphocytes is an independent predictor for PFS through multivariate analysis. This study suggests that progressive elevated levels of CD8(+)CD28(-) suppressor T lymphocytes represent a novel independent predictor of PFS during post-chemotherapy follow-up.

Addition of Rituximab to Involved-Field Radiation Therapy Prolongs Progression-free Survival in Stage I-II Follicular Lymphoma: Results of a Multicenter Study

Energy Technology Data Exchange (ETDEWEB)

Ruella, Marco [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia (United States); Filippi, Andrea Riccardo [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Bruna, Riccardo [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Di Russo, Anna [Radiation Oncology, Istituto Nazionale Tumori, Milano (Italy); Magni, Michele [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Caracciolo, Daniele [Division of Haematology, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Passera, Roberto [Division of Nuclear Medicine, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Matteucci, Paola; Di Nicola, Massimo [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Corradini, Paolo [Division of Haematology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Parvis, Guido [Division of Haematology, San Luigi Gonzaga Hospital, Orbassano, Torino (Italy); Gini, Guido; Olivieri, Attilio [Division of Haematology, Ospedali Riuniti, Ancona (Italy); Ladetto, Marco [Division of Haematology, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Ricardi, Umberto [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Tarella, Corrado, E-mail: corrado.tarella@gmail.com [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Hemato-Oncology Division, European Institute of Oncology, Milano (Italy); Devizzi, Liliana [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy)

2016-03-15

Purpose: Rituximab (Rit) therapy added to involved-field radiation therapy (RT) has been proposed as an effective treatment for stage I-II follicular lymphoma (FL). The results of an observational multicenter study on the Rit-RT combination in limited-stage FL are here reported. Methods and Materials: Data have been collected from 2 consecutive cohorts of 94 patients with stage I-II FL treated between 1985 and 2011 at 5 Italian institutions. All patients had grade 1-3a FL, a median age of 54 years (range: 25-82). The first 51 patients received RT alone (control group), while the subsequent series of 43 patients received 4 rituximab courses (375 mg/m{sup 2}, days 1, 8, 15, 22) before RT (Rit-RT). Molecular disease was evaluated by nested bcl-2/IgH PCR or clonal IgH rearrangement was available in 33 Rit-RT patients. Results: At a median follow-up of 10.9 years (range: 1.8-22.9), the 10-year progression-free survival (PFS) and overall survival (OS) projections for the whole cohort were 57% and 87.5%, respectively. The 10-year PFS was significantly longer (P<.05) in the Rit-RT group (64.6%) compared to RT alone (50.7%), whereas the 10-year OS projections were not significantly different. On bivariate analysis controlling for stage, there was only a trend toward improved PFS for Rit-RT (HR, 0.55; P=.081). Follicular lymphoma international prognostic index and age were associated with OS but not with PFS on Cox regression analysis. Bone marrow molecular analysis showing PCR positivity at diagnosis was strongly associated with relapse risk upon univariate and multivariate analysis. Conclusions: This multicenter observational study suggests a potential benefit of adding rituximab to radiation therapy for stage I-II FL. The results of the currently ongoing randomized studies are required to confirm these results. The study underlines the importance of molecular disease monitoring also for patient with limited-stage disease.

Addition of Rituximab to Involved-Field Radiation Therapy Prolongs Progression-free Survival in Stage I-II Follicular Lymphoma: Results of a Multicenter Study

International Nuclear Information System (INIS)

Ruella, Marco; Filippi, Andrea Riccardo; Bruna, Riccardo; Di Russo, Anna; Magni, Michele; Caracciolo, Daniele; Passera, Roberto; Matteucci, Paola; Di Nicola, Massimo; Corradini, Paolo; Parvis, Guido; Gini, Guido; Olivieri, Attilio; Ladetto, Marco; Ricardi, Umberto; Tarella, Corrado; Devizzi, Liliana

2016-01-01

Purpose: Rituximab (Rit) therapy added to involved-field radiation therapy (RT) has been proposed as an effective treatment for stage I-II follicular lymphoma (FL). The results of an observational multicenter study on the Rit-RT combination in limited-stage FL are here reported. Methods and Materials: Data have been collected from 2 consecutive cohorts of 94 patients with stage I-II FL treated between 1985 and 2011 at 5 Italian institutions. All patients had grade 1-3a FL, a median age of 54 years (range: 25-82). The first 51 patients received RT alone (control group), while the subsequent series of 43 patients received 4 rituximab courses (375 mg/m"2, days 1, 8, 15, 22) before RT (Rit-RT). Molecular disease was evaluated by nested bcl-2/IgH PCR or clonal IgH rearrangement was available in 33 Rit-RT patients. Results: At a median follow-up of 10.9 years (range: 1.8-22.9), the 10-year progression-free survival (PFS) and overall survival (OS) projections for the whole cohort were 57% and 87.5%, respectively. The 10-year PFS was significantly longer (P<.05) in the Rit-RT group (64.6%) compared to RT alone (50.7%), whereas the 10-year OS projections were not significantly different. On bivariate analysis controlling for stage, there was only a trend toward improved PFS for Rit-RT (HR, 0.55; P=.081). Follicular lymphoma international prognostic index and age were associated with OS but not with PFS on Cox regression analysis. Bone marrow molecular analysis showing PCR positivity at diagnosis was strongly associated with relapse risk upon univariate and multivariate analysis. Conclusions: This multicenter observational study suggests a potential benefit of adding rituximab to radiation therapy for stage I-II FL. The results of the currently ongoing randomized studies are required to confirm these results. The study underlines the importance of molecular disease monitoring also for patient with limited-stage disease.

Survivable pulse power space radiator

Science.gov (United States)

Mims, James; Buden, David; Williams, Kenneth

1989-01-01

A thermal radiator system is described for use on an outer space vehicle, which must survive a long period of nonuse and then radiate large amounts of heat for a limited period of time. The radiator includes groups of radiator panels that are pivotally connected in tandem, so that they can be moved to deployed configuration wherein the panels lie largely coplanar, and to a stowed configuration wherein the panels lie in a stack to resist micrometeorite damage. The panels are mounted on a boom which separates a hot power source from a payload. While the panels are stowed, warm fluid passes through their arteries to keep them warm enough to maintain the coolant in a liquid state and avoid embrittlement of material. The panels can be stored in a largely cylindrical shell, with panels progressively further from the boom being of progressively shorter length.

Arrhythmia-free survival and pulmonary vein reconnection patterns after second-generation cryoballoon and contact-force radiofrequency pulmonary vein isolation.

Science.gov (United States)

Buist, Thomas J; Adiyaman, Ahmet; Smit, Jaap Jan J; Ramdat Misier, Anand R; Elvan, Arif

2018-06-01

The aim of this study was to compare second-generation cryoballoon and contact-force radiofrequency point-by-point pulmonary vein isolation (PVI) in atrial fibrillation (AF) patients with regard to pulmonary vein reconnection and arrhythmia-free survival. Altogether, 269 consecutive patients with drug-refractory AF undergoing PVI were included and randomly allocated to second-generation cryoballoon or contact-force point-by-point radiofrequency ablation. Median follow-up duration was 389 days (interquartile range 219-599). Mean age was 59 years (71% male); 136 patients underwent cryoballoon and 133 patients underwent radiofrequency ablation. Acute electrical PVI was 100% for both techniques. Procedure duration was significantly shorter in cryoballoon vs radiofrequency (166.5 vs 184.13 min P = 0.016). Complication rates were similar (6.0 vs 6.7%, P = 1.00). Single procedure freedom of atrial arrhythmias was significantly higher in cryoballoon as compared to radiofrequency (75.2 vs 57.4%, P = 0.013). In multivariate analysis, persistent AF, AF duration, and cryoballoon ablation were associated with freedom of atrial tachyarrhythmias. The number of repeat ablation procedures was significantly lower in the cryoballoon compared to radiofrequency (15.0 vs 24.3%, P = 0.045). At repeat ablation, pulmonary vein reconnection rate was significantly lower after cryoballoon as compared to radiofrequency ablation (36.8 vs 58.1%, P = 0.003). Improved arrhythmia-free survival and more durable pulmonary vein isolation is seen after PVI using second-generation cryoballoon as compared to contact-force radiofrequency, in patients with drug-refractory paroxysmal AF. Complication rates for both ablation techniques are low.

Overexpression of long non-coding RNA colon cancer-associated transcript 2 is associated with advanced tumor progression and poor prognosis in patients with colorectal cancer.

Science.gov (United States)

Zhang, Junling; Jiang, Yong; Zhu, Jing; Wu, Tao; Ma, Ju; Du, Chuang; Chen, Shanwen; Li, Tengyu; Han, Jinsheng; Wang, Xin

2017-12-01

The aim of the present study was to explore the clinicopathological and prognostic significance of long non-coding RNA (lncRNA) colon cancer-associated transcript 2 (CCAT2) expression in human colorectal cancer (CRC). Expression levels of lncRNA CCAT2 in CRC, adjacent non-tumor and healthy colon mucosa tissues were detected by quantitative polymerase chain reaction. The disease-free survival and overall survival rates were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using Cox proportional hazard analysis. The expression level of lncRNA CCAT2 in CRC tissues was increased significantly compared with adjacent normal tissues or non-cancerous tissues. CCAT2 expression was observed to be progressively increased between tumor-node-metastasis (TNM) stages I and IV. A high level of CCAT2 expression was revealed to be associated with poor cell differentiation, deeper tumor infiltration, lymph node metastasis, distance metastasis, vascular invasion and advanced TNM stage. Compared with patients with low levels of CCAT2 expression, patients with high levels of CCAT2 expression had shorter disease-free survival and overall survival times. Multivariate analyses indicated that high CCAT2 expression was an independent poor prognostic factor. Therefore, increased lncRNA CCAT2 expression maybe a potential diagnostic biomarker for CRC, and an independent predictor of prognosis in patients with CRC.

High Numbers of Stromal Cancer-Associated Fibroblasts Are Associated With a Shorter Survival Time in Cats With Oral Squamous Cell Carcinoma.

Science.gov (United States)

Klobukowska, H J; Munday, J S

2016-11-01

Cancer-associated fibroblasts (CAFs) are fibroblastic cells that express α-smooth muscle actin and have been identified in the stroma of numerous epithelial tumors. The presence of CAFs within the tumor stroma has been associated with a poorer prognosis in some human cancers, including oral squamous cell carcinomas (SCCs). Cats frequently develop oral SCCs, and although these are generally highly aggressive neoplasms, there is currently a lack of prognostic markers for these tumors. The authors investigated the prognostic value of the presence of CAFs within the stroma of oral SCC biopsy specimens from 47 cats. In addition, several epidemiologic, clinical, and histologic variables were also assessed for prognostic significance. A CAF-positive stroma was identified in 35 of 47 SCCs (74.5%), and the median survival time (ST) of cats with CAF-positive SCCs (35 days) was significantly shorter than that of cats with CAF-negative SCCs (48.5 days) (P = .031). ST was also associated with the location of the primary tumor (P = .0018): the median ST for oropharyngeal SCCs (179 days) was significantly longer than for maxillary (43.5 days; P = .047), mandibular (42 days; P = .022), and sublingual SCCs (22.5 days; P = .0005). The median ST of sublingual SCCs was also shorter compared with maxillary SCCs (P = .0017). Furthermore, a significant association was identified between site and the presence of stromal CAFs (P = .025). On the basis of this retrospective study, evaluating the tumor stroma for CAFs in feline oral SCC biopsy specimens may be of potential prognostic value. © The Author(s) 2016.

Spindle assembly checkpoint protein expression correlates with cellular proliferation and shorter time to recurrence in ovarian cancer.

LENUS (Irish Health Repository)

McGrogan, Barbara

2014-07-01

Ovarian carcinoma (OC) is the most lethal of the gynecological malignancies, often presenting at an advanced stage. Treatment is hampered by high levels of drug resistance. The taxanes are microtubule stabilizing agents, used as first-line agents in the treatment of OC that exert their apoptotic effects through the spindle assembly checkpoint. BUB1-related protein kinase (BUBR1) and mitotic arrest deficient 2 (MAD2), essential spindle assembly checkpoint components, play a key role in response to taxanes. BUBR1, MAD2, and Ki-67 were assessed on an OC tissue microarray platform representing 72 OC tumors of varying histologic subtypes. Sixty-one of these patients received paclitaxel and platinum agents combined; 11 received platinum alone. Overall survival was available for all 72 patients, whereas recurrence-free survival (RFS) was available for 66 patients. Increased BUBR1 expression was seen in serous carcinomas, compared with other histologies (P = .03). Increased BUBR1 was significantly associated with tumors of advanced stage (P = .05). Increased MAD2 and BUBR1 expression also correlated with increased cellular proliferation (P < .0002 and P = .02, respectively). Reduced MAD2 nuclear intensity was associated with a shorter RFS (P = .03), in ovarian tumors of differing histologic subtype (n = 66). In this subgroup, for those women who received paclitaxel and platinum agents combined (n = 57), reduced MAD2 intensity also identified women with a shorter RFS (P < .007). For the entire cohort of patients, irrespective of histologic subtype or treatment, MAD2 nuclear intensity retained independent significance in a multivariate model, with tumors showing reduced nuclear MAD2 intensity identifying patients with a poorer RFS (P = .05).

Pre-treatment inflammatory indexes as predictors of survival and cetuximab efficacy in metastatic colorectal cancer patients with wild-type RAS.

Science.gov (United States)

Yang, Jing; Guo, Xinli; Wang, Manni; Ma, Xuelei; Ye, Xiaoyang; Lin, Panpan

2017-12-07

This study aims at evaluating the prognostic significance of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation indexes (SII) in metastatic colorectal cancer (mCRC) patients treated with cetuximab. Ninety-five patients receiving cetuximab for mCRC were categorized into the high or low NLR, PLR, LMR, and SII groups based on their median index values. Univariate and multivariate survival analysis were performed to identify the indexes' correlation with progression-free survival (PFS) and overall survival (OS). In the univariate analysis, ECOG performance status, neutrphil counts, lymphocyte counts, monocyte counts, NLR, PLR, and LDH were associated with survival. Multivariate analysis showed that ECOG performance status of 0 (hazard ratio [HR] 3.608, p < 0.001; HR 5.030, p < 0.001, respectively), high absolute neutrophil counts (HR 2.837, p < 0.001; HR 1.922, p = 0.026, respectively), low lymphocyte counts (HR 0.352, p < 0.001; HR 0.440, p = 0.001, respectively), elevated NLR (HR 3.837, p < 0.001; HR 2.467, p = 0.006) were independent predictors of shorter PFS and OS. In conclusion, pre-treatment inflammatory indexes, especially NLR were potential biomarkers to predict the survival of mCRC patients with cetuximab therapy.

Is there a progression-free survival benefit of first-line crizotinib versus standard chemotherapy and second-line crizotinib in ALK-positive advanced lung adenocarcinoma? A retrospective study of Chinese patients.

Science.gov (United States)

Cui, Shaohua; Zhao, Yizhuo; Dong, Lili; Gu, Aiqin; Xiong, Liwen; Qian, Jialin; Zhang, Wei; Niu, Yanjie; Pan, Feng; Jiang, Liyan

2016-06-01

Although crizotinib has demonstrated promising efficacy and acceptable toxicity in patients with advanced non-small cell lung cancer (NSCLC), the available evidence in Chinese populations is currently limited. This study compared the progression-free survival (PFS) of Chinese patients with anaplastic lymphoma kinase (ALK)-positive, advanced lung adenocarcinoma who received first-line crizotinib therapy with that of patients who received first-line standard chemotherapy, and also the PFS benefit of first-line versus second-line crizotinib treatment. Data on 80 patients with ALK-positive, advanced lung adenocarcinoma who received crizotinib or standard chemotherapy as first-line treatments between June 2013 and December 2014 were retrospectively collected; 26 of the patients received crizotinib as second-line therapy after progressive disease (PD) occurred on first-line chemotherapy. Tumor responses were assessed using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The median PFS was 13.3 months (95% CI: 6.5-20.0 months) in patients who received first-line crizotinib as compared with 5.4 months (95% CI: 4.4-6.5 months) in patients who received first-line standard chemotherapy (adjusted hazard ratio for progression or death with crizotinib, 0.20; 95% CI: 0.11-0.36; P benefit of first-line crizotinib versus first-line standard chemotherapy in Chinese patients with ALK-positive lung adenocarcinoma. Additionally, crizotinib showed promising efficacy in patients who received it as second-line therapy after PD had occurred on first-line chemotherapy. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Do Dysphagic Patients with an Absent Pharyngeal Swallow Have a Shorter Survival than Dysphagic Patients with Pharyngeal Swallow? Prognostic Importance of a Therapeutic Videoradiographic Swallowing Study (TVSS)

International Nuclear Information System (INIS)

Buelow, M.; Olsson, R.; Ekberg, O.

2005-01-01

Purpose: To study survival in two groups of dysphagic patients - one group unable to elicit the pharyngeal stage of swallow (APS) and another group with pharyngeal swallow (WPS) - and to compare recommendations regarding nutrition and therapeutic strategies based on the therapeutic swallowing study. Material and Methods: In this retrospective study, the records of dysphagic patients who have undergone a therapeutic videoradiographic swallowing study (TVSS) were reviewed. Forty patients without pharyngeal swallow were matched for age and gender with 40 patients with pharyngeal swallow; altogether 80 patients were included in the study. Survival was registered at 3, 12, and 72 months after the TVSS. Results: In this study, the APS group had a significantly shorter survival time compared to the WPS group when followed-up at 12 months. In the APS group, most patients (37.5% (15/40)) died within the 3 months after TVSS. At 72 months, 62.5% (25/40) of the patients in the APS group had died. In the WPS group, 5% (2/40) had died within 3 months and 47.4% (19/40) after 12 months. At 72 months, 52.5% (21/40) of the patients in the WPS group had died. Regarding nutritional and therapeutic recommendations based on TVSS, 34/40 in the APS group were recommended no oral intake. Eighteen naso-gastric tubes were placed directly after TVSS. The therapeutic strategies recommended were head-positioning, thermal tactile stimulation, and tongue exercises (in 8 patients). In the WPS group, all patients were recommended oral intake. Diet modification was recommended in 29 patients. The therapeutic strategies recommended were head-positioning, thermal tactile stimulation, tongue exercises, supraglottic swallow, and effortful swallow (in 24 patients). Conclusion: Patients unable to elicit the pharyngeal stage of swallow had a shorter survival time than patients with pharyngeal swallow, probably due to a more severe underlying disease. Tube feeding was more frequent in the APS group. Fewer

Higher dietary lycopene intake is associated with longer cardiac event-free survival in patients with heart failure.

Science.gov (United States)

Biddle, Martha; Moser, Debra; Song, Eun Kyeung; Heo, Seongkum; Payne-Emerson, Heather; Dunbar, Sandra B; Pressler, Susan; Lennie, Terry

2013-08-01

The antioxidant lycopene may be beneficial for patients with heart failure (HF). Processed tomato products are a major source of lycopene, although they are also high in sodium. Increased sodium intake may counter the positive antioxidant effect of lycopene. This was a prospective study of 212 patients with HF. Dietary intake of lycopene and sodium was obtained from weighted 4-day food diaries. Patients were grouped by the median split of lycopene of 2471 µg/day and stratified by daily sodium levels above and below 3 g/day. Patients were followed for 1 year to collect survival and hospitalization data. Cox proportional hazards modeling was used to compare cardiac event-free survival between lycopene groups within each stratum of sodium intake. Higher lycopene intake was associated with longer cardiac event-free survival compared with lower lycopene intake (p = 0.003). The worst cardiac event-free survival was observed in the low lycopene intake group regardless of sodium intake (> 3 g/day HR = 3.01; p = 0.027 and ≤ 3 g/day HR= 3.34; p = 0.023). These findings suggest that increased lycopene intake has the potential to improve cardiac event-free survival in patients with HF independent of sodium intake.

HIV-1 Disease Progression and Survival in an Adult Population in Zimbabwe

DEFF Research Database (Denmark)

Zinyama-Gutsire, Rutendo B L; Chasela, Charles; Kallestrup, Per

2015-01-01

HIV infection remains a major global health burden since its discovery in 1983. Sub-Saharan Africa is the region hardest hit by the HIV/AIDS pandemic where 63% of the 33 million infected people live. While there is marked person-to-person variability in susceptibility, progression, and survival...

Association of germline variation in CCNE1 and CDK2 with breast cancer risk, progression and survival among Chinese Han women.

Directory of Open Access Journals (Sweden)

Ji-Yuan Han

Full Text Available BACKGROUND: Somatic alterations of cyclin-dependent kinase 2 (CDK2-cyclin E complex have been shown to contribute to breast cancer (BC development and progression. This study aimed to explore the effects of single nucleotide polymorphisms (SNPs in CDK2 and CCNE1 (a gene encoding G1/S specific cyclin E1 protein, formerly called cyclin E on BC risk, progression and survival in a Chinese Han population. METHODOLOGY/PRINCIPAL FINDINGS: We herein genotyped 6 haplotype-tagging SNPs (htSNPs of CCNE1 and 2 htSNPs of CDK2 in 1207 BC cases and 1207 age-matched controls among Chinese Han women, and then reconstructed haplotype blocks according to our genotyping data and linkage disequilibrium status of these htSNPs. For CCNE1, the minor allele homozygotes of three htSNPs were associated with BC risk (rs3218035: adjusted odds ratio [aOR] = 3.35, 95% confidence interval [CI] = 1.69-6.67; rs3218038: aOR = 1.81, 95% CI = 1.22-2.70; rs3218042: aOR = 2.64, 95% CI = 1.31-5.34, and these three loci showed a dose-dependent manner in increasing BC risk (P(trend = 0.0001. Moreover, the 5-SNP haplotype CCGTC, which carried none of minor alleles of the 3 at-risk SNPs, was associated with a favorable event-free survival (hazard ratio [HR] = 0.53, 95% CI = 0.32-0.90. Stratified analysis suggested that the minor-allele homozygote carriers of rs3218038 had a worse event-free survival among patients with aggressive tumours (in tumour size>2 cm group: HR = 2.06, 95% CI = 1.06-3.99; in positive lymph node metastasis group: HR = 2.41, 95% CI = 1.15-5.03; in stage II-IV group: HR = 2.03, 95% CI = 1.09-3.79. For CDK2, no significant association was found. CONCLUSIONS/SIGNIFICANCE: This study indicates that genetic variants in CCNE1 may contribute to BC risk and survival in Chinese Han population. They may become molecular markers for individual evaluation of BC susceptibility and prognosis. Nevertheless, further validation studies are needed.

Biochemical disease-free survival following I-125 prostate implantation

International Nuclear Information System (INIS)

Beyer, David C.; Priestley, Joseph B.

1995-01-01

Purpose/Objective: To assess the five-year clinical and biochemical results of ultrasound-guided permanent I-125 brachytherapy in early prostate cancer. Biochemical disease-free survival (BDFS) is reported, using PSA follow-up and is compared to the surgical and radiation therapy literature. Materials and Methods: From 12/88 through 12/93, ultrasound-guided brachytherapy was preplanned with I-125 and delivered 16,000 cGy as the sole treatment in 499 patients. All were clinically staged as T1 or T2 - N0M0 adenocarcinoma of the prostate. Within the first year, 19 patients were lost to follow-up and have been excluded from further study. The remaining 480 patients form the basis of this report. Clinical status and PSA values were systematically recorded before and after treatment. Results: With a median follow-up of 35 months (3-70) the actuarial clinical local control is 83%. Both stage and grade are shown to predict for this endpoint. Actuarial BDFS is also correlated with stage, grade, and PSA at presentation. Biochemical disease-free survival at five years is 94% for T1, 70% for unilateral T2, and 34% for T2c tumors. Grade is also predictive, ranging from 85% in low-grade tumors to 30% in high-grade tumors. In a multivariate analysis, the pretreatment PSA is most highly correlated (p 10 had a BDFS of 40%. Complications have been few, with severe urinary urgency or dysuria in 4% and both incontinence and proctitis seen in 1%. Conclusion: While biochemical disease-free survival reports in the literature are immature and have short follow-up, our data compares favorably with studies following radical prostatectomy or radiation therapy. Further follow-up of this cohort is required. The complication rate is low and patient acceptance excellent. Permanent implantation of I-125 as the sole treatment for early prostate cancer is a viable alternative for patients with early stage and low- to moderate-grade cancers. The PSA provides significant prognostic information and

Biochemical disease-free survival following I-125 prostate implantation

Energy Technology Data Exchange (ETDEWEB)

Beyer, David C; Priestley, Joseph B

1995-07-01

Purpose/Objective: To assess the five-year clinical and biochemical results of ultrasound-guided permanent I-125 brachytherapy in early prostate cancer. Biochemical disease-free survival (BDFS) is reported, using PSA follow-up and is compared to the surgical and radiation therapy literature. Materials and Methods: From 12/88 through 12/93, ultrasound-guided brachytherapy was preplanned with I-125 and delivered 16,000 cGy as the sole treatment in 499 patients. All were clinically staged as T1 or T2 - N0M0 adenocarcinoma of the prostate. Within the first year, 19 patients were lost to follow-up and have been excluded from further study. The remaining 480 patients form the basis of this report. Clinical status and PSA values were systematically recorded before and after treatment. Results: With a median follow-up of 35 months (3-70) the actuarial clinical local control is 83%. Both stage and grade are shown to predict for this endpoint. Actuarial BDFS is also correlated with stage, grade, and PSA at presentation. Biochemical disease-free survival at five years is 94% for T1, 70% for unilateral T2, and 34% for T2c tumors. Grade is also predictive, ranging from 85% in low-grade tumors to 30% in high-grade tumors. In a multivariate analysis, the pretreatment PSA is most highly correlated (p < 0.0001). Patients with a normal pretreatment PSA enjoyed 93% BDFS, while those presenting with PSA > 10 had a BDFS of 40%. Complications have been few, with severe urinary urgency or dysuria in 4% and both incontinence and proctitis seen in 1%. Conclusion: While biochemical disease-free survival reports in the literature are immature and have short follow-up, our data compares favorably with studies following radical prostatectomy or radiation therapy. Further follow-up of this cohort is required. The complication rate is low and patient acceptance excellent. Permanent implantation of I-125 as the sole treatment for early prostate cancer is a viable alternative for patients with

Isopropanolic black cohosh extract and recurrence-free survival after breast cancer.

Science.gov (United States)

Henneicke-von Zepelin, H H; Meden, H; Kostev, K; Schröder-Bernhardi, D; Stammwitz, U; Becher, H

2007-03-01

To investigate the influence of an isopropanolic Cimicifuga racemosa extract (iCR) on recurrence-free survival after breast cancer, including estrogen-dependent tumors. This pharmacoepidemiologic observational retrospective cohort study examined breast cancer patients treated at general, gynecological and internal facilities linked to a medical database in Germany. The main endpoint was disease-free survival following a diagnosis of breast cancer. The impact of treatment with iCR following diagnosis was analyzed by Cox-proportional hazards models, controlling for age and other confounders. Of 18,861 patients, a total of 1,102 had received an iCR therapy. The mean overall observation time was 3.6 years. Results showed that iCR was not associated with an increase in the risk of recurrence but associated with prolonged disease-free survival. After 2 years following initial diagnosis, 14% of the control group had developed a recurrence, while the iCR group reached this proportion after 6.5 years. The primary Cox regression model controlling for age, tamoxifen use and other confounders demonstrated a protractive effect of iCR on the rate of recurrence (hazard ratio 0.83, 95% confidence interval 0.69 0.99). This effect remained consistent throughout all variations of the statistical model, including subgroup analyses. TNM status was unknown but did not bias the iCR treatment decision as investigated separately. Hence, it was assumed to be equally distributed between treatment groups. Correlation analyses showed good internal and external validity of the database. An increase in the risk of breast cancer recurrence for women having had iCR treatment, compared to women not treated with iCR is unlikely.

Amputation-Free Survival after Crural Percutaneous Transluminal Angioplasty for Critical Limb Ischemia

DEFF Research Database (Denmark)

Strøm, M; Konge, L; Lönn, L

2016-01-01

BACKGROUND AND AIM: To evaluate the amputation-free survival after below the knee percutaneous transluminal angioplasty in a consecutive group of patients with critical ischemia of the lower extremity. MATERIALS AND METHODS: A total of 70 consecutive patients with critical ischemia were treated......-up clinical examinations were performed within 6 weeks and after 1 year. All medical records were crosschecked with the national vascular registry ensuring a valid 1-year status in 97% of the patients. RESULTS: A total of 15 major amputations were performed during follow-up, with 11 amputations performed...... within the first year. Complications after percutaneous transluminal angioplasty were rare. Cumulative mortality after 1 and 2 years was 22% and 34%, respectively. Amputation-free survival at 1 and 2 years of follow-up was 68% and 58%, respectively. There were no association between known risk factors...

Split-Course, High-Dose Palliative Pelvic Radiotherapy for Locally Progressive Hormone-Refractory Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Gogna, Nirdosh Kumar, E-mail: kumar_gogna@health.qld.gov.au [Radiation Oncology Services, Mater Centre, Brisbane, Queensland (Australia); Baxi, Siddhartha; Hickey, Brigid; Baumann, Kathryn [Radiation Oncology Services, Mater Centre, Brisbane, Queensland (Australia); Burmeister, Elizabeth [Princess Alexandra Hospital, Brisbane, Queensland (Australia); Holt, Tanya [Radiation Oncology Services, Mater Centre, Brisbane, Queensland (Australia)

2012-06-01

Purpose: Local progression, in patients with hormone-refractory prostate cancer, often causes significant morbidity. Pelvic radiotherapy (RT) provides effective palliation in this setting, with most published studies supporting the use of high-dose regimens. The aim of the present study was to examine the role of split-course hypofractionated RT used at our institution in treating this group of patients. Methods and Materials: A total of 34 men with locoregionally progressive hormone-refractory prostate cancer, treated with a split course of pelvic RT (45-60 Gy in 18-24 fractions) between 2000 and 2008 were analyzed. The primary endpoints were the response rate and actuarial locoregional progression-free survival. Secondary endpoints included overall survival, compliance, and acute and late toxicity. Results: The median age was 71 years (range, 53-88). Treatment resulted in an overall initial response rate of 91%, a median locoregional progression-free survival of 43 months, and median overall survival of 28 months. Compliance was excellent and no significant late toxicity was reported. Conclusions: The split course pelvic RT described has an acceptable toxicity profile, is effective, and compares well with other high-dose palliative regimens that have been previously reported.

Quantifying discrimination of Framingham risk functions with different survival C statistics.

Science.gov (United States)

Pencina, Michael J; D'Agostino, Ralph B; Song, Linye

2012-07-10

Cardiovascular risk prediction functions offer an important diagnostic tool for clinicians and patients themselves. They are usually constructed with the use of parametric or semi-parametric survival regression models. It is essential to be able to evaluate the performance of these models, preferably with summaries that offer natural and intuitive interpretations. The concept of discrimination, popular in the logistic regression context, has been extended to survival analysis. However, the extension is not unique. In this paper, we define discrimination in survival analysis as the model's ability to separate those with longer event-free survival from those with shorter event-free survival within some time horizon of interest. This definition remains consistent with that used in logistic regression, in the sense that it assesses how well the model-based predictions match the observed data. Practical and conceptual examples and numerical simulations are employed to examine four C statistics proposed in the literature to evaluate the performance of survival models. We observe that they differ in the numerical values and aspects of discrimination that they capture. We conclude that the index proposed by Harrell is the most appropriate to capture discrimination described by the above definition. We suggest researchers report which C statistic they are using, provide a rationale for their selection, and be aware that comparing different indices across studies may not be meaningful. Copyright © 2012 John Wiley & Sons, Ltd.

Progress towards a Drag-free SmallSat

Science.gov (United States)

Saraf, Shailendhar

The net force acting on a drag-free satellite is purely gravitational as all other forces, mainly atmospheric drag and solar radiation pressure, are canceled out. In order to achieve this, a free floating reference (test mass) inside the satellite is shielded against all forces but gravity and a system of thrusters is commanded by a control algorithm such that the relative displacement between the reference and the satellite stays constant. The main input to that control algorithm is the output of a sensor which measures the relative displacement between the satellite and the test mass. Internal disturbance forces such as electrostatic or magnetic forces cannot be canceled out his way and have to be minimized by a careful design of the satellite. A drag-free technology package is under development at Stanford since 2004. It includes an optical displacement sensor to measure the relative position of the test mass inside the satellite, a caging mechanism to lock the test mass during launch, a UV LED based charge management system to minimize the effect of electrostatic forces, a thermal enclosure, and the drag-free control algorithms. Possible applications of drag-free satellites in fundamental physics (Gravity Probe B, LISA), geodesy (GOCE), and navigation (TRIAD I). In this presentation we will highlight the progress of the technology development towards a drag-free mission. The planned mission on a SaudiSat bus will demonstrate drag-free technology on a small spacecraft at a fraction of the cost of previous drag-free missions. The target acceleration noise is 10-12 m/sec2. With multiple such satellites a GRACE-like mission with improved sensitivity and potentially improved spatial and temporal resolution can be achieved.

IMPACT OF PRE-TRANSPLANT RITUXIMAB ON SURVIVAL AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR DIFFUSE LARGE B-CELL LYMPHOMA

Science.gov (United States)

Fenske, Timothy S.; Hari, Parameswaran N.; Carreras, Jeanette; Zhang, Mei-Jie; Kamble, Rammurti T.; Bolwell, Brian J.; Cairo, Mitchell S.; Champlin, Richard E.; Chen, Yi-Bin; Freytes, César O.; Gale, Robert Peter; Hale, Gregory A.; Ilhan, Osman; Khoury, H. Jean; Lister, John; Maharaj, Dipnarine; Marks, David I.; Munker, Reinhold; Pecora, Andrew L.; Rowlings, Philip A.; Shea, Thomas C.; Stiff, Patrick; Wiernik, Peter H.; Winter, Jane N.; Rizzo, J. Douglas; van Besien, Koen; Lazarus, Hillard M.; Vose, Julie M.

2010-01-01

Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens for diffuse large B-cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, many patients develop refractory or recurrent DLBCL and then receive autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes following AuHCT. Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n=176, “+R” group) or was not (n=818, “ −R” group) administered with front-line or salvage therapy prior to AuHCT. The +R group had superior progression-free survival (50% versus 38%, p=0.008) and overall survival (57% versus 45%, p=0.006) at 3 years. Platelet and neutrophil engraftment were not affected by exposure to rituximab. Non-relapse mortality (NRM) did not differ significantly between the +R and −R groups. In multivariate analysis, the +R group had improved progression-free survival (relative risk of relapse/progression or death 0.64, p<0.001) and improved overall survival (relative risk of death of 0.74, p=0.039). We conclude that pre-transplant rituximab is associated with a lower rate of progression and improved survival following AuHCT for DLBCL, with no evidence of impaired engraftment or increased NRM. PMID:19822306

Low MAD2 expression levels associate with reduced progression-free survival in patients with high-grade serous epithelial ovarian cancer.

LENUS (Irish Health Repository)

Furlong, Fiona

2012-04-01

Epithelial ovarian cancer (EOC) has an innate susceptibility to become chemoresistant. Up to 30% of patients do not respond to conventional chemotherapy [paclitaxel (Taxol®) in combination with carboplatin] and, of those who have an initial response, many patients relapse. Therefore, an understanding of the molecular mechanisms that regulate cellular chemotherapeutic responses in EOC cells has the potential to impact significantly on patient outcome. The mitotic arrest deficiency protein 2 (MAD2), is a centrally important mediator of the cellular response to paclitaxel. MAD2 immunohistochemical analysis was performed on 82 high-grade serous EOC samples. A multivariate Cox regression analysis of nuclear MAD2 IHC intensity adjusting for stage, tumour grade and optimum surgical debulking revealed that low MAD2 IHC staining intensity was significantly associated with reduced progression-free survival (PFS) (p = 0.0003), with a hazard ratio of 4.689. The in vitro analyses of five ovarian cancer cell lines demonstrated that cells with low MAD2 expression were less sensitive to paclitaxel. Furthermore, paclitaxel-induced activation of the spindle assembly checkpoint (SAC) and apoptotic cell death was abrogated in cells transfected with MAD2 siRNA. In silico analysis identified a miR-433 binding domain in the MAD2 3\\' UTR, which was verified in a series of experiments. Firstly, MAD2 protein expression levels were down-regulated in pre-miR-433 transfected A2780 cells. Secondly, pre-miR-433 suppressed the activity of a reporter construct containing the 3\\'-UTR of MAD2. Thirdly, blocking miR-433 binding to the MAD2 3\\' UTR protected MAD2 from miR-433 induced protein down-regulation. Importantly, reduced MAD2 protein expression in pre-miR-433-transfected A2780 cells rendered these cells less sensitive to paclitaxel. In conclusion, loss of MAD2 protein expression results in increased resistance to paclitaxel in EOC cells. Measuring MAD2 IHC staining intensity may predict

Plasma Vascular Endothelial Growth Factor Concentration and Alveolar Nitric Oxide as Potential Predictors of Disease Progression and Mortality in Idiopathic Pulmonary Fibrosis

Directory of Open Access Journals (Sweden)

Jalpa Kotecha

2016-09-01

Full Text Available Background: Declining lung function signifies disease progression in idiopathic pulmonary fibrosis (IPF. Vascular endothelial growth factor (VEGF concentration is associated with declining lung function in 6 and 12-month studies. Alveolar nitric oxide concentration (CANO is increased in patients with IPF, however its significance is unclear. This study investigated whether baseline plasma VEGF concentration and CANO are associated with disease progression or mortality in IPF. Methods: 27 IPF patients were studied (maximum follow-up 65 months. Baseline plasma VEGF concentration, CANO and pulmonary function tests (PFTs were measured. PFTs were performed the preceding year and subsequent PFTs and data regarding mortality were collected. Disease progression was defined as one of: death, relative decrease of ≥10% in baseline forced vital capacity (FVC % predicted, or relative decrease of ≥15% in baseline single breath diffusion capacity of carbon monoxide (TLCO-SB % predicted. Results: Plasma VEGF concentration was not associated with progression-free survival or mortality. There was a trend towards shorter time to disease progression and death with higher CANO. CANO was significantly higher in patients with previous declining versus stable lung function. Conclusion: The role of VEGF in IPF remains uncertain. It may be of value to further investigate CANO in IPF.

Efficacy of bendamustine and rituximab as first salvage treatment in chronic lymphocytic leukemia and indirect comparison with ibrutinib: a GIMEMA, ERIC and UK CLL FORUM study.

Science.gov (United States)

Cuneo, Antonio; Follows, George; Rigolin, Gian Matteo; Piciocchi, Alfonso; Tedeschi, Alessandra; Trentin, Livio; Medina Perez, Angeles; Coscia, Marta; Laurenti, Luca; Musuraca, Gerardo; Farina, Lucia; Rivas Delgado, Alfredo; Orlandi, Ester Maria; Galieni, Piero; Mauro, Francesca Romana; Visco, Carlo; Amendola, Angela; Billio, Atto; Marasca, Roberto; Chiarenza, Annalisa; Meneghini, Vittorio; Ilariucci, Fiorella; Marchetti, Monia; Molica, Stefano; Re, Francesca; Gaidano, Gianluca; Gonzalez, Marcos; Forconi, Francesco; Ciolli, Stefania; Cortelezzi, Agostino; Montillo, Marco; Smolej, Lukas; Schuh, Anna; Eyre, Toby A; Kennedy, Ben; Bowles, Kris M; Vignetti, Marco; de la Serna, Javier; Moreno, Carol; Foà, Robin; Ghia, Paolo

2018-04-19

We performed an observational study on the efficacy of bendamustine and rituximab as first salvage regimen in chronic lymphocytic leukemia. In an intention-to-treat analysis including 237 patients, the median progression free survival was 25 months. The presence of del(17p), unmutated IGHV and advanced stage were associated with a shorter progression free survival at multivariate analysis. The median time-to-next treatment was 31.3 months. Front-line treatment with a chemoimmunotherapy regimen was the only predictive factor for a shorter time to next treatment at multivariate analysis. The median overall survival was 74.5 months. Advanced Binet stage (i.e. III-IV or C) and resistant disease were the only parameters significantly associated with a shorter OS. Grade 3-5 infections were recorded in 6.3% of patients. A matched-adjusted indirect comparison with ibrutinib given second-line within named patient programs in the United Kingdom and in Italy was carried out with overall survival as objective endpoint. When restricting the analysis to patients with intact 17p who had received chemoimmunotherapy in first line, the overall survival did not differ between patients treated with ibrutinib (63% alive at 36 months) and patients treated with BR (74.4% alive at 36 months). BR is an efficacious first salvage regimen in chronic lymphocytic leukemia in a real-life population, including the elderly and unfit patients. BR and ibrutinib may be equally effective in terms of overall survival when used as first salvage treatment in patients without 17p deletion. ClinicalTrials.gov identifier: NCT02491398. Copyright © 2018, Ferrata Storti Foundation.

Tumor Response and Survival Predicted by Post-Therapy FDG-PET/CT in Anal Cancer

International Nuclear Information System (INIS)

Schwarz, Julie K.; Siegel, Barry A.; Dehdashti, Farrokh; Myerson, Robert J.; Fleshman, James W.; Grigsby, Perry W.

2008-01-01

Purpose: To evaluate the response to therapy for anal carcinoma using post-therapy imaging with positron emission tomography (PET)/computed tomography and F-18 fluorodeoxyglucose (FDG) and to compare the metabolic response with patient outcome. Patients and Methods: This was a prospective cohort study of 53 consecutive patients with anal cancer. All patients underwent pre- and post-treatment whole-body FDG-PET/computed tomography. Patients had been treated with external beam radiotherapy and concurrent chemotherapy. Whole-body FDG-PET was performed 0.9-5.4 months (mean, 2.1) after therapy completion. Results: The post-therapy PET scan did not show any abnormal FDG uptake (complete metabolic response) in 44 patients. Persistent abnormal FDG uptake (partial metabolic response) was found in the anal tumor in 9 patients. The 2-year cause-specific survival rate was 94% for patients with a complete vs. 39% for patients with a partial metabolic response in the anal tumor (p = 0.0008). The 2-year progression-free survival rate was 95% for patients with a complete vs. 22% for patients with a partial metabolic response in the anal tumor (p < 0.0001). A Cox proportional hazards model of survival outcome indicated that a complete metabolic response was the most significant predictor of progression-free survival in our patient population (p = 0.0003). Conclusions: A partial metabolic response in the anal tumor as determined by post-therapy FDG-PET is predictive of significantly decreased progression-free and cause-specific survival after chemoradiotherapy for anal cancer

Double-hit lymphomas constitute a highly aggressive subgroup in diffuse large B-cell lymphomas in the era of rituximab.

Science.gov (United States)

Kobayashi, Tsutomu; Tsutsumi, Yasuhiko; Sakamoto, Natsumi; Nagoshi, Hisao; Yamamoto-Sugitani, Mio; Shimura, Yuji; Mizutani, Shinsuke; Matsumoto, Yosuke; Nishida, Kazuhiro; Horiike, Shigeo; Asano, Naoko; Nakamura, Shigeo; Kuroda, Junya; Taniwaki, Masafumi

2012-11-01

The incorporation of rituximab in immunochemotherapy has improved treatment outcomes for diffuse large B-cell lymphoma, but the prognosis for some diffuse large B-cell lymphomas remains dismal. Identification of adverse prognostic subgroups is essential for the choice of appropriate therapeutic strategy. We retrospectively investigated the impact of so-called 'double-hit' cytogenetic abnormalities, i.e. cytogenetic abnormalities involving c-MYC co-existing with other poor prognostic cytogenetic abnormalities involving BCL2, BCL6 or BACH2, on treatment outcomes for 93 consecutive diffuse large B-cell lymphoma patients. According to the revised international prognostic index, no patients were cytogenetically diagnosed with double-hit lymphomas in the 'very good' risk group or in the 'good' risk group, while 5 of 33 patients had double-hit lymphomas in the 'poor' risk group. All the double-hit lymphoma patients possessed both nodal and extranodal involvement. The overall complete response rate was 89.3%, overall survival 87.1% and progression-free survival 75.8% over 2 years (median observation period: 644 days). The complete response rates were 93.2% for the non-double-hit lymphoma patients and 40.0% for the double-hit lymphoma patients. Significantly longer progression-free survival and overall survival were observed for the 'very good' and the 'good' risk patients than for the 'poor' risk patients. Moreover, the progression-free survival of double-hit lymphoma was significantly shorter than that of the non-double-hit lymphoma 'poor' risk patients (P = 0.016). In addition, the overall survival of the double-hit lymphoma patients also tended to be shorter than that of the non-double-hit lymphoma 'poor' risk group. The diagnosis of double-hit lymphoma can help discriminate a subgroup of highly aggressive diffuse large B-cell lymphomas and indicate the need for the development of novel therapeutic strategies for double-hit lymphoma.

Joint modelling of longitudinal CEA tumour marker progression and survival data on breast cancer

Science.gov (United States)

Borges, Ana; Sousa, Inês; Castro, Luis

2017-06-01

This work proposes the use of Biostatistics methods to study breast cancer in patients of Braga's Hospital Senology Unit, located in Portugal. The primary motivation is to contribute to the understanding of the progression of breast cancer, within the Portuguese population, using a more complex statistical model assumptions than the traditional analysis that take into account a possible existence of a serial correlation structure within a same subject observations. We aim to infer which risk factors aect the survival of Braga's Hospital patients, diagnosed with breast tumour. Whilst analysing risk factors that aect a tumour markers used on the surveillance of disease progression the Carcinoembryonic antigen (CEA). As survival and longitudinal processes may be associated, it is important to model these two processes together. Hence, a joint modelling of these two processes to infer on the association of these was conducted. A data set of 540 patients, along with 50 variables, was collected from medical records of the Hospital. A joint model approach was used to analyse these data. Two dierent joint models were applied to the same data set, with dierent parameterizations which give dierent interpretations to model parameters. These were used by convenience as the ones implemented in R software. Results from the two models were compared. Results from joint models, showed that the longitudinal CEA values were signicantly associated with the survival probability of these patients. A comparison between parameter estimates obtained in this analysis and previous independent survival[4] and longitudinal analysis[5][6], lead us to conclude that independent analysis brings up bias parameter estimates. Hence, an assumption of association between the two processes in a joint model of breast cancer data is necessary. Results indicate that the longitudinal progression of CEA is signicantly associated with the probability of survival of these patients. Hence, an assumption of

Alternative promoter usage generates novel shorter MAPT mRNA transcripts in Alzheimer's disease and progressive supranuclear palsy brains.

Science.gov (United States)

Huin, Vincent; Buée, Luc; Behal, Hélène; Labreuche, Julien; Sablonnière, Bernard; Dhaenens, Claire-Marie

2017-10-03

Alternative promoter usage is an important mechanism for transcriptome diversity and the regulation of gene expression. Indeed, this alternative usage may influence tissue/subcellular specificity, protein translation and function of the proteins. The existence of an alternative promoter for MAPT gene was considered for a long time to explain differential tissue specificity and differential response to transcription and growth factors between mRNA transcripts. The alternative promoter usage could explain partly the different tau proteins expression patterns observed in tauopathies. Here, we report on our discovery of a functional alternative promoter for MAPT, located upstream of the gene's second exon (exon 1). By analyzing genome databases and brain tissue from control individuals and patients with Alzheimer's disease or progressive supranuclear palsy, we identified novel shorter transcripts derived from this alternative promoter. These transcripts are increased in patients' brain tissue as assessed by 5'RACE-PCR and qPCR. We suggest that these new MAPT isoforms can be translated into normal or amino-terminal-truncated tau proteins. We further suggest that activation of MAPT's alternative promoter under pathological conditions leads to the production of truncated proteins, changes in protein localization and function, and thus neurodegeneration.

Clinicopathologic Features and Survival of Breast Cancer Subtypes in Northeast Iran

Directory of Open Access Journals (Sweden)

Soodabeh Shahidsales

2018-01-01

Full Text Available Background: Breast cancer can be categorized into different histopathological subtypes based on gene expression profiles. This study aims to evaluate the clinicopathological features and overall survival of various subtypes of breast cancer to assist diagnosis and guide treatment. Methods: The clinicopathologic features of 1095 patients with breast cancer diagnosed over a 10–year period between 2001 and 2011 were analyzed. The Kaplan–Meier method was used to analyze disease-free survival and overall survival. Calculation of the hazard ratio was conducted by multivariate Cox regression. Results: According to the clinicopathologic characteristics of 1095 cases, there were 42% luminal A subtype, 19.2% luminal B, 23% triple negative, and 15% HER2+. The lowest (46.88±12.59 years and highest (50.54±12.32 years mean ages were in the triple negative and HER2+ groups, respectively. There was a significant correlation between histology subtype and age, BMI, lymph node, type of surgery, and stage of disease. There was significantly shorter overall survival and disease free survival in HER2+ breast cancer patients (P<0.001. Multivariate analysis showed that age had the highest hazard ratio of 2.481 (95% Confidence Interval: 1.375-4.477. Conclusion: The results of this study showed the importance of clinicopathological studies of molecular types which help early diagnosis and identification of the best strategy to treat breast cancer.

Podoplanin Expression Correlates with Disease Progression in Mycosis Fungoides.

Science.gov (United States)

Jankowska-Konsur, Alina; Kobierzycki, Christopher; Grzegrzółka, Jędrzej; Piotrowska, Aleksandra; Gomulkiewicz, Agnieszka; Glatzel-Plucinska, Natalia; Reich, Adam; Podhorska-Okołów, Marzenna; Dzięgiel, Piotr; Szepietowski, Jacek C

2017-02-08

The aim of this study was to investigate the role of lymphangiogenesis in the clinical progression and outcome of mycosis fungoides. Immunohistochemistry and Western blot techniques were used to assess the expression of podoplanin and vascular endothelial growth factor C in mycosis fungoides. Expression of vascular endothelial growth factor C measured by immunohistochemistry was significantly higher in mycosis fungoides samples in comparison with control cases (chronic benign dermatoses) (p = 0.0012). Increased expression of podoplanin was found in advanced vs. early mycosis fungoides (p < 0.0001), and was positively correlated with cutaneous and nodal involvement (p < 0.001, p < 0.0001; respectively). Higher podoplanin expression was also significantly associated with shorter survival (p < 0.001). Strong positive correlation was observed between expression of podoplanin analysed by immunohistochemistry and Western blot (r = 0.75, p < 0.0001). A similar association was shown regarding expression of vascular endothelial growth factor C (r = 0.68, p = 0.0007). In conclusion, these results suggest that increased expression of podoplanin is associated with poor clinical course, as well as shorter survival, of patients with mycosis fungoides.

Association between obesity with disease-free survival and overall survival in triple-negative breast cancer: A meta-analysis.

Science.gov (United States)

Mei, Lin; He, Lin; Song, Yuhua; Lv, Yang; Zhang, Lijiu; Hao, Fengxi; Xu, Mengmeng

2018-05-01

To investigate the relationship between obesity and disease-free survival (DFS) and overall survival (OS) of triple-negative breast cancer. Citations were searched in PubMed, Cochrane Library, and Web of Science. Random effect model meta-analysis was conducted by using Revman software version 5.0, and publication bias was evaluated by creating Egger regression with STATA software version 12. Nine studies (4412 patients) were included for DFS meta-analysis, 8 studies (4392 patients) include for OS meta-analysis. There were no statistical significances between obesity with DFS (P = .60) and OS (P = .71) in triple-negative breast cancer (TNBC) patients. Obesity has no impact on DFS and OS in patients with TNBC.

Disease-free survival after hepatic resection in hepatocellular carcinoma patients: a prediction approach using artificial neural network.

Directory of Open Access Journals (Sweden)

Wen-Hsien Ho

Full Text Available BACKGROUND: A database for hepatocellular carcinoma (HCC patients who had received hepatic resection was used to develop prediction models for 1-, 3- and 5-year disease-free survival based on a set of clinical parameters for this patient group. METHODS: The three prediction models included an artificial neural network (ANN model, a logistic regression (LR model, and a decision tree (DT model. Data for 427, 354 and 297 HCC patients with histories of 1-, 3- and 5-year disease-free survival after hepatic resection, respectively, were extracted from the HCC patient database. From each of the three groups, 80% of the cases (342, 283 and 238 cases of 1-, 3- and 5-year disease-free survival, respectively were selected to provide training data for the prediction models. The remaining 20% of cases in each group (85, 71 and 59 cases in the three respective groups were assigned to validation groups for performance comparisons of the three models. Area under receiver operating characteristics curve (AUROC was used as the performance index for evaluating the three models. CONCLUSIONS: The ANN model outperformed the LR and DT models in terms of prediction accuracy. This study demonstrated the feasibility of using ANNs in medical decision support systems for predicting disease-free survival based on clinical databases in HCC patients who have received hepatic resection.

Disease-Free Survival after Hepatic Resection in Hepatocellular Carcinoma Patients: A Prediction Approach Using Artificial Neural Network

Science.gov (United States)

Ho, Wen-Hsien; Lee, King-Teh; Chen, Hong-Yaw; Ho, Te-Wei; Chiu, Herng-Chia

2012-01-01

Background A database for hepatocellular carcinoma (HCC) patients who had received hepatic resection was used to develop prediction models for 1-, 3- and 5-year disease-free survival based on a set of clinical parameters for this patient group. Methods The three prediction models included an artificial neural network (ANN) model, a logistic regression (LR) model, and a decision tree (DT) model. Data for 427, 354 and 297 HCC patients with histories of 1-, 3- and 5-year disease-free survival after hepatic resection, respectively, were extracted from the HCC patient database. From each of the three groups, 80% of the cases (342, 283 and 238 cases of 1-, 3- and 5-year disease-free survival, respectively) were selected to provide training data for the prediction models. The remaining 20% of cases in each group (85, 71 and 59 cases in the three respective groups) were assigned to validation groups for performance comparisons of the three models. Area under receiver operating characteristics curve (AUROC) was used as the performance index for evaluating the three models. Conclusions The ANN model outperformed the LR and DT models in terms of prediction accuracy. This study demonstrated the feasibility of using ANNs in medical decision support systems for predicting disease-free survival based on clinical databases in HCC patients who have received hepatic resection. PMID:22235270

Predictors for long-term survival free from whole brain radiation therapy in patients treated with radiosurgery for limited brain metastases

Directory of Open Access Journals (Sweden)

Daniel eGorovets

2015-05-01

Full Text Available Purpose: To identify predictors for prolonged survival free from salvage whole brain radiation therapy (WBRT in patients with brain metastases treated with stereotactic radiosurgery (SRS as their initial radiotherapy approach. Material and Methods: Patients with brain metastases treated with SRS from 2001-2013 at our institution were identified. SRS without WBRT was typically offered to patients with 1-4 brain metastases, Karnofsky Performance Status ≥70, and life expectancy ≥3 mo. Three hundred and eight patients met inclusion criteria for analysis. Medical records were reviewed for patient, disease, and treatment information. Two comparison groups were identified: those with ≥1-yr WBRT-free survival (N=104, and those who died or required salvage WBRT within 3 mo of SRS (N=56. Differences between these groups were assessed by univariate and multivariate analyses.Results: Median survival for all patients was 11 mo. Among patients with ≥1-yr WBRT-free survival, median survival was 33 mo [12-107 mo] with only 21% requiring salvage WBRT. Factors significantly associated with prolonged WBRT-free survival on univariate analysis (p<0.05 included younger age, asymptomatic presentation, RTOG RPA class I, fewer brain metastases, surgical resection, breast primary, new or controlled primary, absence of extracranial metastatic disease, and oligometastatic disease burden (≤5 metastatic lesions. After controlling for covariates, asymptomatic presentation, breast primary, single brain metastasis, absence of extracranial metastases, and oligometastatic disease burden remained independent predictors for favorable WBRT-free survival.Conclusions: A subset of patients with brain metastases can achieve long-term survival after upfront SRS without the need for salvage WBRT. Predictors identified in this study can help select patients that might benefit most from a treatment strategy of SRS alone.

Disease-free survival after complete mesocolic excision compared with conventional colon cancer surgery

DEFF Research Database (Denmark)

Bertelsen, Claus Anders; Neuenschwander, Anders Ulrich; Jansen, Jens Erik

2015-01-01

BACKGROUND: Application of the principles of total mesorectal excision to colon cancer by undertaking complete mesocolic excision (CME) has been proposed to improve oncological outcomes. We aimed to investigate whether implementation of CME improved disease-free survival compared with conventional...... consisted of patients who underwent CME surgery in a centre validated to perform such surgery; the control group consisted of patients undergoing conventional colon resection in three other hospitals. Data were collected from the Danish Colorectal Cancer Group (DCCG) database and medical charts. Patients...... updated by the National Central Office of Civil Registration. FINDINGS: The CME group consisted of 364 patients and the non-CME group consisted of 1031 patients. For all patients, 4-year disease-free survival was 85.8% (95% CI 81.4-90.1) after CME and 75.9% (72.2-79.7) after non-CME surgery (log-rank p=0...

Free ammonia offers algal crop protection from predators in dairy wastewater and ammonium-rich media.

Science.gov (United States)

Thomas, Patrick K; Dunn, Gary P; Passero, Maxine; Feris, Kevin P

2017-11-01

Cost-effective methods for protecting crops from grazing organisms like rotifers are needed to reduce the risk of pond crashes in mass algal cultures. We present a novel strategy to optimize the exposure time to free ammonia, via control of media pH, in both defined media and dairy anaerobic digester effluent to suppress rotifers and maintain algal productivity. We tested five different free ammonia exposure times (0, 1, 2, 6, and 12h) and found a significant nonlinear effect of exposure time (p0.9) on rotifer survival. In both media types, 6-12h of elevated free ammonia significantly reduced Brachionus plicatilis rotifer survival with no negative effects on Nannochloropsis oculata, while shorter exposure times were insufficient to inhibit rotifers, leading to severe algal culture crashes. These results suggest that algal crops can be protected from rotifers, without productivity loss, by elevating free ammonia for 6 or more hours. Copyright © 2017 Elsevier Ltd. All rights reserved.

PET/CT Improves the Definition of Complete Response and Allows to Detect Otherwise Unidentifiable Skeletal Progression in Multiple Myeloma.

Science.gov (United States)

Zamagni, Elena; Nanni, Cristina; Mancuso, Katia; Tacchetti, Paola; Pezzi, Annalisa; Pantani, Lucia; Zannetti, Beatrice; Rambaldi, Ilaria; Brioli, Annamaria; Rocchi, Serena; Terragna, Carolina; Martello, Marina; Marzocchi, Giulia; Borsi, Enrica; Rizzello, Ilaria; Fanti, Stefano; Cavo, Michele

2015-10-01

To evaluate the role of 18F-FDG PET/CT in 282 symptomatic multiple myeloma patients treated up-front between 2002 and 2012. All patients were studied by PET/CT at baseline, during posttreatment follow-up, and at the time of relapse. Their median duration of follow-up was 67 months. Forty-two percent of the patients at diagnosis had >3 focal lesions, and in 50% SUVmax was >4.2; extramedullary disease was present in 5%. On multivariate analysis, ISS stage 3, SUVmax >4.2, and failure to achieve best complete response (CR) were the leading factors independently associated with shorter progression-free survival (PFS) and overall survival (OS). These 3 variables were used to construct a prognostic scoring system based on the number of risk factors. After treatment, PET/CT negativity (PET-neg) was observed in 70% of patients, whereas conventionally defined CR was achieved in 53%. Attainment of PET-neg favorably influenced PFS and OS. PET-neg was an independent predictor of prolonged PFS and OS for patients with conventionally defined CR. Sixty-three percent of patients experienced relapse or progression; in 12%, skeletal progression was exclusively detected by systematic PET/CT performed during follow-up. A multivariate analysis revealed that persistence of SUVmax >4.2 following first-line treatment was independently associated with exclusive PET/CT progression. PET/CT combined with ISS stage and achievement or not of CR on first-line therapy sorted patients into different prognostic groups. PET/CT led to a more careful evaluation of CR. Finally, in patients with persistent high glucose metabolism after first-line treatment, PET/CT can be recommended during follow-up, to screen for otherwise unidentifiable progression. ©2015 American Association for Cancer Research.

Model-based prediction of progression-free survival in patients with first-line renal cell carcinoma using week 8 tumor size change from baseline.

Science.gov (United States)

Claret, Laurent; Zheng, Jenny; Mercier, Francois; Chanu, Pascal; Chen, Ying; Rosbrook, Brad; Yazdi, Pithavala; Milligan, Peter A; Bruno, Rene

2016-09-01

To assess the link between early tumor shrinkage (ETS) and progression-free survival (PFS) based on historical first-line metastatic renal cell carcinoma (mRCC) data. Tumor size data from 921 patients with first-line mRCC who received interferon-alpha, sunitinib, sorafenib or axitinib in two Phase III studies were modeled. The relationship between model-based estimates of ETS at week 8 as well as the baseline prognostic factors and PFS was tested in multivariate log-logistic models. Model performance was evaluated using simulations of PFS distributions and hazard ratio (HR) across treatments for the two studies. In addition, an external validation was conducted using data from an independent Phase II RCC study. The relationship between expected HR of an investigational treatment vs. sunitinib and the differences in ETS was simulated. A model with a nonlinear ETS-PFS link was qualified to predict PFS distribution by ETS quartiles as well as to predict HRs of sunitinib vs. interferon-alpha and axitinib vs. sorafenib. The model also performed well in simulations of an independent study of axitinib (external validation). The simulations suggested that if a new investigational treatment could further reduce the week 8 ETS by 30 % compared with sunitinib, an expected HR [95 % predictive interval] of the new treatment vs. sunitinib would be 0.59 [0.46, 0.79]. A model has been developed that uses early changes in tumor size to predict the HR for PFS differences between treatment arms for first-line mRCC. Such a model may have utility in predicting the outcome of ongoing studies (e.g., as part of interim futility analyses), supporting early decision making and future study design for investigational agents in development for this indication.

Locoregional Tumor Progression After Radiation Therapy Influences Overall Survival in Pediatric Patients With Neuroblastoma

International Nuclear Information System (INIS)

Pai Panandiker, Atmaram S.; McGregor, Lisa; Krasin, Matthew J.; Wu Shengjie; Xiong Xiaoping; Merchant, Thomas E.

2010-01-01

Purpose: There is renewed attention to primary site irradiation and local control for patients with high-risk neuroblastoma (NB). We conducted a retrospective review to identify factors that might predict for locoregional tumor control and its impact on overall survival. Methods and Materials: Between July 2000 through August 2006, a total of 44 pediatric patients with NB received radiation therapy (RT) with curative intent using computed tomography (CT)-based treatment planning. The median age was 3.4 years and the median cumulative dose was 23.4 Gy. Overall survival and locoregional tumor control were measured from the start of RT to the date of death or event as determined by CT/magnetic resonance imaging/meta-iodobenzylguanidine. The influence of age at irradiation, gender, race, cumulative radiation dose, International Neuroblastoma Staging System stage, treatment protocol and resection status was determined with respect to locoregional tumor control. Results: With a median follow-up of 34 months ± 21 months, locoregional tumor progression was observed in 11 (25%) and was evenly divided between primary site and adjacent nodal/visceral site failure. The influence of locoregional control reached borderline statistical significance (p = 0.06). Age (p = 0.5), dose (p = 0.6), resection status (p = 0.7), and International Neuroblastoma Staging System stage (p = 0.08) did not influence overall survival. Conclusions: Overall survival in high-risk neuroblastoma is influenced by locoregional tumor control. Despite CT-based planning, progression in adjacent nodal/visceral sites appears to be common; this requires further investigation regarding target volume definitions, dose, and the effects of systemic therapy.

Prospective, Randomized, Double-Blind, Phase III Clinical Trial of Anti-T-Lymphocyte Globulin to Assess Impact on Chronic Graft-Versus-Host Disease-Free Survival in Patients Undergoing HLA-Matched Unrelated Myeloablative Hematopoietic Cell Transplantation.

Science.gov (United States)

Soiffer, Robert J; Kim, Haesook T; McGuirk, Joseph; Horwitz, Mitchell E; Johnston, Laura; Patnaik, Mrinal M; Rybka, Witold; Artz, Andrew; Porter, David L; Shea, Thomas C; Boyer, Michael W; Maziarz, Richard T; Shaughnessy, Paul J; Gergis, Usama; Safah, Hana; Reshef, Ran; DiPersio, John F; Stiff, Patrick J; Vusirikala, Madhuri; Szer, Jeff; Holter, Jennifer; Levine, James D; Martin, Paul J; Pidala, Joseph A; Lewis, Ian D; Ho, Vincent T; Alyea, Edwin P; Ritz, Jerome; Glavin, Frank; Westervelt, Peter; Jagasia, Madan H; Chen, Yi-Bin

2017-12-20

Purpose Several open-label randomized studies have suggested that in vivo T-cell depletion with anti-T-lymphocyte globulin (ATLG; formerly antithymocyte globulin-Fresenius) reduces chronic graft-versus-host disease (cGVHD) without compromising survival. We report a prospective, double-blind phase III trial to investigate the effect of ATLG (Neovii Biotech, Lexington, MA) on cGVHD-free survival. Patients and Methods Two hundred fifty-four patients 18 to 65 years of age with acute leukemia or myelodysplastic syndrome who underwent myeloablative HLA-matched unrelated hematopoietic cell transplantation (HCT) were randomly assigned one to one to placebo (n =128 placebo) or ATLG (n = 126) treatment at 27 sites. Patients received either ATLG or placebo 20 mg/kg per day on days -3, -2, -1 in addition to tacrolimus and methotrexate as GVHD prophylaxis. The primary study end point was moderate-severe cGVHD-free survival. Results Despite a reduction in grade 2 to 4 acute GVHD (23% v 40%; P = .004) and moderate-severe cGVHD (12% v 33%; P < .001) in ATLG recipients, no difference in moderate-severe cGVHD-free survival between ATLG and placebo was found (2-year estimate: 48% v 44%, respectively; P = .47). Both progression-free survival (PFS) and overall survival (OS) were lower with ATLG (2-year estimate: 47% v 65% [ P = .04] and 59% v 74% [ P = .034], respectively). Multivariable analysis confirmed that ATLG was associated with inferior PFS (hazard ratio, 1.55; 95% CI, 1.05 to 2.28; P = .026) and OS (hazard ratio, 1.74; 95% CI, 1.12 to 2.71; P = .01). Conclusion In this prospective, randomized, double-blind trial of ATLG in unrelated myeloablative HCT, the incorporation of ATLG did not improve moderate-severe cGVHD-free survival. Moderate-severe cGVHD was significantly lower with ATLG, but PFS and OS also were lower. Additional analyses are needed to understand the appropriate role for ATLG in HCT.

"Internet of Things" Real-Time Free Flap Monitoring.

Science.gov (United States)

Kim, Sang Hun; Shin, Ho Seong; Lee, Sang Hwan

2018-01-01

Free flaps are a common treatment option for head and neck reconstruction in plastic reconstructive surgery, and monitoring of the free flap is the most important factor for flap survival. In this study, the authors performed real-time free flap monitoring based on an implanted Doppler system and "internet of things" (IoT)/wireless Wi-Fi, which is a convenient, accurate, and efficient approach for surgeons to monitor a free flap. Implanted Doppler signals were checked continuously until the patient was discharged by the surgeon and residents using their own cellular phone or personal computer. If the surgeon decided that a revision procedure or exploration was required, the authors checked the consumed time (positive signal-to-operating room time) from the first notification when the flap's status was questioned to the determination for revision surgery according to a chart review. To compare the efficacy of real-time monitoring, the authors paired the same number of free flaps performed by the same surgeon and monitored the flaps using conventional methods such as a physical examination. The total survival rate was greater in the real-time monitoring group (94.7% versus 89.5%). The average time for the real-time monitoring group was shorter than that for the conventional group (65 minutes versus 86 minutes). Based on this study, real-time free flap monitoring using IoT technology is a method that surgeon and reconstruction team can monitor simultaneously at any time in any situation.

Treatment paradigms for advanced stage non-small cell lung cancer in the era of multiple lines of therapy.

Science.gov (United States)

Stinchcombe, Thomas E; Socinski, Mark A

2009-02-01

The duration of first-line and the timing of second-line therapy for advanced non-small cell lung cancer has been an area of recent investigation. Five trials have been performed that have investigated shorter (3-4 cycles) versus longer duration of platinum-based therapy; four trials revealed an equivalent overall survival with the shorter duration of therapy, and one trial revealed superior survival with the longer duration of therapy. The toxicity and quality of life data has either been equivalent or favored the shorter duration of therapy. Two trials have investigated the timing of a second-line therapy after completion of four cycles of platinum-based therapy versus the standard treatment paradigm of initiating second-line therapy upon disease progression. Both of these trials have revealed a statistically significant improvement in the progression-free survival, and a trend towards improved survival for the earlier use of second-line therapy. Only 50 to 60% of patients on the standard treatment arm initiated second-line therapy, and the promising results observed are most likely related to the fact that a higher percentage of patients received second-line therapy on the experimental arm. Several trials have investigated maintenance chemotherapy, and these trials have not revealed a survival benefit probably due to the fact that many patients experience disease progression or unacceptable toxicity during the initial or maintenance therapy. The addition of a targeted agent (bevacizumab or cetuximab) to the initial chemotherapy and the continuation of the targeted agent after completion of the chemotherapy have yielded superior overall survival in comparison to chemotherapy alone. The incremental benefit of the maintenance therapy with the targeted agent is unknown.

Progress in Electrolyte-Free Fuel Cells

International Nuclear Information System (INIS)

Lu, Yuzheng; Zhu, Bin; Cai, Yixiao; Kim, Jung-Sik; Wang, Baoyuan; Wang, Jun; Zhang, Yaoming; Li, Junjiao

2016-01-01

Solid oxide fuel cell (SOFC) represents a clean electrochemical energy conversion technology with characteristics of high conversion efficiency and low emissions. It is one of the most important new energy technologies in the future. However, the manufacture of SOFCs based on the structure of anode/electrolyte/cathode is complicated and time-consuming. Thus, the cost for the entire fabrication and technology is too high to be affordable, and challenges still hinder commercialization. Recently, a novel type of electrolyte-free fuel cell (EFFC) with single component was invented, which could be the potential candidate for the next generation of advanced fuel cells. This paper briefly introduces the EFFC, working principle, performance, and advantages with updated research progress. A number of key R&D issues about EFFCs have been addressed, and future opportunities and challenges are discussed.

Progress in Electrolyte-Free Fuel Cells

Energy Technology Data Exchange (ETDEWEB)

Lu, Yuzheng [Jiangsu Provincial Key Laboratory of Solar Energy Science and Technology, School of Energy and Environment, Southeast University, Nanjing (China); Zhu, Bin, E-mail: binzhu@kth.se [Faculty of Physics and Electronic Technology, Hubei Collaborative Innovation Center for Advanced Organic Materials, Hubei University, Wuhan (China); Department of Energy Technology, Royal Institute of Technology KTH, Stockholm (Sweden); Cai, Yixiao [Ångström Laboratory, Department of Engineering Sciences, Uppsala University, Uppsala (Sweden); Kim, Jung-Sik [Department of Aeronautical and Automotive Engineering, Loughborough University, Loughborough (United Kingdom); Wang, Baoyuan [Faculty of Physics and Electronic Technology, Hubei Collaborative Innovation Center for Advanced Organic Materials, Hubei University, Wuhan (China); Department of Energy Technology, Royal Institute of Technology KTH, Stockholm (Sweden); Wang, Jun, E-mail: binzhu@kth.se; Zhang, Yaoming [Jiangsu Provincial Key Laboratory of Solar Energy Science and Technology, School of Energy and Environment, Southeast University, Nanjing (China); Li, Junjiao [Nanjing Yunna Nano Technology Co., Ltd., Nanjing (China)

2016-05-02

Solid oxide fuel cell (SOFC) represents a clean electrochemical energy conversion technology with characteristics of high conversion efficiency and low emissions. It is one of the most important new energy technologies in the future. However, the manufacture of SOFCs based on the structure of anode/electrolyte/cathode is complicated and time-consuming. Thus, the cost for the entire fabrication and technology is too high to be affordable, and challenges still hinder commercialization. Recently, a novel type of electrolyte-free fuel cell (EFFC) with single component was invented, which could be the potential candidate for the next generation of advanced fuel cells. This paper briefly introduces the EFFC, working principle, performance, and advantages with updated research progress. A number of key R&D issues about EFFCs have been addressed, and future opportunities and challenges are discussed.

Impact of lymphovascular invasion on recurrence and progression rates in patients with pT1 urothelial carcinoma of bladder after transurethral resection

Directory of Open Access Journals (Sweden)

Sha N

2015-11-01

Full Text Available Nan Sha,* Linguo Xie,* Tao Chen,* Chen Xing, Xiaoteng Liu, Yu Zhang, Zhonghua Shen, Hao Xu, Zhouliang Wu, Hailong Hu, Changli Wu Department of Urology, Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China *These authors contributed equally to this work Objective: To evaluate the clinical significance of lymphovascular invasion (LVI on recurrence and progression rates in patients with pT1 urothelial carcinoma of bladder after transurethral resection.Methods: This retrospective study was performed with 155 patients with newly diagnosed pT1 urothelial carcinoma of bladder who were treated with transurethral resection of bladder tumor at our institution from January 2006 to January 2010. The presence or absence of LVI was examined by pathologists. Chi-square test was performed to identify the correlations between LVI and other clinical and pathological features. Kaplan–Meier method was used to estimate the recurrence-free survival (RFS and progression-free survival curves and difference was determined by the log-rank test. Univariate and multivariate analyses were performed to determine the predictive factors through a Cox proportional hazards analysis model.Results: LVI was detected in a total of 34 patients (21.9%. While LVI was associated with high-grade tumors (P<0.001 and intravesical therapy (P=0.009. Correlations with age (P=0.227, sex (P=0.376, tumor size (P=0.969, tumor multiplicity (P=0.196, carcinoma in situ (P=0.321, and smoking (P=0.438 were not statistically significant. There was a statistically significant tendency toward higher recurrence rate and shorter RFS time in LVI-positive patients. However, no statistically significant differences were observed in progression rate between the two groups. Moreover, multivariate Cox proportional hazards analysis revealed that LVI, tumor size, and smoking were independent prognostic predictors of

Circulating tumor cells, disease recurrence and survival in newly diagnosed breast cancer

NARCIS (Netherlands)

Franken, Bas; De Groot, Marco R.; Mastboom, Walter J.B.; Vermes, I.; van der Palen, Jacobus Adrianus Maria; Tibbe, Arjan G.J.; Terstappen, Leonardus Wendelinus Mathias Marie

2012-01-01

Introduction The presence of circulating tumor cells (CTC) is an independent prognostic factor for progression-free survival and breast cancer-related death (BRD) for patients with metastatic breast cancer beginning a new line of systemic therapy. The current study was undertaken to explore whether

{sup 18}F-FDG PET as novel imaging biomarker for disease progression after ablation therapy in colorectal liver metastases

Energy Technology Data Exchange (ETDEWEB)

Samim, M. [University Medical Centre Utrecht, Department Surgery, Utrecht (Netherlands); University Medical Centre Utrecht, Department Radiology and Nuclear Medicine, Utrecht (Netherlands); Prevoo, W.; Wit-van der Veen, B.J. de; Stokkel, M.P.M. [Antoni van Leeuwenhoek Hospital, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); Kuhlmann, K.F.; Ruers, T. [Antoni van Leeuwenhoek Hospital, Department Surgical Oncology, Amsterdam (Netherlands); Hillegersberg, R. van [University Medical Centre Utrecht, Department Surgery, Utrecht (Netherlands); Bosch, M.A.A.J. van den; Verkooijen, H.M.; Lam, M.G.E.H. [University Medical Centre Utrecht, Department Radiology and Nuclear Medicine, Utrecht (Netherlands)

2017-07-15

Recurrent disease following thermal ablation therapy is a frequently reported problem. Preoperative identification of patients with high risk of recurrent disease might enable individualized treatment based on patients' risk profile. The aim of the present work was to investigate the role of metabolic parameters derived from the pre-ablation {sup 18}F-FDG PET/CT as imaging biomarkers for recurrent disease in patients with colorectal liver metastases (CLM). Included in this retrospective study were all consecutive patients with CLM treated with percutaneous or open thermal ablation therapy who had a pre-treatment baseline {sup 18}F-FDG PET/CT available. Multivariable cox regression for survival analysis was performed using different models for the metabolic parameters (SUL{sub peak}, SUL{sub mean}, SUL{sub max}, partial volume corrected SUL{sub mean} (cSUL{sub mean}), and total lesion glycolysis (TLG)) corrected for tumour and procedure characteristics. The study endpoints were defined as local tumour progression free survival (LTP-FS), new intrahepatic recurrence free survival (NHR-FS) and extrahepatic recurrence free survival (EHR-FS). Clinical and imaging follow-up data was used as the reference standard. Fifty-four patients with 90 lesions were selected. Univariable cox regression analysis resulted in eight models. Multivariable analysis revealed that after adjusting for lesion size and the approach of the procedure, none of the metabolic parameters were associated with LTP-FS or EHR-FS. Percutaneous approach was significantly associated with a shorter LTP-FS. It was demonstrated that lower values of SUL{sub peak}, SUL{sub max}, SUL{sub mean}, and cSUL{sub mean} are associated with a significant better NHR-FS, independent of the lesion size and number and prior chemotherapy. We found no association between the metabolic parameters on pre-ablation {sup 18}F-FDG PET/CT and the LTP-FS. However, low values of the metabolic parameters were significantly

Abundance of early functional HIV-specific CD8+ T cells does not predict AIDS-free survival time.

Directory of Open Access Journals (Sweden)

Ingrid M M Schellens

Full Text Available BACKGROUND: T-cell immunity is thought to play an important role in controlling HIV infection, and is a main target for HIV vaccine development. HIV-specific central memory CD8(+ and CD4(+ T cells producing IFNgamma and IL-2 have been associated with control of viremia and are therefore hypothesized to be truly protective and determine subsequent clinical outcome. However, the cause-effect relationship between HIV-specific cellular immunity and disease progression is unknown. We investigated in a large prospective cohort study involving 96 individuals of the Amsterdam Cohort Studies with a known date of seroconversion whether the presence of cytokine-producing HIV-specific CD8(+ T cells early in infection was associated with AIDS-free survival time. METHODS AND FINDINGS: The number and percentage of IFNgamma and IL-2 producing CD8(+ T cells was measured after in vitro stimulation with an overlapping Gag-peptide pool in T cells sampled approximately one year after seroconversion. Kaplan-Meier survival analysis and Cox proportional hazard models showed that frequencies of cytokine-producing Gag-specific CD8(+ T cells (IFNgamma, IL-2 or both shortly after seroconversion were neither associated with time to AIDS nor with the rate of CD4(+ T-cell decline. CONCLUSIONS: These data show that high numbers of functional HIV-specific CD8(+ T cells can be found early in HIV infection, irrespective of subsequent clinical outcome. The fact that both progressors and long-term non-progressors have abundant T cell immunity of the specificity associated with low viral load shortly after seroconversion suggests that the more rapid loss of T cell immunity observed in progressors may be a consequence rather than a cause of disease progression.

Fifteen-Year Biochemical Relapse-Free Survival, Cause-Specific Survival, and Overall Survival Following I125 Prostate Brachytherapy in Clinically Localized Prostate Cancer: Seattle Experience

International Nuclear Information System (INIS)

Sylvester, John E.; Grimm, Peter D.; Wong, Jason; Galbreath, Robert W.; Merrick, Gregory; Blasko, John C.

2011-01-01

Purpose: To report 15-year biochemical relapse-free survival (BRFS), cause-specific survival (CSS), and overall survival (OS) outcomes of patients treated with I 125 brachytherapy monotherapy for clinically localized prostate cancer early in the Seattle experience. Methods and Materials: Two hundred fifteen patients with clinically localized prostate cancer were consecutively treated from 1988 to 1992 with I 125 monotherapy. They were prospectively followed as a tight cohort. They were evaluated for BRFS, CSS, and OS. Multivariate analysis was used to evaluate outcomes by pretreatment clinical prognostic factors. BRFS was analyzed by the Phoenix (nadir + 2 ng/mL) definition. CSS and OS were evaluated by chart review, death certificates, and referring physician follow-up notes. Gleason scoring was performed by general pathologists at a community hospital in Seattle. Time to biochemical failure (BF) was calculated and compared by Kaplan-Meier plots. Results: Fifteen-year BRFS for the entire cohort was 80.4%. BRFS by D'Amico risk group classification cohort analysis was 85.9%, 79.9%, and 62.2% for low, intermediate, and high-risk patients, respectively. Follow-up ranged from 3.6 to 18.4 years; median follow-up was 15.4 years for biochemically free of disease patients. Overall median follow-up was 11.7 years. The median time to BF in those who failed was 5.1 years. CSS was 84%. OS was 37.1%. Average age at time of treatment was 70 years. There was no significant difference in BRFS between low and intermediate risk groups. Conclusion: I 125 monotherapy results in excellent 15-year BRFS and CSS, especially when taking into account the era of treatment effect.

Evaluating Expected Costs and Benefits of Granting Access to New Treatments on the Basis of Progression-Free Survival in Non-Small-Cell Lung Cancer.

Science.gov (United States)

Lakdawalla, Darius N; Chou, Jacquelyn W; Linthicum, Mark T; MacEwan, Joanna P; Zhang, Jie; Goldman, Dana P

2015-05-01

Surrogate end points may be used as proxy for more robust clinical end points. One prominent example is the use of progression-free survival (PFS) as a surrogate for overall survival (OS) in trials for oncologic treatments. Decisions based on surrogate end points may expedite regulatory approval but may not accurately reflect drug efficacy. Payers and clinicians must balance the potential benefits of earlier treatment access based on surrogate end points against the risks of clinical uncertainty. To present a framework for evaluating the expected net benefit or cost of providing early access to new treatments on the basis of evidence of PFS benefits before OS results are available, using non-small-cell lung cancer (NSCLC) as an example. A probabilistic decision model was used to estimate expected incremental social value of the decision to grant access to a new treatment on the basis of PFS evidence. The model analyzed a hypothetical population of patients with NSCLC who could be treated during the period between PFS and OS evidence publication. Estimates for delay in publication of OS evidence following publication of PFS evidence, expected OS benefit given PFS benefit, incremental cost of new treatment, and other parameters were drawn from the literature on treatment of NSCLC. Incremental social value of early access for each additional patient per month (in 2014 US dollars). For "medium-value" model parameters, early reimbursement of drugs with any PFS benefit yields an incremental social cost of more than $170,000 per newly treated patient per month. In contrast, granting early access on the basis of PFS benefit between 1 and 3.5 months produces more than $73,000 in incremental social value. Across the full range of model parameter values, granting access for drugs with PFS benefit between 3 and 3.5 months is robustly beneficial, generating incremental social value ranging from $38,000 to more than $1 million per newly treated patient per month, whereas access

Long-term disease-free survival in advanced melanomas treated with nitrosoureas: mechanisms and new perspectives.

Science.gov (United States)

Durando, Xavier; Thivat, Emilie; D'Incan, Michel; Sinsard, Anne; Madelmont, Jean-Claude; Chollet, Philippe

2005-11-15

Median survival of metastatic malignant melanoma is 6.0 to 7.5 months, with a 5-year survival of approximately 6.0%. Although long-term complete remissions are rare, few reports describe cases after chemotherapy. Fifty-three patients with metastatic melanoma were treated with Cystemustine, a chloroethyl nitrosourea (CENU) (60 or 90 mg/m2). We describe 5 cases, presenting with complete response with long-term disease-free survival of long-term remission of 14, 12, 9, 7 and 6 years after Cystemustine therapy alone. Long-term survival has already been described in literature, but in all cases they have been obtained after chemotherapy associated with or followed by surgery. But despite these noteworthy and encouraging but also rare results, it appears essential to increase Cystemustine efficiency.

Extending 3D near-cloud corrections from shorter to longer wavelengths

International Nuclear Information System (INIS)

Marshak, Alexander; Evans, K. Frank; Várnai, Tamás; Wen, Guoyong

2014-01-01

Satellite observations have shown a positive correlation between cloud amount and aerosol optical thickness (AOT) that can be explained by the humidification of aerosols near clouds, and/or by cloud contamination by sub-pixel size clouds and the cloud adjacency effect. The last effect may substantially increase reflected radiation in cloud-free columns, leading to overestimates in the retrieved AOT. For clear-sky areas near boundary layer clouds the main contribution to the enhancement of clear sky reflectance at shorter wavelengths comes from the radiation scattered into clear areas by clouds and then scattered to the sensor by air molecules. Because of the wavelength dependence of air molecule scattering, this process leads to a larger reflectance increase at shorter wavelengths, and can be corrected using a simple two-layer model [18]. However, correcting only for molecular scattering skews spectral properties of the retrieved AOT. Kassianov and Ovtchinnikov [9] proposed a technique that uses spectral reflectance ratios to retrieve AOT in the vicinity of clouds; they assumed that the cloud adjacency effect influences the spectral ratio between reflectances at two wavelengths less than it influences the reflectances themselves. This paper combines the two approaches: It assumes that the 3D correction for the shortest wavelength is known with some uncertainties, and then it estimates the 3D correction for longer wavelengths using a modified ratio method. The new approach is tested with 3D radiances simulated for 26 cumulus fields from Large-Eddy Simulations, supplemented with 40 aerosol profiles. The results showed that (i) for a variety of cumulus cloud scenes and aerosol profiles over ocean the 3D correction due to cloud adjacency effect can be extended from shorter to longer wavelengths and (ii) the 3D corrections for longer wavelengths are not very sensitive to unbiased random uncertainties in the 3D corrections at shorter wavelengths. - Highlights: �

Progress in Electrolyte-Free Fuel Cells

Directory of Open Access Journals (Sweden)

Yuzheng eLu

2016-05-01

Full Text Available Solid Oxide Fuel Cell (SOFC represents a clean electrochemical energy conversion technology with characteristics of high conversion efficiency and low emissions. It is one of the most important new energy technologies in the future. However, the manufacture of SOFCs based on the structure of anode/electrolyte/cathode is complicated and time-consuming. Thus, the cost for the entire fabrication and technology is too high to be affordable and challenges still hinder commercialization. Recently, a novel type of Electrolyte -free fuel cell (EFFC with single component was invented which could be the potential candidate for the next generation of advanced fuel cells. This paper briefly introduces the EFFC, working principle, performance and advantages with updated research progress. A number of key R&D issues about EFFCs have been addressed and future opportunities and challenges are discussed.

Circulating Tumor Cells with Aberrant ALK Copy Number Predict Progression-Free Survival during Crizotinib Treatment in ALK-Rearranged Non-Small Cell Lung Cancer Patients.

Science.gov (United States)

Pailler, Emma; Oulhen, Marianne; Borget, Isabelle; Remon, Jordi; Ross, Kirsty; Auger, Nathalie; Billiot, Fanny; Ngo Camus, Maud; Commo, Frédéric; Lindsay, Colin R; Planchard, David; Soria, Jean-Charles; Besse, Benjamin; Farace, Françoise

2017-05-01

The duration and magnitude of clinical response are unpredictable in ALK -rearranged non-small cell lung cancer (NSCLC) patients treated with crizotinib, although all patients invariably develop resistance. Here, we evaluated whether circulating tumor cells (CTC) with aberrant ALK -FISH patterns [ ALK -rearrangement, ALK -copy number gain ( ALK -CNG)] monitored on crizotinib could predict progression-free survival (PFS) in a cohort of ALK -rearranged patients. Thirty-nine ALK -rearranged NSCLC patients treated with crizotinib as first ALK inhibitor were recruited prospectively. Blood samples were collected at baseline and at an early time-point (2 months) on crizotinib. Aberrant ALK -FISH patterns were examined in CTCs using immunofluorescence staining combined with filter-adapted FISH after filtration enrichment. CTCs were classified into distinct subsets according to the presence of ALK -rearrangement and/or ALK -CNG signals. No significant association between baseline numbers of ALK -rearranged or ALK -CNG CTCs and PFS was observed. However, we observed a significant association between the decrease in CTC number with ALK -CNG on crizotinib and a longer PFS (likelihood ratio test, P = 0.025). In multivariate analysis, the dynamic change of CTC with ALK -CNG was the strongest factor associated with PFS (HR, 4.485; 95% confidence interval, 1.543-13.030, P = 0.006). Although not dominant, ALK -CNG has been reported to be one of the mechanisms of acquired resistance to crizotinib in tumor biopsies. Our results suggest that the dynamic change in the numbers of CTCs with ALK -CNG may be a predictive biomarker for crizotinib efficacy in ALK -rearranged NSCLC patients. Serial molecular analysis of CTC shows promise for real-time patient monitoring and clinical outcome prediction in this population. Cancer Res; 77(9); 2222-30. ©2017 AACR . ©2017 American Association for Cancer Research.

Survival and prognostic factors in patients treated with stereotactic radiotherapy for brain metastases

DEFF Research Database (Denmark)

Leth, Thomas; Oettingen, Gorm von; Lassen-Ramshad, Yasmin A.

2015-01-01

Abstract Background. Stereotactic radiation therapy (SRT) of brain metastases is used with good effect around the world, but no consensus exists regarding which prognostic factors that are related to favourable or unfavourable prognosis after the treatment. A better definition of these factors...... will ensure a more precise application of the treatment. Material and methods. A consecutive cohort of the 198 patients treated for brain metastases with SRT without concurrent whole-brain radiation therapy at our department from 2001 to 2012 was retrospectively analysed. Results. Median survival was seven...... months and median time to clinical cerebral progression was eight months. The multivariate analysis revealed age ≥ 65 years, Performance Status ≥ 2, extracranial metastases and size of metastasis > 20 mm as independent prognostic factors related to shorter survival. No factors were independently related...

Edge Contrast of the FLAIR Hyperintense Region Predicts Survival in Patients with High-Grade Gliomas following Treatment with Bevacizumab.

Science.gov (United States)

Bahrami, N; Piccioni, D; Karunamuni, R; Chang, Y-H; White, N; Delfanti, R; Seibert, T M; Hattangadi-Gluth, J A; Dale, A; Farid, N; McDonald, C R

2018-04-05

Treatment with bevacizumab is standard of care for recurrent high-grade gliomas; however, monitoring response to treatment following bevacizumab remains a challenge. The purpose of this study was to determine whether quantifying the sharpness of the fluid-attenuated inversion recovery hyperintense border using a measure derived from texture analysis-edge contrast-improves the evaluation of response to bevacizumab in patients with high-grade gliomas. MRIs were evaluated in 33 patients with high-grade gliomas before and after the initiation of bevacizumab. Volumes of interest within the FLAIR hyperintense region were segmented. Edge contrast magnitude for each VOI was extracted using gradients of the 3D FLAIR images. Cox proportional hazards models were generated to determine the relationship between edge contrast and progression-free survival/overall survival using age and the extent of surgical resection as covariates. After bevacizumab, lower edge contrast of the FLAIR hyperintense region was associated with poorer progression-free survival ( P = .009) and overall survival ( P = .022) among patients with high-grade gliomas. Kaplan-Meier curves revealed that edge contrast cutoff significantly stratified patients for both progression-free survival (log-rank χ 2 = 8.3, P = .003) and overall survival (log-rank χ 2 = 5.5, P = .019). Texture analysis using edge contrast of the FLAIR hyperintense region may be an important predictive indicator in patients with high-grade gliomas following treatment with bevacizumab. Specifically, low FLAIR edge contrast may partially reflect areas of early tumor infiltration. This study adds to a growing body of literature proposing that quantifying features may be important for determining outcomes in patients with high-grade gliomas. © 2018 by American Journal of Neuroradiology.

The Change of the Family Life Affected by the Shorter Working Time : From the Point of View of the Home Management

OpenAIRE

平田, 道憲

1994-01-01

In Japan, the working time has been decreasing. However, Japanese working people spend more hours per year to work than those in Western countries. The policy of the shorter working time is conducted by the Japanese Government in order that the working people get more free time. This paper examines whether the shorter working time of working members in the family enrich the time use of the other members of the family. Especially, the effect of the shorter working time of husbands to wives...

Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival

Science.gov (United States)

van Besien, Koen; Hari, Parameswaran; Zhang, Mei-Jie; Liu, Hong-Tao; Stock, Wendy; Godley, Lucy; Odenike, Olatoyosi; Larson, Richard; Bishop, Michael; Wickrema, Amittha; Gergis, Usama; Mayer, Sebastian; Shore, Tsiporah; Tsai, Stephanie; Rhodes, Joanna; Cushing, Melissa M.; Korman, Sandra; Artz, Andrew

2016-01-01

Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, Pdisease (HR=0.26, Pdisease (HR=0.06, Pdisease-free, relapse-free survival was superior with haplo-cord (HR 0.63, P=0.002) but not overall survival (HR=0.97, P=0.85). Haplo-cord transplantation using fludarabine-melphalan-thymoglobulin conditioning hastens hematopoietic recovery with a lower risk of relapse relative to double umbilical cord blood transplantation using the commonly used fludarabine-cyclophosphamide-low-dose total body irradiation conditioning. Graft-versus-host disease-free and relapse-free survival is significantly improved. Haplo-cord is a readily available graft source that improves outcomes and access to transplant for those lacking HLA-matched donors. Trials registered at clinicaltrials.gov identifiers 00943800 and 01810588. PMID:26869630

Gene expression in triple-negative breast cancer in relation to survival.

Science.gov (United States)

Wang, Shuyang; Beeghly-Fadiel, Alicia; Cai, Qiuyin; Cai, Hui; Guo, Xingyi; Shi, Liang; Wu, Jie; Ye, Fei; Qiu, Qingchao; Zheng, Ying; Zheng, Wei; Bao, Ping-Ping; Shu, Xiao-Ou

2018-05-10

The identification of biomarkers related to the prognosis of triple-negative breast cancer (TNBC) is critically important for improved understanding of the biology that drives TNBC progression. We evaluated gene expression in total RNA isolated from formalin-fixed paraffin-embedded tumor samples using the NanoString nCounter assay for 469 TNBC cases from the Shanghai Breast Cancer Survival Study. We used Cox regression to quantify Hazard Ratios (HR) and corresponding confidence intervals (CI) for overall survival (OS) and disease-free survival (DFS) in models that included adjustment for breast cancer intrinsic subtype. Of 302 genes in our discovery analysis, 22 were further evaluated in relation to OS among 134 TNBC cases from the Nashville Breast Health Study and the Southern Community Cohort Study; 16 genes were further evaluated in relation to DFS in 335 TNBC cases from four gene expression omnibus datasets. Fixed-effect meta-analysis was used to combine results across data sources. Twofold higher expression of EOMES (HR 0.90, 95% CI 0.83-0.97), RASGRP1 (HR 0.89, 95% CI 0.82-0.97), and SOD2 (HR 0.80, 95% CI 0.66-0.96) was associated with better OS. Twofold higher expression of EOMES (HR 0.89, 95% CI 0.81-0.97) and RASGRP1 (HR 0.87, 95% CI 0.81-0.95) was also associated with better DFS. On the contrary, a doubling of FA2H (HR 1.14, 95% CI 1.06-1.22) and GSPT1 (HR 1.33, 95% CI 1.14-1.55) expression was associated with shorter DFS. We identified five genes (EOMES, FA2H, GSPT1, RASGRP1, and SOD2) that may serve as potential prognostic biomarkers and/or therapeutic targets for TNBC.

Hypertension, Obesity, Diabetes, and Heart Failure-Free Survival: The Cardiovascular Disease Lifetime Risk Pooling Project.

Science.gov (United States)

Ahmad, Faraz S; Ning, Hongyan; Rich, Jonathan D; Yancy, Clyde W; Lloyd-Jones, Donald M; Wilkins, John T

2016-12-01

This study was designed to quantify the relationship between the absence of heart failure risk factors in middle age and incident heart failure, heart failure-free survival, and overall survival. Quantification of years lived free from heart failure in the context of risk factor burden in mid-life may improve risk communication and prevention efforts. We conducted a pooled, individual-level analysis sampling from communities across the United States as part of 4 cohort studies: the Framingham Heart, Framingham Offspring, Chicago Heart Association Detection Project in Industry, and ARIC (Atherosclerosis Risk In Communities) studies. Participants with and without hypertension (blood pressure ≥140/90 mm Hg or treatment), obesity (body mass index ≥30 kg/m 2 ), or diabetes (fasting glucose ≥126 mg/dl or treatment), and combinations of these factors, at index ages of 45 years and 55 years through 95 years. Competing risk-adjusted Cox models, a modified Kaplan-Meier estimator, and Irwin's restricted mean were used to estimate the association between the absence of risk factors at mid-life and incident heart failure, heart failure-free survival, and overall survival. For participants at age 45 years, over 516,537 person-years of follow-up, 1,677 incident heart failure events occurred. Men and women with no risk factors, compared to those with all 3, had 73% to 85% lower risks of incident heart failure. Men and women without hypertension, obesity, or diabetes at age 45 years lived on average 34.7 years and 38.0 years without incident heart failure, and they lived on average an additional 3 years to 15 years longer free of heart failure than those with 1, 2, or 3 risk factors. Similar trends were seen when stratified by race and at index age 55 years. Prevention of hypertension, obesity, and diabetes by ages 45 years and 55 years may substantially prolong heart failure-free survival, decrease heart failure-related morbidity, and reduce the public health impact of

Predicting neo-adjuvant chemotherapy response and progression-free survival of locally advanced breast cancer using textural features of intratumoral heterogeneity on F-18 FDG PET/CT and diffusion-weighted MR imaging.

Science.gov (United States)

Yoon, Hai-Jeon; Kim, Yemi; Chung, Jin; Kim, Bom Sahn

2018-03-30

Predicting response to neo-adjuvant chemotherapy (NAC) and survival in locally advanced breast cancer (LABC) is important. This study investigated the prognostic value of tumor heterogeneity evaluated with textural analysis through F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and diffusion-weighted imaging (DWI). We enrolled 83 patients with LABC who had completed NAC and curative surgery. Tumor texture indices from pretreatment FDG PET and DWI were extracted from histogram analysis and 7 different parent matrices: co-occurrence matrix, the voxel-alignment matrix, neighborhood intensity difference matrix, intensity size-zone matrix (ISZM), normalized gray-level co-occurrence matrix (NGLCM), neighboring gray-level dependence matrix (NGLDM), and texture spectrum matrix. The predictive values of textural features were tested regarding both pathologic NAC response and progression-free survival. Among 83 patients, 46 were pathologic responders, while 37 were nonresponders. The PET texture indices from 7 parent matrices, DWI texture indices from histogram, and 1 parent matrix (NGLCM) showed significant differences according to NAC response. On multivariable analysis, number nonuniformity of PET extracted from the NGLDM was an independent predictor of pathologic response (P = .009). During a median follow-up period of 17.3 months, 14 patients experienced recurrence. High-intensity zone emphasis (HIZE) and high-intensity short-zone emphasis (HISZE) from PET extracted from ISZM were significant textural predictors (P = .011 and P = .033). On Cox regression analysis, only HIZE was a significant predictor of recurrence (P = .027), while HISZE showed borderline significance (P = .107). Tumor texture indices are useful for NAC response prediction in LABC. Moreover, PET texture indices can help to predict disease recurrence. © 2018 Wiley Periodicals, Inc.

Inflammation-regulating factors in ascites as predictive biomarkers of drug resistance and progression-free survival in serous epithelial ovarian cancers

International Nuclear Information System (INIS)

Lane, Denis; Matte, Isabelle; Garde-Granger, Perrine; Laplante, Claude; Carignan, Alex; Rancourt, Claudine; Piché, Alain

2015-01-01

Platinum-based combination therapy is the standard first-line treatment for women with advanced serous epithelial ovarian carcinoma (EOC). However, about 20 % will not respond and are considered clinically resistant. The availability of biomarkers to predict responses to the initial therapy would provide a practical approach to identify women who would benefit from a more appropriate first-line treatment. Ascites is an attractive inflammatory fluid for biomarker discovery as it is easy and minimally invasive to obtain. The aim of this study was to evaluate whether six selected inflammation-regulating factors in ascites could serve as diagnostic or drug resistance biomarkers in patients with advanced serous EOC. A total of 53 women with stage III/IV serous EOC and 10 women with benign conditions were enrolled in this study. Eleven of the 53 women with serous EOC were considered clinically resistant to treatment with progression-free survival < 6 months. Ascites were collected at the time of the debulking surgery and the levels of cytokines were measured by ELISA. The six selected cytokines were evaluated for their ability to discriminate serous EOC from benign controls, and to discriminate platinum resistant from platinum sensitive patients. Median ascites levels of IL-6, IL-10 and osteoprotegerin (OPG) were significantly higher in women with advanced serous EOC than in controls (P ≤ 0.012). There were no significant difference in the median ascites levels of leptin, soluble urokinase plasminogen activator receptor (suPAR) and CCL18 among serous EOC women and controls. In Receiver Operator curve (ROC) analysis, IL-6, IL-10 and OPG had a high area under the curve value of 0.905, 0.832 and 0.825 respectively for distinguishing EOC from benign controls. ROC analysis of individual cytokines revealed low discriminating potential to stratify patients according to their sensitivity to first-line treatment. The combination of biomarkers with the highest discriminating

Survival in women with ovarian cancer before and after the introduction of adjuvant paclitaxel; a 25-year, single institution review.

LENUS (Irish Health Repository)

Shireen, R

2012-02-01

Adjuvant chemotherapy regime for ovarian cancer patients remains to be a contentious issue. The aim of this study was to compare the overall and progression-free survival of women with ovarian cancer before and after introduction of paclitaxel in our unit in 1992. A sample of 112 women who received adjuvant therapy following surgery for ovarian cancer was collected, 68 (61%) received platinum+alkylating agent before 1992 and later 44 (39%) received platinum+paclitaxel. Five-year survival was same in both treatment groups when there was no macroscopic disease after surgery (78% versus 70%) and when residual disease was <2 cm (50% versus 40%). Survival was greater in women with residual disease >2 cm in the platinum+paclitaxel group (50% versus 24%), (p = 0.04). However, progression-free survival was similar in both groups irrespective of stage or residual volume of disease. Therefore consideration to selective use of paclitaxel could reduce patient morbidity and costs significantly.

Long-term disease-free survival in advanced melanomas treated with nitrosoureas: mechanisms and new perspectives

Directory of Open Access Journals (Sweden)

Sinsard Anne

2005-11-01

Full Text Available Abstract Background Median survival of metastatic malignant melanoma is 6.0 to 7.5 months, with a 5-year survival of ~6.0%. Although long-term complete remissions are rare, few reports describe cases after chemotherapy. Fifty-three patients with metastatic melanoma were treated with Cystemustine, a chloroethyl nitrosourea (CENU (60 or 90 mg/m2. Case presentation We describe 5 cases, presenting with complete response with long-term disease-free survival of long-term remission of 14, 12, 9, 7 and 6 years after Cystemustine therapy alone. Conclusion Long-term survival has already been described in literature, but in all cases they have been obtained after chemotherapy associated with or followed by surgery. But despite these noteworthy and encouraging but also rare results, it appears essential to increase cystemustine efficiency.

Serum immunoglobulin free light-chain measurement in primary amyloidosis: prognostic value and correlations with clinical features.

Science.gov (United States)

Kumar, Shaji; Dispenzieri, Angela; Katzmann, Jerry A; Larson, Dirk R; Colby, Colin L; Lacy, Martha Q; Hayman, Suzanne R; Buadi, Francis K; Leung, Nelson; Zeldenrust, Steve R; Ramirez-Alvarado, Marina; Clark, Raynell J; Kyle, Robert A; Rajkumar, S Vincent; Gertz, Morie A

2010-12-09

Immunoglobulin free light chains (FLCs) are the precursors of amyloid fibrils in primary amyloidosis (AL). We studied the relationship between FLC levels and clinical features in 730 patients with newly diagnosed AL. The plasma cell clone was λ in 72% patients, and κ in 28% patients. κ-AL had more GI tract and liver involvement, where as renal involvement was more with λ-AL. While the overall survival (OS) was similar for κ and λ-AL, the median OS for those without an identifiable serum heavy chain was significantly shorter (12.6 vs 29.9 months; P = .02). The OS was shorter among those with a higher dFLC (involved FLC-uninvolved FLC; κ > 29.4 mg/dL or λ > 18.2 mg/dL using median for cutoff); 10.9 vs 37.1 months; P analysis, dFLC was independent of other prognostic factors. The type of light chain impacts the spectrum of organ involvement and the FLC burden correlates with survival in AL.

Do shorter wavelengths improve contrast in optical mammography?

International Nuclear Information System (INIS)

Taroni, P; Pifferi, A; Torricelli, A; Spinelli, L; Danesini, G M; Cubeddu, R

2004-01-01

The detection of tumours with time-resolved transmittance imaging relies essentially on blood absorption. Previous theoretical and phantom studies have shown that both contrast and spatial resolution of optical images are affected by the optical properties of the background medium, and high absorption and scattering are generally beneficial. Based on these observations, wavelengths shorter than presently used (680-780 nm) could be profitable for optical mammography. A study was thus performed analysing time-resolved transmittance images at 637, 656, 683 and 785 nm obtained from 26 patients bearing 16 tumours and 15 cysts. The optical contrast proved to increase upon decreasing wavelengths for the detection of cancers in late-gated intensity images, with higher gain in contrast for lesions of smaller size (<1.5 cm diameter). For cysts either a progressive increase or decrease in contrast with wavelength was observed in scattering images

A survival model for fractionated radiotherapy with an application to prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Zaider, Marco [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)]. E-mail: Zaiderm@mskcc.org; Zelefsky, Michael J.; Leibel, Steven A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Hanin, Leonid G. [Department of Mathematics, Idaho State University, Pocatello, ID (United States); Tsodikov, Alexander D.; Yakovlev, Andrei Y. [Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT (United States)

2001-10-01

This paper explores the applicability of a mechanistic survival model, based on the distribution of clonogens surviving a course of fractionated radiation therapy, to clinical data on patients with prostate cancer. The study was carried out using data on 1100 patients with clinically localized prostate cancer who were treated with three-dimensional conformal radiation therapy. The patients were stratified by radiation dose (group 1: <67.5 Gy; group 2: 67.5-72.5 Gy; group 3: 72.5-77.5 Gy; group 4: 77.5-87.5 Gy) and prognosis category (favourable, intermediate and unfavourable as defined by pre-treatment PSA and Gleason score). A relapse was recorded when tumour recurrence was diagnosed or when three successive prostate specific antigen (PSA) elevations were observed from a post-treatment nadir PSA level. PSA relapse-free survival was used as the primary end point. The model, which is based on an iterated Yule process, is specified in terms of three parameters: the mean number of tumour clonogens that survive the treatment, the mean of the progression time of post-treatment tumour development and its standard deviation. The model parameters were estimated by the maximum likelihood method. The fact that the proposed model provides an excellent description both of the survivor function and of the hazard rate is prima facie evidence of the validity of the model because closeness of the two survivor functions (empirical and model-based) does not generally imply closeness of the corresponding hazard rates. The estimated cure probabilities for the favourable group are 0.80, 0.74 and 0.87 (for dose groups 1-3, respectively); for the intermediate group: 0.25, 0.51, 0.58 and 0.78 (for dose groups 1-4, respectively) and for the unfavourable group: 0.0, 0.27, 0.33 and 0.64 (for dose groups 1-4, respectively). The distribution of progression time to tumour relapse was found to be independent of prognosis group but dependent on dose. As the dose increases the mean progression

Prognostic nutritional index as a prognostic biomarker for survival in digestive system carcinomas.

Science.gov (United States)

Zhao, Yang; Xu, Peng; Kang, Huafeng; Lin, Shuai; Wang, Meng; Yang, Pengtao; Dai, Cong; Liu, Xinghan; Liu, Kang; Zheng, Yi; Dai, Zhijun

2016-12-27

The prognostic nutritional index (PNI) has been reported to correlate with the prognosis in patients with various malignancies. We performed a meta-analysis to determine the predictive potential of PNI in digestive system cancers. Twenty-three studies with a total of 7,384 patients suffering from digestive system carcinomas were involved in this meta-analysis. A lower PNI was significantly associated with the shorter overall survival (OS) [Hazard Ratio (HR) 1.83, 95% Confidence Interval (CI) 1.62-2.07], the poorer disease-free survival (DFS) (HR 1.85, 95% CI 1.19-2.89), and the higher rate of post-operative complications (HR 2.31, 95% CI 1.63-3.28). In conclusion, PNI was allowed to function as an efficient indicator for the prognosis of patients with digestive system carcinomas.

PKA spectral effects on subcascade structures and free defect survival ratio as estimated by cascade-annealing computer simulation

International Nuclear Information System (INIS)

Muroga, Takeo

1990-01-01

The free defect survival ratio is calculated by ''cascade-annealing'' computer simulation using the MARLOWE and modified DAIQUIRI codes in various cases of Primary Knock-on Atom (PKA) spectra. The number of subcascades is calculated by ''cut-off'' calculation using MARLOWE. The adequacy of these methods is checked by comparing the results with experiments (surface segregation measurements and Transmission Electron Microscope cascade defect observations). The correlation using the weighted average recoil energy as a parameter shows that the saturation of the free defect survival ratio at high PKA energies has a close relation to the cascade splitting into subcascades. (author)

Similar Survival for Patients Undergoing Reduced-Intensity Total Body Irradiation (TBI) Versus Myeloablative TBI as Conditioning for Allogeneic Transplant in Acute Leukemia

Energy Technology Data Exchange (ETDEWEB)

Mikell, John L., E-mail: jmikell@emory.edu [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Waller, Edmund K. [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Switchenko, Jeffrey M. [Department of Biostatistics and Bioinformatics, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Rangaraju, Sravanti; Ali, Zahir; Graiser, Michael [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Hall, William A. [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Langston, Amelia A. [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Esiashvili, Natia [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Khoury, H. Jean [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Khan, Mohammad K. [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

2014-06-01

Purpose: Hematopoietic stem cell transplantation (HSCT) is the mainstay of treatment for adults with acute leukemia. Total body irradiation (TBI) remains an important part of the conditioning regimen for HCST. For those patients unable to tolerate myeloablative TBI (mTBI), reduced intensity TBI (riTBI) is commonly used. In this study we compared outcomes of patients undergoing mTBI with those of patients undergoing riTBI in our institution. Methods and Materials: We performed a retrospective review of all patients with acute leukemia who underwent TBI-based conditioning, using a prospectively acquired database of HSCT patients treated at our institution. Patient data including details of the transplantation procedure, disease status, Karnofsky performance status (KPS), response rates, toxicity, survival time, and time to progression were extracted. Patient outcomes for various radiation therapy regimens were examined. Descriptive statistical analysis was performed. Results: Between June 1985 and July 2012, 226 patients with acute leukemia underwent TBI as conditioning for HSCT. Of those patients, 180 had full radiation therapy data available; 83 had acute lymphoblastic leukemia and 94 had acute myelogenous leukemia; 45 patients received riTBI, and 135 received mTBI. Median overall survival (OS) was 13.7 months. Median relapse-free survival (RFS) for all patients was 10.2 months. Controlling for age, sex, KPS, disease status, and diagnosis, there were no significant differences in OS or RFS between patients who underwent riTBI and those who underwent mTBI (P=.402, P=.499, respectively). Median length of hospital stay was shorter for patients who received riTBI than for those who received mTBI (16 days vs 23 days, respectively; P<.001), and intensive care unit admissions were less frequent following riTBI than mTBI (2.22% vs 12.69%, respectively, P=.043). Nonrelapse survival rates were also similar (P=.186). Conclusions: No differences in OS or RFS were seen between

Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma.

Science.gov (United States)

Reardon, D A; Dresemann, G; Taillibert, S; Campone, M; van den Bent, M; Clement, P; Blomquist, E; Gordower, L; Schultz, H; Raizer, J; Hau, P; Easaw, J; Gil, M; Tonn, J; Gijtenbeek, A; Schlegel, U; Bergstrom, P; Green, S; Weir, A; Nikolova, Z

2009-12-15

We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs). A total of 231 patients with GBM at first recurrence from 21 institutions in 10 countries were enrolled. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 600 mg per day for patients not on EIAEDs and at 500 mg twice a day if on EIAEDs. The primary end point was radiographic response rate and secondary end points were safety, progression-free survival at 6 months (PFS-6), and overall survival (OS). The radiographic response rate after centralised review was 3.4%. Progression-free survival at 6 months and median OS were 10.6% and 26.0 weeks, respectively. Outcome did not appear to differ based on EIAED status. The most common grade 3 or greater adverse events were fatigue (7%), neutropaenia (7%), and thrombocytopaenia (7%). Imatinib in addition to hydroxyurea was well tolerated among patients with recurrent GBM but did not show clinically meaningful anti-tumour activity.

Development and internal validation of a prognostic model to predict recurrence free survival in patients with adult granulosa cell tumors of the ovary

NARCIS (Netherlands)

van Meurs, Hannah S.; Schuit, Ewoud; Horlings, Hugo M.; van der Velden, Jacobus; van Driel, Willemien J.; Mol, Ben Willem J.; Kenter, Gemma G.; Buist, Marrije R.

2014-01-01

Models to predict the probability of recurrence free survival exist for various types of malignancies, but a model for recurrence free survival in individuals with an adult granulosa cell tumor (GCT) of the ovary is lacking. We aimed to develop and internally validate such a prognostic model. We

Bone marrow vascular endothelial growth factor level per platelet count might be a significant predictor for the treatment outcomes of patients with diffuse large B-cell lymphomas.

Science.gov (United States)

Kim, Jung Sun; Gang, Ga Won; Lee, Se Ryun; Sung, Hwa Jung; Park, Young; Kim, Dae Sik; Choi, Chul Won; Kim, Byung Soo

2015-10-01

Developing a parameter to predict bone marrow invasion by non-Hodgkin's lymphoma is an important unmet medical need for treatment decisions. This study aimed to confirm the validity of the hypothesis that bone marrow plasma vascular endothelial growth factor level might be correlated with the risk of bone marrow involvement and the prognosis of patients with diffuse large B-cell non-Hodgkin's lymphoma. Forty-nine diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone regimen were enrolled. Vascular endothelial growth factor level was measured with enzyme-linked immunosorbent assay. The validity of bone marrow plasma vascular endothelial growth factor level and bone marrow vascular endothelial growth factor level per platelet count for predicting treatment response and survival after initial rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone combined chemotherapy was assessed. Bone marrow plasma vascular endothelial growth factor level per platelet count was significantly associated with old age (≥ 65 years), poor performance score (≥ 2), high International prognosis index (≥ 3) and bone marrow invasion. The patients with high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) showed a significantly lower complete response rate than the others. On Kaplan-Meier survival curves, the patients with high bone marrow plasma vascular endothelial growth factor levels (≥ 655 pg/ml) or high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) demonstrated a significantly shorter overall survival and progression-free survival than the others. In the patients without bone marrow involvement, bone marrow plasma vascular endothelial growth factor level per platelet count had a significant relationship with overall survival and progression-free survival. Multivariate analysis revealed that the patients without

Role of MRI in the management of children with diffuse pontine tumors: a study of 15 patients and review of the literature

Energy Technology Data Exchange (ETDEWEB)

Kornreich, Liora; Schwarz, Michael; Karmazyn, Boaz; Horev, Gadi [Schneider Children' s Medical Center of Israel, Department of Imaging, Petah Tiqva (Israel); Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel); Cohen, Ian J.; Shuper, Avinoam; Yaniv, Issac [Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel); Schneider Children' s Medical Center of Israel, Department of Hematology-Oncology, Petah Tiqva (Israel); Michovitz, Shalom [Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel); Schneider Children' s Medical Center of Israel, Department of Neurosurgery, Petah Tiqva (Israel); Fenig, Eyal [Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel); Rabin Medical Center,Beilinson Campus, Institute of Oncology, Radiotherapy Unit, Petah Tiqva (Israel)

2005-09-01

Pontine tumors carry the worst prognosis of all brain tumors. In most cases, the diagnosis is based solely on MR imaging, without biopsy. To describe the MR findings of pontine tumors at diagnosis and during follow-up and correlate those with prognosis and to assess the value of MR imaging in patient management compared to clinical evaluation. Ninety-one MR scans of 15 children with diffuse pontine tumors were reviewed at diagnosis and during follow-up. The parameters analyzed were as follows: tumor extent, area, and volume; encasement of the basilar artery; presence of exophytic component; necrosis; cysts; hydrocephalus; and intensity and enhancement. Findings were correlated to length of progression-free and overall survival. Trends of amelioration or worsening on imaging were compared with the clinical findings. Median length of progression-free survival was 10 months, and median survival was 20 months. Only hydrocephalus at presentation was associated with shorter progression-free survival (P=0.02). On the last examination of each patient, the craniocaudal diameter was significantly greater than at diagnosis (P=0.03). The concordance between the imaging and the clinical findings was good. MR is the mainstay for the diagnosis and management of pontine tumors. Cranial growth seems to be an ominous sign. However, the prognostic value of MR is limited. MR findings correlate well with the clinical examination. (orig.)

Progress of long coated conductors fabrication with fluorine-free CSD method at SWJTU

International Nuclear Information System (INIS)

Zhao, Y.; Wang, W.T.; Lei, M.; Pu, M.H.; Zhang, Y.; Cheng, C.H.

2013-01-01

Highlights: • Recent progress on the long coated conductors fabrication by F-free CSD method is presented. • Single buffer and partial-melting technology and slot-die coating methods have been developed. • Reel-to-reel facilities for continuous process have been achieved. -- Abstract: Recent progress on the fabrication of long high-T c superconducting coated conductors with a fluorine-free chemical solution deposition (CSD) method is presented. Developments including such novel methods as single buffer technology, partial-melting process on YBa 2 Cu 3 O 7 (YBCO), slot-die coating and drying; reel-to-reel facilities for continuous process have been achieved in the effort on high-T c superconducting coated conductors at SWJTU, which form a comprehensive technology to fabricate long coated tapes with high performances

Progress of long coated conductors fabrication with fluorine-free CSD method at SWJTU

Energy Technology Data Exchange (ETDEWEB)

Zhao, Y., E-mail: yzhao@swjtu.edu.cn [Key Lab of Advanced Materials Technologies, Key Lab of Magnetic Levitation Technologies and Maglev Trains (Ministry of Education), Superconductivity and New Energy Center (SNEC), Southwest Jiaotong University, Chengdu 610031 (China); School of Materials Science and Engineering, University of New South Wales, Sydney 2052, NSW (Australia); Wang, W.T.; Lei, M.; Pu, M.H.; Zhang, Y. [Key Lab of Advanced Materials Technologies, Key Lab of Magnetic Levitation Technologies and Maglev Trains (Ministry of Education), Superconductivity and New Energy Center (SNEC), Southwest Jiaotong University, Chengdu 610031 (China); Cheng, C.H. [School of Materials Science and Engineering, University of New South Wales, Sydney 2052, NSW (Australia)

2013-10-15

Highlights: • Recent progress on the long coated conductors fabrication by F-free CSD method is presented. • Single buffer and partial-melting technology and slot-die coating methods have been developed. • Reel-to-reel facilities for continuous process have been achieved. -- Abstract: Recent progress on the fabrication of long high-T{sub c} superconducting coated conductors with a fluorine-free chemical solution deposition (CSD) method is presented. Developments including such novel methods as single buffer technology, partial-melting process on YBa{sub 2}Cu{sub 3}O{sub 7} (YBCO), slot-die coating and drying; reel-to-reel facilities for continuous process have been achieved in the effort on high-T{sub c} superconducting coated conductors at SWJTU, which form a comprehensive technology to fabricate long coated tapes with high performances.

Early Prognostic Value of Monitoring Serum Free Light Chain in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation.

Science.gov (United States)

Özkurt, Zübeyde Nur; Sucak, Gülsan Türköz; Akı, Şahika Zeynep; Yağcı, Münci; Haznedar, Rauf

2017-03-16

We hypothesized the levels of free light chains obtained before and after autologous stem cell transplantation can be useful in predicting transplantation outcome. We analyzed 70 multiple myeloma patients. Abnormal free light chain ratios before stem cell transplantation were found to be associated early progression, although without any impact on overall survival. At day +30, the normalization of levels of involved free light chain related with early progression. According to these results almost one-third reduction of free light chain levels can predict favorable prognosis after autologous stem cell transplantation.

Comparing survival outcomes of gross total resection and subtotal resection with radiotherapy for craniopharyngioma: a meta-analysis.

Science.gov (United States)

Wang, Guoqing; Zhang, Xiaoyang; Feng, Mengzhao; Guo, Fuyou

2018-06-01

Recent studies suggest that subtotal resection (STR) followed by radiation therapy (RT) is an appealing alternative to gross total resection (GTR) for craniopharyngioma, but it remains controversial. We conducted a meta-analysis to determine whether GTR is superior to STR with RT for craniopharyngioma. A systematic search was performed for articles published until October 2017 in the PubMed, Embase, and Cochrane Central databases. The endpoints of interest are overall survival and progression-free survival. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated using a fixed or random-effects model. The data were analyzed using Review Manager 5.3 software. A total of 744 patients (seven cohort studies) were enrolled for analyses. There were no significant differences between the GTR and STR with RT groups when the authors compared the pooled HRs at the end of the follow-up period. Overall survival (pooled HR = 0.76, 95% CI: 0.46-1.25, P = 0.28) and progression-free survival (pooled HR = 1.52, 95% CI: 0.42-5.44, P = 0.52) were similar between the two groups. The current meta-analysis suggests that GTR and STR with RT have the similar survival outcomes for craniopharyngioma. Copyright © 2018 Elsevier Inc. All rights reserved.

Use of various free flaps in progressive hemifacial atrophy.

Science.gov (United States)

Baek, Rongmin; Heo, Chanyeong; Kim, Baek-kyu

2011-11-01

Romberg disease is an uncommon condition manifested by progressive hemifacial atrophy of the skin, soft tissue, and bone. Facial asymmetry with soft tissue deficiency in Romberg disease causes a significant disability affecting the social life and can bring about many psychological problems. The aim of surgical treatment is cosmetic amelioration of the defect. Several conventional reconstructive procedures have been used for correcting facial asymmetry. They include fat injections, dermal fat grafts, filler injections, cartilage and bone grafts, and pedicled and free flaps. We report our experiences with 11 patients involving 11 free flaps with a minimum 1-year follow-up. All patients were classified as having moderate to severe atrophy. The average age at disease onset was 4.5 years; the average duration of atrophy was 5.2 years. No patients were operated on with a quiescent interval of less than 1 year. The average age at operation was 20.1 years, ranging from 10 to 55 years. Reconstruction was performed using 4 groin dermofat free flaps, 4 latissimus dorsi muscle free flaps, and 3 other perforator flaps. To achieve the finest symmetrical and aesthetic results, several ancillary procedures were performed in 4 patients. These procedures included Le Fort I leveling osteotomy, sagittal split ramus osteotomy, reduction malarplasty and angle plasty, rib and calvarial bone graft, correction of alopecia, and additional fat graft. All patients were satisfied with the results. We believe that a free flap transfer is the requisite treatment modality for severe degree of facial asymmetry in Romberg disease.

Prognostic value of preoperative Ca125 and Tag72 serum levels and their correlation to disease relapse and survival in endometrial cancer.

Science.gov (United States)

Myriokefalitaki, Eva; Vorgias, George; Vlahos, George; Rodolakis, Alexandros

2015-09-01

To evaluate preoperative serum levels of Ca125 and Tag72-4 tumour markers and investigate if abnormal levels correlate to mortality and disease-free survival. Retrospective observational study of a cohort of 282 women (mean age 62.3, SD 10.5 years) with primary endometrial cancer included all consecutive cases treated in a tertiary Gynaecological oncology Center. Excluded cases with other cancer or previous cancer treatment, major abdominal pathology or inflammation, endometriosis. Preoperative serum Tag72 and Ca125 levels were determined and evaluated in relation to disease-free survival (DFS) and disease-specific overall survival (DOS). Raised Ca125 correlates to worse overall disease-specific survival (66.1 vs 87.8 months, p = 0.021) and Tag72 correlates to shorter disease-free survival (69.2 vs 67.3 months, p = 0.021) and higher recurrence rate (13.5 vs 6 %, p = 0.021). When both Ca125 and Tag72 are abnormal DFS and DOS are worse. 93.3 % (72.3 months) vs 82.4 %, (61.3 months) p = 0.018 and 96.3 % (74.8 months) vs 88.2 %, (65.9 months) p = 0.021, respectively. This study enhances the value of preoperative tumour markers and their prognostic value. Ca125 and Tag72 appear to be good predictors of poor prognosis in patients with endometrial cancer.

DNA-dependent protein kinase catalytic subunit functions in metastasis and influences survival in advanced-stage laryngeal squamous cell carcinoma.

Science.gov (United States)

He, Sha-Sha; Chen, Yong; Shen, Xiao-Ming; Wang, Hong-Zhi; Sun, Peng; Dong, Jun; Guo, Gui-Fang; Chen, Ju-Gao; Xia, Liang-Ping; Hu, Pei-Li; Qiu, Hui-Juan; Liu, Shou-Sheng; Zhou, Yi-Xin; Wang, Wei; Hu, Wei-Han; Cai, Xiu-Yu

2017-01-01

Background: DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is known to function in several types of cancer. In this study, we investigated the expression and clinicopathologic significance of DNA-PKcs in laryngeal squamous cell carcinoma (LSCC). Methods: We conducted a retrospective study of 208 patients with advanced-stage LSCC treated at Sun Yat-sen University Cancer Center, Guangzhou, China. We assessed DNA-PKcs and p16INK4a (p16) status using immunohistochemistry. We examined the association between DNA-PKcs expression and clinicopathologic features and survival outcomes. To evaluate the independent prognostic relevance of DNA-PKcs, we used univariate and multivariate Cox regression models. We estimated overall survival (OS) and distant metastasis-free survival (DMFS) using the Kaplan-Meier method. Results: Immunohistochemical analyses revealed that 163/208 (78.4%) of the LSCC tissue samples exhibited high DNA-PKcs expression. High DNA-PKcs expression was significantly associated with survival outcomes ( P = 0.016) and distant metastasis ( P = 0.02; chi-squared test). High DNA-PKcs expression was associated with a significantly shorter OS and DMFS than low DNA-PKcs expression ( P = 0.029 and 0.033, respectively; log-rank test), and was associated with poor OS in the p16-positive subgroup ( P = 0.047). Multivariate analysis identified DNA-PKcs as an independent prognostic indicator of OS and DMFS in all patients ( P = 0.039 and 0.037, respectively). Conclusions : Our results suggest that patients with LSCC in whom DNA-PKcs expression is elevated have a higher incidence of distant metastasis and a poorer prognosis. DNA-PKcs may represent a marker of tumor progression in patients with p16-positive LSCC.

Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression

DEFF Research Database (Denmark)

Laklai, Hanane; Miroshnikova, Yekaterina A.; Pickup, Michael W.

2016-01-01

by increasing matricellular fibrosis and tissue tension. In contrast, epithelial STAT3 ablation attenuated tumor progression by reducing the stromal stiffening and epithelial contractility induced by loss of TGF-β signaling. In PDAC patient biopsies, higher matricellular protein and activated STAT3 were......Fibrosis compromises pancreatic ductal carcinoma (PDAC) treatment and contributes to patient mortality, yet antistromal therapies are controversial. We found that human PDACs with impaired epithelial transforming growth factor-β (TGF-β) signaling have high epithelial STAT3 activity and develop...... stiff, matricellular-enriched fibrosis associated with high epithelial tension and shorter patient survival. In several KRAS-driven mouse models, both the loss of TGF-β signaling and elevated β1-integrin mechanosignaling engaged a positive feedback loop whereby STAT3 signaling promotes tumor progression...

Label-free SERS in biological and biomedical applications: Recent progress, current challenges and opportunities

Science.gov (United States)

Zheng, Xiao-Shan; Jahn, Izabella Jolan; Weber, Karina; Cialla-May, Dana; Popp, Jürgen

2018-05-01

To achieve an insightful look within biomolecular processes on the cellular level, the development of diseases as well as the reliable detection of metabolites and pathogens, a modern analytical tool is needed that is highly sensitive, molecular-specific and exhibits fast detection. Surface-enhanced Raman spectroscopy (SERS) is known to meet these requirements and, within this review article, the recent progress of label-free SERS in biological and biomedical applications is summarized and discussed. This includes the detection of biomolecules such as metabolites, nucleic acids and proteins. Further, the characterization and identification of microorganisms has been achieved by label-free SERS-based approaches. Eukaryotic cells can be characterized by SERS in order to gain information about the outer cell wall or to detect intracellular molecules and metabolites. The potential of SERS for medically relevant detection schemes is emphasized by the label-free detection of tissue, the investigation of body fluids as well as applications for therapeutic and illicit drug monitoring. The review article is concluded with an evaluation of the recent progress and current challenges in order to highlight the direction of label-free SERS in the future.

Overall survival patterns in patients with multiple myeloma in the era of novel agents and the role of initial clinical presentation and comorbidities: A population-based study

NARCIS (Netherlands)

Oortgiesen, Berdien; Van Roon, Eric N.; Joosten, Peter; Kibbelaar, Robby; Storm, Huib; Hovenga, Sjoerd; Van Rees, Bas P.; Woolthuis, Gerhard; Veeger, Nic J. G. M.; Hoogendoorn, Mels

2014-01-01

Introduction Clinical trials have shown improved response rates, progression-free survival and overall survival (OS) in patients with multiple myeloma (MM) when using the novel agents thalidomide, lenalidomide and bortezomib. However, outcome data provided by population-based registries, reflecting

Negative effect of cyclin D1 overexpression on recurrence-free survival in stage II-IIIA lung adenocarcinoma and its expression modulation by vorinostat in vitro.

Science.gov (United States)

Lee, Eunju; Jin, DongHao; Lee, Bo Bin; Kim, Yujin; Han, Joungho; Shim, Young Mog; Kim, Duk-Hwan

2015-12-17

This study was aimed at identifying prognostic biomarkers for stage II-IIIA non-small cell lung cancer (NSCLC) according to histology and at investigating the effect of vorinostat on the expression of these biomarkers. Expression levels of cyclin D1, cyclin A2, cyclin E, and p16 proteins that are involved in the G1-to-S phase progression of cell cycle were analyzed using immunohistochemistry in formalin-fixed paraffin-embedded tissues from 372 samples of stage II-IIIA NSCLC. The effect of vorinostat on the expression of these proteins, impacts on cell cycle, and histone modification was explored in lung cancer cells. Abnormal expression of cyclin A2, cyclin D1, cyclin E, and p16 was found in 66, 47, 34, and 51 % of 372 cases, respectively. Amongst the four proteins, only cyclin D1 overexpression was significantly associated with poor recurrence-free survival (adjusted hazard ratio = 1.87; 95 % confidence interval = 1.12 - 2.69, P = 0.02) in adenocarcinoma but not in squamous cell carcinoma (P = 0.44). Vorinostat inhibited cell cycle progression to the S-phase and induced down-regulation of cyclin D1 in vitro. The down-regulation of cyclin D1 by vorinostat was comparable to a siRNA-mediated knockdown of cyclin D1 in A549 cells, but vorinostat in the presence of benzo[a]pyrene showed a differential effect in different lung cancer cell lines. Cyclin D1 down-regulation by vorinostat was associated with the accumulation of dimethyl-H3K9 at the promoter of the gene. The present study suggests that cyclin D1 may be an independent prognostic factor for recurrence-free survival in stage II-IIIA adenocarcinoma of lung and its expression may be modulated by vorinostat.

Management plan for deep sternal wound infection targeting to survival free of recurrence: A prospective evaluation study

Directory of Open Access Journals (Sweden)

Ibrahim Kasb

2016-10-01

Conclusion: Management of DSWI is tedious, has prolonged hospital stay and is associated with high morbidity and mortality rates. Management of DSWI must be personalized according to findings on exploration of the sternal wound and flap coverage must be initiated only when the patient is bacteriologically free. Both PMF and/or VOF provided high acceptable success rate defined as survival free of DSWI recurrence.

Evaluating the Impact of Zimbabwe's Prevention of Mother-to-Child HIV Transmission Program: Population-Level Estimates of HIV-Free Infant Survival Pre-Option A.

Science.gov (United States)

Buzdugan, Raluca; McCoy, Sandra I; Watadzaushe, Constancia; Kang Dufour, Mi-Suk; Petersen, Maya; Dirawo, Jeffrey; Mushavi, Angela; Mujuru, Hilda Angela; Mahomva, Agnes; Musarandega, Reuben; Hakobyan, Anna; Mugurungi, Owen; Cowan, Frances M; Padian, Nancy S

2015-01-01

We estimated HIV-free infant survival and mother-to-child HIV transmission (MTCT) rates in Zimbabwe, some of the first community-based estimates from a UNAIDS priority country. In 2012 we surveyed mother-infant pairs residing in the catchment areas of 157 health facilities randomly selected from 5 of 10 provinces in Zimbabwe. Enrolled infants were born 9-18 months before the survey. We collected questionnaires, blood samples for HIV testing, and verbal autopsies for deceased mothers/infants. Estimates were assessed among i) all HIV-exposed infants, as part of an impact evaluation of Option A of the 2010 WHO guidelines (rolled out in Zimbabwe in 2011), and ii) the subgroup of infants unexposed to Option A. We compared province-level MTCT rates measured among women in the community with MTCT rates measured using program monitoring data from facilities serving those communities. Among 8568 women with known HIV serostatus, 1107 (12.9%) were HIV-infected. Among all HIV-exposed infants, HIV-free infant survival was 90.9% (95% confidence interval (CI): 88.7-92.7) and MTCT was 8.8% (95% CI: 6.9-11.1). Sixty-six percent of HIV-exposed infants were still breastfeeding. Among the 762 infants born before Option A was implemented, 90.5% (95% CI: 88.1-92.5) were alive and HIV-uninfected at 9-18 months of age, and 9.1% (95%CI: 7.1-11.7) were HIV-infected. In four provinces, the community-based MTCT rate was higher than the facility-based MTCT rate. In Harare, the community and facility-based rates were 6.0% and 9.1%, respectively. By 2012 Zimbabwe had made substantial progress towards the elimination of MTCT. Our HIV-free infant survival and MTCT estimates capture HIV transmissions during pregnancy, delivery and breastfeeding regardless of whether or not mothers accessed health services. These estimates also provide a baseline against which to measure the impact of Option A guidelines (and subsequently Option B+).

The impact of intraoperative opioid use on survival after oral cancer surgery.

Science.gov (United States)

Patino, Miguel A; Ramirez, Rafael E; Perez, Carlos A; Feng, Lei; Kataria, Pranav; Myers, Jeffrey; Cata, Juan P

2017-11-01

To investigate the impact of opioid use on cancer recurrence after oral cancer surgery. We hypothesized that the amount of opioids administered during oral cancer surgery is an independent predictor of recurrence free survival (RFS) and overall survival (OS). After Institutional Review Board approval, we collected demographic, tumor related, intraoperative and survival data of patients who had oral cancer surgery. Multivariable Cox proportional hazards models were used to determine the impact of important covariates on RFS and OS. 268 patients were included. After adjusting for significant covariates, the amount of opioids administered during surgery was not an independent predictor of RFS (HR: 1.27 [CI 95%, 0.838-1.924], p=0.26). However, we observed an association between opioid consumption and shorter OS (HR=1.77, [CI 95%=0.995-3.149]. p=0.05). High requirements of opioids during surgery increase the risk of recurrence and mortality by 27% and 77%, although the association is not statically significant. Copyright © 2017 Elsevier Ltd. All rights reserved.

EGFR inhibitor erlotinib delays disease progression but does not extend survival in the SOD1 mouse model of ALS.

Directory of Open Access Journals (Sweden)

Claire E Le Pichon

Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease that causes progressive paralysis due to motor neuron death. Several lines of published evidence suggested that inhibition of epidermal growth factor receptor (EGFR signaling might protect neurons from degeneration. To test this hypothesis in vivo, we treated the SOD1 transgenic mouse model of ALS with erlotinib, an EGFR inhibitor clinically approved for oncology indications. Although erlotinib failed to extend ALS mouse survival it did provide a modest but significant delay in the onset of multiple behavioral measures of disease progression. However, given the lack of protection of motor neuron synapses and the lack of survival extension, the small benefits observed after erlotinib treatment appear purely symptomatic, with no modification of disease course.

Surrogacy of progression free survival for overall survival in metastatic breast cancer studies: Meta-analyses of published studies.

Science.gov (United States)

Kundu, Madan G; Acharyya, Suddhasatta

2017-02-01

PFS is often used as a surrogate endpoint for OS in metastatic breast cancer studies. We have evaluated the association of treatment effect on PFS with significant HR OS (and how this association is affected by other factors) in published prospective metastatic breast cancer studies. A systematic literature search in PubMed identified prospective metastatic breast cancer studies. Treatment effects on PFS were determined using hazard ratio (HR PFS ), increase in median PFS (ΔMED PFS ) and % increase in median PFS (%ΔMED PFS ). Diagnostic accuracy of PFS measures (HR PFS , ΔMED PFS and %ΔMED PFS ) in predicting significant HR OS was assessed using receiver operating characteristic (ROC) curves and classification tree approach (CART). Seventy-four cases (i.e., treatment to control comparisons) from 65 individual publications were identified for the analyses. Of these, 16 cases reported significant treatment effect on HR OS at 5% level of significance. Median number of deaths reported in these cases were 153. Area under the ROC curve (AUC) for diagnostic measures as HR PFS , ΔMED PFS and %ΔMED PFS were 0.69, 0.70 and 0.75, respectively. Classification tree results identified %ΔMED PFS and number of deaths as diagnostic measure for significant HR OS . Only 7.9% (3/39) cases with ΔMED PFS shorter than 48.27% reported significant HR OS . There were 7 cases with ΔMED PFS of 48.27% or more and number of deaths reported as 227 or more - of these 5 cases reported significant HR OS . %ΔMED PFS was found to be a better diagnostic measure for predicting significant HR OS . Our analysis results also suggest that consideration of total number of deaths may further improve its diagnostic performance. Based on our study results, the studies with 50% improvement in median PFS are more likely to produce significant HR OS if the total number of OS events at the time of analysis is 227 or more. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of Laterality on Surgical Outcome of Glioblastoma Patients: A Retrospective Single-Center Study.

Science.gov (United States)

Coluccia, Daniel; Roth, Tabitha; Marbacher, Serge; Fandino, Javier

2018-06-01

Resection of left hemisphere (LH) tumors is often complicated by the risks of causing language dysfunction. Although neurosurgeons' concerns when operating on the presumed dominant hemisphere are well known, literature evaluating laterality as a predictive surgical parameter in glioblastoma (GB) patients is sparse. We evaluated whether tumor laterality correlated with surgical performance, functional outcome, and survival. All patients with GB treated at our institution between 2006 and 2016 were reviewed. Analysis comprised clinical characteristics, extent of resection (EOR), neurologic outcome, and survival in relation to tumor lateralization. Two hundred thirty-five patients were included. Right hemisphere (RH) tumors were larger and more frequently extended into the frontal lobe. Preoperatively, limb paresis was more frequent in RH, whereas language deficits were more frequent in LH tumors (P = 0.0009 and P < 0.0001, respectively). At 6 months after resection, LH patients presented lower Karnofsky Performance Status (KPS) score (P = 0.036). More patients with LH tumors experienced dysphasia (P < 0.0001), and no difference was seen for paresis. Average EOR was comparable, but complete resection was achieved less often in LH tumors (37.7 vs. 64.8%; P = 0.0028). Although overall survival did not differ between groups, progression-free survival was shorter in LH tumors (7.4 vs. 10.1 months; P = 0.0225). Patients with LH tumors had a pronounced KPS score decline and shorter progression-free survival without effects on overall survival. This observation might partially be attributed to a more conservative surgical resection. Further investigation is needed to assess whether systematic use of awake surgery and intraoperative mapping results in increased EOR and improved quality survival of patients with GB. Copyright © 2018 Elsevier Inc. All rights reserved.

Extracellular tumor-related mRNA in plasma of lymphoma patients and survival implications.

Directory of Open Access Journals (Sweden)

Vanesa Garcia

Full Text Available BACKGROUND: We studied anomalous extracellular mRNAs in plasma from patients with diffuse large B-cell lymphoma (DLBCL and their survival implications. mRNAs studied have been reported in the literature as markers of poor (BCL2, CCND2, MYC and favorable outcome (LMO2, BCL6, FN1 in tumors. These markers were also analyzed in lymphoma tissues to test possible associations with their presence in plasma. METHODOLOGY/PRINCIPAL FINDINGS: mRNA from 42 plasma samples and 12 tumors from patients with DLBCL was analyzed by real-time PCR. Samples post-treatment were studied. The immunohistochemistry of BCL2 and BCL6 was defined. Presence of circulating tumor cells was determined by analyzing the clonality of the immunoglobulin heavy-chain genes by PCR. In DLBCL, MYC mRNA was associated with short overall survival. mRNA targets with unfavorable outcome in tumors were associated with characteristics indicative of poor prognosis, with partial treatment response and with short progression-free survival in patients with complete response. In patients with low IPI score, unfavorable mRNA targets were related to shorter overall survival, partial response, high LDH levels and death. mRNA disappeared in post-treatment samples of patients with complete response, and persisted in those with partial response or death. No associations were found between circulating tumor cells and plasma mRNA. Absence of BCL6 protein in tumors was associated with presence of unfavorable plasma mRNA. CONCLUSIONS/SIGNIFICANCE: Through a non-invasive procedure, tumor-derived mRNAs can be obtained in plasma. mRNA detected in plasma did not proceed from circulating tumor cells. In our study, unfavorable targets in plasma were associated with poor prognosis in B-cell lymphomas, mainly MYC mRNA. Moreover, the unfavorable targets in plasma could help us to classify patients with poor outcome within the good prognosis group according to IPI.

Polymorphisms associated with everolimus pharmacokinetics, toxicity and survival in metastatic breast cancer.

Directory of Open Access Journals (Sweden)

Tomas Pascual

Full Text Available Metastatic breast cancer (MBC progressing after endocrine therapy frequently activates PI3K/AKT/mTOR pathway. The BOLERO-2 trial showed that everolimus-exemestane achieves increased progression free survival (PFS compared with exemestane. However, there is great inter-patient variability in toxicity and response to exemestane-everolimus treatment. The objective of this study was to perform an exploratory study analyzing the implication of single nucleotide polymorphisms (SNPs on outcomes from this treatment through a pharmacogenetic analysis.Blood was collected from 90 postmenopausal women with hormone receptor-positive, HER2-negative MBC treated with exemestane-everolimus following progression after prior treatment with a non-steroidal aromatase inhibitor. Everolimus pharmacokinetics was measured in 37 patients. Twelve SNPs in genes involved in everolimus pharmacokinetics and pharmacodynamics were genotyped and associations assessed with drug plasma levels, clinically relevant toxicities (non-infectious pneumonitis, mucositis, hyperglycemia and hematological toxicities, dose reductions or treatment suspensions due to toxicity, progression free survival (PFS and overall survival.We found that CYP3A4 rs35599367 variant (CYP3A4*22 allele carriers had higher everolimus blood concentration compared to wild type patients (P = 0.019. ABCB1 rs1045642 was associated with risk of mucositis (P = 0.031, while PIK3R1 rs10515074 and RAPTOR rs9906827 were associated with hyperglycemia and non-infectious pneumonitis (P = 0.016 and 0.024, respectively. Furthermore, RAPTOR rs9906827 was associated with PFS (P = 0.006.CYP3A4*22 allele influenced plasma concentration of everolimus and several SNPs in PI3K/AKT/mTOR pathway genes were associated with treatment toxicities and prognosis. These results require replication, but suggest that germline variation could influence everolimus outcomes in MBC.

Phase II study of cabozantinib in patients with progressive glioblastoma: subset analysis of patients naive to antiangiogenic therapy

Science.gov (United States)

Drappatz, Jan; de Groot, John; Prados, Michael D; Reardon, David A; Schiff, David; Chamberlain, Marc; Mikkelsen, Tom; Desjardins, Annick; Holland, Jaymes; Ping, Jerry; Weitzman, Ron; Cloughesy, Timothy F

2018-01-01

Abstract Background Cabozantinib is a tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 (VEGFR2) and MET that has demonstrated clinical activity in advanced solid tumors. This open-label, phase II trial evaluated cabozantinib in patients with recurrent or refractory glioblastoma (GBM). Methods Patients were initially enrolled at a starting dose of 140 mg/day, but the starting dose was amended to 100 mg/day because of toxicity. Treatment continued until disease progression or unacceptable toxicity. The primary endpoint was objective response rate assessed by an independent radiology facility using modified Response Assessment in Neuro-Oncology criteria. Additional endpoints included duration of response, 6-month and median progression-free survival, overall survival, and safety. Results Among 152 patients naive to prior antiangiogenic therapy, the objective response rate was 17.6% and 14.5% in the 140 mg/day and 100 mg/day groups, respectively, which did not meet the predefined statistical target for success. The proportions of patients alive and progression free at 6 months were 22.3% and 27.8%, respectively. Median progression-free survival was 3.7 months in both groups, and median overall survival was 7.7 months and 10.4 months, respectively. The incidence of grade 3/4 adverse events (AEs) was 79.4% and 84.7% in the 140 mg/day and 100 mg/day groups, respectively, and dose reductions due to AEs were experienced by 61.8% and 72.0%, respectively. Common grade 3/4 AEs included fatigue, diarrhea, and palmar-plantar erythrodysesthesia syndrome. Conclusions Cabozantinib showed evidence of clinical activity in patients with recurrent GBM naive to antiangiogenic therapy, although the predefined statistical target for success was not met. At the starting doses assessed, AEs were frequently managed with dose reductions. Clinical Trials Registration Number NCT00704288 (https://www.clinicaltrials.gov/ct2/show/NCT00704288) PMID

Stereotactic body radiation therapy for liver oligo-recurrence and oligo-progression from various tumors

Energy Technology Data Exchange (ETDEWEB)

Cha, Yu Jin; Kim, Mi Sook; Jang, Won Il; Seo, Young Seok; Cho, Chul Koo; Yoo, Hyung Jun; Paik, Eun Kyung [Dept. of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2017-06-15

To evaluate the outcomes of stereotactic body radiation therapy (SBRT) for patients with liver oligo-recurrence and oligo-progression from various primary tumors. Between 2002 and 2013, 72 patients with liver oligo-recurrence (oligo-metastasis with a controlled primary tumor) and oligo-progression (contradictory progression of a few sites of disease despite an overall tumor burden response to therapy) underwent SBRT. Of these, 9 and 8 patients with uncontrollable distant metastases and patients immediate loss to follow-up, respectively, were excluded. The total planning target volume was used to select the SBRT dose (median, 48 Gy; range, 30 to 60 Gy, 3–4 fractions). Toxicity was evaluated using the Common Toxicity Criteria for Adverse Events v4.0. We evaluated 55 patients (77 lesions) treated with SBRT for liver metastases. All patients had controlled primary lesions, and 28 patients had stable lesions at another site (oligo-progression). The most common primary site was the colon (36 patients), followed by the stomach (6 patients) and other sites (13 patients). The 2-year local control and progression-free survival rates were 68% and 22%, respectively. The 2- and 5-year overall survival rates were 56% and 20%, respectively. The most common adverse events were grade 1–2 fatigue, nausea, and vomiting; no grade ≥3 toxicities were observed. Univariate analysis revealed that oligo-progression associated with poor survival. SBRT for liver oligo-recurrence and oligo-progression appears safe, with similar local control rates. For liver oligo-progression, criteria are needed to select patients in whom improved overall survival can be expected through SBRT.

Detection methods predict differences in biology and survival in breast cancer patients

International Nuclear Information System (INIS)

Redondo, Maximino; Pereda, Teresa; Domingo, Laia; Morales-Suarez Varela, María; Sala, Maria; Rueda, Antonio; Funez, Rafael; Medina-Cano, Francisco; Rodrigo, Isabel; Acebal, Mercedes; Tellez, Teresa; Roldan, M Jose; Hortas, M Luisa; Bellinvia, Ana

2012-01-01

The aim of this study was to measure the biological characteristics involved in tumorigenesis and the progression of breast cancer in symptomatic and screen-detected carcinomas to identify possible differences. For this purpose, we evaluated clinical-pathological parameters and proliferative and apoptotic activities in a series of 130 symptomatic and 161 screen-detected tumors. After adjustment for the smaller size of the screen-detected carcinomas compared with symptomatic cancers, those detected in the screening program presented longer disease-free survival (RR = 0.43, CI = 0.19-0.96) and had high estrogen and progesterone receptor concentrations more often than did symptomatic cancers (OR = 3.38, CI = 1.72-6.63 and OR = 3.44, CI = 1.94-6.10, respectively). Furthermore, the expression of bcl-2, a marker of good prognosis in breast cancer, was higher and HER2/neu expression was lower in screen-detected cancers than in symptomatic cancers (OR = 1.77, CI = 1.01-3.23 and OR = 0.64, CI = 0.40-0.98, respectively). However, when comparing prevalent vs incident screen-detected carcinomas, prevalent tumors were larger (OR = 2.84, CI = 1.05-7.69), were less likely to be HER2/neu positive (OR = 0.22, CI = 0.08-0.61) and presented lower Ki67 expression (OR = 0.36, CI = 0.17-0.77). In addition, incident tumors presented a shorter survival time than did prevalent ones (RR = 4.88, CI = 1.12-21.19). Incident carcinomas include a variety of screen-detected carcinomas that exhibit differences in biology and prognosis relative to prevalent carcinomas. The detection method is important and should be taken into account when making therapy decisions

Phase II study of Gleevec® plus hydroxyurea in adults with progressive or recurrent low-grade glioma1

Science.gov (United States)

Reardon, David A.; Desjardins, Annick; Vredenburgh, James J.; Herndon, James E.; Coan, April; Gururangan, Sridharan; Peters, Katherine B.; McLendon, Roger; Sathornsumetee, Sith; Rich, Jeremy N.; Lipp, Eric S.; Janney, Dorothea; Friedman, Henry S.

2013-01-01

Background We evaluated the efficacy of imatinib plus hydroxyurea in patients with progressive/recurrent low-grade glioma. Methods A total of 64 patients with recurrent/progressive low-grade glioma were enrolled in this single-center study that stratified patients into astrocytoma and oligodendroglioma cohorts. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 400 mg per day for patients not on EIAEDs and at 500 mg twice a day if on EIAEDs. The primary endpoint was progression-free survival at 12 months (PFS-12) and secondary endpoints were safety, median progression-free survival and radiographic response rate. Results Thirty-two patients were enrolled into each cohort. Eleven patients (17%) had prior radiotherapy and 24 (38%) had received prior chemotherapy. The median PFS and PFS-12 were 11 months and 39%, respectively. Outcome did not differ between the histologic cohorts. No patient achieved a radiographic response. The most common grade 3 or greater adverse events were neutropenia (11%), thrombocytopenia (3%) and diarrhea (3%). Conclusions Imatinib plus hydroxyurea was well tolerated among recurrent/progressive LGG patients but this regimen demonstrated negligible anti-tumor activity. PMID:22371319

Evaluating the Impact of Zimbabwe’s Prevention of Mother-to-Child HIV Transmission Program: Population-Level Estimates of HIV-Free Infant Survival Pre-Option A

Science.gov (United States)

Buzdugan, Raluca; McCoy, Sandra I.; Watadzaushe, Constancia; Kang Dufour, Mi-Suk; Petersen, Maya; Dirawo, Jeffrey; Mushavi, Angela; Mujuru, Hilda Angela; Mahomva, Agnes; Musarandega, Reuben; Hakobyan, Anna; Mugurungi, Owen; Cowan, Frances M.; Padian, Nancy S.

2015-01-01

Objective We estimated HIV-free infant survival and mother-to-child HIV transmission (MTCT) rates in Zimbabwe, some of the first community-based estimates from a UNAIDS priority country. Methods In 2012 we surveyed mother-infant pairs residing in the catchment areas of 157 health facilities randomly selected from 5 of 10 provinces in Zimbabwe. Enrolled infants were born 9–18 months before the survey. We collected questionnaires, blood samples for HIV testing, and verbal autopsies for deceased mothers/infants. Estimates were assessed among i) all HIV-exposed infants, as part of an impact evaluation of Option A of the 2010 WHO guidelines (rolled out in Zimbabwe in 2011), and ii) the subgroup of infants unexposed to Option A. We compared province-level MTCT rates measured among women in the community with MTCT rates measured using program monitoring data from facilities serving those communities. Findings Among 8568 women with known HIV serostatus, 1107 (12.9%) were HIV-infected. Among all HIV-exposed infants, HIV-free infant survival was 90.9% (95% confidence interval (CI): 88.7–92.7) and MTCT was 8.8% (95% CI: 6.9–11.1). Sixty-six percent of HIV-exposed infants were still breastfeeding. Among the 762 infants born before Option A was implemented, 90.5% (95% CI: 88.1–92.5) were alive and HIV-uninfected at 9–18 months of age, and 9.1% (95%CI: 7.1–11.7) were HIV-infected. In four provinces, the community-based MTCT rate was higher than the facility-based MTCT rate. In Harare, the community and facility-based rates were 6.0% and 9.1%, respectively. Conclusion By 2012 Zimbabwe had made substantial progress towards the elimination of MTCT. Our HIV-free infant survival and MTCT estimates capture HIV transmissions during pregnancy, delivery and breastfeeding regardless of whether or not mothers accessed health services. These estimates also provide a baseline against which to measure the impact of Option A guidelines (and subsequently Option B+). PMID:26248197

S-1 monotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck after progression on platinum-based chemotherapy

International Nuclear Information System (INIS)

Yokota, Tomoya; Onozawa, Yusuke; Boku, Narikazu

2011-01-01

Platinum compounds play pivotal roles in treatment for squamous cell carcinoma of the head and neck. The objective was to evaluate the efficacy of S-1 monotherapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after failure of platinum-based chemotherapy. We retrospectively analyzed 39 consecutive patients with recurrent or metastatic squamous cell carcinoma of the head and neck who received S-1 monotherapy after failure of platinum-based chemotherapy or chemoradiotherapy at the Shizuoka Cancer Center between August 2003 and October 2010. S-1 was given orally twice daily (80 mg/m 2 /day) for 28 days followed by a 14-day rest. The median follow-up period in survivors was 31.5 months. Among 38 patients with measurable lesions, 9 (24%) showed partial response and 15 (39%) showed stable disease. The median progression-free survival was 4.9 months and the median overall survival was 13.2 months. The median progression-free survival for oropharyngeal cancer (n=7) was significantly longer than for other cancers (n=32) (14.9 vs. 4.7 months, P=0.035). The response rate in patients with a recurrence-free interval since the last platinum administration >6.0 months was significantly better than with a recurrence-free interval 6.0 months also showed a significantly better progression-free survival (6.0 vs. 2.6 months, P=0.045). The frequency of Grade 3/4 toxicities was less than 10%. S-1 monotherapy shows promising signs of efficacy and tolerability in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after failure of platinum-based chemotherapy in this retrospective cohort and warrants further investigation in this population. (author)

The Napoleon Complex: When Shorter Men Take More.

Science.gov (United States)

Knapen, Jill E P; Blaker, Nancy M; Van Vugt, Mark

2018-05-01

Inspired by an evolutionary psychological perspective on the Napoleon complex, we hypothesized that shorter males are more likely to show indirect aggression in resource competitions with taller males. Three studies provide support for our interpretation of the Napoleon complex. Our pilot study shows that men (but not women) keep more resources for themselves when they feel small. When paired with a taller male opponent (Study 1), shorter men keep more resources to themselves in a game in which they have all the power (dictator game) versus a game in which the opponent also has some power (ultimatum game). Furthermore, shorter men are not more likely to show direct, physical aggression toward a taller opponent (Study 2). As predicted by the Napoleon complex, we conclude that (relatively) shorter men show greater behavioral flexibility in securing resources when presented with cues that they are physically less competitive. Theoretical and practical implications are discussed.

Survival analysis with functional covariates for partial follow-up studies.

Science.gov (United States)

Fang, Hong-Bin; Wu, Tong Tong; Rapoport, Aaron P; Tan, Ming

2016-12-01

Predictive or prognostic analysis plays an increasingly important role in the era of personalized medicine to identify subsets of patients whom the treatment may benefit the most. Although various time-dependent covariate models are available, such models require that covariates be followed in the whole follow-up period. This article studies a new class of functional survival models where the covariates are only monitored in a time interval that is shorter than the whole follow-up period. This paper is motivated by the analysis of a longitudinal study on advanced myeloma patients who received stem cell transplants and T cell infusions after the transplants. The absolute lymphocyte cell counts were collected serially during hospitalization. Those patients are still followed up if they are alive after hospitalization, while their absolute lymphocyte cell counts cannot be measured after that. Another complication is that absolute lymphocyte cell counts are sparsely and irregularly measured. The conventional method using Cox model with time-varying covariates is not applicable because of the different lengths of observation periods. Analysis based on each single observation obviously underutilizes available information and, more seriously, may yield misleading results. This so-called partial follow-up study design represents increasingly common predictive modeling problem where we have serial multiple biomarkers up to a certain time point, which is shorter than the total length of follow-up. We therefore propose a solution to the partial follow-up design. The new method combines functional principal components analysis and survival analysis with selection of those functional covariates. It also has the advantage of handling sparse and irregularly measured longitudinal observations of covariates and measurement errors. Our analysis based on functional principal components reveals that it is the patterns of the trajectories of absolute lymphocyte cell counts, instead of

Magnitude of the benefit of progression-free survival as a potential surrogate marker in phase 3 trials assessing targeted agents in molecularly selected patients with advanced non-small cell lung cancer: systematic review.

Directory of Open Access Journals (Sweden)

Katsuyuki Hotta

Full Text Available BACKGROUND: In evaluation of the clinical benefit of a new targeted agent in a phase 3 trial enrolling molecularly selected patients with advanced non-small cell lung cancer (NSCLC, overall survival (OS as an endpoint seems to be of limited use because of a high level of treatment crossover for ethical reasons. A more efficient and useful indicator for assessing efficacy is needed. METHODS AND FINDINGS: We identified 18 phase 3 trials in the literature investigating EGFR-tyrosine kinase inhibitor (TKIs or ALK-TKIs, now approved for use to treat NSCLC, compared with standard cytotoxic chemotherapy (eight trials were performed in molecularly selected patients and ten using an "all-comer" design. Receiver operating characteristic analysis was used to identify the best threshold by which to divide the groups. Although trials enrolling molecularly selected patients and all-comer trials had similar OS-hazard ratios (OS-HRs (0.99 vs. 1.04, the former exhibited greater progression-free survival-hazard ratios (PFS-HR (mean, 0.40 vs. 1.01; P<0.01. A PFS-HR of 0.60 successfully distinguished between the two types of trials (sensitivity 100%, specificity 100%. The odds ratio for overall response was higher in trials with molecularly selected patients than in all-comer trials (mean: 6.10 vs. 1.64; P<0.01. An odds ratio of 3.40 for response afforded a sensitivity of 88% and a specificity of 90%. CONCLUSION: The notably enhanced PFS benefit was quite specific to trials with molecularly selected patients. A PFS-HR cutoff of ∼0.6 may help detect clinical benefit of molecular targeted agents in which OS is of limited use, although desired threshold might differ in an individual trial.

Progress towards a leprosy-free country: The experience of Oman.

Science.gov (United States)

Al Awaidy, Salah T

2017-11-01

The World Health Organization (WHO) released the Global Leprosy Strategy 2016-2020 towards a leprosy-free world. The author described the progress made towards the elimination of leprosy and suggested recommendations for the acceleration towards a Leprosy-free country according to WHO laid out criterion. Case record review of Leprosy patients managed between the years 1992 to 2015 were registered and analyzed. Data were collected from annual reports of the Ministry of Health including demographics, classification of leprosy new cases, relapse, childhood, grades of disability (GD) and multidrug therapy (MDT) completion rates. Leprosy prevalence rate declined from 1.64 to 0.09 per 10,000 population during the period 1992 and 2015 (pOman as they left the country shortly after diagnosis of leprosy due to a very short term contract, discretionary employment practices by the employers and prefer to go home to complete their treatment. Oman has met the elimination goals and made great strides towards becoming a leprosy-free country. However, challenges such as improving surveillance system efficiency and sensitivity for detecting timely leprosy cases, as well as foreign-born workers are still a major concerns.

Pretreatment PSA predicts for biochemical disease free survival in patients treated with post-prostatectomy external beam irradiation

International Nuclear Information System (INIS)

Crane, C.H.; Kelly, M.; Rich, T.A.

1996-01-01

Objective: To assess the outcome and determine prognostic factors for patients treated with external beam radiotherapy following radical prostatectomy. Methods and Materials: Forty-four patients were treated after prostatectomy with radiotherapy between March 1988 and October 1993. All patients were free from clinically or radiographically suspicious local or distant disease. One patient underwent neoadjuvant hormonal therapy, but no other patients received hormonal therapy prior to radiation. Pre-radiotherapy PSA and follow-up PSA data were available in all patients. Four patients had undetectable PSA ( 7, and 11% had nodal involvement. Survival was analyzed using the life table method. Actuarial freedom from biochemical (BCM) failure, defined as a rise of greater than 10% or an undetectable PSA becoming detectable, was the primary endpoint studied. Results: Fifty-nine percent of patients had a detectable PSA return to undetectable levels after XRT. The actuarial five year freedom from biochemical failure for all patients was 24%. A significant difference in BCM disease free survival was seen for patients irradiated with a pre-XRT PSA ≤2.7 versus a pre-XRT PSA >2.7 (p=0.0001). Sixty percent of the former group were BCM disease free versus 0% in the latter. Biochemical disease free survival was not affected by preoperative PSA level, presence of undetectable PSA after surgery, surgery to radiation interval, seminal vesicle invasion, clinical stage, pathologic stage, Gleasons grade, or total dose. There were no symptomatic or clinically suspicious local failures, and there were no grade 3, 4, or 5 acute or late complications. There were 69% grade 1 and 2 acute reactions and one grade 2 late complication. Conclusions: Pelvic radiotherapy for patients with a PSA of ≤2.7 after prostatectomy was effective in biochemically controlling 60% of the patients with four years median follow up. To our knowledge these data represent the longest follow-up for this patient

HN1L Promotes Triple-Negative Breast Cancer Stem Cells through LEPR-STAT3 Pathway

Directory of Open Access Journals (Sweden)

Yi Liu

2018-01-01

Full Text Available Here, we show that HEMATOLOGICAL AND NEUROLOGICAL EXPRESSED 1-LIKE (HN1L is a targetable breast cancer stem cell (BCSC gene that is altered in 25% of whole breast cancer and significantly correlated with shorter overall or relapse-free survival in triple-negative breast cancer (TNBC patients. HN1L silencing reduced the population of BCSCs, inhibited tumor initiation, resensitized chemoresistant tumors to docetaxel, and hindered cancer progression in multiple TNBC cell line-derived xenografts. Additionally, gene signatures associated with HN1L correlated with shorter disease-free survival of TNBC patients. We defined HN1L as a BCSC transcription regulator for genes involved in the LEPR-STAT3 signaling axis as HN1L binds to a putative consensus upstream sequence of STAT3, LEPTIN RECEPTOR, and MIR-150. Our data reveal that BCSCs in TNBC depend on the transcription regulator HN1L for the sustained activation of the LEPR-STAT3 pathway, which makes it a potentially important target for both prognosis and BCSC therapy.

Driving for shorter outages

International Nuclear Information System (INIS)

Tritch, S.

1996-01-01

Nuclear plant outages are necessary to complete activities that cannot be completed during the operating cycle, such as steam generator inspection and testing, refueling, installing modifications, and performing maintenance tests. The time devoted to performing outages is normally the largest contributor to plant unavailability. Similarly, outage costs are a sizable portion of the total plant budget. The scope and quality of work done during outages directly affects operating reliability and the number of unplanned outages. Improved management and planning of outages enhances the margin of safety during the outage and results in increased plant reliability. The detailed planning and in-depth preparation that has become a necessity for driving shorter outage durations has also produced safer outages and improved post-outage reliability. Short outages require both plant and vendor management to focus on all aspects of the outage. Short outage durations, such as 26 days at South Texas or 29 days at North Anna, require power plant inter-department and intra-department teamwork and communication and vendor participation. In this paper shorter and safer outage at the 3-loop plants in the United States are explained. (J.P.N.)

Selections of appropriate regimen of high-dose chemotherapy combined with adoptive cellular therapy with dendritic and cytokine-induced killer cells improved progression-free and overall survival in patients with metastatic breast cancer: reargument of such contentious therapeutic preferences.

Science.gov (United States)

Ren, Jun; Di, Lijun; Song, Guohong; Yu, Jing; Jia, Jun; Zhu, Yuling; Yan, Ying; Jiang, Hanfang; Liang, Xu; Che, Li; Zhang, Jie; Wan, Fengling; Wang, Xiaoli; Zhou, Xinna; Lyerly, Herbert Kim

2013-10-01

We hypothesized that combination of dendritic cell (DC) with autologous cytokine-induced killer (CIK) immunotherapy in setting of high-dose chemotherapy (HDC) would be effective for selected metastatic breast cancer (MBC) patients. Our previous work showed thiotepa could eradicate breast cancer stem cells. From 2004 to 2009, 79 patients received standard dose chemotherapy (SDC) of 75 mg/m(2) docetaxel and 75 mg/m(2) thiotepa versus 87 patients of HDC + DC/CIK: 120 mg/m(2) docetaxel to mobilize peripheral CD34(+) progenitor cells, a sequence of HDC (120 mg/m(2) docetaxel, plus 175 mg/m(2) thiotepa) + DC/CIK, with or without 400 mg/m(2) carboplatin depending upon bone marrow function. The endpoints were response rates (RR), progression-free survival (PFS), and overall survival (OS). Compared with SDC, PFS and OS were improved in HDC + DC/CIK (median PFS 10.2 vs. 3.7 months, P < 0.001; median OS 33.1 vs. 15.2 months, P < 0.001). Patients of pre-menopausal, HDC as first-line treatment after metastasis, or with visceral metastasis showed prolonged PFS and OS. SDC group also achieved the similar response as previous reports. Our study demonstrated the novel combination of HDC with DC/CIK to be an effective choice for the selected MBC population, in which choosing appropriate chemo regimens played important roles, and also specific HDC regimen plus DC/CIK immunotherapy showed the clinical benefits compared with chemotherapy alone.

Effect of an Oral Adsorbent, AST-120, on Dialysis Initiation and Survival in Patients with Chronic Kidney Disease

Directory of Open Access Journals (Sweden)

Shingo Hatakeyama

2012-01-01

Full Text Available The oral adsorbent AST-120 has the potential to delay dialysis initiation and improve survival of patients on dialysis. We evaluated the effect of AST-120 on dialysis initiation and its potential to improve survival in patients with chronic kidney disease. The present retrospective pair-matched study included 560 patients, grouped according to whether or not they received AST-120 before dialysis (AST-120 and non-AST-120 groups. The cumulative dialysis initiation free rate and survival rate were compared by the Kaplan-Meier method. Multivariate analysis was used to determine the impact of AST-120 on dialysis initiation. Our results showed significant differences in the 12- and 24-month dialysis initiation free rate (P<0.001, although no significant difference was observed in the survival rate between the two groups. In conclusion, AST-120 delays dialysis initiation in chronic kidney disease (CKD patients but has no effect on survival. AST-120 is an effective therapy for delaying the progression of CKD.

Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

NARCIS (Netherlands)

Gast, M.C.; van Tinteren, H.; Bontenbal, M.; van Hoesel, R.Q.; Nooij, M.A.; Rodenhuis, S.; Span, P.N.; Tjan-Heijnen, V.C.; de Vries, E.G.; Harris, N.; Twisk, J.W.R.; Schellens, J.H.; Beijnen, J.H.

2008-01-01

Background: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. Methods: Two

Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

NARCIS (Netherlands)

M.C.W. Gast; H. van Tinteren (Harm); M. Bontenbal (Marijke); R.Q.G.C.M. van Hoesel (René); M.A. Nooij; S. Rodenhuis (Sjoerd); P.N. Span (Paul); V.C.G. Tjan-Heijnen (Vivianne); E. de Vries (Esther); N. Harris (Nathan); J.W.R. Twisk (Jos); J.H.M. Schellens (Jan); J.H. Beijnen (Jos)

2008-01-01

textabstractBackground: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival.

Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

NARCIS (Netherlands)

Gast, Marie-Christine W.; van Tinteren, Harm; Bontenbal, Marijke; van Hoesel, Rene Q. G. C. M.; Nooij, Marianne A.; Rodenhuis, Sjoerd; Span, Paul N.; Tjan-Heijnen, Vivianne C. G.; de Vries, Elisabeth G. E.; Harris, Nathan; Twisk, Jos W. R.; Schellens, Jan H. M.; Beijnen, Jos H.

2008-01-01

ABSTRACT: BACKGROUND: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival.

Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients.

NARCIS (Netherlands)

Gast, M.C.; Tinteren, H. van; Bontenbal, M.; Hoesel, R.Q. van; Nooij, M.A.; Rodenhuis, S.; Span, P.N.; Tjan-Heijnen, V.C.; Vries, E.G.F. de; Harris, N.; Twisk, J.W.R.; Schellens, J.H.; Beijnen, J.H.

2008-01-01

BACKGROUND: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. METHODS: Two

Long survival in a patient with metastatic colorrectal carcinoma: reality or utopia?

Science.gov (United States)

Illán, Andrea; Aires, Jonathan; Quintana, Laura

2017-09-01

We report the case of a 42-year-old male patient with mucinous-type metastatic colorectal carcinoma of eight years of evolution. He has received multiple lines of cytostatic treatment with acceptable tolerance and without significant impairment in his quality of life. At present, it is estimated that the overall survival of metastatic colon cancer in cytostatic treatment is around 24 months. However, a small subset of patients may present prolonged survivals of 5 to 10 years after diagnosis, revealing heterogeneity of tumor behavior and response to treatment. Our clinical case represents a long survivor patient despite the advanced stage of his oncological mucinous-colorrectal disease, endorsed in the scientific literature as having worse rates of objective response and less survival. There are different therapeutic approaches that can achieve a significant overall survival. It is essential in clinical practice to use all drugs available to achieve increase of progression-free survival and overall survival, with maintenance of an adequate quality of life.

Prognostic value of the pretreatment neutrophil-to-lymphocyte ratio in cervical cancer: a meta-analysis and systematic review.

Science.gov (United States)

Wu, Jiayuan; Chen, Manyu; Liang, Caixia; Su, Wenmei

2017-02-21

The prognostic value of pretreatment neutrophil-to-lymphocyte ratio (NLR) in cervical cancer remains controversial. We conducted a meta-analysis based on the data from 13 studies with 3729 patients to evaluate the association between the pretreatment NLR and the clinical outcomes of overall survival and progression-free survival in patients with cervical cancer. The relationship between NLR and clinicopathological parameters was also assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis indicated that elevated pretreatment NLR was a poor prognostic marker for patients with cervical cancer because it predicted unfavorable overall survival (HR = 1.375, 95% CI: 1.200-1.576) and progression-free survival (HR = 1.646, 95% CI: 1.313-2.065). Increased NLR is also significantly associated with the larger tumor size (OR = 1.780, 95% CI: 1.090-2.908), advanced clinical stage (OR = 2.443, 95% CI: 1.730-3.451), and positive lymph node metastasis (OR = 2.380, 95% CI: 1.775-3.190). By these results, high pretreatment NLR predicted a shorter survival period for patients with cervical cancer, and it could be served as a novel index of prognostic evaluation in patients with cervical cancer.

Expression of Transketolase like gene 1 (TKTL1 predicts disease-free survival in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy

Directory of Open Access Journals (Sweden)

Hofmann Wolf-Karsten

2011-08-01

Full Text Available Abstract Background For patients with locally advanced rectal cancer (LARC neoadjuvant chemoradiotherapy is recommended as standard therapy. So far, no predictive or prognostic molecular factors for patients undergoing multimodal treatment are established. Increased angiogenesis and altered tumour metabolism as adaption to hypoxic conditions in cancers play an important role in tumour progression and metastasis. Enhanced expression of Vascular-endothelial-growth-factor-receptor (VEGF-R and Transketolase-like-1 (TKTL1 are related to hypoxic conditions in tumours. In search for potential prognostic molecular markers we investigated the expression of VEGFR-1, VEGFR-2 and TKTL1 in patients with LARC treated with neoadjuvant chemoradiotherapy and cetuximab. Methods Tumour and corresponding normal tissue from pre-therapeutic biopsies of 33 patients (m: 23, f: 10; median age: 61 years with LARC treated in phase-I and II trials with neoadjuvant chemoradiotherapy (cetuximab, irinotecan, capecitabine in combination with radiotherapy were analysed by quantitative PCR. Results Significantly higher expression of VEGFR-1/2 was found in tumour tissue in pre-treatment biopsies as well as in resected specimen after neoadjuvant chemoradiotherapy compared to corresponding normal tissue. High TKTL1 expression significantly correlated with disease free survival. None of the markers had influence on early response parameters such as tumour regression grading. There was no correlation of gene expression between the investigated markers. Conclusion High TKTL-1 expression correlates with poor prognosis in terms of 3 year disease-free survival in patients with LARC treated with intensified neoadjuvant chemoradiotherapy and may therefore serve as a molecular prognostic marker which should be further evaluated in randomised clinical trials.

Lung microbiome and disease progression in idiopathic pulmonary fibrosis: an analysis of the COMET study.

Science.gov (United States)

Han, MeiLan K; Zhou, Yueren; Murray, Susan; Tayob, Nabihah; Noth, Imre; Lama, Vibha N; Moore, Bethany B; White, Eric S; Flaherty, Kevin R; Huffnagle, Gary B; Martinez, Fernando J

2014-07-01

The role of the lung microbiome in the pathogenesis of idiopathic pulmonary fibrosis is unknown. We investigated whether unique microbial signatures were associated with progression of idiopathic pulmonary fibrosis. Patients (aged 35-80 years) with idiopathic pulmonary fibrosis within 4 years of diagnosis from the Correlating Outcomes with biochemical Markers to Estimate Time-progression (COMET) in idiopathic pulmonary fibrosis study were followed up for a maximum of 80 weeks. Progression-free survival was defined as time to death, acute exacerbation, lung transplant, or decrease in forced vital capacity (FVC) of 10% or greater or decrease in diffusion capacity of the lung (DLCO) of 15% or greater. DNA was isolated from 55 samples of bronchoscopic alveolar lavage. 454 pyrosequencing was used to assign operational taxonomic units (OTUs) to bacteria based on a 3% sequence divergence. Adjusted Cox models were used to identify OTUs that were significantly associated with progression-free survival at a pidiopathic pulmonary fibrosis is associated with the presence of specific members within the Staphylococcus and Streptococcus genera. Additional research will be needed to identify the specific bacterial species and to ascertain whether this is a causal association. National Institutes of Health. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical features, outcome, and prognostic factors for survival and evolution to multiple myeloma of solitary plasmacytomas: a report of the Greek myeloma study group in 97 patients.

Science.gov (United States)

Katodritou, Eirini; Terpos, Evangelos; Symeonidis, Argiris S; Pouli, Anastasia; Kelaidi, Charikleia; Kyrtsonis, Marie-Christine; Kotsopoulou, Maria; Delimpasi, Sosana; Christoforidou, Anna; Giannakoulas, Nikolaos; Viniou, Nora-Athina; Stefanoudaki, Ekaterini; Hadjiaggelidou, Christina; Christoulas, Dimitrios; Verrou, Evgenia; Gastari, Vassiliki; Papadaki, Sofia; Polychronidou, Genovefa; Papadopoulou, Athina; Giannopoulou, Evlambia; Kastritis, Efstathios; Kouraklis, Alexandra; Konstantinidou, Pavlina; Anagnostopoulos, Achilles; Zervas, Konstantinos; Dimopoulos, Meletios A

2014-08-01

Solitary plasmacytoma (SP) is a rare plasma cell dyscrasia characterized by the presence of bone or extramedullary plasma cell tumors. The treatment of choice is local radiotherapy (R/T) ± surgical excision. The role of adjuvant chemotherapy (C/T) or novel agents (NA) is uncertain. Data related to prognostic factors are inconclusive. Herein, we describe the clinical features, survival and prognosis of 97 consecutive patients, 65 with bone SP (SBP), and 32 with extramedullary SP (SEP), diagnosed and treated in 12 Greek Myeloma Centers. Objective response rate (≥PR) and complete response (CR) was 91.8% and 61.9%, respectively, and did not differ between the 2 groups. Overall, 38 patients relapsed or progressed to multiple myeloma (MM). After a median follow-up of 60 months, 5 and 10-year overall survival (OS) probability was 92% and 89% in SEP and 86% and 69% in SBP, respectively (P = 0.2). The 5- and 10-year MM-free survival (MMFS) probability was 90% and 70% for patients with SEP vs. 59% and 50% for patients with SBP, respectively (P = 0.054). Overall, the 5- and 10-year OS probability, plasmacytoma relapse-free survival (PRFS), progression-free survival and MMFS was 84% and 78%, 72% and 58%, 58% and 43%, and 70% and 59%, respectively. In the multivariate analysis, prolonged PRFS and young age were positive predictors of OS. Achievement of CR was the only positive predictor of PRFS. Immunoparesis was the only negative predictor of progression to MM. The addition of C/T or NA-based treatment increased toxicity without offering any survival advantage over R/T. © 2014 Wiley Periodicals, Inc.

Simultaneous analysis of the expression of 14 genes with individual prognostic value in myelodysplastic syndrome patients at diagnosis: WT1 detection in peripheral blood adversely affects survival.

Science.gov (United States)

Santamaría, Carlos; Ramos, Fernando; Puig, Noemi; Barragán, Eva; de Paz, Raquel; Pedro, Carme; Insunza, Andrés; Tormo, Mar; Del Cañizo, Consuelo; Diez-Campelo, María; Xicoy, Blanca; Salido, Eduardo; Sánchez del Real, Javier; Hernández, Montserrat; Chillón, Carmen; Sanz, Guillermo F; García-Sanz, Ramón; San Miguel, Jesús F; González, Marcos

2012-12-01

Several studies have evaluated the prognostic value of the individual expression of certain genes in patients with myelodysplastic syndromes (MDS). However, none of them includes their simultaneous analysis by quantitative polymerase chain reaction (PCR). We evaluated relative expression levels of 14 molecular markers in 193 peripheral blood samples from untreated MDS patients using real-time PCR. Detectable WT1 expression levels, low TET2, and low IER3 gene expression were the only markers showing in univariate analysis a poor prognostic value for all treatment-free (TFS), progression-free (PFS), and overall survival (OS). In multivariate analysis, molecular parameters associated with a shorter TFS were: WT1 detection (p = 0.014), low TET2 (p = 0.002), and low IER3 expression (p = 0.025). WT1 detection (p = 0.006) and low TET2 (p = 0.006) expression were associated with a shorter PFS when multivariate analysis was carried out by including only molecular markers. Molecular values with an independent value in OS were: WT1 detection (p = 0.003), high EVI1 expression (p = 0.001), and undetectatable p15-CDKN2B (p = 0.037). WT1 expressers were associated with adverse clinical-biological features, high IPSS and WPSS scoring, and unfavorable molecular expression profile. In summary, detectable WT1 expression levels, and low TET2 and low IER3 expression in peripheral blood showed a strong association with adverse prognosis in MDS patients at diagnosis. However, WT1 was the only molecular marker displaying an independent prognostic value in both OS and TFS.

Nanoparticle albumin-bound paclitaxel: a novel Cremphor-EL-free formulation of paclitaxel.

Science.gov (United States)

Stinchcombe, Thomas E

2007-08-01

Standard formulation paclitaxel requires the use of solvents, such as Cremphor-EL, which contribute to some of the toxicities commonly associated with paclitaxel-based therapy. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a novel solvent-free formulation of paclitaxel. The formulation is prepared by high-pressure homogenization of paclitaxel in the presence of serum albumin into a nanoparticle colloidal suspension. The human albumin-stabilized paclitaxel particles have an average size of 130 nm. Nab-paclitaxel has several practical advantages over Cremphor-EL-paclitaxel, including a shorter infusion time (30 min) and no need for premedications for hypersensitivity reactions. The nab-paclitaxel formulation eliminates the impact of Cremphor-EL on paclitaxel pharmacokinetics and utilizes the endogenous albumin transport mechanisms to concentrate nab-paclitaxel within the tumor. A recent Phase III trial compared nab- and Cremphor-EL-paclitaxel in patients with metastatic breast cancer. Patients treated with nab-paclitaxel experienced a higher response, longer time to tumor progression and, in patients receiving second-line or greater therapy, a longer median survival. Patients treated with nab-paclitaxel had a significantly lower rate of severe neutropenia and a higher rate of sensory neuropathy. The preclinical and clinical data indicate that the nab-paclitaxel formulation has significant advantages over Cremphor-EL-paclitaxel.

Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma

Science.gov (United States)

San Miguel, Jesus F.; Weisel, Katja C.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Moreau, Philippe; Banos, Anne; Oriol, Albert; Garderet, Laurent; Cavo, Michele; Ivanova, Valentina; Alegre, Adrian; Martinez-Lopez, Joaquin; Chen, Christine; Renner, Christoph; Bahlis, Nizar Jacques; Yu, Xin; Teasdale, Terri; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Dimopoulos, Meletios A.

2015-01-01

Pomalidomide is a distinct oral IMiD® immunomodulatory agent with direct antimyeloma, stromal-support inhibitory, and immunomodulatory effects. The pivotal, multicenter, open-label, randomized phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma after failure of bortezomib and lenalidomide treatment. Initial results demonstrated significantly longer progression-free survival and overall survival with an acceptable tolerability profile for pomalidomide + low-dose dexamethasone vs high-dose dexamethasone. This secondary analysis describes patient outcomes by treatment history and depth of response. Pomalidomide + low-dose dexamethasone significantly prolonged progression-free survival and favored overall survival vs high-dose dexamethasone for all subgroups analyzed, regardless of prior treatments or refractory status. Both univariate and multivariate analyses showed that no variable relating to either the number (≤ or > 3) or type of prior treatment was a significant predictor of progression-free survival or overall survival. No cross-resistance with prior lenalidomide or thalidomide treatment was observed. Patients achieving a minimal response or better to pomalidomide + low-dose dexamethasone treatment experienced a survival benefit, which was even higher in those achieving at least a partial response (17.2 and 19.9 months, respectively, as compared with 7.5 months for patients with less than minimal response). These data suggest that pomalidomide + low-dose dexamethasone should be considered a standard of care in patients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment. ClinicalTrials.gov: NCT01311687; EudraCT: 2010-019820-30. PMID:26160879

KRAS polymorphisms are associated with survival of CRC in Chinese population.

Science.gov (United States)

Dai, Qiong; Wei, Hui Lian; Huang, Juan; Zhou, Tie Jun; Chai, Li; Yang, Zhi-Hui

2016-04-01

rs12245, rs12587, rs9266, rs1137282, rs61764370, and rs712 of KRAS oncogene are characterized in the 3'UTR. The study highlights the important role of these polymorphisms playing in the susceptibility, oxaliplatin-based chemotherapy sensitivity, progression, and prognosis of CRC. Improved multiplex ligation detection reaction (iMLDR) technique is used for genotyping. An unconditional logistic regression model was used to estimate the association of certain polymorphism and CRC risk. The Kaplan-Meier method, log-rank test, and Cox regression model were used to evaluate the effects of polymorphisms on survival analysis. Results demonstrated that TT genotype and T allele of rs712 were associated with the increased risk of CRC; the patients with GG genotype and G allele of rs61764370 had a shorter survival and a higher risk of relapse or metastasis of CRC. Our studies supported the conclusions that rs61764370 and rs712 polymorphisms of the KRAS are functional and it may play an important role in the development of CRC and oxaliplatin-based chemotherapy efficiency and prognosis of CRC.

Tissue inhibitor of metalloproteinase-4 is elevated in early-stage breast cancers with accelerated progression and poor clinical course.

Science.gov (United States)

Liss, Michaelann; Sreedhar, Nandhini; Keshgegian, Albert; Sauter, Guido; Chernick, Michael R; Prendergast, George C; Wallon, U Margaretha

2009-09-01

An increasing number of breast cancer patients are diagnosed with small, localized, early-stage tumors. These patients are typically thought to have a good prognosis for long-term disease-free survival, but epidemiological studies indicate that up to 30% may have a recurrence within 3 to 5 years of diagnosis. Identifying patients with a high risk of recurrence and/or progression is important because they could be more aggressively treated at diagnosis to improve their chances for disease-free survival. Recent evidence suggests that elevated levels of the matrix metalloproteinase inhibitor, tissue inhibitor of metalloproteinase (TIMP)-4, are associated with malignant progression of ductal carcinoma in situ, a precancerous lesion. To examine the association of TIMP-4 with survival outcomes, we conducted a retrospective immunohistochemical analysis of 314 cases from patients with early-stage disease, defined as tumors smaller than 2 cm and no spread to lymph nodes (tumor-node-metastasis staging: T1N0MX). We found that tumors with elevated levels of TIMP-4 were correlated with a reduced probability of long-term disease-free survival, especially in patients with estrogen receptor-negative tumors. Our findings prompt further evaluation of TIMP-4 as a simple prognostic marker that may help identify patients with early-stage breast cancer who could benefit from more aggressive treatment at diagnosis.

Prognostic implication of aquaporin 1 overexpression in resected lung adenocarcinoma.

Science.gov (United States)

Bellezza, Guido; Vannucci, Jacopo; Bianconi, Fortunato; Metro, Giulio; Del Sordo, Rachele; Andolfi, Marco; Ferri, Ivana; Siccu, Paola; Ludovini, Vienna; Puma, Francesco; Sidoni, Angelo; Cagini, Lucio

2017-12-01

Aquaporins (AQPs) are a group of transmembrane water-selective channel proteins thought to play a role in the regulation of water permeability for plasma membranes. Indeed, high AQP levels have been suggested to promote the progression, invasion and metastasis of tumours. Specifically, AQP1 and AQP5 overexpression in lung adenocarcinoma (AC) have been suggested to be involved in molecular mechanisms in lung cancer. The aim of this retrospective cohort single-centre study was to assess both the levels of expression and therein the prognostic significance, regarding outcome of AQP1 and AQP5 in resected AC patients. Patients with histological diagnoses of lung AC submitted to pulmonary resection were included in this cohort study. Tissue microarrays containing cores from 185 ACs were prepared. AQP1 and AQP5 expressions were assessed by immunohistochemistry. Results were scored as either low (Score 0-2) or high (Score 3-9). Clinical data, pathological tumour-node-metastasis staging and follow-up were recorded. Multivariate Cox survival analysis and Fisher's t-test were performed. AQP1 overexpression was detected in 85 (46%) patients, while AQP5 overexpression was observed in 45 (24%) patients. AQP1 did not result being significantly correlated with clinical and pathological parameters, while AQP5 resulted more expressed in AC with mucinous and papillary predominant patterns. Patients with AQP1 overexpression had shorter disease-free survival (P = 0.001) compared with patients without AQP1 overexpression. Multivariate analysis confirmed that AQP1 overexpression was significantly associated with shorter disease-free survival (P = 0.001). Our results evidenced that AQP1 overexpression resulted in a shorter disease-free survival in lung AC patients. Being so, AQP1 overexpression might be an important prognostic marker in lung AC. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights

Tracking progress towards equitable child survival in a Nicaraguan community: neonatal mortality challenges to meet the MDG 4

Directory of Open Access Journals (Sweden)

Persson Lars-Åke

2011-06-01

Full Text Available Abstract Background Nicaragua has made progress in the reduction of the under-five mortality since 1980s. Data for the national trends indicate that this poor Central American country is on track to reach the Millennium Development Goal-4 by 2015. Despite this progress, neonatal mortality has not showed same progress. The aim of this study is to analyse trends and social differentials in neonatal and under-five mortality in a Nicaraguan community from 1970 to 2005. Methods Two linked community-based reproductive surveys in 1993 and 2002 followed by a health and demographic surveillance system providing information on all births and child deaths in urban and rural areas of León municipality, Nicaragua. A total of 49 972 live births were registered. Results A rapid reduction in under-five mortality was observed during the late 1970s (from 103 deaths/1000 live births and the 1980s, followed by a gradual decline to the level of 23 deaths/1000 live births in 2005. This community is on track for the Millennium Development Goal 4 for improved child survival. However, neonatal mortality increased lately in spite of a good coverage of skilled assistance at delivery. After some years in the 1990s with a very small gap in neonatal survival between children of mothers of different educational levels this divide is increasing. Conclusions After the reduction of high under-five mortality that coincided with improved equity in survival in this Nicaraguan community, the current challenge is the neonatal mortality where questions of an equitable perinatal care of good quality must be addressed.

On the role of classical and novel forms of vitamin D in melanoma progression and management.

Science.gov (United States)

Slominski, Andrzej T; Brożyna, Anna A; Skobowiat, Cezary; Zmijewski, Michal A; Kim, Tae-Kang; Janjetovic, Zorica; Oak, Allen S; Jozwicki, Wojciech; Jetten, Anton M; Mason, Rebecca S; Elmets, Craig; Li, We; Hoffman, Robert M; Tuckey, Robert C

2018-03-01

Melanoma represents a significant clinical problem affecting a large segment of the population with a relatively high incidence and mortality rate. Ultraviolet radiation (UVR) is an important etiological factor in malignant transformation of melanocytes and melanoma development. UVB, while being a full carcinogen in melanomagenesis, is also necessary for the cutaneous production of vitamin D3 (D3). Calcitriol (1,25(OH) 2 D3) and novel CYP11A1-derived hydroxyderivatives of D3 show anti-melanoma activities and protective properties against damage induced by UVB. The former activities include inhibitory effects on proliferation, plating efficiency and anchorage-independent growth of cultured human and rodent melanomas in vitro, as well as the in vivo inhibition of tumor growth by 20(OH)D3 after injection of human melanoma cells into immunodeficient mice. The literature indicates that low levels of 25(OH)D3 are associated with more advanced melanomas and reduced patient survivals, while single nucleotide polymorphisms of the vitamin D receptor or the D3 binding protein gene affect development or progression of melanoma, or disease outcome. An inverse correlation of VDR and CYP27B1 expression with melanoma progression has been found, with low or undetectable levels of these proteins being associated with poor disease outcomes. Unexpectedly, increased expression of CYP24A1 was associated with better melanoma prognosis. In addition, decreased expression of retinoic acid orphan receptors α and γ, which can also bind vitamin D3 hydroxyderivatives, showed positive association with melanoma progression and shorter disease-free and overall survival. Thus, inadequate levels of biologically active forms of D3 and disturbances in expression of the target receptors, or D3 activating or inactivating enzymes, can affect melanomagenesis and disease progression. We therefore propose that inclusion of vitamin D into melanoma management should be beneficial for patients, at least as

Comparative Survival in Patients With Postresection Recurrent Versus Newly Diagnosed Non-Small-Cell Lung Cancer Treated With Radiotherapy

International Nuclear Information System (INIS)

Cai Xuwei; Xu Luying; Wang Li; Hayman, James A.; Chang, Andrew C.; Pickens, Allan; Cease, Kemp B.; Orringer, Mark B.; Kong, F.-M.

2010-01-01

Purpose: To compare the survival of postresection recurrent vs. newly diagnosed non-small-cell lung cancer (NSCLC) patients treated with radiotherapy or chemoradiotherapy. Methods and Materials: The study population consisted of 661 consecutive patients with NSCLC registered in the radiation oncology databases at two medical centers in the United States between 1992 and 2004. Of the 661 patients, 54 had postresection recurrent NSCLC and 607 had newly diagnosed NSCLC. Kaplan-Meier and Cox regression models were used for the survival analyses. Results: The distribution of relevant clinical factors between these two groups was similar. The median survival time and 5-year overall survival rates were 19.8 months (95% confidence interval [CI], 13.9-25.7) and 14.8% (95% confidence interval, 5.4-24.2%) vs. 12.2 months (95% CI, 10.8-13.6) and 11.0% (95% CI, 8.5-13.5%) for recurrent vs. newly diagnosed patients, respectively (p = .037). For Stage I-III patients, no significant difference was observed in the 5-year overall survival (p = .297) or progression-free survival (p = .935) between recurrent and newly diagnosed patients. For the 46 patients with Stage I-III recurrent disease, multivariate analysis showed that chemotherapy was a significant prognostic factor for 5-year progression-free survival (hazard ratio, 0.45; 95% CI, 0.224-0.914; p = .027). Conclusion: Our institutional data have shown that patients with postresection recurrent NSCLC achieved survival comparable to that of newly diagnosed NSCLC patients when they were both treated with radiotherapy or chemoradiotherapy. These findings suggest that patients with postresection recurrent NSCLC should be treated as aggressively as those with newly diagnosed disease.

Measuring coverage in MNCH: population HIV-free survival among children under two years of age in four African countries.

Directory of Open Access Journals (Sweden)

Jeffrey S A Stringer

Full Text Available Population-based evaluations of programs for prevention of mother-to-child HIV transmission (PMTCT are scarce. We measured PMTCT service coverage, regimen use, and HIV-free survival among children ≤24 mo of age in Cameroon, Côte D'Ivoire, South Africa, and Zambia.We randomly sampled households in 26 communities and offered participation if a child had been born to a woman living there during the prior 24 mo. We tested consenting mothers with rapid HIV antibody tests and tested the children of seropositive mothers with HIV DNA PCR or rapid antibody tests. Our primary outcome was 24-mo HIV-free survival, estimated with survival analysis. In an individual-level analysis, we evaluated the effectiveness of various PMTCT regimens. In a community-level analysis, we evaluated the relationship between HIV-free survival and community PMTCT coverage (the proportion of HIV-exposed infants in each community that received any PMTCT intervention during gestation or breastfeeding. We also compared our community coverage results to those of a contemporaneous study conducted in the facilities serving each sampled community. Of 7,985 surveyed children under 2 y of age, 1,014 (12.7% were HIV-exposed. Of these, 110 (10.9% were HIV-infected, 851 (83.9% were HIV-uninfected, and 53 (5.2% were dead. HIV-free survival at 24 mo of age among all HIV-exposed children was 79.7% (95% CI: 76.4, 82.6 overall, with the following country-level estimates: Cameroon (72.6%; 95% CI: 62.3, 80.5, South Africa (77.7%; 95% CI: 72.5, 82.1, Zambia (83.1%; 95% CI: 78.4, 86.8, and Côte D'Ivoire (84.4%; 95% CI: 70.0, 92.2. In adjusted analyses, the risk of death or HIV infection was non-significantly lower in children whose mothers received a more complex regimen of either two or three antiretroviral drugs compared to those receiving no prophylaxis (adjusted hazard ratio: 0.60; 95% CI: 0.34, 1.06. Risk of death was not different for children whose mothers received a more complex regimen

Timely disclosure of progress in long-term cancer survival: the boomerang method substantially improved estimates in a comparative study.

Science.gov (United States)

Brenner, Hermann; Jansen, Lina

2016-02-01

Monitoring cancer survival is a key task of cancer registries, but timely disclosure of progress in long-term survival remains a challenge. We introduce and evaluate a novel method, denoted "boomerang method," for deriving more up-to-date estimates of long-term survival. We applied three established methods (cohort, complete, and period analysis) and the boomerang method to derive up-to-date 10-year relative survival of patients diagnosed with common solid cancers and hematological malignancies in the United States. Using the Surveillance, Epidemiology and End Results 9 database, we compared the most up-to-date age-specific estimates that might have been obtained with the database including patients diagnosed up to 2001 with 10-year survival later observed for patients diagnosed in 1997-2001. For cancers with little or no increase in survival over time, the various estimates of 10-year relative survival potentially available by the end of 2001 were generally rather similar. For malignancies with strongly increasing survival over time, including breast and prostate cancer and all hematological malignancies, the boomerang method provided estimates that were closest to later observed 10-year relative survival in 23 of the 34 groups assessed. The boomerang method can substantially improve up-to-dateness of long-term cancer survival estimates in times of ongoing improvement in prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Virtual HDR CyberKnife SBRT for Localized Prostatic Carcinoma: 5-year Disease-free Survival and Toxicity Observations

Directory of Open Access Journals (Sweden)

Donald Blake Fuller

2014-11-01

Full Text Available PURPOSEProstate stereotactic body radiotherapy (SBRT may substantially recapitulate the dose distribution of high-dose-rate (HDR brachytherapy, representing an externally delivered Virtual HDR treatment method. Herein we present 5-year outcomes from a cohort of consecutively treated Virtual HDR SBRT prostate cancer patients.METHODSSeventy-nine patients were treated from 2006 - 2009, 40 low-risk and 39 intermediate-risk, under IRB-approved clinical trial, to 38 Gy in 4 fractions. The planning target volume (PTV included prostate plus a 2-mm volume expansion in all directions, with selective use of a 5-mm prostate-to-PTV expansion and proximal seminal vesicle coverage in intermediate-risk patients, to better cover potential extraprostatic disease; rectal PTV margin reduced to zero in all cases. The prescription dose covered > 95% of the PTV (V100 >= 95%, with a minimum 150% PTV dose escalation to create HDR-like PTV dose distribution.RESULTSMedian pre-SBRT PSA level of 5.6 ng/mL decreased to 0.05 ng/mL 5 years out and 0.02 ng/mL 6 years out. At least one PSA bounce was seen in 55 patients (70% but only 3 of them subsequently relapsed, Biochemical-relapse-free survival was 100% and 92% for low-risk and intermediate-risk patients, respectively, by ASTRO definition (98% and 92% by Phoenix definition. Local relapse did not occur, distant metastasis-free survival was 100% and 95% by risk-group, and disease-specific survival was 100%. Acute and late grade 2 GU toxicity incidence was 10% and 9%, respectively; with 6% late grade 3 GU toxicity. Acute urinary retention did not occur. Acute and late grade 2 GI toxicity was 0% and 1%, respectively, with no grade 3 or higher toxicity. Of patients potent pre-SBRT, 65% remained so at 5 years.CONCLUSIONSVirtual HDR prostate SBRT creates a very low PSA nadir, a high rate of 5-year disease-free survival and an acceptable toxicity incidence, with results closely resembling those reported post-HDR brachytherapy.

Immune infiltrates as predictive markers of survival in pancreatic cancer patients

Directory of Open Access Journals (Sweden)

Maria Pia eProtti

2013-08-01

Full Text Available Pancreatic cancer is a devastating disease with dismal prognosis. The tumor microenvironment is composed by multiple cell types, molecular factors and extracellular matrix forming a strong desmoplastic reaction, which is a hallmark of the disease. A complex cross-talk between tumor cells and the stroma exists with reciprocal influence that dictates tumor progression and ultimately the clinical outcome. In this context, tumor infiltrating immune cells through secretion of chemokine and cytokines exert an important regulatory role. Here we review the correlation between the immune infiltrates, evaluated on tumor samples of pancreatic cancer patients underwent surgical resection, and disease free and/or overall survival after surgery. Specifically, we focus on tumor infiltrating lymphocytes, mast cells and macrophages that all contribute to a Th2-type inflammatory and immunosuppressive microenvironment. In these patients tumor immune infiltrates not only do not contribute to disease eradication but rather the features of Th2-type inflammation and immunosuppression is significantly associated with more rapid disease progression and reduced survival.

Survival and progression rates of anadromous brown trout kelts Salmo trutta during downstream migration in freshwater and at sea

DEFF Research Database (Denmark)

Aarestrup, Kim; Baktoft, Henrik; Thorstad, EB

2015-01-01

The marine migration of post-spawning anadromous fish remains poorly understood. The present study examined survival and progression rates of anadromous brown trout Salmo trutta L. after spawning (kelts) during downriver, fjord, and sea migration. Kelts (n = 49) were captured in the Danish River...... completing the reach within 4 d, suggesting that the kelts spent limited time foraging after returning to the fjord. The total survival during the entire marine migration, including the fjord, was a minimum of 29%. Our study provides data that are important for management of anadromous brown trout...

Cycling Towards Progress: Ribociclib, CDK 4/6 inhibitor for Breast Cancer.

Science.gov (United States)

Spring, Laura; Bardia, Aditya

2018-04-23

Ribociclib is an orally active, highly selective inhibitor of cyclin-dependent kinase (CDK) 4 and 6. It is the second CDK 4/6 inhibitor approved for hormone receptor-positive breast cancer. The addition of ribociclib to an aromatase inhibitor has resulted in marked improvements in progression-free survival for patients with metastatic breast cancer. Copyright ©2018, American Association for Cancer Research.

Plasma miR-200b in ovarian carcinoma patients: distinct pattern of pre/post-treatment variation compared to CA-125 and potential for prediction of progression-free survival.

Science.gov (United States)

Kapetanakis, Nikiforos-Ioannis; Uzan, Catherine; Jimenez-Pailhes, Anne-Sophie; Gouy, Sébastien; Bentivegna, Enrica; Morice, Philippe; Caron, Olivier; Gourzones-Dmitriev, Claire; Le Teuff, Gwénaël; Busson, Pierre

2015-11-03

Ovarian carcinomas (OvCa) are highly heterogeneous malignancies. We investigated four circulating plasma microRNAs (miR-21, miR-34a, miR-200b and miR-205) as candidate biomarkers. Using qPCR, we assessed the plasma concentration of these markers in 101 women, including 51 previously untreated OvCa patients, 25 healthy women and 25 patients bearing benign pelvic lesions. For a subset of 33 OvCa patients, the assay was repeated at the end of the primary treatment. The pattern of variations (post- minus pre-treatment) of concentration was compared to that of CA-125. A Cox regression model was used to study the association between variations and the progression-free survival (PFS). Plasma miR-200b proved to have a greater average concentration in OvCa samples (median 2-ΔΔCt = 15.18) than in samples linked to non-malignant lesions (median 2-ΔΔCt = 1.26, p-value = 0.0004). Its concentration was highly heterogeneous among OvCa patients, without any correlations with the FIGO stage and the pre-treatment CA-125 level. The decrease in CA-125 concentration was constant and often dramatic, while the variations of miR-200b concentration were much more diverse. The variation of miR-200b was marginally associated with the PFS (hazard ratio=2.95 95%CI=[0.94; 9.28], p=0.06) while miR-200b as a continuous time-dependent variable was significantly associated (HR=1.06 [1.02; 1.10], p=0.003). This study is the first direct empirical evidence that miR-200b can provide additional information, independent of CA-125 in OvCa patients.

Survival in the pre-senile dementia frontotemporal lobar degeneration with TDP-43 proteinopathy: effects of genetic, demographic and neuropathological variables

Directory of Open Access Journals (Sweden)

Richard A. Armstrong

2016-06-01

Full Text Available Factors associated with survival were studied in 84 neuropathologically documented cases of the pre-senile dementia frontotemporal dementia lobar degeneration (FTLD with transactive response (TAR DNA-binding protein of 43 kDa (TDP-43 proteinopathy (FTLD-TDP. Kaplan-Meier survival analysis estimated mean survival as 7.9 years (range: 1-19 years, SD = 4.64. Familial and sporadic cases exhibited similar survival, including progranulin (GRN gene mutation cases. No significant differences in survival were associated with sex, disease onset, Braak disease stage, or disease subtype, but higher survival was associated with lower post-mortem brain weight. Survival was significantly reduced in cases with associated motor neuron disease (FTLD-MND but increased with Alzheimer’s disease (AD or hippocampal sclerosis (HS co-morbidity. Cox regression analysis suggested that reduced survival was associated with increased densities of neuronal cytoplasmic inclusions (NCI while increased survival was associated with greater densities of enlarged neurons (EN in the frontal and temporal lobes. The data suggest that: (1 survival in FTLD-TDP is more prolonged than typical in pre-senile dementia but shorter than some clinical subtypes such as the semantic variant of primary progressive aphasia (svPPA, (2 MND co-morbidity predicts poor survival, and (3 NCI may develop early and EN later in the disease. The data have implications for both neuropathological characterization and subtyping of FTLD-TDP.

Shock progression and survival after use of a condom uterine balloon tamponade package in women with uncontrolled postpartum hemorrhage.

Science.gov (United States)

Burke, Thomas F; Danso-Bamfo, Sandra; Guha, Moytrayee; Oguttu, Monica; Tarimo, Vincent; Nelson, Brett D

2017-10-01

To examine the outcomes of women in advanced shock from uncontrolled postpartum hemorrhage (PPH) who underwent placement of an Every Second Matters for Mothers and Babies Uterine Balloon Tamponade (ESM-UBT) device. In a prospective case series, data were collected for women who received an ESM-UBT device at healthcare facilities in Kenya, Senegal, Sierra Leone, and Tanzania between September 1, 2012, and September 30, 2016. Shock class was assigned on the basis of recorded blood pressures and mental status at the time of UBT placement. Data for 306 women with uncontrolled PPH from uterine atony across 117 facilities were analyzed. Normal vital signs or class I/II shock were reported for 166 (54.2%). In this group, one death occurred and was attributed to PPH (survival rate 99.4%). There were no cases of shock progression. One hundred and eleven (36.3%) were in class III shock and 29 (9.5%) in class IV shock; the respective survival rates were 97.3% (n=108) and 86.2% (n=25). The ESM-UBT device arrests hemorrhage, prevents shock progression, and is associated with high survival rates among women with uncontrolled PPH from uterine atony. © 2017 International Federation of Gynecology and Obstetrics.

Foxp3 overexpression in tumor cells predicts poor survival in oral squamous cell carcinoma

International Nuclear Information System (INIS)

Song, Jing-Jing; Zhao, Si-Jia; Fang, Juan; Ma, Da; Liu, Xiang-Qi; Chen, Xiao-Bing; Wang, Yun; Cheng, Bin; Wang, Zhi

2016-01-01

Forkhead Box P3 (Foxp3) is a regulatory T cells marker, and its expression correlates with prognosis in a number of malignancies. The aim of this study is to determine the relationship of Foxp3 expression with clinicopathological parameters and prognosis in oral squamous cell carcinoma (OSCC). Foxp3 expression was examined using immunohistochemistry (IHC) in paraffin-embedded tissue samples from 273 OSCC patients. Statistical analysis was performed to evaluate the associations between Foxp3 expression, the clinicopathologic characteristics and prognostic factors in OSCC. Foxp3 protein expression was significantly associated with lymph node metastasis (P <0.01). Both univariate and multivariate analyses revealed that Foxp3 was an independent factor for both 5 years overall survival (OS) and relapse-free survival (RFS) (both P <0.01). Patients with Foxp3 overexpression had shorter OS and RFS. Our results determined that elevated Foxp3 protein expression was a predictive factor of outcome in OSCC and could act as a promising therapeutic target

Weight Gain in Advanced Non-Small-Cell Lung Cancer Patients During Treatment With Split-Course Concurrent Chemoradiotherapy Is Associated With Superior Survival

Energy Technology Data Exchange (ETDEWEB)

Gielda, Benjamin T., E-mail: Benjamin_gielda@rush.edu [Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (United States); Mehta, Par [Department of Radiation Oncology at Rush Copley Medical Center, Aurora, IL (United States); Khan, Atif [Department of Radiation Oncology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School and Cancer Institute of New Jersey, New Brunswick, NJ (United States); Marsh, James C.; Zusag, Thomas W. [Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (United States); Warren, William H. [Department of Cardiothoracic Surgery, Rush University Medical Center, Chicago, IL (United States); Fidler, Mary Jo [Section of Medical Oncology, Rush University Medical Center, Chicago, IL (United States); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (United States); Bonomi, Philip [Section of Medical Oncology, Rush University Medical Center, Chicago, IL (United States); Liptay, Michael; Faber, L. Penfield [Department of Cardiothoracic Surgery, Rush University Medical Center, Chicago, IL (United States)

2011-11-15

Background: Preoperative concurrent chemoradiotherapy (CRT) is an accepted treatment for potentially resectable, locally advanced, non-small-cell lung cancer (NSCLC). We reviewed a decade of single institution experience with preoperative split-course CRT followed by surgical resection to evaluate survival and identify factors that may be helpful in predicting outcome. Methods and Materials: All patients treated with preoperative split-course CRT and resection at Rush University Medical Center (RUMC) between January 1999 and December 2008 were retrospectively analyzed. Endpoints included overall survival (OS), progression-free survival (PFS), local-regional progression-free survival (LRPFS), and distant metastasis-free survival (DMFS). Patient and treatment related variables were assessed for correlation with outcomes. Results: A total of 54 patients were analyzed, 76% Stage IIIA, 18% Stage IIIB, and 6% oligometastatic. The pathologic complete response (pCR) rate was 31.5%, and the absence of nodal metastases (pN0) was 64.8%. Median OS and 3-year actuarial survival were 44.6 months and 50%, respectively. Univariate analysis revealed initial stage (p < 0.01) and percent weight change during CRT (p < 0.01) significantly correlated with PFS/OS. On multivariate analysis initial stage (HR, 2.4; 95% CI, 1.18-4.90; p = 0.02) and percent weight change (HR, 0.79; 95% CI, 0.67-0.93; p < 0.01) maintained significance with respect to OS. There were no cases of Grade 3+ esophagitis, and there was a single case of Grade 3 febrile neutropenia. Conclusions: The strong correlation between weight change during CRT and OS/PFS suggests that this clinical parameter may be useful as a complementary source of predictive information in addition to accepted factors such as pathological response.

36 CFR 223.81 - Shorter advertising periods in emergencies.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Shorter advertising periods... OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER Timber Sale Contracts Advertisement and Bids § 223.81 Shorter advertising periods in emergencies. In emergency situations where prompt...

["That flesh, pink and perishable": analysis of disease-free survival analysis in breast cancer in Gipuzkoa (Spain) in the presence of competing risks].

Science.gov (United States)

Martínez-Camblor, Pablo; Larrañaga, Nerea; Sarasqueta, Cristina; Mitxelena, María José; Basterretxea, Mikel

2009-01-01

To analyze time of disease-free survival and relative survival in women diagnosed with breast cancer in the province of Gipuzkoa within the context of competing risks by assessing differences between the direct use of the Kaplan-Meier estimator and the multiple decrement method on the one hand, and relative survival on the other. All registered breast cancer cases in Gipuzkoa in 1995 and 1996 with stages other than stage IV were included. An 8-year follow-up for recurrence and a 10-year follow-up for survival were performed. Time of disease-free survival was studied by the multiple decrement model. Observed survival and survival corrected by the expected mortality in the population (relative survival) were also studied. Estimation of the probability of recurrence at 8 years with the multiple decrement method was 8.8% lower than that obtained with the Kaplan-Meier method. The difference between the observed and relative survival rates at 10 years was 10.8%. Both results show how, in this case, the Kaplan-Meier estimator overestimates both the probability of recurrence and that of mortality from the disease. Two issues are often overlooked when performing survival analyses: firstly, because of the lack of independence between survival time and censoring time, the results obtained by the Kaplan-Meier estimator are uninterpretable; secondly, it is an incontrovertible fact that one way or another, everyone causes failures. In this approach, survival analyses must take into account the probability of failure in the general population of reference. The results obtained in this study show that superficial use of the Kaplan Meier estimator overestimates both the probability of recurrence and that of mortality caused by the disease.

A retrospective analysis of survival and prognostic factors after stereotactic radiosurgery for aggressive meningiomas

International Nuclear Information System (INIS)

Ferraro, Daniel J; Zoberi, Imran; Simpson, Joseph R; Jaboin, Jerry J; Funk, Ryan K; Blackett, John William; Ju, Michelle R; DeWees, Todd A; Chicoine, Michael R; Dowling, Joshua L; Rich, Keith M; Drzymala, Robert E

2014-01-01

While most meningiomas are benign, aggressive meningiomas are associated with high levels of recurrence and mortality. A single institution’s Gamma Knife radiosurgical experience with atypical and malignant meningiomas is presented, stratified by the most recent WHO classification. Thirty-one patients with atypical and 4 patients with malignant meningiomas treated with Gamma Knife radiosurgery between July 2000 and July 2011 were retrospectively reviewed. All patients underwent prior surgical resection. Overall survival was the primary endpoint and rate of disease recurrence in the brain was a secondary endpoint. Patients who had previous radiotherapy or prior surgical resection were included. Kaplan-Meier and Cox proportional hazards models were used to estimate survival and identify factors predictive of recurrence and survival. Post-Gamma Knife recurrence was identified in 11 patients (31.4%) with a median overall survival of 36 months and progression-free survival of 25.8 months. Nine patients (25.7%) had died. Three-year overall survival (OS) and progression-free survival (PFS) rates were 78.0% and 65.0%, respectively. WHO grade II 3-year OS and PFS were 83.4% and 70.1%, while WHO grade III 3-year OS and PFS were 33.3% and 0%. Recurrence rate was significantly higher in patients with a prior history of benign meningioma, nuclear atypia, high mitotic rate, spontaneous necrosis, and WHO grade III diagnosis on univariate analysis; only WHO grade III diagnosis was significant on multivariate analysis. Overall survival was adversely affected in patients with WHO grade III diagnosis, prior history of benign meningioma, prior fractionated radiotherapy, larger tumor volume, and higher isocenter number on univariate analysis; WHO grade III diagnosis and larger treated tumor volume were significant on multivariate analysis. Atypical and anaplastic meningiomas remain difficult tumors to treat. WHO grade III diagnosis and treated tumor volume were significantly

Case of Six-Year Disease-Free Survival with Undifferentiated Carcinoma of the Pancreas

Directory of Open Access Journals (Sweden)

Hiroyuki Saito

2016-08-01

Full Text Available Undifferentiated carcinoma of the pancreas (UDC is rare and has a dismal prognosis. Here, we report a case of 6-year disease-free survival with a mixed type of UDC and UDC with osteoclast-like giant cells, with a high mitotic index as well as perineural, lymphatic, vessel, and diaphragmatic invasion. The patient underwent radical distal pancreatectomy and was subsequently treated with adjuvant chemotherapy using gemcitabine plus S-1 followed by maintenance chemotherapy with oral tegafur-uracil. The patient has been doing well with no evidence of recurrence for more than 6 years after surgery.

Prognostic relevance of cytochrome C oxidase in primary glioblastoma multiforme.

Directory of Open Access Journals (Sweden)

Corinne E Griguer

Full Text Available Patients with primary glioblastoma multiforme (GBM have one of the lowest overall survival rates among cancer patients, and reliable biomarkers are necessary to predict patient outcome. Cytochrome c oxidase (CcO promotes the switch from glycolytic to OXPHOS metabolism, and increased CcO activity in tumors has been associated with tumor progression after chemotherapy failure. Thus, we investigated the relationship between tumor CcO activity and the survival of patients diagnosed with primary GBM. A total of 84 patients with grade IV glioma were evaluated in this retrospective cohort study. Cumulative survival was calculated by the Kaplan-Meier method and analyzed by the log-rank test, and univariate and multivariate analyses were performed with the Cox regression model. Mitochondrial CcO activity was determined by spectrophotometrically measuring the oxidation of cytochrome c. High CcO activity was detected in a subset of glioma tumors (∼30%, and was an independent prognostic factor for shorter progression-free survival and overall survival [P = 0.0087 by the log-rank test, hazard ratio = 3.57 for progression-free survival; P<0.001 by the log-rank test, hazard ratio = 10.75 for overall survival]. The median survival time for patients with low tumor CcO activity was 14.3 months, compared with 6.3 months for patients with high tumor CcO activity. High CcO activity occurs in a significant subset of high-grade glioma patients and is an independent predictor of poor outcome. Thus, CcO activity may serve as a useful molecular marker for the categorization and targeted therapy of GBMs.

A phase II trial with bevacizumab and irinotecan for patients with primary brain tumors and progression after standard therapy

DEFF Research Database (Denmark)

Møller, Søren; Grunnet, Kirsten; Hansen, Steinbjørn

2012-01-01

The combination of irinotecan and bevacizumab has shown efficacy in the treatment of recurrent glioblastoma multiforme (GBM). A prospective, phase II study of 85 patients with various recurrent brain tumors was carried out. Primary endpoints were progression free survival (PFS) and response rate....

The polymorphism and haplotypes of XRCC1 and survival of non-small-cell lung cancer after radiotherapy

International Nuclear Information System (INIS)

Yoon, Sang Min; Hong, Yun-Chul; Park, Heon Joo; Lee, Jong-Eun; Kim, Sang Yoon; Kim, Jong Hoon; Lee, Sang-Wook; Park, So-Yeon; Lee, Jung Shin; Choi, Eun Kyung

2005-01-01

Purpose: The X-ray repair cross-complementing Group 1 (XRCC1) protein is involved mainly in the base excision repair of the DNA repair process. This study examined the association of 3 polymorphisms (codon 194, 280, and 399) of XRCC1 and lung cancer in terms of whether or not these polymorphisms have an effect on the survival of lung cancer patients who have received radiotherapy. Methods and Materials: Between January 2000 and April 2004, 229 lung cancer patients with non-small-cell lung cancer in Stages I-III were enrolled. Genotyping was performed by single base primer extension assay using the SNP-IT Kit with genomic DNA samples from all patients. The haplotype of the XRCC1 polymorphisms was estimated by PHASE version 2.1. Results: The patients consisted of 191 (83.4%) males and 38 (16.6%) females with a median age of 62 (range, 26-88 years). Sixty percent of the patients were included in Stage I-IIIa. The median progression-free and overall survival was 13 months and 16 months, respectively. The XRCC1 codon 194, histology, and stage were shown to be significant predictors of the progression-free survival. The 6 haplotypes among the XRCC1 polymorphisms (194, 280, and 399) were estimated by PHASE v.2.1. The patients with haplotype pairs other than the homozygous TGG haplotype pairs survived significantly longer (p = 0.04). Conclusions: Polymorphisms of XRCC1 have an effect on the survival of lung cancer patients treated with radiotherapy, and this effect seems to be more significant after the haplotype pairs are considered

Early Postoperative Low Expression of RAD50 in Rectal Cancer Patients Associates with Disease-Free Survival

Directory of Open Access Journals (Sweden)

Vincent Ho

2017-11-01

Full Text Available Background: Molecular biomarkers have the potential to predict response to the treatment of rectal cancer. In this study, we aimed to evaluate the prognostic and clinicopathological implication of RAD50 (DNA repair protein RAD50 homolog expression in rectal cancer. Methods: A total of 266 rectal cancer patients who underwent surgery and received chemo- and radiotherapy between 2000 and 2011 were involved in the study. Postoperative RAD50 expression was determined by immunohistochemistry in surgical samples (n = 266. Results: Using Kaplan–Meier survival analysis, we found that low RAD50 expression in postoperative samples was associated with worse disease free survival (p = 0.001 and overall survival (p < 0.001 in early stage/low-grade tumors. In a comparison of patients with low vs. high RAD50 expression, we found that low levels of postoperative RAD50 expression in rectal cancer tissues were significantly associated with perineural invasion (p = 0.002. Conclusion: Expression of RAD50 in rectal cancer may serve as a prognostic biomarker for long-term survival of patients with perineural invasion-positive tumors and for potential use in early stage and low-grade rectal cancer assessment.

24-month HIV-free survival among infants born to HIV-positive women enrolled in Option B+ program in Kigali, Rwanda: The Kabeho Study.

Science.gov (United States)

Gill, Michelle M; Hoffman, Heather J; Ndatimana, Dieudonne; Mugwaneza, Placidie; Guay, Laura; Ndayisaba, Gilles F; Bobrow, Emily A; Asiimwe, Anita; Mofenson, Lynne M

2017-12-01

Lifelong antiretroviral therapy (ART) provision to all pregnant HIV-positive women ("Option B+") has been recommended by the World Health Organization since 2013, but there remain limited data on the effects of Option B+ on long-term HIV-free survival in breastfeeding HIV-exposed infants. The Kigali Antiretroviral and Breastfeeding Assessment for the Elimination of HIV (Kabeho) study enrolled HIV-positive women from the third trimester of pregnancy to 2 weeks postpartum in 14 heath facilities implementing Option B+ in Kigali, Rwanda. Mother-child pairs in the longitudinal observational cohort were followed until 24 months postpartum, with HIV diagnostic testing at 6 weeks, and 9, 18 and 24 months. The Kaplan-Meier method was used to estimate HIV transmission, survival, and HIV-free survival through 24 months. We enrolled 608 HIV-positive women in 2013-2014; birth outcome data were available for 600 women and 597 live-born infants. By 6 weeks, 11 infants had died and 3 infants had confirmed HIV infection (0.5% transmission; 95% confidence interval [CI] 0.2-1.6). At 9 months, there were 9 additional deaths and 2 new infections (cumulative transmission 0.9%, 95% CI 0.4-2.2). At 18 months, there were 6 additional deaths and no new infant infections. At 24 months, there were no additional child deaths and 1 new infection (cumulative 2.2%, 95% CI 0.7-7.0), for an overall 24-month HIV-free survival of 93.2% (95% CI 89.5-95.6). Low transmission rates and high HIV-free survival at 24 months were achieved in breastfeeding infants of HIV-positive mothers receiving universal ART in urban health facilities in Rwanda, though vigilance on maintaining viral suppression for ART-experienced women is needed. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

LEF-1 and TCF4 expression correlate inversely with survival in colorectal cancer

Directory of Open Access Journals (Sweden)

Kirchner Thomas

2010-11-01

Full Text Available Abstract Background Most colorectal carcinomas are driven by an activation of the canonical Wnt signalling pathway, which promotes the expression of multiple target genes mediating proliferation inavasion and invasion. Upon activation of the Wnt signalling pathway its key player β-catenin translocates from the cytoplasm to the nucleus and binds to members of the T-cell factor (TCF/lymphoid enhancer factor (LEF-1 family namely LEF-1 and TCF4 which are central mediators of transcription. In this study we investigated the expression of β-Catenin, LEF1 and TCF4 in colorectal carcinomas and their prognostic significance. Methods Immunohistochemical analyses of LEF-1, TCF4 and nuclear β-Catenin were done using a tissue microarray with 214 colorectal cancer specimens. The expression patterns were compared with each other and the results were correlated with clinicopathologic variables and overall survival in univariate and multivariate analysis. Results LEF-1 expression was found in 56 (26% and TCF4 expression in 99 (46% of colorectal carcinomas and both were heterogenously distributed throughout the tumours. Comparing LEF-1, TCF4 and β-catenin expression patterns we found no correlation. In univariate analysis, TCF4 expression turned out to be a negative prognostic factor being associated with shorter overall survival (p = 0.020, whereas LEF-1 expression as well as a LEF-1/TCF4 ratio were positive prognostic factors and correlated with longer overall survival (p = 0.015 respectively p = 0.001. In multivariate analysis, LEF-1 and TCF4 expression were confirmed to be independent predictors of longer respectively shorter overall survival, when considered together with tumour stage, gender and age (risk ratio for LEF-1: 2.66; p = 0.027 risk ratio for TCF4: 2.18; p = 0.014. Conclusions This study demonstrates different prognostic values of LEF-1 and TCF4 expression in colorectal cancer patients indicating different regulation of these transcription

Additional androgen deprivation makes the difference. Biochemical recurrence-free survival in prostate cancer patients after HDR brachytherapy and external beam radiotherapy

International Nuclear Information System (INIS)

Schiffmann, Jonas; Tennstedt, Pierre; Beyer, Burkhard; Boehm, Katharina; Tilki, Derya; Salomon, Georg; Graefen, Markus; Lesmana, Hans; Platz, Volker; Petersen, Cordula; Kruell, Andreas; Schwarz, Rudolf

2015-01-01

The role of additional androgen deprivation therapy (ADT) in prostate cancer (PCa) patients treated with combined HDR brachytherapy (HDR-BT) and external beam radiotherapy (EBRT) is still unknown. Consecutive PCa patients classified as D'Amico intermediate and high-risk who underwent HDR-BT and EBRT treatment ± ADT at our institution between January 1999 and February 2009 were assessed. Multivariable Cox regression models predicting biochemical recurrence (BCR) were performed. BCR-free survival was assessed with Kaplan-Meier analyses. Overall, 392 patients were assessable. Of these, 221 (56.4 %) underwent trimodality (HDR-BT and EBRT and ADT) and 171 (43.6 %) bimodality (HDR-BT and EBRT) treatment. Additional ADT administration reduced the risk of BCR (HR: 0.4, 95 % CI: 0.3-0.7, p < 0.001). D'Amico high-risk patients had superior BCR-free survival when additional ADT was administered (log-rank p < 0.001). No significant difference for BCR-free survival was recorded when additional ADT was administered to D'Amico intermediate-risk patients (log-rank p = 0.2). Additional ADT administration improves biochemical control in D'Amico high-risk patients when HDR-BT and EBRT are combined. Physicians should consider the oncological benefit of ADT administration for these patients during the decision-making process. (orig.) [de

Correlation of 18F-FDG PET and MRI Apparent Diffusion Coefficient Histogram Metrics with Survival in Diffuse Intrinsic Pontine Glioma: A Report from the Pediatric Brain Tumor Consortium.

Science.gov (United States)

Zukotynski, Katherine A; Vajapeyam, Sridhar; Fahey, Frederic H; Kocak, Mehmet; Brown, Douglas; Ricci, Kelsey I; Onar-Thomas, Arzu; Fouladi, Maryam; Poussaint, Tina Young

2017-08-01

The purpose of this study was to describe baseline 18 F-FDG PET voxel characteristics in pediatric diffuse intrinsic pontine glioma (DIPG) and to correlate these metrics with baseline MRI apparent diffusion coefficient (ADC) histogram metrics, progression-free survival (PFS), and overall survival. Methods: Baseline brain 18 F-FDG PET and MRI scans were obtained in 33 children from Pediatric Brain Tumor Consortium clinical DIPG trials. 18 F-FDG PET images, postgadolinium MR images, and ADC MR images were registered to baseline fluid attenuation inversion recovery MR images. Three-dimensional regions of interest on fluid attenuation inversion recovery MR images and postgadolinium MR images and 18 F-FDG PET and MR ADC histograms were generated. Metrics evaluated included peak number, skewness, and kurtosis. Correlation between PET and MR ADC histogram metrics was evaluated. PET pixel values within the region of interest for each tumor were plotted against MR ADC values. The association of these imaging markers with survival was described. Results: PET histograms were almost always unimodal (94%, vs. 6% bimodal). None of the PET histogram parameters (skewness or kurtosis) had a significant association with PFS, although a higher PET postgadolinium skewness tended toward a less favorable PFS (hazard ratio, 3.48; 95% confidence interval [CI], 0.75-16.28 [ P = 0.11]). There was a significant association between higher MR ADC postgadolinium skewness and shorter PFS (hazard ratio, 2.56; 95% CI, 1.11-5.91 [ P = 0.028]), and there was the suggestion that this also led to shorter overall survival (hazard ratio, 2.18; 95% CI, 0.95-5.04 [ P = 0.067]). Higher MR ADC postgadolinium kurtosis tended toward shorter PFS (hazard ratio, 1.30; 95% CI, 0.98-1.74 [ P = 0.073]). PET and MR ADC pixel values were negatively correlated using the Pearson correlation coefficient. Further, the level of PET and MR ADC correlation was significantly positively associated with PFS; tumors with higher

Common genetic polymorphisms of microRNA biogenesis pathway genes and breast cancer survival

International Nuclear Information System (INIS)

Sung, Hyuna; Ahn, Sei-Hyun; Kang, Daehee; Jeon, Sujee; Lee, Kyoung-Mu; Han, Sohee; Song, Minkyo; Choi, Ji-Yeob; Park, Sue K; Yoo, Keun-Young; Noh, Dong-Young

2012-01-01

Although the role of microRNA’s (miRNA’s) biogenesis pathway genes in cancer development and progression has been well established, the association between genetic variants of this pathway genes and breast cancer survival is still unknown. We used genotype data available from a previously conducted case–control study to investigate association between common genetic variations in miRNA biogenesis pathway genes and breast cancer survival. We investigated the possible associations between 41 germ-line single-nucleotide polymorphisms (SNPs) and both disease free survival (DFS) and overall survival (OS) among 488 breast cancer patients. During the median follow-up of 6.24 years, 90 cases developed disease progression and 48 cases died. Seven SNPs were significantly associated with breast cancer survival. Two SNPs in AGO2 (rs11786030 and rs2292779) and DICER1 rs1057035 were associated with both DFS and OS. Two SNPs in HIWI (rs4759659 and rs11060845) and DGCR8 rs9606250 were associated with DFS, while DROSHA rs874332 and GEMIN4 rs4968104 were associated with only OS. The most significant association was observed in variant allele of AGO2 rs11786030 with 2.62-fold increased risk of disease progression (95% confidence interval (CI), 1.41-4.88) and in minor allele homozygote of AGO2 rs2292779 with 2.94-fold increased risk of death (95% CI, 1.52-5.69). We also found cumulative effects of SNPs on DFS and OS. Compared to the subjects carrying 0 to 2 high-risk genotypes, those carrying 3 or 4–6 high-risk genotypes had an increased risk of disease progression with a hazard ratio of 2.16 (95% CI, 1.18- 3.93) and 4.47 (95% CI, 2.45- 8.14), respectively (P for trend, 6.11E-07). Our results suggest that genetic variants in miRNA biogenesis pathway genes may be associated with breast cancer survival. Further studies in larger sample size and functional characterizations are warranted to validate these results

Increased tumour ascorbate is associated with extended disease-free survival and decreased hypoxia-inducible factor-1 activation in human colorectal cancer

Directory of Open Access Journals (Sweden)

Caroline eKuiper

2014-02-01

Full Text Available Ascorbate is a co-factor for the hydroxylases that regulate the transcription factor hypoxia-inducible factor (HIF-1, which provides cancer cells with a metabolic and survival advantage in the hypoxic environment of solid tumors. However, whether ascorbate affects tumor development is a highly debated issue. We aimed to determine whether tumor ascorbate was associated with HIF-1 activation and patient disease-free survival. In this study we undertook a retrospective observational analysis of tissue-banked tumor and paired normal tissue from 49 colorectal cancer patients, measuring ascorbate levels, HIF-1α and its downstream gene products BNIP3 and VEGF. Patient survival was monitored for the first six years after surgery. We found that ascorbate levels were lower in tumor tissue compared to normal tissue (p< 0.001 but overall levels varied considerably. HIF-1α, VEGF and BNIP3 were elevated in tumor samples (p< 0.01. There was an inverse relationship between tumor ascorbate content and HIF-1 pathway activation (p=0.002 and tumor size (p=0.018. Higher tumor ascorbate content was associated with significantly improved disease-free survival in the first 6 years after surgery (p=0.006, with 141 - 1,094 additional disease free days. This was independent of tumor grade and stage. Survival advantage was associated with the amount of ascorbate in the tumor, but not with the amount in adjacent normal tissue. Our results demonstrate that higher tumor ascorbate content is associated decreased HIF-1 activation, most likely due to the co-factor activity of ascorbate for the regulatory HIF hydroxylases. Our findings support the need for future studies to determine whether raising tumor ascorbate is possible with clinical intervention and whether this results in modification of hydroxylase-dependent pathways in the tumor.

Serum levels of IGF-1 and IGF-BP3 are associated with event-free survival in adult Ewing sarcoma patients treated with chemotherapy

Directory of Open Access Journals (Sweden)

de Groot S

2017-06-01

Full Text Available Stefanie de Groot,1 Hans Gelderblom,1 Marta Fiocco,2,3 Judith VMG Bovée,4 Jacobus JM van der Hoeven,1 Hanno Pijl,5 Judith R Kroep1 1Department of Medical Oncology, 2Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, 3Mathematical Department, Leiden University, 4Department of Pathology, 5Department of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands Background: Activation of the insulin-like growth factor 1 (IGF-1 pathway is involved in cell growth and proliferation and is associated with tumorigenesis, tumor progression, and therapy resistance in solid tumors. We examined whether variability in serum levels of IGF-1, IGF-2, and IGF-binding protein 3 (IGF-BP3 can predict event-free survival (EFS and overall survival (OS in Ewing sarcoma patients treated with chemotherapy.Patients and methods: Serum levels of IGF-1, IGF-2, and IGF-BP3 of 22 patients with localized or metastasized Ewing sarcoma treated with six cycles of vincristine/ifosfamide/doxorubicin/etoposide (VIDE chemotherapy were recorded. Baseline levels were compared with presixth cycle levels using paired t-tests and were tested for associations with EFS and OS. Continuous variables were dichotomized according to the Contal and O’Quigley procedure. Survival analyses were performed using Cox regression analysis.Results: High baseline IGF-1 and IGF-BP3 serum levels were associated with EFS (hazard ratio [HR] 0.075, 95% confidence interval [CI] 0.009–0.602 and HR 0.090, 95% CI 0.011–0.712, respectively in univariate and multivariate analyses (HR 0.063, 95% CI 0.007–0.590 and HR 0.057, 95% CI 0.005–0.585, respectively. OS was improved, but this was not statistically significant. IGF-BP3 and IGF-2 serum levels increased during treatment with VIDE chemotherapy (P=0.055 and P=0.023, respectively.Conclusion: High circulating serum levels of IGF-1 and IGF-BP3 and the molar ratio of IGF-1:IGF-BP3 serum levels were associated

Expression of aurora kinase A is associated with metastasis-free survival in node-negative breast cancer patients

International Nuclear Information System (INIS)

Siggelkow, Wulf; Koelbl, Heinz; Gehrmann, Mathias; Marchan, Rosemarie; Cadenas, Cristina; Hengstler, Jan G; Schmidt, Marcus; Boehm, Daniel; Gebhard, Susanne; Battista, Marco; Sicking, Isabel; Lebrecht, Antje; Solbach, Christine; Hellwig, Birte; Rahnenführer, Jörg

2012-01-01

Inhibitors targeting the cell cycle-regulated aurora kinase A (AURKA) are currently being developed. Here, we examine the prognostic impact of AURKA in node-negative breast cancer patients without adjuvant systemic therapy (n = 766). AURKA was analyzed using microarray-based gene-expression data from three independent cohorts of node-negative breast cancer patients. In multivariate Cox analyses, the prognostic impact of age, histological grade, tumor size, estrogen receptor (ER), and HER2 were considered. Patients with higher AURKA expression had a shorter metastasis-free survival (MFS) in the Mainz (HR 1.93; 95% CI 1.34 – 2.78; P < 0.001), Rotterdam (HR 1.95; 95% CI 1.45– 2.63; P<0.001) and Transbig (HR 1.52; 95% CI 1.14–2.04; P=0.005) cohorts. AURKA was also associated with MFS in the molecular subtype ER+/HER2- carcinomas (HR 2.10; 95% CI 1.70–2.59; P<0.001), but not in ER-/HER2- nor in HER2+ carcinomas. In the multivariate Cox regression adjusted to age, grade and tumor size, AURKA showed independent prognostic significance in the ER+/HER2- subtype (HR 1.73; 95% CI 1.24–2.42; P=0.001). Prognosis of patients in the highest quartile of AURKA expression was particularly poor. In addition, AURKA correlated with the proliferation metagene (R=0.880; P<0.001), showed a positive association with grade (P<0.001), tumor size (P<0.001) and HER2 (P<0.001), and was inversely associated with ER status (P<0.001). AURKA is associated with worse prognosis in estrogen receptor positive breast carcinomas. Patients with the highest AURKA expression (>75% percentile) have a particularly bad prognosis and may profit from therapy with AURKA inhibitors

Economic evaluation of nivolumab for the treatment of second-line advanced squamous NSCLC in Canada: a comparison of modeling approaches to estimate and extrapolate survival outcomes.

Science.gov (United States)

Goeree, Ron; Villeneuve, Julie; Goeree, Jeff; Penrod, John R; Orsini, Lucinda; Tahami Monfared, Amir Abbas

2016-06-01

Background Lung cancer is the most common type of cancer in the world and is associated with significant mortality. Nivolumab demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients with advanced squamous non-small cell lung cancer (NSCLC) who were previously treated. The cost-effectiveness of nivolumab has not been assessed in Canada. A contentious component of projecting long-term cost and outcomes in cancer relates to the modeling approach adopted, with the two most common approaches being partitioned survival (PS) and Markov models. The objectives of this analysis were to estimate the cost-utility of nivolumab and to compare the results using these alternative modeling approaches. Methods Both PS and Markov models were developed using docetaxel and erlotinib as comparators. A three-health state model was used consisting of progression-free, progressed disease, and death. Disease progression and time to progression were estimated by identifying best-fitting survival curves from the clinical trial data for PFS and OS. Expected costs and health outcomes were calculated by combining health-state occupancy with medical resource use and quality-of-life assigned to each of the three health states. The health outcomes included in the model were survival and quality-adjusted-life-years (QALYs). Results Nivolumab was found to have the highest expected per-patient cost, but also improved per-patient life years (LYs) and QALYs. Nivolumab cost an additional $151,560 and $140,601 per QALY gained compared to docetaxel and erlotinib, respectively, using a PS model approach. The cost-utility estimates using a Markov model were very similar ($152,229 and $141,838, respectively, per QALY gained). Conclusions Nivolumab was found to involve a trade-off between improved patient survival and QALYs, and increased cost. It was found that the use of a PS or Markov model produced very similar estimates of expected cost

Survival Advantage Associated with Decrease in Stage at Detection from Stage IIIC to Stage IIIA Epithelial Ovarian Cancer

Science.gov (United States)

Lefringhouse, Jason; Pavlik, Edward; Miller, Rachel; DeSimone, Christopher; Ueland, Frederick; Kryscio, Richard; van Nagell, J. R.

2014-01-01

Objective. The aim of this study was to document the survival advantage of lowering stage at detection from Stage IIIC to Stage IIIA epithelial ovarian cancer. Methods. Treatment outcomes and survival were evaluated in patients with Stage IIIA and Stage IIIC epithelial ovarian cancer treated from 2000 to 2009 at the University of Kentucky Markey Cancer Center (UKMCC) and SEER institutions. Results. Cytoreduction to no visible disease (P < 0.0001) and complete response to platinum-based chemotherapy (P < 0.025) occurred more frequently in Stage IIIA than in Stage IIIC cases. Time to progression was shorter in patients with Stage IIIC ovarian cancer (17 ± 1 months) than in those with Stage II1A disease (36 ± 8 months). Five-year overall survival (OS) improved from 41% in Stage IIIC patients to 60% in Stage IIIA patients treated at UKMCC and from 37% to 56% in patients treated at SEER institutions for a survival advantage of 19% in both data sets. 53% of Stage IIIA and 14% of Stage IIIC patients had NED at last followup. Conclusions. Decreasing stage at detection from Stage IIIC to stage IIIA epithelial ovarian cancer is associated with a 5-year survival advantage of nearly 20% in patients treated by surgical tumor cytoreduction and platinum-based chemotherapy. PMID:25254047

The effect of obesity on pathological complete response and survival in breast cancer patients receiving uncapped doses of neoadjuvant anthracycline-taxane-based chemotherapy.

Science.gov (United States)

Farr, Alex; Stolz, Myriam; Baumann, Lukas; Bago-Horvath, Zsuzsanna; Oppolzer, Elisabeth; Pfeiler, Georg; Seifert, Michael; Singer, Christian F

2017-06-01

The effect of obesity in breast cancer patients undergoing neoadjuvant chemotherapy (NAC) remains controversial. The aim of this study was to determine the obesity-related effect on pathological complete response (pCR) and survival in women receiving full uncapped doses of NAC. We retrospectively analyzed the data of all consecutive women who underwent anthracycline-taxane-based NAC for primary breast cancer between 2005 and 2015 at the Department of Obstetrics and Gynecology, Medical University of Vienna. Following the WHO criteria, women with a body mass index (BMI) ≥30 kg/m 2 at baseline were considered obese, whereas those with a BMI <30 kg/m 2 were considered non-obese. Those with dose reductions or dose capping were not eligible for study inclusion. Cox regression and logistic regression were performed. The Kaplan-Meier method was used to analyze disease-free, progression-free, and overall survival. The pCR served as the main outcome measure. Among 120 women who received neoadjuvant epirubicin plus cyclophosphamide and docetaxel, 28 (23.3%) were obese and 92 (76.7%) were non-obese. In the multivariate logistic regression model that adjusted for potentially confounding variables, obesity had an independent positive predictive effect on pCR (OR 4.29, 95% CI, 1.42-13.91; p = 0.011), which was significant in the postmenopausal subgroup (OR 4.72, 95% CI, 1.47-15.84; p = 0.01). When comparing non-obese with obese women, we found that obese women experienced longer progression-free survival (HR 0.10, 95% CI, 8.448 × 10 -4 -0.81; p = 0.025). Obese women receiving full uncapped doses of anthracycline-taxane-based NAC have increased pCR and favorable progression-free survival. This could result from increased dose intensity with increased efficacy and toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Progress update of NASA's free-piston Stirling space power converter technology project

Science.gov (United States)

Dudenhoefer, James E.; Winter, Jerry M.; Alger, Donald

1992-01-01

A progress update is presented of the NASA LeRC Free-Piston Stirling Space Power Converter Technology Project. This work is being conducted under NASA's Civil Space Technology Initiative (CSTI). The goal of the CSTI High Capacity Power Element is to develop the technology base needed to meet the long duration, high capacity power requirements for future NASA space initiatives. Efforts are focused upon increasing system power output and system thermal and electric energy conversion efficiency at least five fold over current SP-100 technology, and on achieving systems that are compatible with space nuclear reactors. This paper will discuss progress toward 1050 K Stirling Space Power Converters. Fabrication is nearly completed for the 1050 K Component Test Power Converter (CTPC); results of motoring tests of the cold end (525 K), are presented. The success of these and future designs is dependent upon supporting research and technology efforts including heat pipes, bearings, superalloy joining technologies, high efficiency alternators, life and reliability testing, and predictive methodologies. This paper will compare progress in significant areas of component development from the start of the program with the Space Power Development Engine (SPDE) to the present work on CTPC.

Delay of Treatment Initiation Does Not Adversely Affect Survival Outcome in Breast Cancer.

Science.gov (United States)

Yoo, Tae-Kyung; Han, Wonshik; Moon, Hyeong-Gon; Kim, Jisun; Lee, Jun Woo; Kim, Min Kyoon; Lee, Eunshin; Kim, Jongjin; Noh, Dong-Young

2016-07-01

Previous studies examining the relationship between time to treatment and survival outcome in breast cancer have shown inconsistent results. The aim of this study was to analyze the overall impact of delay of treatment initiation on patient survival and to determine whether certain subgroups require more prompt initiation of treatment. This study is a retrospective analysis of stage I-III patients who were treated in a single tertiary institution between 2005 and 2008. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to evaluate the impact of interval between diagnosis and treatment initiation in breast cancer and various subgroups. A total of 1,702 patients were included. Factors associated with longer delay of treatment initiation were diagnosis at another hospital, medical comorbidities, and procedures performed before admission for surgery. An interval between diagnosis and treatment initiation as a continuous variable or with a cutoff value of 15, 30, 45, and 60 days had no impact on disease-free survival (DFS). Subgroup analyses for hormone-responsiveness, triple-negative breast cancer, young age, clinical stage, and type of initial treatment showed no significant association between longer delay of treatment initiation and DFS. Our results show that an interval between diagnosis and treatment initiation of 60 days or shorter does not appear to adversely affect DFS in breast cancer.

Deregulation of HOX B13 expression in urinary bladder cancer progression.

Science.gov (United States)

Marra, L; Cantile, M; Scognamiglio, G; Perdonà, S; La Mantia, E; Cerrone, M; Gigantino, V; Cillo, C; Caraglia, M; Pignata, S; Facchini, G; Botti, G; Chieffi, S; Chieffi, P; Franco, R

2013-02-01

Urinary bladder cancer is a common malignancy in industrialized countries. More than 90% of bladder cancer originates in the transitional cells. Bladder transitional cancer prognosis is, according to the most recent definition related to the level of tumor infiltration, characterized by two main phenotypes, Non Muscle Invasive Bladder Transitional Cancer (NMIBC) and Muscle Invasive Bladder Transitional Cancer (MIBC). The genetic profile and the clinical course of the two subtypes are completely different, however among NMIBC the prognosis is not completely predictable, since 20% of the cases experience a relapse, even in the form of MIBC. It has recently been reported that the chromosomal region 12q13-15, containing crucial cancer genes such as MDM2, CDK4, GLI and an entire cluster of HOX genes, is amplified in bladder cancer. HOX genes codify for transcriptionl factor, involved in embryonal development and cancer progression, with main nuclear expression. Particularly it was also described the strong involvement of HOX B13 in several tumors of urogenital system. In this study we have been investigated, by immunohistochemisty and quantitative Real Time PCR, the HOX B13 expression in bladder cancer evolution and progression, evaluating its ability to discriminate between NMIBC and MBCI phenotypes. Cytoplasmic HOX B13 delocalization significantly relates with muscle invasion (p 0.004). In addition in the series of NMIBC nuclear HOX B13 expression loss is significantly associated to shorter disease free survival (p-value=0.038) defining a potential prognostic role. Overexpression of HOX B13 in more aggressive phenotype is also demonstrate at gene level by quantitative RT-PCR. The de-regulation and delocalization of HOX B13 in urinary bladder cancer supports again the important role of HOX genes in tumor evolution and represents a starting point to establish an integrated analysis, in which HOX genes represent important prognostic and predictive markers for bladder

High serum levels of YKL-40 in patients with squamous cell carcinoma of the head and neck are associated with short survival

DEFF Research Database (Denmark)

Roslind, A.; Johansen, J.S.; Christensen, L.J.

2008-01-01

by immunohistochemistry in 50 patients. Pretreatment serum YKL-40 was elevated in 53%. Patients with high serum YKL-40 had shorter survival than patients with normal serum YKL-40 (33 vs. 84 months; p = 0.008). Multivariate Cox analysis including pretreatment serum YKL-40, age, sex, primary tumor site, TNM classification...... and treatment demonstrated that TNM classification (HR = 2.61, p = 0.02) and serum YKL-40 (log-transformed continuous variable: HR = 1.55, p classification (HR = 5.77, p = 0.001) and serum...... YKL-40 (dichotomous variable: HR = 2.75, p = 0.01) were independent predictors of recurrence-free survival. During follow-up after radiotherapy, a high serum YKL-40 (log-transformed continuous variable) in patients with TNM Stage III and TV disease predicted poorer OS within 6 months (HR = 1.95, p

Prognostic factors in breast cancer with extracranial oligometastases and the appropriate role of radiation therapy.

Science.gov (United States)

Yoo, Gyu Sang; Yu, Jeong Il; Park, Won; Huh, Seung Jae; Choi, Doo Ho

2015-12-01

To identify prognostic factors for disease progression and survival of patients with extracranial oligometastatic breast cancer (EOMBC), and to investigate the role of radiation therapy (RT) for metastatic lesions. We retrospectively reviewed the medical records of 50 patients who had been diagnosed with EOMBC following standard treatment for primary breast cancer initially, and received RT for metastatic lesions, with or without other systemic therapy between January 2004 and December 2008. EOMBC was defined as breast cancer with five or less metastases involving any organs except the brain. All patients had bone metastasis (BM) and seven patients had pulmonary, hepatic, or lymph node metastasis. Median RT dose applied to metastatic lesions was 30 Gy (range, 20 to 60 Gy). The 5-year tumor local control (LC) and 3-year distant progression-free survival (DPFS) rate were 66.1% and 36.8%, respectively. High RT dose (≥50 Gy10) was significantly associated with improved LC. The 5-year overall survival (OS) rate was 49%. Positive hormone receptor status, pathologic nodal stage of primary cancer, solitary BM, and whole-lesion RT (WLRT), defined as RT whose field encompassed entire extent of disease, were associated with better survival. On analysis for subgroup of solitary BM, high RT dose was significantly associated with improved LC and DPFS, shorter metastasis-to-RT interval (≤1 month) with improved DPFS, and WLRT with improved DPFS and OS, respectively. High-dose RT in solitary BM status and WLRT have the potential to improve the progression-free survival and OS of patients with EOMBC.

Prognostic factors in breast cancer with extracranial oligometastases and the appropriate role of radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Yoo, Gyu Sang; Yu, Jeong Il; Park, Won; Huh, Seung Jae; Choi, Doo Ho [Dept. of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2015-12-15

To identify prognostic factors for disease progression and survival of patients with extracranial oligometastatic breast cancer (EOMBC), and to investigate the role of radiation therapy (RT) for metastatic lesions. We retrospectively reviewed the medical records of 50 patients who had been diagnosed with EOMBC following standard treatment for primary breast cancer initially, and received RT for metastatic lesions, with or without other systemic therapy between January 2004 and December 2008. EOMBC was defined as breast cancer with five or less metastases involving any organs except the brain. All patients had bone metastasis (BM) and seven patients had pulmonary, hepatic, or lymph node metastasis. Median RT dose applied to metastatic lesions was 30 Gy (range, 20 to 60 Gy). The 5-year tumor local control (LC) and 3-year distant progression-free survival (DPFS) rate were 66.1% and 36.8%, respectively. High RT dose (> or =50 Gy10) was significantly associated with improved LC. The 5-year overall survival (OS) rate was 49%. Positive hormone receptor status, pathologic nodal stage of primary cancer, solitary BM, and whole-lesion RT (WLRT), defined as RT whose field encompassed entire extent of disease, were associated with better survival. On analysis for subgroup of solitary BM, high RT dose was significantly associated with improved LC and DPFS, shorter metastasis-to-RT interval (< or =1 month) with improved DPFS, and WLRT with improved DPFS and OS, respectively. High-dose RT in solitary BM status and WLRT have the potential to improve the progression-free survival and OS of patients with EOMBC.

Anthropometric characteristics and ovarian cancer risk and survival.

Science.gov (United States)

Minlikeeva, Albina N; Moysich, Kirsten B; Mayor, Paul C; Etter, John L; Cannioto, Rikki A; Ness, Roberta B; Starbuck, Kristen; Edwards, Robert P; Segal, Brahm H; Lele, Sashikant; Odunsi, Kunle; Diergaarde, Brenda; Modugno, Francesmary

2018-02-01

Multiple studies have examined the role of anthropometric characteristics in ovarian cancer risk and survival; however, their results have been conflicting. We investigated the associations between weight change, height and height change and risk and outcome of ovarian cancer using data from a large population-based case-control study. Data from 699 ovarian cancer cases and 1,802 controls who participated in the HOPE study were included. We used unconditional logistic regression adjusted for age, race, number of pregnancies, use of oral contraceptives, and family history of breast or ovarian cancer to examine the associations between self-reported height and weight and height change with ovarian cancer risk. Cox proportional hazards regression models adjusted for age and stage were used to examine the association between the exposure variables and overall and progression-free survival among ovarian cancer cases. We observed an increased risk of ovarian cancer mortality and progression for gaining more than 20 pounds between ages 18-30, HR 1.36; 95% CI 1.05-1.76, and HR 1.31; 95% CI 1.04-1.66, respectively. Losing weight and gaining it back multiple times was inversely associated with both ovarian cancer risk, OR 0.78; 95% CI 0.63-0.97 for 1-4 times and OR 0.73; 95% CI 0.54-0.99 for 5-9 times, and mortality, HR 0.63; 95% CI 0.40-0.99 for 10-14 times. Finally, being taller during adolescence and adulthood was associated with increased risk of mortality. Taller stature and weight gain over lifetime were not related to ovarian cancer risk. Our results suggest that height and weight and their change over time may influence ovarian cancer risk and survival. These findings suggest that biological mechanisms underlying these associations may be hormone driven and may play an important role in relation to ovarian carcinogenesis and tumor progression.

Does delay in diagnosing colorectal cancer in symptomatic patients affect tumor stage and survival? A population-based observational study

Directory of Open Access Journals (Sweden)

Visser Otto

2010-06-01

Full Text Available Abstract Background Diagnosing colorectal cancer (CRC at an early stage improves survival. To what extent any delay affects outcome once patients are symptomatic is still unclear. Our objectives were to evaluate the association between diagnostic delay and survival in symptomatic patients with early stage CRC and late stage CRC. Methods Prospective population-based observational study evaluating daily clinical practice in Northern Holland. Diagnostic delay was determined through questionnaire-interviews. Dukes' stage was classified into two groups: early stage (Dukes A or B and late stage (Dukes C or D cancer. Patients were followed up for 3.5 years after diagnosis. Results In total, 272 patients were available for analysis. Early stage CRC was present in 136 patients while 136 patients had late stage CRC. The mean total diagnostic delay (SE was 31 (1.5 weeks in all CRC patients. No significant difference was observed in the mean total diagnostic delay in early versus late stage CRC (p = 0.27. In early stage CRC, no difference in survival was observed between patients with total diagnostic delay shorter and longer than the median (Kaplan-Meier, log-rank p = 0.93. In late stage CRC, patients with a diagnostic delay shorter than the median had a shorter survival than patients with a diagnostic delay longer than the median (log-rank p = 0.01. In the multivariate Cox regression model with survival as dependent variable and median delay, age, open access endoscopy, number and type of symptoms as independent variables, the odd's ratio for survival in patients with long delay (>median versus short delay (≤median was 1.8 (95% confidence interval (CI 1.1 to 3.0; p = 0.01. Tumor-site was not associated with patient survival. When separating late stage CRC in Dukes C and Dukes D tumors, a shorter delay was associated with a shorter survival in Dukes D tumors only and not in Dukes C tumors. Conclusion In symptomatic CRC patients, a longer diagnostic and

Effect of time interval between capecitabine intake and radiotherapy on local recurrence-free survival in preoperative chemoradiation for locally advanced rectal cancer

Energy Technology Data Exchange (ETDEWEB)

Kim, Yeon Joo; Kim, Jong Hoon; Yu, Chang Sik; Kim, Tae Won; Jang, Se Jin; Choi, Eun Kyung; Kim, Jin Cheon [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Won Sik [University of Ulsan College of Medicine, Gangneung (Korea, Republic of)

2017-06-15

The concentration of capecitabine peaks at 1–2 hours after administration. We therefore assumed that proper timing of capecitabine administration and radiotherapy would maximize radiosensitization and influence survival among patients with locally advanced rectal cancer. We retrospectively reviewed 223 patients with locally advanced rectal cancer who underwent preoperative chemoradiation, followed by surgery from January 2002 to May 2006. All patients underwent pelvic radiotherapy (50 Gy/25 fractions) and received capecitabine twice daily at 12-hour intervals (1,650 mg/m2/day). Patients were divided into two groups according to the time interval between capecitabine intake and radiotherapy. Patients who took capecitabine 1 hour before radiotherapy were classified as Group A (n = 109); all others were classified as Group B (n = 114). The median follow-up period was 72 months (range, 7 to 149 months). Although Group A had a significantly higher rate of good responses (44% vs. 25%; p = 0.005), the 5-year local recurrence-free survival rates of 93% in Group A and 97% in Group B did not differ significantly (p = 0.519). The 5-year disease-free survival and overall survival rates were also comparable between the groups. Despite the better pathological response in Group A, the time interval between capecitabine and radiotherapy administration did not have a significant effect on survivals. Further evaluations are needed to clarify the interaction of these treatment modalities.

Free Base Lysine Increases Survival and Reduces Metastasis in Prostate Cancer Model.

Science.gov (United States)

Ibrahim-Hashim, Arig; Wojtkowiak, Jonathan W; de Lourdes Coelho Ribeiro, Maria; Estrella, Veronica; Bailey, Kate M; Cornnell, Heather H; Gatenby, Robert A; Gillies, Robert J

2011-11-19

Malignant tumor cells typically metabolize glucose anaerobically to lactic acid even under normal oxygen tension, a phenomenon called aerobic glycolysis or the Warburg effect. This results in increased acid production and the acidification of the extracellular microenvironment in solid tumors. H + ions tend to flow along concentration gradients into peritumoral normal tissue causing extracellular matrix degradation and increased tumor cell motility thus promoting invasion and metastasis. We have shown that reducing this acidity with sodium bicarbonate buffer decreases the metastatic fitness of circulating tumor cells in prostate cancer and other cancer models. Mathematical models of the tumor-host dynamics predicted that buffers with a pka around 7 will be more effective in reducing intra- and peri-tumoral acidosis and, thus, and possibly more effective in inhibiting tumor metastasis than sodium bicarbonate which has a pKa around 6. Here we test this prediction the efficacy of free base lysine; a non-bicarbonate/non-volatile buffer with a higher pKa (~10), on prostate tumor metastases model. Oxygen consumption and acid production rate of PC3M prostate cancer cells and normal prostate cells were determined using the Seahorse Extracellular Flux (XF-96) analyzer. In vivo effect of 200 mM lysine started four days prior to inoculation on inhibition of metastasis was examined in PC3M-LUC-C6 prostate cancer model using SCID mice. Metastases were followed by bioluminescence imaging. PC3M prostate cancer cells are highly acidic in comparison to a normal prostate cell line indicating that reduction of intra- and perit-tumoral acidosis should inhibit metastases formation. In vivo administration of 200 mM free base lysine increased survival and reduced metastasis. PC3M prostate cancer cells are highly glycolytic and produce large amounts of acid when compared to normal prostate cells. Administration of non-volatile buffer decreased growth of metastases and improved survival

18F-Fluoride PET/CT tumor burden quantification predicts survival in breast cancer.

Science.gov (United States)

Brito, Ana E; Santos, Allan; Sasse, André Deeke; Cabello, Cesar; Oliveira, Paulo; Mosci, Camila; Souza, Tiago; Amorim, Barbara; Lima, Mariana; Ramos, Celso D; Etchebehere, Elba

2017-05-30

In bone-metastatic breast cancer patients, there are no current imaging biomarkers to identify which patients have worst prognosis. The purpose of our study was to investigate if skeletal tumor burden determined by 18F-Fluoride PET/CT correlates with clinical outcomes and may help define prognosis throughout the course of the disease. Bone metastases were present in 49 patients. On multivariable analysis, skeletal tumor burden was significantly and independently associated with overall survival (p breast cancer patients (40 for primary staging and the remainder for restaging after therapy). Clinical parameters, primary tumor characteristics and skeletal tumor burden were correlated to overall survival, progression free-survival and time to bone event. The median follow-up time was 19.5 months. 18F-Fluoride PET/CT skeletal tumor burden is a strong independent prognostic imaging biomarker in breast cancer patients.

Hope, optimism and survival in a randomised trial of chemotherapy for metastatic colorectal cancer.

Science.gov (United States)

Schofield, Penelope E; Stockler, M R; Zannino, D; Tebbutt, N C; Price, T J; Simes, R J; Wong, N; Pavlakis, N; Ransom, D; Moylan, E; Underhill, C; Wyld, D; Burns, I; Ward, R; Wilcken, N; Jefford, M

2016-01-01

Psychological responses to cancer are widely believed to affect survival. We investigated associations between hope, optimism, anxiety, depression, health utility and survival in patients starting first-line chemotherapy for metastatic colorectal cancer. Four hundred twenty-nine subjects with metastatic colorectal cancer in a randomised controlled trial of chemotherapy completed baseline questionnaires assessing the following: hopefulness, optimism, anxiety and depression and health utility. Hazard ratios (HRs) and P values were calculated with Cox models for overall survival (OS) and progression-free survival (PFS) in univariable and multivariable analyses. Median follow-up was 31 months. Univariable analyses showed that OS was associated negatively with depression (HR 2.04, P optimism, anxiety or hopefulness. PFS was not associated with hope, optimism, anxiety or depression in any analyses. Depression and health utility, but not optimism, hope or anxiety, were associated with survival after controlling for known prognostic factors in patients with advanced colorectal cancer. Further research is required to understand the nature of the relationship between depression and survival. If a causal mechanism is identified, this may lead to interventional possibilities.

P02.03INCREASED COUNTS OF NK AND NKT CELLS ARE ASSOCIATED WITH PROLONGED SURVIVAL IN PRIMARY GLIOBLASTOMA PATIENTS TREATED WITH DENDRITIC CELL IMMUNOTHERAPY IN COMBINATION WITH RADIO- AND CHEMO-THERAPY

Science.gov (United States)

Pellegatta, S.; Eoli, M.; Cantini, G.; Anghileri, E.; Antozzi, C.; Frigerio, S.; Bruzzone, M.; Pollo, B.; Parati, E.; Finocchiaro, G.

2014-01-01

Two clinical studies, DENDR1 and DENDR2 including, respectively, the treatment of first diagnosis and recurrent glioblastoma (GB) patients with dendritic cells (DCs) loaded with autologous tumor lysate are currently active at Istituto Neurologico Besta, Milan. Our first results obtained on a group of recurrent GB patients demonstrated that the response of NK cells correlates with significantly prolonged survival. Here we provide results of the interim analysis on 22 patients affected by primary GB. Patients with post-surgery volume ≤10 cc underwent leukapheresis before radiotherapy and chemotherapy with temozolomide (TMZ). Three intradermal injections of mature DC were done before adjuvant chemotherapy. The subsequent 4 injections were performed 17 ± 3 days after adjuvant TMZ. MRI, clinical and immunological follow-up were performed every 2 months. The median age at surgery was 54.5 years (28-69). RT-TMZ induced significant lymphopenia (1000 lymphocytes/microl (5/22) before first vaccination had shorter PFS than others (p < 0.005). Peripheral Blood Lymphocytes (PBLs) were analyzed by flow cytometry to identify CD8+ T cells, NK and NKT cells before and after DC vaccines. The ratio of vaccination/baseline frequencies and counts (V/B ratio) of all of the immunological parameters for each patient was calculated, and the median of all of the observations used as the cut off value to separate patients. V/B ratio was correlated with the progression free survival (PFS) of each patient. Increased V/B ratio for NK cells and in particular NKT cells, but not for CD8 T lymphocytes, was significantly associated with prolonged PFS (median PFS 14 vs 8.0 mo, p = 0.01; 15.0 vs 8.0 mo, respectively). Interferon (IFN)-γ in PBLs was significantly higher in patients with PFS12 (p < 0.02), increasing immediately after the second vaccination as evaluated by real time-PCR. No changes in the expression levels of IFN-γ were observed in the other patients. After a median follow up of 14

Biochemical response to ursodeoxycholic acid predicts survival in a North American cohort of primary biliary cirrhosis patients.

Science.gov (United States)

Lammert, Craig; Juran, Brian D; Schlicht, Erik; Chan, Landon L; Atkinson, Elizabeth J; de Andrade, Mariza; Lazaridis, Konstantinos N

2014-10-01

Biochemical response to ursodeoxycholic acid among patients with primary biliary cirrhosis remains variable, and there is no agreement of an ideal model. Novel assessment of response coupled to histologic progression was recently defined by the Toronto criteria. We retrospectively assessed transplant-free survival and clinical outcomes associated with ursodeoxycholic acid response to evaluate the Toronto criteria using a large North American cohort of PBC patients. Three hundred and ninety-eight PBC patients from the Mayo Clinic PBC Genetic Epidemiology Registry were assessed for ursodeoxycholic acid treatment and biochemical response per the Toronto criteria. Responders were defined by reduction in alkaline phosphatase to less than or equal to 1.67 times the upper normal limit by 2 years of treatment, whereas non-responders had alkaline phosphatase values greater than 1.67 times the upper normal limit. Probability of survival was estimated using the Kaplan-Meier method. Three hundred and two (76 %) patients were responders and 96 (24 %) were non-responders. Significantly more non-responders developed adverse events related to chronic liver disease compared to responders (hazard ratio (HR) 2.77, P = 0.001). Biochemical responders and early-stage disease at treatment start was associated with improved overall transplant-free survival compared to non-responders (HR 1.9) and patients with late-stage disease (HR 2.7) after age and sex adjustment. The Toronto criteria are capable of identifying ursodeoxycholic acid-treated primary biliary cirrhosis patients at risk of poor transplant-free survival and adverse clinical outcomes. Our data reveal that despite advanced disease at diagnosis, biochemical response per the Toronto criteria associates with improved overall transplant-free survival.

HE4 as a predictor of adjuvant chemotherapy resistance and survival in patients with epithelial ovarian cancer

DEFF Research Database (Denmark)

Aarenstrup Karlsen, Mona; Høgdall, Claus; Nedergaard, Lotte

2016-01-01

The aim of this study was to investigate the value of serum human epididymis protein 4 (HE4) and HE4 tissue protein expression to predict tumor resistance to adjuvant chemotherapy, progression-free survival (PFS), and overall survival in patients with epithelial ovarian cancer (EOC). Consecutive...... inclusion of 198 patients diagnosed with EOC was conducted. Blood samples were collected prior to surgery and tissue samples during surgery. Patient data were registered prospectively in the Danish Gynecologic Cancer Database. The association between serum HE4 and HE4 tissue protein expression, resistance...... significantly (p tissue protein expression...

Low-dose fractionated radiotherapy and concomitant chemotherapy for recurrent or progressive glioblastoma. Final report of a pilot study

Energy Technology Data Exchange (ETDEWEB)

Balducci, M.; Diletto, B.; Chiesa, S.; D' Agostino, G.R.; Gambacorta, M.A.; Ferro, M.; Valentini, V. [Catholic University of the Sacred Heart, Department of Radiation Oncology, Rome (Italy); Colosimo, C. [Catholic University of the Sacred Heart, Department of Radiology, Rome (Italy); Maira, G.; Anile, C. [Catholic University of the Sacred Heart, Department of Neurosurgery, Rome (Italy)

2014-04-15

Evaluated in this study were the feasibility and the efficacy of concurrent low dose fractionated radiotherapy (LD-FRT) and chemotherapy as palliative treatment for recurrent/progressive glioblastoma multiforme (GBM). Eligible patients had recurrent or progressive GBM, Karnofsky performance status ≥70, prior surgery, and standard radiochemotherapy treatment. Recurrence/progression disease during temozolomide (TMZ) received cisplatin (CDDP; 30 mg/m{sup 2} on days 1, 8, 15), fotemustine (FTM; 40 mg/m{sup 2} on days 2, 9, 16), and concurrent LD-FRT (0.3 Gy twice daily); recurrence/progression after 4 months from the end of adjuvant TMZ were treated by TMZ (150/200 mg/m{sup 2} on days 1-5) concomitant with LD-FRT (0.4 Gy twice daily). Primary endpoints were safety and toxicity. A total of 32 patients were enrolled. Hematologic toxicity G1-2 was observed in 18.7% of patients and G3-4 in 9.4%. One patient (3.1%) had complete response, 3 (9.4%) had partial response, 8 (25%) had stable disease for at least 8 weeks, while 20 patients (62.5%) experienced progressive disease. The clinical benefit was 37.5%. Median progression-free survival (PFS) and overall survival (OS) were 5 and 8 months, respectively. Survival rate at 12 months was of 27.8%. LD-FRT and chemotherapy for recurrent/progressive GBM have a good toxicity profile and clinical outcomes, even though further investigation of this novel palliative treatment approach is warranted. (orig.)

Prostaglandin receptor EP3 regulates cell proliferation and migration with impact on survival of endometrial cancer patients.

Science.gov (United States)

Zhu, Junyan; Trillsch, Fabian; Mayr, Doris; Kuhn, Christina; Rahmeh, Martina; Hofmann, Simone; Vogel, Marianne; Mahner, Sven; Jeschke, Udo; von Schönfeldt, Viktoria

2018-01-02

Prostaglandin E2 (PGE2) receptor 3 (EP3) regulates tumor cell proliferation, migration, and invasion in numerous cancers. The role of EP3 as a prognostic biomarker in endometrial cancer remains unclear. The primary aim of this study was to analyze the prognostic significance of EP3 expression in endometrial cancer. We analyzed the EP3 expression of 140 endometrial carcinoma patients by immunohistochemistry. RL95-2 endometrial cancer cell line was chosen from four endometrial cancer cell lines (RL95-2, Ishikawa, HEC-1-A, and HEC-1-B) according to EP3 expression level. Treated with PGE2 and EP3 antagonist, RL95-2 cells were investigated by MTT, BrdU, and wound healing assay for functional assessment of EP3. EP3 staining differed significantly according to WHO tumor grading in both whole cohort (p = 0.01) and the subgroup of endometrioid carcinoma (p = 0.01). Patients with high EP3 expression in their respective tumors had impaired progression-free survival as well as overall survival in both cohorts above. EP3 expression in the overall cohort was identified as an independent prognostic marker for progression-free survival (HR 1.014, 95%CI 1.003-1.024, p = 0.01) when adjusted for age, stage, grading, and recurrence. Treatment with EP3 antagonists induced upregulation of estrogen receptor β and decreased activity of Ras and led to attenuated proliferation and migration of RL95-2 cells. EP3 seems to play a crucial role in endometrial cancer progression. In the context of limited systemic treatment options for endometrial cancer, this explorative analysis identifies EP3 as a potential target for diagnostic workup and therapy.

Results of radiotherapy in recurrent endometrial carcinoma: A retrospective analysis of 51 patients

International Nuclear Information System (INIS)

Kuten, A.; Grigsby, P.W.; Perez, C.A.; Fineberg, B.; Garcia, D.M.; Simpson, J.R.

1989-01-01

A retrospective analysis was performed of 51 patients with locoregional recurrence of endometrial carcinoma, treated by radiotherapy between 1959 and 1986. There were 17 patients (33%) with isolated vaginal recurrence, 12 patients (24%) with vaginal recurrence with pelvic extension, 7 patients (14%) with pelvic recurrence only, and 15 patients (29%) with simultaneous locoregional and distant failure. Eighty percent of the recurrences occurred within 3.5 years from primary treatment; time to relapse was shorter in patients with advanced-stage, high-grade malignancy at original diagnosis. Locoregional control was achieved in 18 patients (35%). Complete tumor regression in the vagina, irrespective of extravaginal pelvic disease status or distant metastasis, occurred in 28 of 34 patients with vaginal involvement (82%). The 5- and 10-year overall actuarial survivals for all patients were 18 and 12.5%, respectively. The 5- and 10-year progression-free survivals of patients with isolated vaginal recurrences were 40% and 29%, respectively; the 5-year progression-free survival of patients with vaginal recurrence with pelvic extension was 20%. There were no survivors beyond 1.5 years among patients with pelvic recurrence (p = 0.02). All patients with simultaneous locoregional and distant failure were dead by 3.5 years. Stage at original diagnosis, time to relapse from primary treatment, histologic pattern, and grade of malignancy were prognosticators of survival. Five patients (10%) developed a total of ten radiation-related sequelae

Association of tRNA methyltransferase NSUN2/IGF-II molecular signature with ovarian cancer survival.

Science.gov (United States)

Yang, Jia-Cheng; Risch, Eric; Zhang, Meiqin; Huang, Chan; Huang, Huatian; Lu, Lingeng

2017-09-01

To investigate the association between NSUN2/IGF-II signature and ovarian cancer survival. Using a publicly accessible dataset of RNA sequencing and clinical follow-up data, we performed Classification and Regression Tree and survival analyses. Patients with NSUN2 high IGF-II low had significantly superior overall and disease progression-free survival, followed by NSUN2 low IGF-II low , NSUN2 high IGF-II high and NSUN2 low IGF-II high (p IGF-II signature with the risks of death and relapse remained significant in multivariate Cox regression models. Random-effects meta-analyses show the upregulated NSUN2 and IGF-II expression in ovarian cancer versus normal tissues. The NSUN2/IGF-II signature associates with heterogeneous outcome and may have clinical implications in managing ovarian cancer.

The Additional Costs per Month of Progression-Free Survival and Overall Survival: An Economic Model Comparing Everolimus with Cabozantinib, Nivolumab, and Axitinib for Second-Line Treatment of Metastatic Renal Cell Carcinoma.

Science.gov (United States)

Swallow, Elyse; Messali, Andrew; Ghate, Sameer; McDonald, Evangeline; Duchesneau, Emilie; Perez, Jose Ricardo

2018-04-01

When considering optimal second-line treatments for metastatic renal cell carcinoma (mRCC), clinicians and payers seek to understand the relative clinical benefits and costs of treatment. To use an economic model to compare the additional cost per month of overall survival (OS) and of progression-free survival (PFS) for cabozantinib, nivolumab, and axitinib with everolimus for the second-line treatment of mRCC from a third-party U.S. payer perspective. The model evaluated mean OS and PFS and costs associated with drug acquisition/administration; adverse event (AE) treatment; monitoring; and postprogression (third-line treatment, monitoring, and end-of-life costs) over 1- and 2-year horizons. Efficacy, safety, and treatment duration inputs were estimated from regimens' pivotal clinical trials; for everolimus, results were weighted across trials. Mean 1- and 2-year OS and mean 1-year PFS were estimated using regimens' reported OS and PFS Kaplan-Meier curves. Dosing and administration inputs were consistent with approved prescribing information and the clinical trials used to estimate efficacy and safety inputs. Cost inputs came from published literature and public data. Additional cost per additional month of OS or PFS was calculated using the ratio of the cost difference per treated patient and the corresponding difference in mean OS or PFS between everolimus and each comparator. One-way sensitivity analyses were conducted by varying efficacy and cost inputs. Compared with everolimus, cabozantinib, nivolumab, and axitinib were associated with 1.6, 0.3, and 0.5 additional months of PFS, respectively, over 1 year. Cabozantinib and nivolumab were associated with additional months of OS compared with everolimus (1 year: 0.7 and 0.8 months; 2 years: 1.6 and 2.3 months; respectively); axitinib was associated with fewer months (1 year: -0.2 months; 2 years: -0.7 months). The additional costs of treatment with cabozantinib, nivolumab, or axitinib versus everolimus over 1

Elevation in inflammatory serum biomarkers predicts response to trastuzumab-containing therapy.

Directory of Open Access Journals (Sweden)

Ahmed A Alkhateeb

Full Text Available Approximately half of all HER2/neu-overexpressing breast cancer patients do not respond to trastuzumab-containing therapy. Therefore, there remains an urgent and unmet clinical need for the development of predictive biomarkers for trastuzumab response. Recently, several lines of evidence have demonstrated that the inflammatory tumor microenvironment is a major contributor to therapy resistance in breast cancer. In order to explore the predictive value of inflammation in breast cancer patients, we measured the inflammatory biomarkers serum ferritin and C-reactive protein (CRP in 66 patients immediately before undergoing trastuzumab-containing therapy and evaluated their progression-free and overall survival. The elevation in pre-treatment serum ferritin (>250 ng/ml or CRP (>7.25 mg/l was a significant predictor of reduced progression-free survival and shorter overall survival. When patients were stratified based on their serum ferritin and CRP levels, patients with elevation in both inflammatory biomarkers had a markedly poorer response to trastuzumab-containing therapy. Therefore, the elevation in inflammatory serum biomarkers may reflect a pathological state that decreases the clinical efficacy of this therapy. Anti-inflammatory drugs and life-style changes to decrease inflammation in cancer patients should be explored as possible strategies to sensitize patients to anti-cancer therapeutics.

CD133 expression in well-differentiated pancreatic neuroendocrine tumors: a potential predictor of progressive clinical courses.

Science.gov (United States)

Sakai, Yasuhiro; Hong, Seung-Mo; An, Soyeon; Kim, Joo Young; Corbeil, Denis; Karbanová, Jana; Otani, Kyoko; Fujikura, Kohei; Song, Ki-Byung; Kim, Song Cheol; Akita, Masayuki; Nanno, Yoshihide; Toyama, Hirochika; Fukumoto, Takumi; Ku, Yonson; Hirose, Takanori; Itoh, Tomoo; Zen, Yoh

2017-03-01

The present study aimed to elucidate whether the stemness molecule, CD133, is expressed in well-differentiated pancreatic neuroendocrine tumors (PanNETs; World Health Organization grades 1 and 2) and establish its clinical relevance using 2 separate cohorts. In the first series (n = 178) in which tissue microarrays were available, immunohistochemistry revealed that CD133 was expressed in 14 cases (8%). CD133+ PanNETs had higher TNM stages (P < .01), more frequent lymphovascular invasion (P = .01), and higher recurrence rates (P = .01). In the second cohort (n = 56), the expression of CD133 and CK19 was examined in whole tissue sections. CD133 and CK19 were positive in 10 (18%) and 36 (64%) cases, respectively. CD133 expression correlated with higher pT scores (P < .01), the presence of microscopic venous infiltration (P = .03), and shorter disease-free periods (P < .01). When cases were divided into grade 1 and 2 neoplasms, patients with CD133+ PanNET continued to have shorter disease-free periods than did those with CD133- tumors in both groups (P < .01 and P = .02, respectively). Although CK19+ cases had shorter disease-free periods than did CK19- cases in the whole cohort (P = .02), this difference was less apparent in subanalyses of grade 1 and 2 cases. CD133 expression also appeared to be an independent predictive factor for tumor recurrence in a multivariate analysis (P = .018). The CD133 phenotype was identical between primary and metastatic foci in 17 of 18 cases from which tissues of metastatic deposits were available. In conclusion, the combination of CD133 phenotyping and World Health Organization grading may assist in stratifying patients in terms of the risk of progressive clinical courses. Copyright © 2016 Elsevier Inc. All rights reserved.

Postoperative serum CEA level as predictive factor for survival in patients with colorectal cancer

International Nuclear Information System (INIS)

Lemberger, J.J.; Bogar, M.L.; Takacs Kucsera, M.F.; Csernetics, I.F.

2002-01-01

Aim: It is known that routine follow-up of patients with resected colorectal cancer includes serial CEA determinations. In this retrospective study we have investigated relationship between CEA level and survival and whether achieved results enable differentiation of tumors with slow and rapid growth. Material and Methods: Mainly between 1995 and 1999 periodic CEA determination by IRMA were performed in 269 patients after curative resection of colorectal carcinoma. Number of CEA determination/patient were 2-16(median 6). Survival ranged 4,5 and>249,7 months. Based on CEA results patients were divided in group with normal (<10ng/ml) and elevated (=10ng/ml) values regardless of postoperative treatment. Survival curves were computed by Kaplan-Meier method and difference was evaluated by logrank test and difference between proportions. Results:Normal end elevated CEA was found in 193 and 76 patients, respectively. The difference of survival curves between patients with normal and elevated CEA are highly significant (p<0,0001). However, only 10 months after tumor resection is the difference between survived proportions significant suggesting already presence of CEA produced micrometastases contributing to progression of neoplastic process. The mean survival time at normal and elevated CEA values are 142,54±17,86(median 128,60±24,04) and 34,15±4,28 (median 25,20±1,97) months, respectively. No significant difference of survival was found regarding tumor localization. Conclusion:The results show that with regard to CEA level it is possible to divide colorectal tumors on marker negative and positive. Marker negative are with slower growth and relatively good prognosis. Marker positive are associated with elevated CEA level and with considerable shorter survival. Postoperative CEA level is valuable parameter in prediction of patient's outcome

Tumoural Expression of Connective Tissue Growth Factor (CTGF) Impacts on Survival in Patients Diagnosed with Hepatocellular Carcinoma (HCC).

Science.gov (United States)

Lamarca, Angela; Mendiola, Marta; Bernal, Elsa; Heredia, Victoria; Díaz, Esther; Miguel, María; Pastrian, Laura G; Burgos, Emilio; Feliu, Jaime; Barriuso, Jorge

2015-01-01

Hepatocellular carcinoma (HCC) tends to develop in the liver when there is a high level of background inflammation (cirrhosis). Treatment options are limited and mainly based on systemic therapies such as anti-angiogenic drugs (e.g. sorafenib). Connective tissue growth factor (CTGF) is a matricellular protein involved in inflammation, tumour growth and angiogenesis. The aim of this study is to determine the expression of CTGF and hypoxia inducible factors (HIF) in HCC and to clarify its impact on relapse and survival. Eligibility criteria for the study consisted of patients with a diagnosis of HCC, formalin-fixed and paraffin-embedded (FFPE) biopsy tissue, as well as relapse and available survival data. A tissue microarray was constructed from ≥ 70% tumoural sections. The expressions of CTGF, HIF1α and HIF2α were analysed by immunohistochemistry. The relationship between expression of CTGF/HIF1α and CTGF/HIF2α were analysed. Univariate and multivariate analyses were performed. Fifty-three patients were screened; 39 patients were eligible for this study. Patients were treated with radical intent. At the end of follow up, 59% patients relapsed (28.2% locally, 10.3% multicentric liver relapse and 7.7% distant metastases). Estimated median disease-free survival (DFS) and overall survival (OS) were 23.4 (95%CI 7.18-39.66) and 38.6 months (95%CI 30.7-46.6), respectively. Expression of CTGF was: negative 23.1%, focal 48.7% and diffuse 23.1%. A non-statistically significant relationship between expression of CTGF and HIF was shown supporting an alternative pathway for CTGF expression in HCC. In multivariate analysis CTGF expression was an independent factor related to OS, with shorter survival in those patients with focal/diffuse CTGF expression (HR 2.46; 95%CI 1.18-5.15). Our results support that expression of CTGF is an independent factor associated with shorter OS in HCC. Further analysis of CTGF expression in a larger series of HCC patients is required to confirm

Chemotherapy response as a prognosticator for survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy

International Nuclear Information System (INIS)

Eagan, R.T.; Fleming, T.R.; Lee, R.E.; Ingle, J.N.; Frytak, S.; Creagan, E.T.

1980-01-01

Twenty-two patients with limited unresectable squamous cell lung cancer were treated with 6 courses of combination chemotherapy consisting of cyclophosphamide, adriamycin, cisplatin, and bleomycin (CAP-Bleo) and short-course thoracic irradiation started after the first 4 weeks of chemotherapy. Of 20 patients with visible tumor who were treated with 4 weeks of chemotherapy alone, 10 (50%) had a tumor regression in that 4 week period and 10 did not. Those patients with tumor regression had significantly better progression free and overall survivals than did patients with no chemotherapy regressions (medians of 258 days vs. 136 days and 356 days vs. 150 days respectively). The original bleomycin dose had to be reduced by 50% primarily because of excessive radiation esophagitis that has not been reported with use of either the CAP regimen or bleomycin along in conjunction with thoracic irradiation. An initial chemotherapy regression seems to be a good prognosticator for progression-free and overall survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy

Sarcopenia predicts survival outcomes among patients with urothelial carcinoma of the upper urinary tract undergoing radical nephroureterectomy: a retrospective multi-institution study.

Science.gov (United States)

Ishihara, Hiroki; Kondo, Tsunenori; Omae, Kenji; Takagi, Toshio; Iizuka, Junpei; Kobayashi, Hirohito; Hashimoto, Yasunobu; Tanabe, Kazunari

2017-02-01

We aimed to evaluate the effect of sarcopenia, a condition of low muscle mass, on the survival among patients who were undergoing radical nephroureterectomy (RNU) for urothelial carcinoma of the upper urinary tract (UCUT). We retrospectively reviewed consecutive patients with UCUT (cT[any]N0M0) who underwent RNU between 2003 and 2013 at our department and its affiliated institutions. Preoperative computed tomography images were used to calculate each patient's skeletal muscle index, an indicator of whole-body muscle mass. Sarcopenia was defined according to the sex-specific consensus definitions, based on the patient's skeletal muscle and body mass indexes. We analyzed the relapse-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) after RNU to identify factors that predicted patient survival. A total of 137 patients were included, and 90 patients (65.7 %) were diagnosed with sarcopenia. Compared to the non-sarcopenic patients, the sarcopenic patients had a significant inferior 5-year RFS (48.8 vs. 79.6 %, p = 0.0002), CSS (57.1 vs. 92.6 %, p sarcopenia was an independent predictor of shorter RFS, CSS, and OS (all, p Sarcopenia was an independent predictor of survival among patients with UCUT who were undergoing RNU.

General practitioners' home visit tendency and readmission-free survival after COPD hospitalisation

DEFF Research Database (Denmark)

Lykkegaard, Jesper; Larsen, Pia V; Paulsen, Maja S

2014-01-01

Background:The tendency of general practitioners (GPs) to conduct home visits is considered an important aspect of practices' accessibility and quality of care.Aims:To investigate whether GPs' tendency to conduct home visits affects 30-day readmission or death after hospitalisation with chronic...... obstructive pulmonary disease.Methods:All Danish patients first-time hospitalised with COPD during the years 2006-2008 were identified. The association between the GP's tendency to conduct home visits and the time from hospital discharge until death or all-cause readmission was analysed by means of Cox...... been readmitted and 1.6% had died without readmission. A U-shaped dose-response relationship was found between GP home visit tendency and readmission-free survival. The lowest adjusted risk of readmission or death was recorded among patients who were listed with a general practice in which >20...

Preoperative Tracheostomy Is Associated with Poor Disease-Free Survival in Recurrent Laryngeal Cancer.

Science.gov (United States)

Birkeland, Andrew C; Rosko, Andrew J; Beesley, Lauren; Bellile, Emily; Chinn, Steven B; Shuman, Andrew G; Prince, Mark E; Wolf, Gregory T; Bradford, Carol R; Brenner, J Chad; Spector, Matthew E

2017-09-01

Objectives It is unknown if preoperative tracheostomy for persistent/recurrent laryngeal squamous cell carcinoma (LSCC) plays a role in unrecognized local disease spread and disease recurrence after salvage laryngectomy. The goals of this study were to determine the effect of preoperative tracheostomy on disease-free survival (DFS) in patients with recurrent/persistent LSCC undergoing salvage laryngectomy. Study Design Retrospective case series derived from prospectively maintained database. Setting Tertiary care academic center. Subjects Patients with recurrent/persistent LSCC after radiation/chemoradiation (RT/CRT) who underwent salvage laryngectomy at the University of Michigan from 1997 to 2015. Methods Demographic, clinical, pathologic, and survival data were collected. Kaplan-Meier survival estimates were performed. Results DFS was worse for patients with tracheostomy prior to laryngectomy than patients without a tracheostomy (5 year: 39% vs 67%; P tracheostomy prior to RT/CRT compared to patients with tracheostomy after RT/CRT or patients without a tracheostomy had worse DFS (5-year: 25%, 49%, and 67%, respectively; P tracheostomy was associated with worse DFS. In multivariable analysis, presence of a preoperative tracheostomy had a worse DFS (hazard ratio, 1.63; 95% confidence interval, 1.00-2.67; P = .048). Conclusion Preoperative tracheostomy is associated with disease recurrence in patients with persistent/recurrent LSCC undergoing salvage laryngectomy, particularly in patients who had tracheostomy prior to completion of initial RT/CRT. Notably, preoperative tracheostomy as a causal factor vs marker for disease recurrence is difficult to ascertain. Nevertheless, clinicians should be aware of the increased risk of locoregional recurrence in patients with preoperative tracheostomy when counseling on surgical salvage and when considering the role of additional therapy.

Metformin blocks progression of obesity-activated thyroid cancer in a mouse model.

Science.gov (United States)

Park, Jeongwon; Kim, Won Gu; Zhao, Li; Enomoto, Keisuke; Willingham, Mark; Cheng, Sheue-Yann

2016-06-07

Compelling epidemiologic evidence indicates that obesity is associated with a high risk of human malignancies, including thyroid cancer. We previously demonstrated that a high fat diet (HFD) effectively induces the obese phenotype in a mouse model of aggressive follicular thyroid cancer (ThrbPV/PVPten+/-mice). We showed that HFD promotes cancer progression through aberrant activation of the leptin-JAK2-STAT3 signaling pathway. HFD-promoted thyroid cancer progression allowed us to test other molecular targets for therapeutic opportunity for obesity-induced thyroid cancer. Metformin is a widely used drug to treat patients with type II diabetes. It has been shown to reduce incidences of neoplastic diseases and cancer mortality in type II diabetes patients. The present study aimed to test whether metformin could be a therapeutic for obesity-activated thyroid cancer. ThrbPV/PVPten+/-mice were fed HFD together with metformin or vehicle-only, as controls, for 20 weeks. While HFD-ThrbPV/PVPten+/-mice had shorter survival than LFD-treated mice, metformin had no effects on the survival of HFD-ThrbPV/PVPten+/-mice. Remarkably, metformin markedly decreased occurrence of capsular invasion and completely blocked vascular invasion and anaplasia in HFD-ThrbPV/PVPten+/-mice without affecting thyroid tumor growth. The impeded cancer progression was due to the inhibitory effect of metformin on STAT3-ERK-vimentin and fibronectin-integrin signaling to decrease tumor cell invasion and de-differentiation. The present studies provide additional molecular evidence to support the link between obesity and thyroid cancer risk. Importantly, our findings suggest that metformin could be used as an adjuvant in combination with antiproliferative modalities to improve the outcome of patients with obesity-activated thyroid cancer.

Progression and prognosis in multiple system atrophy: an analysis of 230 Japanese patients.

Science.gov (United States)

Watanabe, Hirohisa; Saito, Yufuko; Terao, Shinichi; Ando, Tetsuo; Kachi, Teruhiko; Mukai, Eiichiro; Aiba, Ikuko; Abe, Yuji; Tamakoshi, Akiko; Doyu, Manabu; Hirayama, Masaaki; Sobue, Gen

2002-05-01

We investigated the disease progression and survival in 230 Japanese patients with multiple system atrophy (MSA; 131 men, 99 women; 208 probable MSA, 22 definite; mean age at onset, 55.4 years). Cerebellar dysfunction (multiple system atrophy-cerebellar; MSA-C) predominated in 155 patients, and parkinsonism (multiple system atrophy-parkinsonian; MSA-P) in 75. The median time from initial symptom to combined motor and autonomic dysfunction was 2 years (range 1-10). Median intervals from onset to aid-requiring walking, confinement to a wheelchair, a bedridden state and death were 3, 5, 8 and 9 years, respectively. Patients manifesting combined motor and autonomic involvement within 3 years of onset had a significantly increased risk of not only developing advanced disease stage but also shorter survival (P bedridden state, P bedridden state (P = 0.03) and death (P bedridden state and survival were no worse. Gender was not associated with differences in worsening of function or survival. On MRI, a hyperintense rim at the lateral edge of the dorsolateral putamen was seen in 34.5% of cases, and a 'hot cross bun' sign in the pontine basis (PB) in 63.3%. These putaminal and pontine abnormalities became more prominent as MSA-P and MSA-C features advanced. The atrophy of the cerebellar vermis and PB showed a significant correlation particularly with the interval following the appearance of cerebellar symptoms in MSA-C (r = 0.71, P r = 0.76 and P < 0.01, respectively), but the relationship between atrophy and functional status was highly variable among the individuals, suggesting that other factors influenced the functional deterioration. Atrophy of the corpus callosum was seen in a subpopulation of MSA, suggesting hemispheric involvement in a subgroup of MSA patients. The present study suggested that many factors are involved in the progression of MSA but, most importantly, the interval from initial symptom to combined motor and autonomic dysfunction can predict functional

Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

Directory of Open Access Journals (Sweden)

Harris Nathan

2008-12-01

Full Text Available Abstract Background Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. Methods Two sample sets of high-risk primary breast cancer patients participating in a randomised national trial investigating the effectiveness of high-dose chemotherapy were analysed. Sera in set I (n = 63 were analysed by surface enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS for biomarker finding. Initial results were validated by analysis of sample set II (n = 371, using one-dimensional gel-electrophoresis. Results In sample set I, the expression of a peak at mass-to-charge ratio 9198 (relative intensity ≤ 20 or > 20, identified as haptoglobin (Hp alpha-1 chain, was strongly associated with recurrence free survival (global Log-rank test; p = 0.0014. Haptoglobin is present in three distinct phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2, of which only individuals with phenotype Hp 1-1 or Hp 2-1 express the haptoglobin alpha-1 chain. As the expression of the haptoglobin alpha-1 chain, determined by SELDI-TOF MS, corresponds to the phenotype, initial results were validated by haptoglobin phenotyping of the independent sample set II by native one-dimensional gel-electrophoresis. With the Hp 1-1 phenotype as the reference category, the univariate hazard ratio for recurrence was 0.87 (95% CI: 0.56 – 1.34, p = 0.5221 and 1.03 (95% CI: 0.65 – 1.64, p = 0.8966 for the Hp 2-1 and Hp 2-2 phenotypes, respectively, in sample set II. Conclusion In contrast to our initial results, the haptoglobin phenotype was not identified as a predictor of recurrence free survival in high-risk primary breast cancer in our validation set. Our initial observation in the discovery set was probably the result of a type I error (i.e. false positive

Comparison of survival and toxicities of concurrent radiotherapy with Carboplatin/Paclitaxel or Cisplatin/Etoposide in unresectable stage III non-small cell lung cancers: retrospective analysis in the Department of Pneumology of CHU Nancy between 2008 and 2014

International Nuclear Information System (INIS)

Huet, Dimitri

2015-01-01

In concomitant chemo-radiotherapy treatment for inoperable stage III NSCLC, different combinations of chemotherapies have been recommended. The objective of this study was to compare progression-free survival, overall survival, and tolerability of two treatment regimens: Cisplatin-etoposide concomitant radio-chemotherapy versus concomitant carboplatin-Paclitaxel based radio-chemotherapy in these patients. A retrospective analysis of 62 patients treated with concomitant radio-chemotherapy for inoperable stage III NSCLC has been carried out in the Department of Pneumology (University Hospital of Nancy). The patients were divided into 2 groups according to the chemotherapy protocol, group 1: Cisplatin-etoposide (27 patients) and group 2: Carboplatin-Paclitaxel (35 patients). The two groups were comparable in terms of age and gender (mean age 58 in group 1 versus age 61 in group 2, and 85 pc of men in group 1 versus 80 pc in group 2). The median overall survival was 19 months in group 1 versus 15.3 months in group 2 (p = 0.22). The median progression-free survival was higher in group 1, 9 months versus 3.3 months in group 2 (p = 0.01). Hematologic toxicity was higher in group 1 than in group 2 (neutropenia 85.2 pc versus 54.3 pc, p = 0.01, anemia 92.3 pc versus 54.3 pc, p = 0.001). Radiation esophagitis and radiation pneumonitis rates were higher in group 1 than in group 2: 44.4 pc versus 11.4 pc (p = 0.01), and 44.4 pc versus 11.4 pc (p = 0.001) respectively. In this mono-centric and retrospective study, the Cisplatin-etoposide - thoracic radiotherapy combination to treat inoperable stage III NSCLC was associated with a significantly higher progression-free survival than the Carboplatin-Paclitaxel-radiotherapy combination. This increase in survival was accompanied by a significantly higher hematological and organ toxicity [fr

Counterbalancing angiogenic regulatory factors control the rate of cancer progression and survival in a stage-specific manner.

Science.gov (United States)

Xie, Liang; Duncan, Michael B; Pahler, Jessica; Sugimoto, Hikaru; Martino, Margot; Lively, Julie; Mundel, Thomas; Soubasakos, Mary; Rubin, Kristofer; Takeda, Takaaki; Inoue, Masahiro; Lawler, Jack; Hynes, Richard O; Hanahan, Douglas; Kalluri, Raghu

2011-06-14

Whereas the roles of proangiogenic factors in carcinogenesis are well established, those of endogenous angiogenesis inhibitors (EAIs) remain to be fully elaborated. We investigated the roles of three EAIs during de novo tumorigenesis to further test the angiogenic balance hypothesis, which suggests that blood vessel development in the tumor microenvironment can be governed by a net loss of negative regulators of angiogenesis in addition to the well-established principle of up-regulated angiogenesis inducers. In a mouse model of pancreatic neuroendocrine cancer, administration of endostatin, thrombospondin-1, and tumstatin peptides, as well as deletion of their genes, reveal neoplastic stage-specific effects on angiogenesis, tumor progression, and survival, correlating with endothelial expression of their receptors. Deletion of tumstatin and thrombospondin-1 in mice lacking the p53 tumor suppressor gene leads to increased incidence and reduced latency of angiogenic lymphomas associated with diminished overall survival. The results demonstrate that EAIs are part of a balance mechanism regulating tumor angiogenesis, serving as intrinsic microenvironmental barriers to tumorigenesis.

Intensity-modulated radiotherapy prolongs the survival of patients with nasopharyngeal carcinoma compared with conventional two-dimensional radiotherapy: A 10-year experience with a large cohort and long follow-up.

Science.gov (United States)

Zhang, Meng-Xia; Li, Jing; Shen, Guo-Ping; Zou, Xiong; Xu, Jun-Jie; Jiang, Rou; You, Rui; Hua, Yi-Jun; Sun, Ying; Ma, Jun; Hong, Ming-Huang; Chen, Ming-Yuan

2015-11-01

To evaluate the survival benefit of intensity-modulated radiotherapy (IMRT) compared with conventional two-dimensional radiotherapy (2D-CRT) in nasopharyngeal carcinoma (NPC) using a large cohort with long follow-up. We retrospectively analysed 7081 non-metastatic NPC patients who received curative IMRT or 2D-CRT from February 2002 to December 2011. Of the 7081 patients, 2245 (31.7%) were administered IMRT, while 4836 (68.3%) were administered 2D-CRT. At 5 years, the patients administered IMRT had significantly higher local relapse-free survival (LRFS), loco-regional relapse-free survival (LRRFS), progression-free survival (PFS) and overall survival (OS) (95.6%, 92.5%, 82.1% and 87.4%, respectively) than those administered 2D-CRT (90.8%, 88.5%, 76.7% and 84.5%, respectively; p<0.001). The distant metastasis-free survival (DMFS) was higher for IMRT than 2D-CRT, with borderline significance (87.6% and 85.7%, respectively; p=0.056). However, no difference was observed between IMRT and 2D-CRT in nodal relapse-free survival (NRFS; 96.3% and 97.4%, respectively; p=0.217). Multivariate analyses showed that IMRT was an independent protective prognostic factor for LRFS, LRRFS and PFS, but not NRFS, DMFS or OS. IMRT provided an improved LRFS, LRRFS and PFS in both the early and advanced T classifications and overall stage for non-disseminated NPC compared with 2D-CRT. However, no significant advantage was observed in NRFS, DMFS or OS when IMRT was used. Copyright © 2015 Elsevier Ltd. All rights reserved.

The impact of carboplatin and toceranib phosphate on serum vascular endothelial growth factor (VEGF) and metalloproteinase-9 (MMP-9) levels and survival in canine osteosarcoma.

Science.gov (United States)

Gieger, Tracy L; Nettifee-Osborne, Julie; Hallman, Briana; Johannes, Chad; Clarke, Dawn; Nolan, Michael W; Williams, Laurel E

2017-07-01

In this pilot study, 10 dogs with osteosarcoma (OSA) were treated with amputation and subsequent carboplatin chemotherapy (300 mg/m 2 IV q3wk × 4 doses) followed by toceranib phosphate (2.75 mg/kg PO q48h starting at day 14 post carboplatin). Monthly clinical monitoring and serum measurements of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were acquired. No dogs were removed from the study due to toxicity. Levels of VEGF and MMP-9 did not change over time. Seven dogs died related to local recurrence and/or pulmonary or bone metastasis and the remainder died of other causes. Median OSA-free survival was 238 d with 34% 1-year progression-free survival. Median overall survival was 253 d with 30% alive at 1.5 y and 10% alive at 2 y. Although this regimen was well-tolerated, survival times did not exceed previously published data from dogs treated with amputation plus chemotherapy alone.

Influence of intravenous amifostine on xerostomia, tumor control, and survival after radiotherapy for head-and- neck cancer: 2-year follow-up of a prospective, randomized, phase III trial

International Nuclear Information System (INIS)

Wasserman, Todd H.; Brizel, David M.; Henke, Michael; Monnier, Alain; Eschwege, Francois; Sauer, Rolf; Strnad, Vratislav

2005-01-01

Purpose: To evaluate chronic xerostomia and tumor control 18 and 24 months after initial treatment with amifostine in a randomized controlled trial of patients with head-and-neck cancer; at 12 months after radiotherapy (RT), amifostine had been shown to reduce xerostomia without changing tumor control. Methods and Materials: Adults with head-and-neck cancer who underwent once-daily RT for 5-7 weeks (total dose, 50-70 Gy) received either open-label amifostine (200 mg/m 2 i.v.) 15-30 min before each fraction of radiation (n = 150) or RT alone (control; n = 153). Results: Amifostine administration was associated with a reduced incidence of Grade ≥2 xerostomia over 2 years of follow-up (p = 0.002), an increase in the proportion of patients with meaningful (>0.1 g) unstimulated saliva production at 24 months (p = 0.011), and reduced mouth dryness scores on a patient benefit questionnaire at 24 months (p < 0.001). Locoregional control rate, progression-free survival, and overall survival were not significantly different between the amifostine group and the control group. Conclusions: Amifostine administration during head-and-neck RT reduces the severity and duration of xerostomia 2 years after treatment and does not seem to compromise locoregional control rates, progression-free survival, or overall survival

Postoperative radiotherapy appeared to improve the disease free survival rate of patients with extrahepatic bile duct cancer at high risk of loco-regional recurrence

Energy Technology Data Exchange (ETDEWEB)

Kim, Mi Young; Kim, Jin Hee; Kim, Yong Hoon [Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of); Byun, Sang Jun [Dept. of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

2016-12-15

To investigate the outcomes of postoperative radiotherapy (RT), in patients with extrahepatic bile duct (EHBD) cancer by comparing the survival rate between patients undergoing surgery alone or surgery plus postoperative RT, and to identify the prognostic factors affecting survival. Between 2000 and 2013, 52 patients with EHBD cancer underwent surgical resection. Of these, 33 patients did not receive postoperative RT (group I), and 19 patients did (group II). R1 resection was significantly more frequent in group II. The median radiation dose was 5,040 cGy. The 3-year overall survival (OS) rate for group I and group II was 38% and 56%, respectively (p = 0.274). The 3-year disease free survival (DFS) rate for group I and group II was 20% and 31%, respectively (p = 0.049), and the 3-year loco-regional recurrence free survival (LRFS) rates were 19% and 58%, respectively (p = 0.002). Multivariate analyses showed that postoperative RT and lymphovascular invasion were independent prognostic factors for DFS and LRFS. Overall, 42 patients (80%) experienced treatment failure. Distant metastasis was the predominant pattern of failure in group II. Postoperative RT after surgical resection appeared to improve the loco-regional control and DFS rate. More effort is needed to reduce distant metastasis, the major pattern of failure, in patients who receive postoperative RT.

Analysis of audiometric relapse-free survival in patients with immune-mediated hearing loss exclusively treated with corticosteroids.

Science.gov (United States)

Mata-Castro, Nieves; García-Chilleron, Raimon; Gavilanes-Plasencia, Javier; Ramírez-Camacho, Rafael; García-Fernández, Alfredo; García-Berrocal, José Ramón

2017-10-12

To describe the results in terms of audiometric relapse-free survival and relapse rate in immunomediated hearing loss patients treated exclusively with corticosteroids. Retrospective study of patients with audiometric relapses, monitored from 1995 to 2014, in two centres of the Community of Madrid. We evaluated 31 patients with a mean age of 48.52 years (14.67 SD), of which 61.3% were women. Most hearing loss was fluctuating (48.4%). Only 16.1% of patients had systemic autoimmune disease. There is a moderate positive correlation between the sex variable and the systemic involvement variable (Spearman's correlation coefficient=0.356): specifically, between being female and systemic disease. The relative incidence rate of relapse in the first year was 2.01 relapses/year with a 95% CI (1.32 to 2.92). The mean survival time of the event (audiometric relapse) was 5.25 months (SD 0.756). With multivariate analysis, the only variable that achieved statistical significance was age, with a hazard ratio of 1.032 (95% CI; 1.001-1.063, P=.043). Immune-mediated disease of the inner ear is a chronic disease with relapses. Half of the patients with immunomediated hearing loss treated exclusively with corticosteroids relapse before 6 months of follow-up. In addition, if a patient has not relapsed, they are more likely to relapse as each year passes. Analysis of the of audiometric relapse- free survival will enable the effect of future treatments to be compared and their capacity to reduce the rhythm of relapses. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

Recurrence-free survival, but not surgical therapy per se, determines 583 patients' long-term satisfaction following primary pilonidal sinus surgery.

Science.gov (United States)

Doll, Dietrich; Luedi, Markus M; Evers, Theo; Kauf, Peter; Matevossian, Edouard

2015-05-01

With pilonidal sinus disease (PSD) incidence increasing and patients freely choosing their surgeon, patients' interest issues have been brought forward estimating patient satisfaction following pilonidal sinus surgery. The influence of wound healing time and long-term recurrence rate on patient satisfaction in primary PSD surgery has not been investigated yet. Five hundred eighty-three patients (German military cohort) were interviewed, compiling wound healing time, aesthetic satisfaction, long-term recurrence-free survival and patient satisfaction having undergone primary open (PO) treatment, marsupialization (MARS) or primary midline closure (PMC) treatment. Recurrence rate was determined by Kaplan-Meier calculation following up to 20 years after primary PSD surgery. Patient satisfaction ranking from 1 to 10 (10 = max. satisfied) showed an average satisfaction of 8.2 (range 0-10; 95% confidence interval (CI) 7891-8250). In-hospital stay time was significantly longer in primary open (PO) and marsupialization (MARS) group as compared to primary midline closure (PMC; p < 0.0001, Kruskal-Wallis test). Satisfaction was comparable between treatment groups, and was neither linked to in-hospital stay time nor to longer outpatient wound care period or total treatment time. Recurrence-free survival, as seen in the PO and PMC treatment group, revealed a highly significant difference for all patients. Improvement in MARS patients with versus without recurrence was low, as satisfaction with primary treatment was lower as the other groups. Neither choice of surgical treatment nor treatment duration within hospital or after hospital influences patient satisfaction, as long as recurrence-free survival can be provided. Marsupialization was ranked lower in both groups (with or without recurrence), and should be abandoned, as patients are significantly less satisfied with either results, independent of recurrence.

Isolated thoracic perfusion with chemofiltration for progressive malignant pleural mesothelioma

Directory of Open Access Journals (Sweden)

Aigner KR

2017-06-01

-year survival was 18%. Median overall survival was 12 months and progression-free survival 9 months.Conclusion: ITP-F for patients with advanced pleural mesothelioma, progressive after standard therapies, is an effective and well-tolerated treatment modality, offering comparably long survival data at a good QoL. Keywords: regional chemotherapy, isolation perfusion, mesothelioma, intra-arterial chemotherapy, stop flow, locally advanced cancers, thoracic malignancies

End points for adjuvant therapy trials: has the time come to accept disease-free survival as a surrogate end point for overall survival?

Science.gov (United States)

Gill, Sharlene; Sargent, Daniel

2006-06-01

The intent of adjuvant therapy is to eradicate micro-metastatic residual disease following curative resection with the goal of preventing or delaying recurrence. The time-honored standard for demonstrating efficacy of new adjuvant therapies is an improvement in overall survival (OS). This typically requires phase III trials of large sample size with lengthy follow-up. With the intent of reducing the cost and time of completing such trials, there is considerable interest in developing alternative or surrogate end points. A surrogate end point may be employed as a substitute to directly assess the effects of an intervention on an already accepted clinical end point such as mortality. When used judiciously, surrogate end points can accelerate the evaluation of new therapies, resulting in the more timely dissemination of effective therapies to patients. The current review provides a perspective on the suitability and validity of disease-free survival (DFS) as an alternative end point for OS. Criteria for establishing surrogacy and the advantages and limitations associated with the use of DFS as a primary end point in adjuvant clinical trials and as the basis for approval of new adjuvant therapies are discussed.

Survival differences in European patients with AIDS, 1979-89. The AIDS in Europe Study Group

DEFF Research Database (Denmark)

Lundgren, Jens Dilling; Pedersen, C; Clumeck, N

1994-01-01

. The regional differences in survival were less pronounced for patients diagnosed in 1989 compared with earlier years. Improved survival in recent years was observed for patients with a variety of manifestations used to define AIDS but was significant only for patients diagnosed with Pneumocystis carinii...... pneumonia. The three year survival, however, remains unchanged over time. CONCLUSIONS--Survival of AIDS patients seems to vary within Europe, being shorter in southern than central and northern Europe. The magnitude of these differences, however, has declined gradually over time. Short term survival has...

Progress in High Power Free-Piston Stirling Convertor Development

Science.gov (United States)

Brandhorst, Henry W., Jr.; Kirby, Raymond L.; Chapman, Peter A.; Walter, Thomas J.

2008-09-01

The U.S. Space Exploration Policy has established a vision for human exploration of the moon and Mars. One option for power for future outposts on the lunar and Martian surfaces is a nuclear reactor coupled with a free-piston Stirling convertor at a power level of 30-40 kWe. A 25 kW convertor was developed in the 1990s under the SP-100 program. This system consisted of two 12.5 kWe engines connected at their hot ends and mounted in tandem to cancel vibration. Recently, NASA began a new project with Auburn University to develop a 5 kWe, single convertor for use in such a possible lunar power system. Goals of this development program include a specific power in excess of 140 We/kg at the convertor level, lifetime in excess of five years and a control system that will safely manage the convertors in case of an emergency. Foster-Miller, Inc. is developing the 5 kWe Stirling Convertor Assembly. The characteristics of the design along with progress in developing the system will be described.

Results From the Phase III Randomized Trial of Onartuzumab Plus Erlotinib Versus Erlotinib in Previously Treated Stage IIIB or IV Non-Small-Cell Lung Cancer: METLung.

Science.gov (United States)

Spigel, David R; Edelman, Martin J; O'Byrne, Kenneth; Paz-Ares, Luis; Mocci, Simonetta; Phan, See; Shames, David S; Smith, Dustin; Yu, Wei; Paton, Virginia E; Mok, Tony

2017-02-01

Purpose The phase III OAM4971g study (METLung) examined the efficacy and safety of onartuzumab plus erlotinib in patients with locally advanced or metastatic non-small-cell lung cancer selected by MET immunohistochemistry whose disease had progressed after treatment with a platinum-based chemotherapy regimen. Patients and Methods Patients were randomly assigned at a one-to-one ratio to receive onartuzumab (15 mg/kg intravenously on day 1 of each 21-day cycle) plus daily oral erlotinib 150 mg or intravenous placebo plus daily oral erlotinib 150 mg. The primary end point was overall survival (OS) in the intent-to-treat population. Secondary end points included median progression-free survival, overall response rate, biomarker analysis, and safety. Results A total of 499 patients were enrolled (onartuzumab, n = 250; placebo, n = 249). Median OS was 6.8 versus 9.1 months for onartuzumab versus placebo (stratified hazard ratio [HR], 1.27; 95% CI, 0.98 to 1.65; P = .067), with a greater number of deaths in the onartuzumab arm (130 [52%] v 114 [46%]). Median progression-free survival was 2.7 versus 2.6 months (stratified HR, 0.99; 95% CI, 0.81 to 1.20; P = .92), and overall response rate was 8.4% and 9.6% for onartuzumab versus placebo, respectively. Exploratory analyses using MET fluorescence in situ hybridization status and gene expression showed no benefit for onartuzumab; patients with EGFR mutations showed a trend toward shorter OS with onartuzumab treatment (HR, 4.68; 95% CI, 0.97 to 22.63). Grade 3 to 5 adverse events were reported by 56.0% and 51.2% of patients, with serious AEs in 33.9% and 30.7%, for experimental versus control arms, respectively. Conclusion Onartuzumab plus erlotinib did not improve clinical outcomes, with shorter OS in the onartuzumab arm, compared with erlotinib in patients with MET-positive non-small-cell lung cancer.

TIA model is attainable in Wistar rats by intraluminal occlusion of the MCA for 10min or shorter.

Science.gov (United States)

Durukan Tolvanen, A; Tatlisumak, E; Pedrono, E; Abo-Ramadan, U; Tatlisumak, T

2017-05-15

Transient ischemic attack (TIA) has received only little attention in the experimental research field. Recently, we introduced a TIA model for mice, and here we set similar principles for simulating this human condition in Wistar rats. In the model: 1) transient nature of the event is ensured, and 2) 24h after the event animals are free from any sensorimotor deficit and from any detectable lesion by magnetic resonance imaging (MRI). Animals experienced varying durations of ischemia (5, 10, 12.5, 15, 25, and 30min, n=6-8pergroup) by intraluminal middle cerebral artery occlusion (MCAO). Ischemia severity and reperfusion rates were controlled by cerebral blood flow measurements. Sensorimotor neurological evaluations and MRI at 24h differentiated between TIA and ischemic stroke. Hematoxylin and eosin staining and apoptotic cell counts revealed pathological correlates of the event. We found that already 12.5min of ischemia was long enough to induce ischemic stroke in Wistar rats. Ten min or shorter durations induced neither gross neurological deficits nor infarcts visible on MRI, but histologically caused selective neuronal necrosis. A separate group of animals with 10min of ischemia followed up to 1week after reperfusion remained free of infarction and any MRI signal change. Thus, 10min or shorter focal cerebral ischemia induced by intraluminal MCAO in Wistar rats provides a clinically relevant TIA the rat. This model is useful for studying molecular correlates of TIA. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of mercury on health and first-year survival of free-ranging great egrets (Ardea albus) from southern Florida.

Science.gov (United States)

Sepúlveda, M S; Williams, G E; Frederick, P C; Spalding, M G

1999-10-01

The objectives of this study were to determine whether elevated mercury (Hg) concentrations have a negative impact on the health and survival of nestling and juvenile free-ranging great egrets (Ardea albus) from southern Florida. During 1994, when health and survival was monitored in a cohort of young birds with naturally variable concentrations of Hg, packed cell volume was positively correlated with blood Hg concentrations, and high Hg concentration in blood was not related to the probability of surviving during the first 10.5 months of life. During 1995, 70 first-hatched great egret chicks were included in a Hg field-dosing experiment to compare the effects of elevated Hg on health and survival. Birds were dosed while in the nest orally every 2.5 days for 15 days with 0.5 mg of methyl mercury chloride (MeHgCl) for an estimated intake of 1.54 mg MeHgCl/kg food intake. These birds were compared with controls, which received an estimated 0.41 mg MeHgCl/kg food. No differences were observed in health parameters or in the probability of surviving during the first 8 months of age between egrets that were dosed with Hg and those that were not. A likely explanation for the lack of any effects on health and survival between both groups could be that chicks at this age were eliminating most of the dietary Hg through the production of new feathers.

History of Comorbidities and Survival of Ovarian Cancer Patients, Results from the Ovarian Cancer Association Consortium

DEFF Research Database (Denmark)

Minlikeeva, Albina N; Freudenheim, Jo L; Eng, Kevin H

2017-01-01

carcinoma who participated in 23 studies included in the Ovarian Cancer Association Consortium, we explored associations between histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, and neurological diseases and overall and progression-free survival...... with ovarian cancer outcome in the overall sample nor in strata defined by histologic subtype, weight status, age at diagnosis, or stage of disease (local/regional vs. advanced).Conclusions: Histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, or neurologic......Background: Comorbidities can affect survival of ovarian cancer patients by influencing treatment efficacy. However, little evidence exists on the association between individual concurrent comorbidities and prognosis in ovarian cancer patients.Methods: Among patients diagnosed with invasive ovarian...

Improved Metastasis- and Disease-Free Survival With Preoperative Sequential Short-Course Radiation Therapy and FOLFOX Chemotherapy for Rectal Cancer Compared With Neoadjuvant Long-Course Chemoradiotherapy: Results of a Matched Pair Analysis.

Science.gov (United States)

Markovina, Stephanie; Youssef, Fady; Roy, Amit; Aggarwal, Sonya; Khwaja, Shariq; DeWees, Todd; Tan, Benjamin; Hunt, Steven; Myerson, Robert J; Chang, Daniel T; Parikh, Parag J; Olsen, Jeffrey R

2017-10-01

To compare treatment and toxicity outcomes between a phase 2 institutional trial of near total neoadjuvant therapy (nTNT) for locally advanced rectal cancer and a similar historical control cohort treated at Washington University in St. Louis with the current US standard of care, defined as neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant FOLFOX chemotherapy; to expand the comparison to an additional institution, patients treated with similar NCRT at Stanford University were included. Sixty-nine patients with cT3-4N0-2M0 rectal adenocarcinoma enrolled on the Washington University in St. Louis phase 2 study of nTNT were included for analysis. Patients treated at the same institution with conventional NCRT and adjuvant FOLFOX were matched for exact cTNM stage. Forty-one patients treated with NCRT at Stanford University were included in a second analysis. Kaplan-Meier analysis with log-rank test was used to compare local control, distant metastasis-free survival, disease-free survival, and overall survival. Median follow-up was 49 and 54 months for nTNT and NCRT, respectively. Pathologic complete response and T-downstaging rates were 28% versus 16% (P=.21) and 75% versus 41% (P<.001) in the nTNT and NCRT cohorts, respectively. Three-year disease-free survival (85% vs 68%, P=.032) was significantly better in the nTNT group. Actuarial 3-year local control (92% vs 96%, P=.36) and overall survival (96% vs 88%, P=.67) were similar. The Stanford cohort had significantly lower clinical stage. After controlling for clinical stage, age, tumor location, institution, and number of chemotherapy cycles, nTNT treatment remained significantly associated with lower risk of recurrence (P=.006). Patients treated with nTNT had higher T-downstaging and superior distant metastasis-free survival and disease-free survival compared with conventional NCRT when matched for tumor location and exact cTNM stage. Near total neoadjuvant therapy remained a

Serum Free Light Chains

Science.gov (United States)

... lab's website in order to provide you with background information about the test(s) you had performed. You will need to return ... the free light chains have a much shorter half-life (3-5 hours) than ... cell disorders, the test is also used for assessing response and minimal ...

Secretory IgM Exacerbates Tumor Progression by Inducing Accumulations of MDSCs in Mice.

Science.gov (United States)

Tang, Chih-Hang Anthony; Chang, Shiun; Hashimoto, Ayumi; Chen, Yi-Ju; Kang, Chang Won; Mato, Anthony R; Del Valle, Juan R; Gabrilovich, Dmitry I; Hu, Chih-Chi Andrew

2018-06-01

Chronic lymphocytic leukemia (CLL) cells can secrete immunoglobulin M. However, it is not clear whether secretory IgM (sIgM) plays a role in disease progression. We crossed the Eμ-TCL1 mouse model of CLL, in which the expression of human TCL1 oncogene was driven by the V(H) promoter-Ig(H)-Eμ enhancer, with MD4 mice whose B cells produced B-cell receptor (membrane-bound IgM) and sIgM with specificity for hen egg lysozyme (HEL). CLL cells that developed in these MD4/Eμ-TCL1 mice reactivated a parental Ig gene allele and secreted IgM, and did not recognize HEL. The MD4/Eμ-TCL1 mice had reduced survival, increased myeloid-derived suppressor cells (MDSC), and decreased numbers of T cells. We tested whether sIgM could contribute to the accumulation of MDSCs by crossing μS -/- mice, which could not produce sIgM, with Eμ-TCL1 mice. The μS -/- /Eμ-TCL1 mice survived longer than Eμ-TCL1 mice and developed decreased numbers of MDSCs which were less able to suppress proliferation of T cells. We targeted the synthesis of sIgM by deleting the function of XBP-1s and showed that targeting XBP-1s genetically or pharmacologically could lead to decreased sIgM, accompanied by decreased numbers and reduced functions of MDSCs in MD4/Eμ-TCL1 mice. Additionally, MDSCs from μS -/- mice grafted with Lewis lung carcinoma were inefficient suppressors of T cells, resulting in slower tumor growth. These results demonstrate that sIgM produced by B cells can upregulate the functions of MDSCs in tumor-bearing mice to aggravate cancer progression. In a mouse model of CLL, production of secretory IgM led to more MDSCs, fewer T cells, and shorter survival times for the mice. Thus, secretory IgM may aggravate the progression of this cancer. Cancer Immunol Res; 6(6); 696-710. ©2018 AACR . ©2018 American Association for Cancer Research.

Insulin-like Growth Factor Receptor 1 mRNA Expression as a Prognostic Marker in Advanced Non-small Cell Lung Cancer

DEFF Research Database (Denmark)

Vilmar, Adam; Santoni-Rugiu, Eric; Cillas, Jesus Garcia-Fon

2014-01-01

BACKGROUND: The insulin-like growth factor 1 receptor (IGF1R) has yet to be established as a biomarker in non-small cell lung cancer (NSCLC) but could prove useful in customized chemotherapy. We explored its prognostic value using both quantitative real-time reverse transcriptase polymerase chain......-points. RESULTS: Surgical tissue samples were available from 33 patients deemed inoperable. IGF1R status varied according to histopathology. Patients with tumors positive for IGF1R mRNA expression had a shorter progression-free and overall survival when compared to the negative sub-group (6.1 vs. 7.4 months, p=0...

Medulloblastoma: progress over time

International Nuclear Information System (INIS)

Smee, Robert I.; Williams, Janet R.; De-loyde, Katie J.; Meagher, Nicola S.; Cohn, Richard

2012-01-01

Medulloblastoma is the most common central nervous system tumour in children aged 0–4 years, with 75% of cases occurring in patients <16 years, and rare in adults. The intent of this audit is to review a single centre's experience and to compare outcomes with other centres' outcomes. This Ethics approved retrospective audit evaluates the paediatric population aged <16 years who received radiotherapy as their initial or salvage treatment at the Prince of Wales Hospital Cancer Centre between 1972 and 2007. The primary and secondary end-points were progression-free survival (PFS) and cancer-specific survival (CSS), with comparisons made between patients treated before and after 1990, and the impact of high- and low-risk disease. There were 80 eligible patients, 78 who had radiotherapy at initial presentation, and 2 at the time of recurrence. Median age was 6.5 years, 52 were boys and 28 were girls. Seventy-eight patients had a surgical procedure and ultimately received craniospinal radiotherapy. Of these 78 patients, 32 (40%) had a macroscopically complete resection. The 5-year PFS was 69.7%. The 5-year PFS for patients treated pre and post 1990 was 66.1% and 71.8%, respectively. The 5-year CSS for high- and low-risk patients was 61.1% and 78.4%, respectively. Ultimately, 33% of patients were dead due to disease. This audit demonstrates those children referred to this facility for treatment have comparable survival to that of other major centres.

Cachexia at diagnosis is associated with poor survival in head and neck cancer patients.

Science.gov (United States)

Orell-Kotikangas, Helena; Österlund, Pia; Mäkitie, Outi; Saarilahti, Kauko; Ravasco, Paula; Schwab, Ursula; Mäkitie, Antti A

2017-07-01

One third of the patients had cachexia with an association of significantly shorter survival. These results suggest that combining HGS and MAMA seems to be a practical method to screen cachexia in patients with head and neck cancer and may also be used when assessing their prognosis. The aim of this study was to analyze the hypothesis that cachexia defined as both low mid-arm muscle area (MAMA) and handgrip strength (HGS) is associated with decreased survival in patients with head and neck squamous cell carcinoma (HNSCC). Sixty-five consecutive patients with primary HNSCC were enrolled prior to cancer therapy. Cachexia was defined as low handgrip strength (HGS) and low mid-arm muscle area (MAMA). Nutritional status was assessed by patient-generated subjective global assessment (PG-SGA) and sarcopenia by low MAMA. Biochemical parameters reflecting nutritional status and S-25-OHD were measured. Cachexia was seen in 31% and sarcopenia in 46% of patients. Altogether, 34% of patients were malnourished. Disease-free survival was 13 months (3-62) in cachectic patients, compared with 66 months (31-78) in non-cachectic patients (p = 0.009). S-25-OHD was 28 nmol/l in cachectic patients, compared with 46 nmol/l in non-cachectic patients (p = 0.009) and prealbumin 187 mg/l and 269 mg/l, respectively (p < 0.001).

Hepatocellular Carcinoma within Milan Criteria: No-Touch Multibipolar Radiofrequency Ablation for Treatment-Long-term Results.

Science.gov (United States)

Seror, Olivier; N'Kontchou, Gisèle; Nault, Jean-Charles; Rabahi, Yacine; Nahon, Pierre; Ganne-Carrié, Nathalie; Grando, Véronique; Zentar, Nora; Beaugrand, Michel; Trinchet, Jean-Claude; Diallo, Abou; Sellier, Nicolas

2016-08-01

Purpose To assess the long-term outcome in 108 consecutive patients treated with no-touch multibipolar radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) that met the Milan criteria. Materials and Methods This retrospective study was approved by the ethical review board, and the need to obtain informed consent was waived. Between November 1, 2006, and December 31, 2011, 132 HCC tumors (diameter, 10-45 mm; 39 tumors ≥ 30 mm) in 108 consecutive patients (106 with cirrhosis) that met Milan criteria were treated with no-touch multibipolar RFA, which consisted of activating, in bipolar mode, three or four electrodes inserted just beyond the tumor margins. Follow-up was performed every 3 months for 2 years and every 6 months thereafter with computed tomographic or magnetic resonance imaging. Survival probabilities were computed by using the Kaplan-Meier method. Predictive factors of tumor progression and overall survival were assessed by using the Cox proportional hazard model. Results No technical failure occurred, and complete ablation was achieved for all the nodules. After a median of 40.5 months (range, 2-84 months) of follow-up, 3- and 5-year local and overall tumor progression-free survival were 96%, 94%, 52%, and 32%, respectively. Neither tumor diameter greater than 30 mm nor location abutting a large vessel were associated with local tumor progression. Tumor diameter greater than 30 mm was the only parameter predictive of overall tumor progression (P = .0036). Independent factors associated with shorter overall survival were Child-Pugh class B disease, age greater than 65 years, and platelet count of less than 150 g/L (P touch multibipolar RFA for HCC tumors that meet Milan criteria provides a high local tumor progression-free survival rate. An ongoing randomized trial might help to clarify the role of this new approach for the treatment of early HCC. (©) RSNA, 2016 Online supplemental material is available for this article. An earlier

Imaging and histologic prognostic factors in triple-negative breast cancer and carcinoma in situ as a prognostic factor.

Science.gov (United States)

Sebastián Sebastián, C; García Mur, C; Cruz Ciria, S; Rosero Cuesta, D S; Gros Bañeres, B

2016-01-01

To analyze what factors in magnetic resonance imaging (MRI) and histological study of triple-negative breast cancers are related to tumor recurrence and to shorter disease-free survival. To analyze survival and recurrence in function of the presence of an in situ component. This was a retrospective study of MRI staging examinations in 122 women with triple-negative breast cancer done from 2007 through 2014. In the MRI, we evaluated morphological variables (size, margins, morphology, internal signal in T2-weighted sequences) and dynamic variables (perfusion and diffusion). In the histological study, we evaluated Ki67, p53, CK5/6, nuclear grade, and Scarff-Bloom grade, as well as the presence of an in situ component and tumor grade (high grade or not high grade). We compared the variables between patients with tumor recurrence and those without, and we conducted a survival analysis. Non-nodular enhancement was more common in patients with tumor recurrence (p=0.038) and was associated with shorter disease-free survival (p=0.023). Neither diffusion restriction (p=0.079) nor ki67 (p=0.052) was associated with a worse prognosis. An in situ component was detected in 44% of triple-negative tumors, and a greater proportion of patients in the group with tumor recurrence had an in situ component; however, the presence of an in situ component was not associated with shorter survival (p = 0.185). Non-nodular enhancement was associated with a worse prognosis. Diffusion restriction, ki67, and the presence of an in situ component were not associated with shorter disease-free survival. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Postmastectomy radiotherapy improves disease-free survival of high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

Directory of Open Access Journals (Sweden)

Zhen-Yu He

Full Text Available The indications for post-mastectomy radiotherapy (PMRT with T1-2 breast cancer and 1-3 positive axillary lymph nodes is still controversial. The purpose of this study was to investigate the role of PMRT in T1-2 breast cancer with 1-3 positive axillary lymph node.We retrospectively reviewed the file records of 79 patients receiving PMRT and not receiving PMRT (618 patients.The median follow-up was 65 months. Multivariate analysis showed that PMRT was an independent prognostic factor of locoregional recurrence-free survival (LRFS (P = 0.010. Subgroup analysis of patients who did not undergo PMRT showed that pT stage, number of positive axillary lymph nodes, and molecular subtype were independent prognostic factors of LRFS. PMRT improved LRFS in the entire group (P = 0.005, but did not affect distant metastasis-free survival (DMFS (P = 0.494, disease-free survival (DFS (P = 0.215, and overall survival (OS (P = 0.645. For patients without PMRT, the 5-year LRFS of low-risk patients (0-1 risk factor for locoregional recurrence of 94.5% was significantly higher than that of high-risk patients (2-3 risk factors for locoregional recurrence (80.9%, P < 0.001. PMRT improved LRFS (P = 0.001 and DFS (P = 0.027 in high-risk patients, but did not improve LRFS, DMFS, DFS, and OS in low-risk patients.PMRT is beneficial in patients with high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

SOXs in human prostate cancer: implication as progression and prognosis factors

International Nuclear Information System (INIS)

Zhong, Wei-de; Chen, Xi-bin; Lin, Zhuo-yuan; Deng, Ye-han; Wu, Shu-lin; He, Hui-chan; Wu, Chin-lee; Qin, Guo-qiang; Dai, Qi-shan; Han, Zhao-dong; Chen, Shan-ming; Ling, Xiao-hui; Fu, Xin; Cai, Chao; Chen, Jia-hong

2012-01-01

SOX genes play an important role in a number of developmental processes. Potential roles of SOXs have been demonstrated in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and types. The aim of this study was to investigate the involvement of SOXs in the progression and prognosis of human prostate cancer (PCa). The gene expression changes of SOXs in human PCa tissues compared with non-cancerous prostate tissues was detected using gene expression microarray, and confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohositochemistry. The roles of these genes in castration resistance were investigated in LNCaP xenograft model of PCa. The microarray analysis identified three genes (SOX7, SOX9 and SOX10) of SOX family that were significantly dis-regulated in common among four PCa specimens. Consistent with the results of the microarray, differential mRNA and protein levels of three selected genes were found in PCa tissues by QRT-PCR analysis and immunohistochemistry. Additionally, we found that the immunohistochemical staining scores of SOX7 in PCa tissues with higher serum PSA level (P = 0.02) and metastasis (P = 0.03) were significantly lower than those with lower serum PSA level and without metastasis; the increased SOX9 protein expression was frequently found in PCa tissues with higher Gleason score (P = 0.02) and higher clinical stage (P < 0.0001); the down-regulation of SOX10 tend to be found in PCa tissues with higher serum PSA levels (P = 0.03) and advanced pathological stage (P = 0.01). Moreover, both univariate and multivariate analyses showed that the down-regulation of SOX7 and the up-regulation of SOX9 were independent predictors of shorter biochemical recurrence-free survival. Furthermore, we discovered that SOX7 was significantly down-regulated and SOX9 was significantly up-regulated during the progression to castration resistance. Our data offer the convince

Classical and anaplastic seminoma: Difference in survival

International Nuclear Information System (INIS)

Bobba, V.S.; Mittal, B.B.; Hoover, S.V.; Kepka, A.

1987-01-01

The authors undertook a retrospective study of seminoma patients treated with radiation therapy between 1961 and 1985. The classical group consisted of 66 patients, of whom 47 were stage I and 19 were stage II. The anaplastic group consisted of 21 patients, of whom 11 were stage I, nine were stage II, and one was stage III. The median follow-up was 66 months. The five-year crude survival rate for the entire group was 92%, for classical 96%, and for anaplastic 78% (P<.005). Similarly, there was a significant difference (P<.005) in actuarial relapse-free survival at 5 years between classical and anaplastic seminoma. For classical stage I, the relapse-free actuarial 5-year survival rate was 96; for classical stage II, 84%. For anaplastic stage I the relapse-free actuarial 5-year survival rate was 82%, and for stage II 75%. Six patients in the classical group (9%) failed treatment. In the anaplastic group, five patients or 24 failed treatment. Therefore, the authors' data suggest a difference in survival and failure rate between classical and anaplastic seminoma. Extratesticular seminoma with anaplastic histology has an even worse prognosis

Determinants of IPO survival on the Johannesburg securities exchange

Directory of Open Access Journals (Sweden)

Brownhilder Ngek Neneh

2014-10-01

Full Text Available The purpose of this paper was to establish the determinants of IPO survival on the Johannesburg Securities Exchange (JSE. Using the Kaplan-Meier test, this study established that firms less than five years prior to listing on the JSE have a significant smaller mean survival time; firms with a gross proceed less than the median have a significant shorter mean survival time; overpriced IPOs have a significant higher survival time; IPOs listed during the hot market period on the JSE have a significant smaller mean survival time and IPOs with return on asset, operating profit margin, and return on equity less than or equal to zero have a low mean survival time. Also, being in the internet industry significantly shortens the mean survival time of an IPO. Moreover, based on the Cox Proportional Hazard model, it was established that the determinants of IPO survivability on the JSE are the firms’ age, size, market period, return on equity and operating profit margin are. These findings provide investors and companies in the JSE with empirical evidence of the determinants of IPO survivability of the JSE. As such, investors are advised to consider these factors when selecting their portfolios

Counterbalancing angiogenic regulatory factors control the rate of cancer progression and survival in a stage-specific manner

Science.gov (United States)

Xie, Liang; Duncan, Michael B.; Pahler, Jessica; Sugimoto, Hikaru; Martino, Margot; Lively, Julie; Mundel, Thomas; Soubasakos, Mary; Rubin, Kristofer; Takeda, Takaaki; Inoue, Masahiro; Lawler, Jack; Hynes, Richard O.; Hanahan, Douglas; Kalluri, Raghu

2011-01-01

Whereas the roles of proangiogenic factors in carcinogenesis are well established, those of endogenous angiogenesis inhibitors (EAIs) remain to be fully elaborated. We investigated the roles of three EAIs during de novo tumorigenesis to further test the angiogenic balance hypothesis, which suggests that blood vessel development in the tumor microenvironment can be governed by a net loss of negative regulators of angiogenesis in addition to the well-established principle of up-regulated angiogenesis inducers. In a mouse model of pancreatic neuroendocrine cancer, administration of endostatin, thrombospondin-1, and tumstatin peptides, as well as deletion of their genes, reveal neoplastic stage-specific effects on angiogenesis, tumor progression, and survival, correlating with endothelial expression of their receptors. Deletion of tumstatin and thrombospondin-1 in mice lacking the p53 tumor suppressor gene leads to increased incidence and reduced latency of angiogenic lymphomas associated with diminished overall survival. The results demonstrate that EAIs are part of a balance mechanism regulating tumor angiogenesis, serving as intrinsic microenvironmental barriers to tumorigenesis. PMID:21622854

The Circadian Schedule for Childhood Acute Lymphoblastic Leukemia Maintenance Therapy does not Influence Event-Free Survival in the NOPHO ALL92 Protocol

DEFF Research Database (Denmark)

Clemmensen, Kim K. B.; Christensen, Regitse H.; Shabaneh, Diana N.

2014-01-01

BACKGROUND: The event-free survival of childhood acute lymphoblastic leukemia (ALL) has been reported to be superior when oral methotrexate (MTX) and 6-mercaptopurine (6MP) maintenance therapy (MT) is administered in the evening compared to the morning. PROCEDURE: In the ALL92 MT study we prospec...

The role of stereotactic body radiation therapy in oligometastatic colorectal cancer: Clinical case report of a long-responder patient treated with regorafenib beyond progression.

Science.gov (United States)

Roberto, Michela; Falcone, Rosa; Mazzuca, Federica; Archibugi, Livia; Castaldi, Nadia; Botticelli, Andrea; Osti, Mattia Falchetto; Marchetti, Paolo

2017-12-01

Regorafenib is the new standard third-line therapy in metastatic colorectal cancer (mCRC). However, the reported 1-year overall survival rate does not exceed 25%. A 55-year-old man affected by mCRC, treated with regorafenib combined with stereotactic body radiotherapy (SBRT), showing a durable response. After 6 months of regorafenib, a PET/CT scan revealed a focal uptake in a solid lung nodule which was treated with SBRT, whereas continuing regorafenib administration. Fourteen months later, the patient had further progression in a parasternal lymph node, but treatment with regorafenib was continued. The regorafenib-associated side effects, such us the hand-foot syndrome, were favorable managed by reducing the dose from 160 to 120 mg/day. Patient-reported outcome was characterized by a progression-free survival of approximately 3 years. in presence of oligometastatic progression, a local SBRT while retaining the same systemic therapy may be a better multidisciplinary approach. Moreover, disease progression is no longer an absolute contraindication for continuing the regorafenib treatment.

Metformin Use and Endometrial Cancer Survival

Science.gov (United States)

Nevadunsky, Nicole S.; Van Arsdale, Anne; Strickler, Howard D.; Moadel, Alyson; Kaur, Gurpreet; Frimer, Marina; Conroy, Erin; Goldberg, Gary L.; Einstein, Mark H.

2013-01-01

Objective Impaired glucose tolerance and diabetes are risk factors for the development of uterine cancer. Although greater progression free survival among diabetic patients with ovarian and breast cancer using metformin have been reported, no studies have assessed the association of metformin use with survival in women with endometrial cancer (EC). Methods We conducted a single-institution retrospective cohort study of all patients treated for uterine cancer from January 1999 through December 2009. Demographic, medical, social, and survival data were abstracted from medical records and the national death registry. Overall survival (OS) was estimated using Kaplan-Meier methods. Cox models were utilized for multivariate analysis. All statistical tests were two-sided. Results Of 985 patients, 114 (12%) had diabetes and were treated with metformin, 136 (14%) were diabetic but did not use metformin, and 735 (74%) had not been diagnosed with diabetes. Greater OS was observed in diabetics with non-endometrioid EC who used metformin than in diabetic cases not using metformin and non-endometrioid EC cases without diabetes (log rank test (p=0.02)). This association remained significant (hazard ratio = 0.54, 95% CI: 0.30–0.97, p<0.04) after adjusting for age, clinical stage, grade, chemotherapy treatment, radiation treatment and presence of hyperlipidemia in multivariate analysis. No association between metformin use and OS in diabetics with endometrioid histology was observed. Conclusion Diabetic EC patients with non-endometrioid tumors who used metformin had lower risk of death than women with EC who did not use metformin. These data suggest that metformin might be useful as adjuvant therapy for non-endometrioid EC. PMID:24189334

Equivalent biochemical failure-free survival after external beam radiation therapy or radical prostatectomy in patients with a pretreatment prostate specific antigen of > 4-20 ng/ml

International Nuclear Information System (INIS)

D'Amico, Anthony V.; Whittington, Richard; Kaplan, Irving; Beard, Clair; Jiroutek, Michael; Malkowicz, S. Bruce; Wein, Alan; Coleman, C. Norman

1997-01-01

Purpose: Biochemical failure-free survival stratified by the pretreatment prostate-specific antigen (PSA) and biopsy Gleason score (bGl) is determined for prostate cancer patients managed definitively with external beam radiation therapy or radical retropubic prostatectomy. Methods and Materials: A Cox regression multivariable analysis evaluating the variables of PSA, bGl, and clinical stage was used to evaluate the end point of time to PSA failure in 867 and 757 consecutive prostate cancer patients managed definitively with external beam radiation therapy or radical retropubic prostatectomy, respectively. PSA failure-free survival was determined using Kaplan-Meier analysis. Comparisons were made using the log rank test. Results: The pretreatment PSA, bGl, and clinical stage (T3,4 vs. T1,T2) were found to be independent predictors of time to post-treatment PSA failure for both surgically and radiation managed patients using Cox regression multivariable analysis. Patients with a pretreatment PSA of > 4 ng/ml and ≤ 20 ng/ml could be classified into risk groups for time to post-therapy PSA failure: low = PSA > 4-10 ng/ml and bGl ≤ 4; intermediate = PSA > 4-10 and bGl 5-7; or PSA > 10-20 ng/ml and bGl ≤ 7; high = PSA > 4-20 ng/ml and bGl ≥ 8. Two-year PSA failure-free survival for surgically managed and radiation-managed patients, respectively, were 98% vs. 92% (p = 0.45), 77% vs. 81% (p = 0.86), and 51% vs. 53% (p = 0.48) for patients at low, intermediate, and high risk for post-therapy PSA failure. Conclusions: There was no statistical difference in the 2-year PSA failure-free survival for potentially curable patients managed definitively with surgery or radiation therapy when a retrospective comparison stratifying for the pretreatment PSA and bGl was performed

Phase II study of radiopeptide {sup 177}Lu-octreotate and capecitabine therapy of progressive disseminated neuroendocrine tumours

Energy Technology Data Exchange (ETDEWEB)

Claringbold, Phillip G. [Fremantle Hospital, Department of Oncology, Fremantle, WA (Australia); Brayshaw, Paul A.; Turner, J.H. [University of Western Australia, Department of Nuclear Medicine, Fremantle Hospital, Fremantle, WA (Australia); Price, Richard A. [Fremantle Hospital, Department of Radiology, Fremantle, WA (Australia)

2011-02-15

In this phase II study we investigated the safety and efficacy of combination capecitabine and {sup 177}Lu-octreotate for the treatment of disseminated, progressive, unresectable neuroendocrine tumours (NETs). Enrolled in the study were 33 patients with biopsy-proven NETs, positive {sup 111}In-octreotide scintigraphy and progressive disease measurable by CT/MRI who were to receive four cycles of 7.8 GBq {sup 177}Lu-octreotate 8-weekly, with 14 days of 1,650 mg/m{sup 2} capecitabine per day. Of the 33 patients, 25 completed four cycles. Minimal transient myelosuppression at 3-4 weeks caused grade 3 thrombocytopenia in one patient but no neutropenia. Nephrotoxicity was absent. Critical organ radiation dosimetry provided median estimates of the dose per cycle to the kidneys of 2.4 Gy and to the liver of 4.8 Gy, and showed cumulative doses all below toxic thresholds. Objective response rates (ORR) were 24% partial response (PR), 70% stable disease (SD) and 6% progressive disease. Median progression-free survival and median overall survival had not been reached at a median follow-up of 16 months (range 5-33 months). Survival at 1 and 2 years was 91% (95% CI 75-98%) and 88% (95% CI 71-96%), respectively. The addition of capecitabine radiosensitizing chemotherapy does not increase the minimal toxicity of {sup 177}Lu-octreotate radiopeptide therapy and led to an ORR of 24% PR and 70% minor response or SD in patients with progressive metastatic NETs. Tumour control and stabilization of disease was obtained in 94% of these patients. (orig.)

[Disease-free survival related factors in breast cancer].

Science.gov (United States)

Dávila-Arias, Cristina; Ocón, Olga; Fernández, Mariana F; Arrebola, Juan Pedro; Sánchez, María José; Aneiros, José; Torné, Pablo; Olea, Nicolás

2014-10-07

To evaluate the relationship between the clinical and pathological parameters of the primary tumor and disease-free survival (DFS) in a sample of hospital cases of invasive breast cancer. We performed a retrospective cohort study in 635 patients recruited at San Cecilio University Hospital in Granada (Spain) between 1994 and 2006. Information on the primary tumor and the outcomes of patients was collected by reviewing the medical records. Predictors of recurrence and/or metastasis and DFS (follow up of 3, 5 and 10 years) were analyzed by using Cox regression analysis. Multivariate models adjusted for age, tumor size, lymph nodal status, histological grade and estrogen and progesterone receptor expression showed a higher risk of recurrence and/or metastasis and lower DFS (adjusted relative risk, 95% confidence intervals) with tumor size (3 yrs: 3.00, 1.79-5.03; 5 yrs: 2.56, 1.65-3.98; 10 yrs: 2.16, 1.44-3.24), lymph nodal status (3 yrs: 4.58, 2.42-8.65; 5 yrs: 3.84, 2.35-6.30; 10 yrs: 3.08, 2.05-4.61), lymphovascular invasion (5 yrs: 1.88, 1.16-3.04; 10 yrs: 2.19, 1.43-3.35), multifocal and/or multicenter tumors (3 yrs: 2.69, 1.46-4.96; 5 yrs: 1.90, 1.08-3.35) and p53 protein expression (3 yrs: 2.03, 1.00-4.09). DFS was positively associated with an increased expression of progesterone receptor (3 yr: 0.48, 0.26-0.89; 5 yrs: 0.58, 0.35-0.97; 10 yrs: 0.59, 0.38-0.90). The biological characteristics of the primary tumor can be used to identify patients with distinctive prognoses and DFS, and could be helpful in making individual follow up strategies. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Vinflunine treatment in patients with metastatic urothelial cancer

DEFF Research Database (Denmark)

Holmsten, Karin; Dohn, Line; Jensen, Niels Viggo

2016-01-01

prognostic parameters. In particular, patients with ECOG PS 2 receiving vinflunine had a shorter mOS and a higher frequency of severe toxicity, and, thus, should be treated with caution. Furthermore, the present study observed large inter-individual differences in radiological response and OS, indicating...... of evaluating treatment patterns, response, survival parameters and side-effects. Data were collected retrospectively from the first 100 mUC patients treated with vinflunine at three Nordic cancer centers associated with the Nordic Urothelial Cancer Oncology Group. The overall response rate was 23% and complete...... response was observed in one patient. The median progression-free survival (mPFS) and median overall survival (mOS) were 2.8 (range, 0.5-34.3) and 6.3 (range, 0.3-39.7) months, respectively. An Eastern Cooperative Oncology Group performance status (ECOG PS) of 2 was present in 20% of the patients...

Exposure-survival analyses of pazopanib in renal cell carcinoma and soft tissue sarcoma patients: opportunities for dose optimization.

Science.gov (United States)

Verheijen, R B; Swart, L E; Beijnen, J H; Schellens, J H M; Huitema, A D R; Steeghs, N

2017-12-01

Pazopanib is an angiogenesis inhibitor approved for the treatment of renal cell carcinoma and soft tissue sarcoma. Post hoc analysis of a clinical trial demonstrated a relationship between pazopanib trough concentrations (C min ) and treatment efficacy. The aim of this study was to explore the pharmacokinetics and exposure-survival relationships of pazopanib in a real-world patient cohort. Renal cell cancer and soft tissue sarcoma patients who had at least one pazopanib plasma concentration available were included. Using calculated C min values and a threshold of > 20 mg/L, univariate and multivariate exposure-survival analyses were performed. Sixty-one patients were included, of which 16.4% were underexposed (mean C min   20 mg/L was related to longer progression free survival in renal cell cancer patients (34.1 vs. 12.5 weeks, n = 35, p = 0.027) and the overall population (25.0 vs. 8.8 weeks, n = 61, p = 0.012), but not in the sarcoma subgroup (18.7 vs. 8.8 weeks, n = 26, p = 0.142). In multivariate analysis C min  > 20 mg/L was associated with hazard ratios of 0.25 (p = 0.021) in renal cancer, 0.12 (p = 0.011) in sarcoma and 0.38 (p = 0.017) in a pooled analysis. This study confirms that pazopanib C min  > 20 mg/L relates to better progression free survival in renal cancer and points towards a similar trend in sarcoma patients. C min monitoring of pazopanib can help identify patients with low C min for whom individualized treatment at a higher dose may be appropriate.

Fat-free muscle mass in magnetic resonance imaging predicts acute-on-chronic liver failure and survival in decompensated cirrhosis

DEFF Research Database (Denmark)

Praktiknjo, Michael; Book, Marius; Luetkens, Julian

2018-01-01

of sarcopenia using magnetic resonance imaging (MRI) in decompensated cirrhotic patients with transjugular intrahepatic portosystemic shunt (TIPS). METHODS: The total erector spinae muscle area and the intramuscular fat tissue area were measured and subtracted to calculate the fat-free muscle area (FFMA) in 116...... in a validation cohort of 45 patients. RESULTS: FFMA correlated with follistatin and TPMT and showed slightly better association with survival than TPMT. Gender-specific cut-off values for FFMA were determined for sarcopenia. Decompensation (ascites, overt hepatic encephalopathy) persisted after TIPS...... in the sarcopenia group but resolved in the non-sarcopenia group. Sarcopenic patients showed no clinical improvement after TIPS as well as higher mortality, mainly due to development of acute-on-chronic liver failure (ACLF). FFMA was an independent predictor of survival in these patients. CONCLUSION: This study...

Magnetic resonance imaging in breast cancer treated with neoadjuvant chemotherapy: radiologic-pathologic correlation of the response and disease-free survival depending on molecular subtype.

Science.gov (United States)

Cruz Ciria, S; Jiménez Aragón, F; García Mur, C; Esteban Cuesta, H; Gros Bañeres, B

2014-01-01

To evaluate the radiologic and pathologic responses to neoadjuvant chemotherapy and their correlation in the molecular subtypes of breast cancer and to analyze their impact in disease-free survival. We included 205 patients with breast cancer treated with neoadjuvant chemotherapy. We evaluated the radiologic response by comparing MRI images acquired before and after chemotherapy. The pathologic response was classified on the Miller and Payne scale. For each subtype (HER2+, TN, luminal A, luminal B HER2-, and luminal B HER2+), we used the χ(2) test, Student's t-test, ANOVA, and Kendall's Tau-b to evaluate the radiologic response and the pathologic response, the radiologic-pathologic correlation, and the disease-free survival. The subtypes HER2+ (62.1%) and TN (45.2%) had higher rates of complete radiologic response. The pathologic response was 65.5% in the HER2+ subtype, 38.1% in the TN subtype, 2.6% in the luminal A subtype, 8.2% in the luminal B HER2- subtype, and 31% in the luminal B HER2+ subtype. The rate of radiologic-pathologic correlation was significant in all subtypes, higher in TN and HER2 (Tau-b coefficients 0.805 and 0.717, respectively). Disease-free survival was higher in HER2+ (91.9±3.3 months) and lower in TN (69.5±6.3 months), with significant differences between the cases with poor and good radiologic responses (P=.040). Survival was greater in cases with good radiologic response, except in cases with luminal A subtype. MRI can be a useful tool that provides information about the evolution of breast cancer treated with neoadjuvant chemotherapy, which varies with the immunohistochemical subtype. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

Survival of free and microencapsulated human-derived oral probiotic Lactobacillus paracasei SD1 in orange and aloe vera juices

Directory of Open Access Journals (Sweden)

Rawee Teanpaisan

2015-06-01

Full Text Available Microencapsulation was evaluated as a means of preserving Lactobacillus paracasei SD1, a human-derived strain with probiotic potential, in orange and aloe vera juices. The microencapsulation parameters included alginate concentration, calcium chloride concentration and hardening-time, and the efficacy of microencapsulation to preserve the survival of microencapsulated bacteria compared to free cells during exposure in fruit juices were determined. The results revealed that the viable count of free-cell form markedly decreased compared to microencapsulated form. The microencapsulation of 2% alginate (w/v and 0.05 M CaCl2 gave the best result to preserve the probiotic. It was found that viability of microencapsulated probiotic bacteria was significantly higher than free-cell in fruit juices during 8 weeks of storage time in the refrigerator. The potential probiotic trait related to inhibitory effect was not affected after microencapsulation process. In summary, the microencapsulation method may be an alternative way of preserving the viability of probiotic L. paracasei SD1.

46 CFR 117.130 - Stowage of survival craft.

Science.gov (United States)

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Stowage of survival craft. 117.130 Section 117.130... AND ARRANGEMENTS Survival Craft Arrangements and Equipment § 117.130 Stowage of survival craft. (a) Each survival craft must be: (1) Secured to the vessel by a painter with a float-free link permanently...

HLA class I expression predicts prognosis and therapeutic benefits from tyrosine kinase inhibitors in metastatic renal-cell carcinoma patients.

Science.gov (United States)

Wang, Jiajun; Liu, Li; Qu, Yang; Xi, Wei; Xia, Yu; Bai, Qi; Xiong, Ying; Long, Qilai; Xu, Jiejie; Guo, Jianming

2018-01-01

Classical HLA class I antigen is highly involved in antigen presentation and adaptive immune response against tumor. In this study, we explored its predictive value for treatment response and survival in metastatic renal-cell carcinoma (mRCC) patients. A TKI cohort of 111 mRCC patients treated with sunitinib or sorafenib and a non-TKI cohort of 160 mRCC patients treated with interleukin-2 or interferon-α-based immunotherapy at a single institution were retrospectively enrolled. HLA class I expression and cytotoxic T lymphocyte (CTL) density was assessed by immunohistochemistry on tissue microarrays. Association between HLA class I and CTL was also assessed in the TCGA KIRC cohort. In the TKI cohort, down-regulated HLA class I was associated with lower objective response rate of TKI therapy (P = 0.004), shorter overall survival (OS) (P = 0.001), and shorter progression free survival (PFS) (P class I was not significantly associated with survival. HLA class I expression was associated with CTL infiltration and function, and its prognostic value was more predominant in CTL high-density tumors (P class I expression can serve as a potential predictive biomarker for TKI therapy in mRCC patients. Its predictive value was restricted in CTL high-density tumors. However, further external validations and functional investigations are still required.

First-line intra-arterial versus intravenous chemotherapy in unilateral sporadic group D retinoblastoma: evidence of better visual outcomes, ocular survival and shorter time to success with intra-arterial delivery from retrospective review of 20 years of treatment.

Science.gov (United States)

Munier, Francis L; Mosimann, Pascal; Puccinelli, Francesco; Gaillard, Marie-Claire; Stathopoulos, Christina; Houghton, Susan; Bergin, Ciara; Beck-Popovic, Maja

2017-08-01

The introduction of intra-arterial chemotherapy (IAC) as salvage treatment has improved the prognosis for eye conservation in group D retinoblastoma. The aim of this study was to compare the outcomes of consecutive patients with advanced unilateral disease treated with either first-line intravenous chemotherapy (IVC) or first-line IAC. This is a retrospective mono-centric comparative review of consecutive patients. Sporadic unilateral retinoblastoma group D cases treated conservatively at Jules-Gonin Eye Hospital and CHUV between 1997 and 2014. From January 1997 to August 2008, IVC, combined with focal treatments, was the primary treatment approach. From September 2008 to October 2014, IAC replaced IVC as first-line therapy. 48 patients met the inclusion criteria, receiving only either IAC or IVC as primary treatment modality. Outcomes of 23 patients treated by IVC were compared with those of 25 treated by IAC; mean follow-up was 105.3 months (range 29.2-218.6) and 41.7 months (range 19.6-89.5), respectively. Treatment duration was significantly shorter in the IAC group (pchemotherapy treatment. Despite this, the results reported here imply that eyes treated with first-line IAC will have shorter treatment period, better ocular survival and visual acuity than first-line IVC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Validation of Progression‐Free Survival as a Surrogate Endpoint for Overall Survival in Malignant Mesothelioma: Analysis of Cancer and Leukemia Group B and North Central Cancer Treatment Group (Alliance) Trials

Science.gov (United States)

Wang, Xiaoyi; Hodgson, Lydia; George, Stephen L.; Sargent, Daniel J.; Foster, Nate R.; Ganti, Apar Kishor; Stinchcombe, Thomas E.; Crawford, Jeffrey; Kratzke, Robert; Adjei, Alex A.; Kindler, Hedy L.; Vokes, Everett E.; Pang, Herbert

2017-01-01

Abstract Purpose. The aim of this study was to investigate whether progression‐free survival (PFS) can be considered a surrogate endpoint for overall survival (OS) in malignant mesothelioma. Materials and Methods. Individual data were collected from 15 Cancer and Leukemia Group B (615 patients) and 2 North Central Cancer Treatment Group (101 patients) phase II trials. The effects of 5 risk factors for OS and PFS, including age, histology, performance status (PS), white blood cell count, and European Organisation for Research and Treatment of Cancer (EORTC) risk score, were used in the analysis. Individual‐level surrogacy was assessed by Kendall's tau through a Clayton bivariate Copula survival (CBCS) model. Summary‐level surrogacy was evaluated via the association between logarithms of the hazard ratio (log HR)—log HROS and log HRPFS—measured in R2 from a weighted least‐square (WLS) regression model and the CBCS model. Results. The median PFS for all patients was 3.0 months (95% confidence interval [CI], 2.8–3.5 months) and the median OS was 7.2 months (95% CI, 6.5–8.0 months). Moderate correlations between PFS and OS were observed across all risk factors at the individual level, with Kendall's tau ranging from 0.46 to 0.47. The summary‐level surrogacy varied among risk factors. The Copula R2 ranged from 0.51 for PS to 0.78 for histology. The WLS R2 ranged from 0.26 for EORTC and PS to 0.67 for age. Conclusions. The analyses demonstrated low to moderate individual‐level surrogacy between PFS and OS. At the summary level, the surrogacy between PFS and OS varied significantly across different risk factors. With a short postprogression survival and a moderate correlation between PFS and OS, there is no evidence that PFS is a valid surrogate endpoint for OS in malignant mesothelioma. Implications for Practice. For better disease management and for more efficient clinical trial designs, it is important to know if progression‐free survival (PFS) is

Progression-free survival results in postmenopausal Asian women: subgroup analysis from a phase III randomized trial of fulvestrant 500 mg vs anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON).

Science.gov (United States)

Noguchi, Shinzaburo; Ellis, Matthew J; Robertson, John F R; Thirlwell, Jackie; Fazal, Mehdi; Shao, Zhimin

2018-05-01

The international, phase III FALCON study (NCT01602380) in postmenopausal patients with hormone receptor-positive, locally advanced/metastatic breast cancer (LA/MBC) who had not received prior endocrine therapy, demonstrated statistically significant improvement in progression-free survival (PFS) for patients who received fulvestrant 500 mg vs anastrozole 1 mg. This subgroup analysis evaluated PFS in Asian (randomized in China, Japan, or Taiwan) and non-Asian patients from the FALCON study. Eligible patients (estrogen receptor- and/or progesterone receptor-positive LA/MBC; World Health Organization performance status 0-2; ≥ 1 measurable/non-measurable lesion[s]) were randomized. PFS was assessed via Response Evaluation Criteria in Solid Tumours version 1.1, surgery/radiotherapy for disease worsening, or death (any cause). Secondary endpoints included: objective response rate, clinical benefit rate, duration of response, and duration of clinical benefit. Consistency of effect across subgroups was assessed via hazard ratios and 95% confidence intervals (CIs) using a log-rank test. Adverse events (AEs) were evaluated. Of the 462 randomized patients, the Asian and non-Asian subgroups comprised 67 and 395 patients, respectively. In the Asian subgroup, median PFS was 16.6 and 15.9 months with fulvestrant and anastrozole, respectively (hazard ratio 0.81; 95% CI 0.44-1.50). In the non-Asian subgroup, median PFS was 16.5 and 13.8 months, respectively (hazard ratio 0.79; 95% CI 0.62-1.01). Secondary outcomes were numerically improved with fulvestrant vs anastrozole in both subgroups. AE profiles were generally consistent between Asian and non-Asian subgroups. Results of this subgroup analysis suggest that treatment effects in the Asian patient subgroup are broadly consistent with the non-Asian population.

High-dose therapy followed by bone marrow transplantation for relapsed follicular non-Hodgkin's lymphoma

NARCIS (Netherlands)

Schouten, IC; Raemaekers, JJM; Kluin-Nelemans, HC; vanKamp, H; Mellink, WAM; vantVeer, MB

1996-01-01

Purpose: To analyze whether, in addition to survival, and disease-free survival progression-free interval after transplantation would be longer than the last progression-free interval before transplantation, supporting the argument that high-dose therapy may change the biologic behavior of the

PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: updated survival data.

Science.gov (United States)

Aguiar, Pedro N; De Mello, Ramon Andrade; Hall, Peter; Tadokoro, Hakaru; Lima Lopes, Gilberto de

2017-05-01

The treatment of non-small-cell lung cancer has changed after the development of the immune checkpoint inhibitors. Although the most studied biomarker is PD-L1 expression, its clinical significance is still debatable. In this article, we show the updated survival analysis of all published data. We searched in network and conference data sources for relevant clinical studies of immunotherapy for non-small-cell lung cancer that assessed the PD-L1 expression even as an exploratory analysis. The updated survival hazard ratios (HR) were included in the analysis. 14 studies with 2857 patients were included (2019 treated with immunotherapy). The response rate was as higher among PD-L1-positive patients (RR: 2.19, 95% CI: 1.63-2.94). PD-L1 expression was also related to better progression-free survival (HR: 0.69, 95% CI: 0.57-0.85) and better overall survival (HR: 0.77, 95% CI: 0.67-0.89). PD-L1 overexpression predicts activity as well as better survival for patients treated with immune checkpoint inhibitors.

Concurrent Chemoradiotherapy Improves Survival in Patients With Hypopharyngeal Cancer

Energy Technology Data Exchange (ETDEWEB)

Paximadis, Peter, E-mail: ppaximad@med.wayne.edu [Department of Radiation Oncology, Wayne State University, Detroit, MI (United States); Yoo, George; Lin, Ho-Sheng; Jacobs, John [Department of Otolaryngology, Barbara Ann Karmanos Cancer Institute, Detroit, MI (United States); Sukari, Ammar [Department of Medical Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI (United States); Dyson, Greg [Department of Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI (United States); Christensen, Michael; Kim, Harold [Department of Radiation Oncology, Wayne State University, Detroit, MI (United States)

2012-03-15

Purpose: To retrospectively review our institutional experience with hypopharyngeal carcinoma with respect to treatment modality. Methods and Materials: A total of 70 patients with hypopharyngeal cancer treated between 1999 and 2009 were analyzed for functional and survival outcomes. The treatments included surgery alone (n = 5), surgery followed by radiotherapy (RT) (n = 3), surgery followed by chemoradiotherapy (CRT) (n = 13), RT alone (n = 2), CRT alone (n = 22), induction chemotherapy followed by RT (n = 3), and induction chemotherapy followed by CRT (n = 22). Results: The median follow-up was 18 months. The median overall survival and disease-free survival for all patients was 28.3 and 17.6 months, respectively. The 1- and 2-year local control rate for all patients was 87.1% and 80%. CRT, given either as primary therapy or in the adjuvant setting, improved overall survival and disease-free survival compared with patients not receiving CRT. The median overall survival and disease-free survival for patients treated with CRT was 36.7 and 17.6 months vs. 14.0 and 8.0 months, respectively (p < .01). Of the patients initially treated with an organ-preserving approach, 4 (8.2%) required salvage laryngectomy for local recurrence or persistent disease; 8 (16.3%) and 12 (24.5%) patients were dependent on a percutaneous gastrostomy and tracheostomy tube, respectively. The 2-year laryngoesophageal dysfunction-free survival rate for patients treated with an organ-preserving approach was estimated at 31.7%. Conclusions: Concurrent CRT improves survival in patients with hypopharyngeal cancer. CRT given with conventional radiation techniques yields poor functional outcomes, and future efforts should be directed at determining the feasibility of pharyngeal-sparing intensity-modulated radiotherapy in patients with hypopharyngeal tumors.

Expression of the TPα and TPβ isoforms of the thromboxane prostanoid receptor (TP) in prostate cancer: clinical significance and diagnostic potential.

Science.gov (United States)

Mulvaney, Eamon P; Shilling, Christine; Eivers, Sarah B; Perry, Antoinette S; Bjartell, Anders; Kay, Elaine W; Watson, R William; Kinsella, B Therese

2016-11-08

The prostanoid thromboxane (TX)A2 plays a central role in haemostasis and is increasingly implicated in cancer progression. TXA2 signals through two T Prostanoid receptor (TP) isoforms termed TPα and TPβ, with both encoded by the TBXA2R gene. Despite exhibiting several functional and regulatory differences, the role of the individual TP isoforms in neoplastic diseases is largely unknown.This study evaluated expression of the TPα and TPβ isoforms in tumour microarrays of the benign prostate and different pathological (Gleason) grades of prostate cancer (PCa). Expression of TPβ was significantly increased in PCa relative to benign tissue and strongly correlated with increasing Gleason grade. Furthermore, higher TPβ expression was associated with increased risk of biochemical recurrence (BCR) and significantly shorter disease-free survival time in patients post-surgery. While TPα was more variably expressed than TPβ in PCa, increased/high TPα expression within the tumour also trended toward increased BCR and shorter disease-free survival time. Comparative genomic CpG DNA methylation analysis revealed substantial differences in the extent of methylation of the promoter regions of the TBXA2R that specifically regulate expression of TPα and TPβ, respectively, both in benign prostate and in clinically-derived tissue representative of precursor lesions and progressive stages of PCa. Collectively, TPα and TPβ expression is differentially regulated both in the benign and tumourigenic prostate, and coincides with clinical pathology and altered CpG methylation of the TBXA2R gene. Analysis of TPβ, or a combination of TPα/TPβ, expression levels may have significant clinical potential as a diagnostic biomarker and predictor of PCa disease recurrence.

Clinical and molecular markers of long-term survival after oligometastasis-directed stereotactic body radiotherapy (SBRT).

Science.gov (United States)

Wong, Anthony C; Watson, Sydeaka P; Pitroda, Sean P; Son, Christina H; Das, Lauren C; Stack, Melinda E; Uppal, Abhineet; Oshima, Go; Khodarev, Nikolai N; Salama, Joseph K; Weichselbaum, Ralph R; Chmura, Steven J

2016-07-15

The selection of patients for oligometastasis-directed ablative therapy remains a challenge. The authors report on clinical and molecular predictors of survival from a stereotactic body radiotherapy (SBRT) dose-escalation trial for oligometastases. Patients who had from 1 to 5 metastases, a life expectancy of >3 months, and a Karnofsky performance status of >60 received escalating SBRT doses to all known cancer sites. Time to progression, progression-free survival, and overall survival (OS) were calculated at the completion of SBRT, and clinical predictors of OS were modeled. Primary tumor microRNA expression was analyzed to identify molecular predictors of OS. Sixty-one evaluable patients were enrolled from 2004 to 2009. The median follow-up was 2.3 years for all patients (range, 0.2-9.3 years) and 6.8 years for survivors (range, 2.0-9.3 years). The median, 2-year, and 5-year estimated OS were 2.4 years, 57%, and 32%, respectively. The rate of progression after SBRT was associated with an increased risk of death (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.24-1.82). The time from initial cancer diagnosis to metastasis (HR, 0.98; 95% CI, 0.98-0.99), the time from metastasis to SBRT (HR, 0.98; 95% CI, 0.98-0.99), and breast cancer histology (HR, 0.12; 95% CI, 0.07-0.37) were significant predictors of OS. In an exploratory analysis, a candidate classifier using expression levels of 3 microRNAs (miR-23b, miR-449a, and miR-449b) predicted survival among 17 patients who had primary tumor microRNA expression data available. A subset of oligometastatic patients achieves long-term survival after metastasis-directed SBRT. Clinical features and primary tumor microRNA expression profiling, if validated in an independent dataset, may help select oligometastatic patients most likely to benefit from metastasis-directed therapy. Cancer 2016;122:2242-50. © 2016 American Cancer Society. © 2016 American Cancer Society.

Expression of the Hippo transducer TAZ in association with WNT pathway mutations impacts survival outcomes in advanced gastric cancer patients treated with first-line chemotherapy.

Science.gov (United States)

Melucci, Elisa; Casini, Beatrice; Ronchetti, Livia; Pizzuti, Laura; Sperati, Francesca; Pallocca, Matteo; De Nicola, Francesca; Goeman, Frauke; Gallo, Enzo; Amoreo, Carla Azzurra; Sergi, Domenico; Terrenato, Irene; Vici, Patrizia; Di Lauro, Luigi; Diodoro, Maria Grazia; Pescarmona, Edoardo; Barba, Maddalena; Mazzotta, Marco; Mottolese, Marcella; Fanciulli, Maurizio; Ciliberto, Gennaro; De Maria, Ruggero; Buglioni, Simonetta; Maugeri-Saccà, Marcello

2018-02-05

An extensive crosstalk co-regulates the Hippo and Wnt pathway. Preclinical studies revealed that the Hippo transducers YAP/TAZ mediate a number of oncogenic functions in gastric cancer (GC). Moreover, comprehensive characterization of GC demonstrated that the Wnt pathway is targeted by oncogenic mutations. On this ground, we hypothesized that YAP/TAZ- and Wnt-related biomarkers may predict clinical outcomes in GC patients treated with chemotherapy. In the present study, we included 86 patients with advanced GC treated with first-line chemotherapy in prospective phase II trials or in routine clinical practice. Tissue samples were immunostained to evaluate the expression of YAP/TAZ. Mutational status of key Wnt pathway genes (CTNNB1, APC and FBXW7) was assessed by targeted DNA next-generation sequencing (NGS). Survival curves were estimated and compared by the Kaplan-Meier product-limit method and the log-rank test, respectively. Variables potentially affecting progression-free survival (PFS) were verified in univariate Cox proportional hazard models. The final multivariate Cox models were obtained with variables testing significant at the univariate analysis, and by adjusting for all plausible predictors of the outcome of interest (PFS). We observed a significant association between TAZ expression and Wnt mutations (Chi-squared p = 0.008). Combined TAZ expression and Wnt mutations (TAZ pos /WNT mut ) was more frequently observed in patients with the shortest progression-free survival (negative outliers) (Fisher p = 0.021). Uni-and multivariate Cox regression analyses revealed that patients whose tumors harbored the TAZ pos /WNT mut signature had an increased risk of disease progression (univariate Cox: HR 2.27, 95% CI 1.27-4.05, p = 0.006; multivariate Cox: HR 2.73, 95% CI 1.41-5.29, p = 0.003). Finally, the TAZ pos /WNT mut signature negatively impacted overall survival. Collectively, our findings indicate that the oncogenic YAP/TAZ-Wnt crosstalk may be

Role of Intra-operative MRI (iMRI) in Improving Extent of Resection and Survival in Patients with Glioblastoma Multiforme.

Science.gov (United States)

Khan, Inamullah; Waqas, Muhammad; Shamim, Muhammad Shahzad

2017-07-01

Multiple intraoperative aids have been introduced to improve the extent of resection (EOR) in Glioblastoma Multiforme (GBM) patients, avoiding any new neurological deficits. Intraoperative MRI (iMRI) has been debated for its utility and cost for nearly two decades in neurosurgical literature. Review of literature suggests improved EOR in GBM patients who underwent iMRI assisted surgical resections leading to higher overall survival (OS) and progression free survival (PFS). iMRI provides real time intraoperative imaging with reasonable quality. Higher risk for new postoperative deficits with increased EOR is not reported in any study using iMRI. The level of evidence regarding prognostic benefits of iMRI is still of low quality..

Survival of patients with Ewing's sarcoma in Yazd-Iran.

Science.gov (United States)

Akhavan, Ali; Binesh, Fariba; Shamshiri, Hadi; Ghanadi, Fazllolah

2014-01-01

The Ewing's sarcoma family is a group of small round cell tumors which accounts for 10-15% of all primary bone neoplasms. The aim of this study was to evaluate the survival of Ewing's sarcoma patients in our province and to determine of influencing factors. All patients with documented Ewing's sarcoma/ primitive neuroectodermal tumor(PNET) family pathology were enrolled in this study during a period of eight years. For all of them local and systemic therapy were carried out. Overall and event free survival and prognostic factors were evaluated. Thirty two patients were enrolled in the study. The median age was 17.5 years. Twenty (65.2%) were male and 9 (28.1%) were aged 14 years or less. Mean disease free survival was 26.8 (95%CI; 13.8-39.9) months and five year disease free survival was 26%. Mean overall survival was 38.7 months (95%CI; 25.9-50.6) and median overall survival was 24 months. Five year overall survival was 25%. From the variables evaluated , only presence of metastatic disease at presentation (p value=0. 028) and complete response (p value =0. 006) had significant relations to overall survival. Survival of Ewing's sarcoma in our province is disappointing. It seems to be mostly due to less effective treatment. Administration of adequate chemotherapy dosage, resection of tumor with negative margins and precise assessment of irradiation volume may prove helpful.

Pretreatment neutrophil to lymphocyte ratio in determining the prognosis of head and neck cancer: a meta-analysis.

Science.gov (United States)

Yu, Yalian; Wang, Hongbo; Yan, Aihui; Wang, Hailong; Li, Xinyao; Liu, Jiangtao; Li, Wei

2018-04-04

Recent studies have reported a relationship between prognosis and neutrophil-to-lymphocyte ratio (NLR) in patients with head and neck cancer (HNC). As the results are still controversial, we conducted a meta-analysis of pretreatment NLR in peripheral blood and prognosis in HNC patients. We retrieved articles from PubMed, Medline, Cochrane Library, Embase and Web of Science. A comparative analysis was conducted for the effect of pretreatment NLR in peripheral blood on overall survival (OS), progression-free survival, disease-free survival (DFS), disease-specific survival, metastasis-free survival, and recurrence-free survival of HNC patients. The analysis applied the criteria for systematic reviews described in the Cochrane Handbook and was conducted using hazard ratios (HRs) to estimate effect size, and calculated by Stata/SE version 13.0. The meta-analysis included eligible cohort studies (5475 cases). The OS data indicated increased mortality risk in HNC patients with a high NLR (HR = 1.84, 95% confidence interval (CI): 1.53-2.23; P Analysis of subgroups stratified by NLR cutoff values revealed increased mortality risk and significantly shorter DFS in patients with high NLR compared to those with low NLR (HR = 2.18, 95% CI: 1.46-3.24; P analysis results were stable, as shown by sensitivity analysis. No publication bias was detected by the Egger test (P = 0.135). HNC patients with elevated pretreatment NLR in peripheral blood have poor prognosis and are prone to local invasion and distant metastasis. NLR values are easily obtained from routinely collected blood samples and could assist clinicians to determine prognosis of HNC patients.

Stereotactic body radiotherapy for low-risk prostate cancer: five-year outcomes

Directory of Open Access Journals (Sweden)

King Christopher R

2011-01-01

Full Text Available Abstract Purpose Hypofractionated, stereotactic body radiotherapy (SBRT is an emerging treatment approach for prostate cancer. We present the outcomes for low-risk prostate cancer patients with a median follow-up of 5 years after SBRT. Method and Materials Between Dec. 2003 and Dec. 2005, a pooled cohort of 41 consecutive patients from Stanford, CA and Naples, FL received SBRT with CyberKnife for clinically localized, low-risk prostate cancer. Prescribed dose was 35-36.25 Gy in five fractions. No patient received hormone therapy. Kaplan-Meier biochemical progression-free survival (defined using the Phoenix method and RTOG toxicity outcomes were assessed. Results At a median follow-up of 5 years, the biochemical progression-free survival was 93% (95% CI = 84.7% to 100%. Acute side effects resolved within 1-3 months of treatment completion. There were no grade 4 toxicities. No late grade 3 rectal toxicity occurred, and only one late grade 3 genitourinary toxicity occurred following repeated urologic instrumentation. Conclusion Five-year results of SBRT for localized prostate cancer demonstrate the efficacy and safety of shorter courses of high dose per fraction radiation delivered with SBRT technique. Ongoing clinical trials are underway to further explore this treatment approach.

Lymphatic vessel invasion detected by the endothelial lymphatic marker D2-40 (podoplanin is predictive of regional lymph node status and an independent prognostic factor in patients with resected esophageal cancer

Directory of Open Access Journals (Sweden)

Jerzy Laudański

2011-04-01

Full Text Available The discovery of markers to lymphatic endothelial cells and the development of novel antibodies to these markers have brought increasing attention to the lymphatics and progress in the understanding of lymphangiogenesis and cancer metastasis. In this study, we investigate the presence of lymphatic vessel invasion (LVI detected by D2-40 immunohistochemical staining in resected esophageal cancer and correlated with clinicopathologic data and patient survival. Sixty nine patients, who had a primary resection of esophageal cancer, were analyzed by univariate and multivariate logistic regression, and univariate and multivariate survival analysis. The total rate of LVI was 72% (50/69. Positive LVI was significantly correlated with lymph node metastasis (p < 0.001, tumor size (p < 0.001, histological grading (p = 0.017, tumor depth (p = 0.001, and stage (p < 0.001. Multivariate logistic analysis identified LVI (p = 0.036 as a predictor of regional lymph node metastasis. On univariate survival analysis, patients with LVI had a significantly shorter disease-free survival, cancer-specific survival and overall survival. Multivariate analysis proved that LVI diagnosed by D2-40 is an independent prognostic factor of both disease-free survival (p = 0.04 and overall survival (p = 0.032 in resected esophageal cancer. These results show that LVI assessment identifies patients at high risk for regional lymph node metastasis and that LVI is an independent prognostic factor in patients with esophageal cancer. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 90–97