Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins

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Squitieri, Ferdinando; Orobello, Sara; Cannella, Milena; Martino, Tiziana [IRCCS Neuromed, Neurogenetics Unit and Centre for Rare Disease, Pozzilli (Italy); Romanelli, Pantaleo [IRCCS Neuromed, Department of Neurosurgery, Pozzilli (Italy); Giovacchini, Giampiero; Ciarmiello, Andrea [S. Andrea Hospital, Unit of Nuclear Medicine, La Spezia (Italy); Frati, Luigi [University ' ' Sapienza' ' , Department of Experimental Medicine, Rome (Italy); Mansi, Luigi [Second University of Naples, Department of Nuclear Medicine, Naples (Italy)

2009-07-15

Huntington disease (HD) mutation increases gain-of-toxic functions contributing to glutamate-mediated excitotoxicity. Riluzole interferes with glutamatergic neurotransmission, thereby reducing excitotoxicity, enhancing neurite formation in damaged motoneurons and increasing serum concentrations of BDNF, a brain cortex neurotrophin protecting striatal neurons from degeneration. We investigated metabolic and volumetric differences in distinct brain areas between 11 riluzole-treated and 12 placebo-treated patients by MRI and {sup 18}F-fluoro-2-deoxy-d-glucose (FDG) PET scanning, according to fully automated protocols. We also investigated the influence of riluzole on peripheral growth factor blood levels. Placebo-treated patients showed significantly greater proportional volume loss of grey matter and decrease in metabolic FDG uptake than patients treated with riluzole in all cortical areas (p<0.05). The decreased rate of metabolic FDG uptake correlated with worsening clinical scores in placebo-treated patients, compared to those who were treated with riluzole. The progressive decrease in metabolic FDG uptake observed in the frontal, parietal and occipital cortex correlated linearly with the severity of motor scores calculated by Unified Huntington Disease Rating Scale (UHDRS-I) in placebo-treated patients. Similarly, the rate of metabolic changes in the frontal and temporal areas of the brain cortex correlated linearly with worsening behavioural scores calculated by UHDRS-III in the placebo-treated patients. Finally, BDNF and transforming growth factor beta-1 serum levels were significantly higher in patients treated with riluzole. The linear correlation between decreased metabolic FDG uptake and worsening clinical scores in the placebo-treated patients suggests that FDG-PET may be a valuable procedure to assess brain markers of HD. (orig.)

Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins

International Nuclear Information System (INIS)

Squitieri, Ferdinando; Orobello, Sara; Cannella, Milena; Martino, Tiziana; Romanelli, Pantaleo; Giovacchini, Giampiero; Ciarmiello, Andrea; Frati, Luigi; Mansi, Luigi

2009-01-01

Huntington disease (HD) mutation increases gain-of-toxic functions contributing to glutamate-mediated excitotoxicity. Riluzole interferes with glutamatergic neurotransmission, thereby reducing excitotoxicity, enhancing neurite formation in damaged motoneurons and increasing serum concentrations of BDNF, a brain cortex neurotrophin protecting striatal neurons from degeneration. We investigated metabolic and volumetric differences in distinct brain areas between 11 riluzole-treated and 12 placebo-treated patients by MRI and 18 F-fluoro-2-deoxy-d-glucose (FDG) PET scanning, according to fully automated protocols. We also investigated the influence of riluzole on peripheral growth factor blood levels. Placebo-treated patients showed significantly greater proportional volume loss of grey matter and decrease in metabolic FDG uptake than patients treated with riluzole in all cortical areas (p<0.05). The decreased rate of metabolic FDG uptake correlated with worsening clinical scores in placebo-treated patients, compared to those who were treated with riluzole. The progressive decrease in metabolic FDG uptake observed in the frontal, parietal and occipital cortex correlated linearly with the severity of motor scores calculated by Unified Huntington Disease Rating Scale (UHDRS-I) in placebo-treated patients. Similarly, the rate of metabolic changes in the frontal and temporal areas of the brain cortex correlated linearly with worsening behavioural scores calculated by UHDRS-III in the placebo-treated patients. Finally, BDNF and transforming growth factor beta-1 serum levels were significantly higher in patients treated with riluzole. The linear correlation between decreased metabolic FDG uptake and worsening clinical scores in the placebo-treated patients suggests that FDG-PET may be a valuable procedure to assess brain markers of HD. (orig.)

A clinical tool for predicting survival in ALS.

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Knibb, Jonathan A; Keren, Noa; Kulka, Anna; Leigh, P Nigel; Martin, Sarah; Shaw, Christopher E; Tsuda, Miho; Al-Chalabi, Ammar

2016-12-01

Amyotrophic lateral sclerosis (ALS) is a progressive and usually fatal neurodegenerative disease. Survival from diagnosis varies considerably. Several prognostic factors are known, including site of onset (bulbar or limb), age at symptom onset, delay from onset to diagnosis and the use of riluzole and non-invasive ventilation (NIV). Clinicians and patients would benefit from a practical way of using these factors to provide an individualised prognosis. 575 consecutive patients with incident ALS from a population-based registry in South-East England register for ALS (SEALS) were studied. Their survival was modelled as a two-step process: the time from diagnosis to respiratory muscle involvement, followed by the time from respiratory involvement to death. The effects of predictor variables were assessed separately for each time interval. Younger age at symptom onset, longer delay from onset to diagnosis and riluzole use were associated with slower progression to respiratory involvement, and NIV use was associated with lower mortality after respiratory involvement, each with a clinically significant effect size. Riluzole may have a greater effect in younger patients and those with longer delay to diagnosis. A patient's survival time has a roughly 50% chance of falling between half and twice the predicted median. A simple and clinically applicable graphical method of predicting an individual patient's survival from diagnosis is presented. The model should be validated in an independent cohort, and extended to include other important prognostic factors. 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/.

Safety and efficacy of rasagiline as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomised, double-blind, parallel-group, placebo-controlled, phase 2 trial.

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Ludolph, Albert C; Schuster, Joachim; Dorst, Johannes; Dupuis, Luc; Dreyhaupt, Jens; Weishaupt, Jochen H; Kassubek, Jan; Weiland, Ulrike; Petri, Susanne; Meyer, Thomas; Grosskreutz, Julian; Schrank, Berthold; Boentert, Matthias; Emmer, Alexander; Hermann, Andreas; Zeller, Daniel; Prudlo, Johannes; Winkler, Andrea S; Grehl, Torsten; Heneka, Michael T; Wollebæk Johannesen, Siw; Göricke, Bettina

2018-06-18

Rasagiline, a monoamine oxidase B inhibitor with neuroprotective potential in Parkinson's disease, has shown a disease-modifying effect in the SOD1-Gly93Ala low-expressing mouse model of amyotrophic lateral sclerosis, both alone and in combination with riluzole. We sought to test whether or not rasagiline 1 mg/day can prolong survival in patients with amyotrophic lateral sclerosis also receiving riluzole. Patients with possible, probable, or definite amyotrophic lateral sclerosis were enrolled to our randomised, placebo-controlled, parallel-group, double-blind, phase 2 trial from 15 German network for motor neuron diseases (MND-NET) centres (university hospitals or clinics). Eligible patients were aged at least 18 years, had onset of progressive weakness within the 36 months before the study, had disease duration of more than 6 months and less than 3 years, and had a best-sitting slow vital capacity of at least 50%. After a 4-week screening period, eligible patients were randomly assigned (1:1) to receive either rasagiline (1 mg/day) or placebo in addition to riluzole (100 mg/day), after stratification for site of onset (bulbar or spinal) and study centre. Patients and all personnel assessing outcome parameters were masked to treatment allocation. Patients were followed up 2, 6, 12, and 18 months after randomisation. The primary endpoint was survival time, defined as the time to death or time to study cutoff date (ie, the last patient's last visit plus 14 days). Analyses of primary outcome and safety measures were done in all patients who received at least one dose of trial treatment (intention-to-treat population). The trial is registered with ClinicalTrials.gov, number NCT01879241. Between July 2, 2013, and Nov 11, 2014, 273 patients were screened for eligibility, and 252 patients were randomly assigned to receive rasagiline (n=127) or placebo (n=125). 126 patients taking rasagiline and 125 taking placebo were included in the intention-to-treat analysis. For the

A pilot study of hippocampal volume and N-acetylaspartate (NAA) as response biomarkers in riluzole-treated patients with GAD.

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Abdallah, Chadi G; Coplan, Jeremy D; Jackowski, Andrea; Sato, João R; Mao, Xiangling; Shungu, Dikoma C; Mathew, Sanjay J

2013-04-01

Anxiolytic benefit following chronic treatment with the glutamate modulating agent riluzole in patients with generalized anxiety disorder (GAD) was previously associated with differential changes in hippocampal NAA concentrations. Here, we investigated the association between hippocampal volume and hippocampal NAA in the context of riluzole response in GAD. Eighteen medication-free adult patients with GAD received 8-week of open-label riluzole. Ten healthy subjects served as a comparison group. Participants underwent magnetic resonance imaging and spectroscopy at baseline and at the end of Week 8. GAD patients who completed all interventions were classified as remitters (n=7) or non-remitters (n=6), based on final Hamilton Anxiety Rating Scale (HAM-A) scores ≤7. At baseline, GAD patients had a significant reduction in total hippocampal volume compared to healthy subjects (F(1,21)=6.55, p=0.02). This reduction was most pronounced in the remitters, compared to non-remitters and healthy subjects. Delta (final-baseline) hippocampal volume was positively correlated with delta NAA in GAD. This positive association was highly significant in the right hippocampus in GAD [r=0.81, p=0.002], with no significant association in healthy subjects [Fisher r-to-z p=0.017]. Across all GAD patients, delta hippocampal volume was positively associated with improvement in HAM-A (rspearman=0.62, p=0.03). These preliminary findings support hippocampal NAA and volume as neural biomarkers substantially associated with therapeutic response to a glutamatergic drug. Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.

Blockade of persistent sodium currents contributes to the riluzole-induced inhibition of spontaneous activity and oscillations in injured DRG neurons.

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Rou-Gang Xie

Full Text Available In addition to a fast activating and immediately inactivating inward sodium current, many types of excitable cells possess a noninactivating or slowly inactivating component: the persistent sodium current (I(NaP. The I(NaP is found in normal primary sensory neurons where it is mediated by tetrodotoxin-sensitive sodium channels. The dorsal root ganglion (DRG is the gateway for ectopic impulses that originate in pathological pain signals from the periphery. However, the role of I(NaP in DRG neurons remains unclear, particularly in neuropathic pain states. Using in vivo recordings from single medium- and large-diameter fibers isolated from the compressed DRG in Sprague-Dawley rats, we show that local application of riluzole, which blocks the I(NaP, also inhibits the spontaneous activity of A-type DRG neurons in a dose-dependent manner. Significantly, riluzole also abolished subthreshold membrane potential oscillations (SMPOs, although DRG neurons still responded to intracellular current injection with a single full-sized spike. In addition, the I(NaP was enhanced in medium- and large-sized neurons of the compressed DRG, while bath-applied riluzole significantly inhibited the I(NaP without affecting the transient sodium current (I(NaT. Taken together, these results demonstrate for the first time that the I(NaP blocker riluzole selectively inhibits I(NaP and thereby blocks SMPOs and the ectopic spontaneous activity of injured A-type DRG neurons. This suggests that the I(NaP of DRG neurons is a potential target for treating neuropathic pain at the peripheral level.

Blockade of persistent sodium currents contributes to the riluzole-induced inhibition of spontaneous activity and oscillations in injured DRG neurons.

Science.gov (United States)

Xie, Rou-Gang; Zheng, Da-Wei; Xing, Jun-Ling; Zhang, Xu-Jie; Song, Ying; Xie, Ya-Bin; Kuang, Fang; Dong, Hui; You, Si-Wei; Xu, Hui; Hu, San-Jue

2011-04-25

In addition to a fast activating and immediately inactivating inward sodium current, many types of excitable cells possess a noninactivating or slowly inactivating component: the persistent sodium current (I(NaP)). The I(NaP) is found in normal primary sensory neurons where it is mediated by tetrodotoxin-sensitive sodium channels. The dorsal root ganglion (DRG) is the gateway for ectopic impulses that originate in pathological pain signals from the periphery. However, the role of I(NaP) in DRG neurons remains unclear, particularly in neuropathic pain states. Using in vivo recordings from single medium- and large-diameter fibers isolated from the compressed DRG in Sprague-Dawley rats, we show that local application of riluzole, which blocks the I(NaP), also inhibits the spontaneous activity of A-type DRG neurons in a dose-dependent manner. Significantly, riluzole also abolished subthreshold membrane potential oscillations (SMPOs), although DRG neurons still responded to intracellular current injection with a single full-sized spike. In addition, the I(NaP) was enhanced in medium- and large-sized neurons of the compressed DRG, while bath-applied riluzole significantly inhibited the I(NaP) without affecting the transient sodium current (I(NaT)). Taken together, these results demonstrate for the first time that the I(NaP) blocker riluzole selectively inhibits I(NaP) and thereby blocks SMPOs and the ectopic spontaneous activity of injured A-type DRG neurons. This suggests that the I(NaP) of DRG neurons is a potential target for treating neuropathic pain at the peripheral level.

UPLC-MS/MS assay of riluzole in human plasma and cerebrospinal fluid (CSF): Application in samples from spinal cord injured patients.

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Sarkar, Mahua; Grossman, Robert G; Toups, Elizabeth G; Chow, Diana S-L

2017-11-30

In the present study, a sensitive and robust LC-MS/MS method has been developed and validated for the quantification of riluzole in human plasma and cerebrospinal fluid (CSF) in clinical samples from patients with spinal cord injury (SCI). Riluzole and its labeled internal standard (IS) were isolated from plasma and CSF by liquid-liquid extraction using ethyl acetate. Riluzole (m/z 235→166) and IS (m/z 238→169) were detected by electrospray ionization (ESI) using multiple reaction monitoring (MRM) in a positive mode. The assay was linear in the concentration range of 0.5 (LLOQ, signal/noise ratio>10)-800ng/ml in plasma, and 1.0 (LLOQ)-800ng/ml in CSF samples. The intra- and inter-day accuracy in plasma were 94.2-110.0% and 97.8-102.0%, respectively, and those in CSF were 87.6-105.1% and 91.9-98.8%, respectively. The intra- and inter-day precision were 2.2-7.2% and 4.0-9.1%, respectively, in plasma, and 1.4-14.1% and 2.6-11.5%, respectively in CSF. Matrix effect was negligible from both matrices with signal percentages of 97.6-100.6% in plasma and 99.4-106.4% in CSF. The recoveries were >75% in plasma, >84% in CSF with low protein (53.9mg/dl), and >68% in CSF with high protein (348.2mg/dl). This method was successfully applied to quantify riluzole concentrations in plasma and CSF from patients with SCI. Copyright © 2017 Elsevier B.V. All rights reserved.

A validated HPLC assay to monitor riluzole plasma or serum concentrations in patients with amyotrophic lateral sclerosis

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van Kan, H. J. M.; Spieksma, M.; Groeneveld, G. J.; Toraño, J. Sastre; van den Berg, L. H.; Guchelaar, H. J.

2004-01-01

A specific, accurate and precise high-performance liquid chromatographic assay was developed for the determination of riluzole, a drug used to treat patients with amyotrophic lateral sclerosis. Samples were treated by extraction with dichloromethane followed by reversed-phase chromatography with

The role of hERG1 ion channels in epithelial-mesenchymal transition and the capacity of riluzole to reduce cisplatin resistance in colorectal cancer cells.

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Fortunato, Angelo

2017-08-01

The transition of cells from the epithelial to the mesenchymal state (EMT) plays an important role in tumor progression. EMT allows cells to acquire mobility, stem-like behavior and resistance to apoptosis and drug treatment. These features turn EMT into a central process in tumor biology. Ion channels are attractive targets for the treatment of cancer since they play critical roles in controlling a wide range of physiological processes that are frequently deregulated in cancer. Here, we investigated the role of ether-a-go-go-related 1 (hERG1) ion channels in the EMT of colorectal cancer cells. We studied the epithelial-mesenchymal profile of different colorectal cancer-derived cell lines and the expression of hERG1 potassium channels in these cell lines using real-time PCR. Next, we knocked down hERG1 expression in HCT116 cells using lentivirus mediated RNA interference and characterized the hERG1 silenced cells in vitro and in vivo. Finally, we investigated the capacity of riluzole, an ion channel-modulating drug used in humans to treat amyotrophic lateral sclerosis, to reduce the resistance of the respective colorectal cancer cells to the chemotherapeutic drug cisplatin. We found that of the colorectal cancer-derived cell lines tested, HCT116 showed the highest mesenchymal profile and a high hERG1 expression. Subsequent hERG1 expression knockdown induced a change in cell morphology, which was accompanied by a reduction in the proliferative and tumorigenic capacities of the cells. Notably, we found that hERG1expression knockdown elicited a reversion of the EMT profile in HCT116 cells with a reacquisition of the epithelial-like profile. We also found that riluzole increased the sensitivity of HCT116 cisplatin-resistant cells to cisplatin. Our data indicate that hERG1 plays a role in the EMT of colorectal cancer cells and that its knockdown reduces the proliferative and tumorigenic capacities of these cells. In addition, we conclude that riluzole may be used in

Neuroprotective effects of riluzole in early phase Parkinson's disease on clinically relevant parameters in the marmoset MPTP model

NARCIS (Netherlands)

Verhave, P.S.; Jongsma, M.J.; Berg, R.M. van den; Vanwersch, R.A.P.; Smit, A.B.; Philippens, I.H.C.H.M.

2012-01-01

The present study evaluates neuroprotection in a marmoset MPTP (1-methyl-1,2,3,6-tetrahydropyridine) model representing early Parkinson's disease (PD). The anti-glutamatergic compound riluzole is used as a model compound for neuroprotection. The compound is one of the few protective compounds used

Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic lateral sclerosis (LiCALS) [Eudract number: 2008-006891-31].

Science.gov (United States)

Al-Chalabi, Ammar; Shaw, Pamela J; Young, Carolyn A; Morrison, Karen E; Murphy, Caroline; Thornhill, Marie; Kelly, Joanna; Steen, I Nicholas; Leigh, P Nigel

2011-09-21

Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disorder characterised by loss of motor neurons leading to severe weakness and death from respiratory failure within 3-5 years. Riluzole prolongs survival in ALS. A published report has suggested a dramatic effect of lithium carbonate on survival. 44 patients were studied, with 16 randomly selected to take LiCO3 and riluzole and 28 allocated to take riluzole alone. In the group treated with lithium, no patients had died (i.e., 100% survival) at the end of the study (15 months from entry), compared to 71% surviving in the riluzole-only group. Although the trial can be criticised on several grounds, there is a substantial rationale from other laboratory studies that lithium is worth investigating therapeutically in amyotrophic lateral sclerosis. LiCALS is a multi-centre double-blind randomised parallel group controlled trial of the efficacy, safety, and tolerability of lithium carbonate (LiCO3) at doses to achieve stable 'therapeutic' plasma levels (0.4-0.8 mmol/L), plus standard treatment, versus matched placebo plus standard treatment, in patients with amyotrophic lateral sclerosis. The study will be based in the UK, in partnership with the MND Association and DeNDRoN (the Dementias and Neurodegnerative Diseases Clinical Research Network). 220 patients will be recruited. All patients will be on the standard treatment for ALS of riluzole 100 mg daily. The primary outcome measure will be death from any cause at 18 months defined from the date of randomisation. Secondary outcome measures will be changes in three functional rating scales, the ALS Functional Rating Scale-Revised, The EuroQOL (EQ-5D), and the Hospital Anxiety and Depression Scale.Eligible patients will have El Escorial Possible, Laboratory-supported Probable, Probable or Definite amyotrophic lateral sclerosis with disease duration between 6 months and 36 months (inclusive), vital capacity ≥ 60% of predicted within 1 month prior to

Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic Lateral Sclerosis (LiCALS [Eudract number: 2008-006891-31

Directory of Open Access Journals (Sweden)

Kelly Joanna

2011-09-01

Full Text Available Abstract Background Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disorder characterised by loss of motor neurons leading to severe weakness and death from respiratory failure within 3-5 years. Riluzole prolongs survival in ALS. A published report has suggested a dramatic effect of lithium carbonate on survival. 44 patients were studied, with 16 randomly selected to take LiCO3 and riluzole and 28 allocated to take riluzole alone. In the group treated with lithium, no patients had died (i.e., 100% survival at the end of the study (15 months from entry, compared to 71% surviving in the riluzole-only group. Although the trial can be criticised on several grounds, there is a substantial rationale from other laboratory studies that lithium is worth investigating therapeutically in amyotrophic lateral sclerosis. Methods/Design LiCALS is a multi-centre double-blind randomised parallel group controlled trial of the efficacy, safety, and tolerability of lithium carbonate (LiCO3 at doses to achieve stable 'therapeutic' plasma levels (0.4-0.8 mmol/L, plus standard treatment, versus matched placebo plus standard treatment, in patients with amyotrophic lateral sclerosis. The study will be based in the UK, in partnership with the MND Association and DeNDRoN (the Dementias and Neurodegnerative Diseases Clinical Research Network. 220 patients will be recruited. All patients will be on the standard treatment for ALS of riluzole 100 mg daily. The primary outcome measure will be death from any cause at 18 months defined from the date of randomisation. Secondary outcome measures will be changes in three functional rating scales, the ALS Functional Rating Scale-Revised, The EuroQOL (EQ-5D, and the Hospital Anxiety and Depression Scale. Eligible patients will have El Escorial Possible, Laboratory-supported Probable, Probable or Definite amyotrophic lateral sclerosis with disease duration between 6 months and 36 months (inclusive, vital

Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic Lateral Sclerosis (LiCALS) [Eudract number: 2008-006891-31

OpenAIRE

Kelly Joanna; Thornhill Marie; Murphy Caroline; Morrison Karen E; Young Carolyn A; Shaw Pamela J; Al-Chalabi Ammar; Steen I Nicholas; Leigh P Nigel

2011-01-01

Abstract Background Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disorder characterised by loss of motor neurons leading to severe weakness and death from respiratory failure within 3-5 years. Riluzole prolongs survival in ALS. A published report has suggested a dramatic effect of lithium carbonate on survival. 44 patients were studied, with 16 randomly selected to take LiCO3 and riluzole and 28 allocated to take riluzole alone. In the group treated with lithium, n...

Lithium for treatment of amyotrophic lateral sclerosis: much ado about nothing.

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Gamez, J; Salvado, M; Martínez de la Ossa, A; Badia, M

2016-10-01

Lithium was proposed in 2008 as an effective candidate in the treatment of ALS after a report claimed that it was able to delay functional deterioration by 40% and that none of the 16 patients treated with a combination of lithium plus riluzole had died during a 15-month follow-up period. The excellent results of this pilot study engendered considerable optimism among patients, their families, patients' associations, and the scientific community. This report sparked numerous phase ii clinical trials. Many patients who were not included in these studies used all resources at their disposal to access the drug as treatment under a compassionate use programme. To evaluate the effectiveness of lithium in ALS using a meta-analysis of the information reported in 12 studies which were examined for methodological quality. . Searches were performed using MEDLINE, EMBASE, the Cochrane Neuromuscular Disease Group Trials Register, ClinicalTrials.gov, and EudraCT (January 1996-August 2012). To date, we have information on more 1100 patients treated with lithium. Unfortunately, the results do not confirm the positive effect described in the pilot study, which suggests that this drug is not effective at slowing disease progression. Two trials had to be suspended before the scheduled completion date due to the ineffectiveness of the drug as well as numerous adverse effects. A recently published study also ruled out any possible modest effect. There is evidence to suggest that lithium has no short-term benefits in ALS. A comparison of the group of patients treated with lithium+riluzole and the control group treated with riluzole alone showed no statistically significant differences in rates of functional decline, deterioration of respiratory function, or survival time. Furthermore, there was no evidence that it was more effective than the placebo. Copyright © 2012 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Benign meningiomas: primary treatment selection affects survival

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Condra, Kellie S.; Buatti, John M.; Mendenhall, William M.; Friedman, William A.; Marcus, Robert B.; Rhoton, Albert L.

1997-01-01

Purpose: To examine the effect of primary treatment selection on outcomes for benign intracranial meningiomas at the University of Florida. Methods and Materials: For 262 patients, the impact of age, Karnofsky performance status, pathologic features, tumor size, tumor location, and treatment modality on local control and cause-specific survival was analyzed (minimum potential follow-up, 2 years; median follow-up, 8.2 years). Extent of surgery was classified by Simpson grade. Treatment groups: surgery alone (n = 229), surgery and postoperative radiotherapy (RT) (n = 21), RT alone (n = 7), radiosurgery alone (n = 5). Survival analysis: Kaplan-Meier method with univariate and multivariate analysis. Results: At 15 years, local control was 76% after total excision (TE) and 87% after subtotal excision plus RT (SE+RT), both significantly better (p = 0.0001) than after SE alone (30%). Cause-specific survival at 15 years was reduced after treatment with SE alone (51%), compared with TE (88%) or SE+RT (86%) (p = 0.0003). Recurrence after primary treatment portended decreased survival, independent of initial treatment group or salvage treatment selection (p = 0.001). Atypical pathologic features predicted reduced 15-year local control (54 vs. 71%) and cause-specific survival rates (57 vs. 86%). Multivariate analysis for cause-specific survival revealed treatment group (SE vs. others; p = 0.0001), pathologic features (atypical vs. typical; p = 0.0056), and Karnofsky performance status (≥80 vs. <80; p = 0.0153) as significant variables. Conclusion: Benign meningiomas are well managed by TE or SE+RT. SE alone is inadequate therapy and adversely affects cause-specific survival. Atypical pathologic features predict a poorer outcome, suggesting possible benefit from more aggressive treatment. Because local recurrence portends lower survival rates, primary treatment choice is important

Poor survival of treatment-related acute nonlymphocytic leukemia

International Nuclear Information System (INIS)

Neugut, A.I.; Nieves, J.; Murray, T.; Tsai, Weiyann; Robinson, E.

1990-01-01

Population-based data on more than 1 million patients registered in the Surveillance, Epidemiology, and End-Results Program of the National Cancer Institute, 1973-1984, were analyzed to determine the survival of patients with de novo acute nonlymphocytic leukemia (ANLL) and following a first primary tumor treated (with chemotherapy and/or radiation therapy) or untreated. Cases that occurred within 12 months of the first malignant neoplasm were excluded. Survival was estimated using Cox proportional-hazards modeling, with age, sex, and specific type of ANLL as covariates. The 6,271 patients with de novo ANLL had an estimated 12-month survival of 30%, while the 107 patients with treatment-related ANLL had an estimated 12-month survival of 10%. The authors conclude that ANLL that occurs after chemotherapy or radiation therapy is biologically more aggressive and/or resistant to therapy than spontaneous ANLL. This provides a rationale for current studies on treatment-induced cellular changes and on more aggressive therapy for these patients

Prognostic Factors, Treatment, and Survival in Dermatofibrosarcoma Protuberans.

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Criscito, Maressa C; Martires, Kathryn J; Stein, Jennifer A

2016-12-01

There is limited information regarding the influence of patient demographics, tumor characteristics, and treatment type on the survival of patients with dermatofibrosarcoma protuberans (DFSP). To assess prognostic factors and to evaluate the influence of treatment modality on overall survival of patients with DFSP. We examined DFSP using data for 3686 patients with histologically confirmed cases of DFSP diagnosed between 1972 and 2012 from the 18 US regional registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program, with linkage to demographic data from the US Census Bureau for median household income (MHI). The analysis was performed in February 2016. The primary outcome measures were tumor characteristics, prognostic factors, and overall survival in months. There were 3686 cases of DFSP examined. Older age (hazard ratio [HR], 1.08; 95% CI, 1.06-1.10; P < .001), male sex (HR, 1.97; 95% CI, 1.09-3.55; P = .03), and tumor size (HR, 1.09; 95% CI, 1.01-1.18; P = .04) were significantly associated with poorer overall survival in a controlled analysis. Older age (odds ratio [OR], 1.01; 95% CI, 1.00-1.02; P = .01), male sex (OR, 1.95; 95% CI, 1.57-2.42; P < .001), and black race (OR, 1.78; 95% CI, 1.37-2.32; P < .001) were associated with larger (≥3.0 cm) tumors at presentation. Treatment modality did not influence overall survival; however, differences in patient characteristics affected the treatment received. Older age at presentation (OR, 1.02; 95% CI, 1.01-1.03; P =.01), black race (OR, 1.82; 95% CI, 1.13-2.92; P = .01), large tumor size (OR, 1.15; 95% CI, 1.09-1.21; P < .001), and head or neck location (OR, 4.63; 95% CI, 2.66-8.07; P <.001) increased the likelihood of a patient receiving surgery and radiation over surgery alone. In addition, white patients (OR, 0.51; 95% CI, 0.30-0.87; P=.01), women (OR, 0.53; 95% CI, 0.36-0.78; P <.001), and patients with a higher MHI (OR, 1.27; 95

Audit in radiation therapy: long-term survival and cost of treatment

International Nuclear Information System (INIS)

Stevens, G.; Firth, I.

1997-01-01

In order to determine the cost of radiation treatment and the survival rate of a cohort of patients treated in a 6 month period in 1988, estimates of the capital and recurrent costs of this service were made for the calendar year 1988, expressed as $A(1988). Data collected prospectively included workload statistics (including number of attendances), field treated and complexity of treatment. Patient and tumour-related data included tumour site, intent of treatment and survival. The survival rate of patients during this period was determined in June 1995. The cost per field in 1988 was estimated at $A44.32. The 1988 costs of courses of definitive, adjuvant and palliative radiation therapy were estimated at $A2545, $A2482 and $A929, respectively. The major contributor to the cost of salaries and consumables within the Radiation Oncology Department (81.6%), with capital costs accounting for 13.5%, overheads accounting for 4.5% of the costs and planned admissions accounting for 0.2%. The median survival time of 580 patients with malignant disease treated during this period in 1988 was 12.4 months. The overall 5 year survival rate was 27%. For 105 patients treated definitively with radiation therapy, the median and 5 year survival rate figures were 26.0 months and 40%. For 149 patients treated with adjuvant radiation therapy, the 5 year survival rate was 62% (median survival rate not reached). For 279 patients treated palliatively, median and 5 year survival rate figures were 5.2 months and 3%. The cost per month of survival for all patients with malignancy was $A67; the figures for definitive , adjuvant and palliative treatments being $A74, $A48 and $A105, respectively. A sensitivity analysis indicated that these figures were robust. The cost of radiation treatment per field was comparable to reports for other centres and emphasizes the utility of radiation therapy as a cost-effective cancer treatment modality. 7 refs., 6 tabs., 2 figs

Treatment Extends Survival for Women with Cervical Cancer

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Patients with locally advanced cervical cancer who received gemcitabine (Gemzar®) both as part of initial treatment and as part of therapy following primary treatment had improved survival compared with patients whose treatment did not include gemcitabine, according to findings presented at the 2009 ASCO meeting in Orlando.

Improved survival in HIV treatment programs in Asia

Science.gov (United States)

De La Mata, Nicole L; Kumarasamy, Nagalingeswaran; Khol, Vohith; Ng, Oon Tek; Van Nguyen, Kinh; Merati, Tuti Parwati; Pham, Thuy Thanh; Lee, Man Po; Durier, Nicolas; Law, Matthew

2016-01-01

Background Antiretroviral treatment (ART) for HIV-positive patients has expanded rapidly in Asia over the last ten years. Our study aimed to describe the time trends and risk factors for overall survival in patients receiving first-line ART in Asia. Methods We included HIV-positive adult patients who initiated ART between 2003–2013 (n=16 546), from seven sites across six Asia-Pacific countries. Patient follow-up was to May 2014. We compared survival for each country and overall by time period of ART initiation using Kaplan-Meier curves. Factors associated with mortality were assessed using Cox regression, stratified by site. We also summarized first-line ART regimens, CD4 count at ART initiation, and CD4 and HIV viral load testing frequencies. Results There were 880 deaths observed over 54 532 person-years of follow-up, a crude rate of 1.61 (1.51, 1.72) per 100 person-years. Survival significantly improved in more recent years of ART initiation. The survival probabilities at 4 years follow-up for those initiating ART in 2003–05 was 92.1%, 2006–09 was 94.3% and 2010–2013 was 94.5% (pAsia have improved survival in more recent years of ART initiation. This is likely a consequence of improvements in treatment and, patient management and monitoring over time. PMID:26961354

Time to treatment as a quality metric in lung cancer: Staging studies, time to treatment, and patient survival

International Nuclear Information System (INIS)

Gomez, Daniel R.; Liao, Kai-Ping; Swisher, Stephen G.; Blumenschein, George R.; Erasmus, Jeremy J.; Buchholz, Thomas A.; Giordano, Sharon H.; Smith, Benjamin D.

2015-01-01

Purpose: Prompt staging and treatment are crucial for non-small cell lung cancer (NSCLC). We determined if predictors of treatment delay after diagnosis were associated with prognosis. Materials and methods: Medicare claims from 28,732 patients diagnosed with NSCLC in 2004–2007 were used to establish the diagnosis-to-treatment interval (ideally ⩽35 days) and identify staging studies during that interval. Factors associated with delay were identified with multivariate logistic regression, and associations between delay and survival by stage were tested with Cox proportional hazard regression. Results: Median diagnosis-to-treatment interval was 27 days. Receipt of PET was associated with delays (57.4% of patients with PET delayed [n = 6646/11,583] versus 22.8% of those without [n = 3908/17,149]; adjusted OR = 4.48, 95% CI 4.23–4.74, p < 0.001). Median diagnosis-to-PET interval was 15 days; PET-to-clinic, 5 days; and clinic-to-treatment, 12 days. Diagnosis-to-treatment intervals <35 days were associated with improved survival for patients with localized disease and those with distant disease surviving ⩾1 year but not for patients with distant disease surviving <1 year. Conclusion: Delays between diagnosing and treating NSCLC are common and associated with use of PET for staging. Reducing time to treatment may improve survival for patients with manageable disease at diagnosis

Impact of different treatment methods on survival in advanced pancreatic cancer

International Nuclear Information System (INIS)

Brasiuniene, B.; Juozaityte, E.; Barauskas, G.

2005-01-01

The aim of the study was to evaluate the impact of different treatment methods on survival of patients treated for advanced pancreatic cancer at Kaunas University of Medicine Hospital from 1987 to 2003. Data on 262 patients with advanced pancreatic cancer treated from 1987 to 2003 were analyzed retrospectively. Four groups of patients were analyzed. One hundred eighty patients underwent palliative bypass or endoscopic bile duct stenting or observation alone. Forty three patients in addition to surgery were treated by radiotherapy. Twenty five patients received gemcitabine in standard doses and schedules. Fourteen patients received concomitant chemoradiotherapy (with gemcitabine or 5-fluorouracil). All patients were grouped by treatment method and median survival was analyzed. Median survival of patients treated by palliative surgery only or observation alone was 1.9 month, and for patients treated by palliative surgery and radiotherapy was 6.1 months (p=0.00007). Median survival of patients treated with gemcitabine was 9.5 months (p<0.001), and median survival of patients treated with concomitant chemoradiotherapy was 8.5 months (p=0.00003). Patients diagnosed with advanced pancreatic cancer in addition to surgical treatment should be treated by chemotherapy, concomitant chemoradiotherapy or radiotherapy. (author)

Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.

Science.gov (United States)

Miller, R G; Jackson, C E; Kasarskis, E J; England, J D; Forshew, D; Johnston, W; Kalra, S; Katz, J S; Mitsumoto, H; Rosenfeld, J; Shoesmith, C; Strong, M J; Woolley, S C

2009-10-13

To systematically review evidence bearing on the management of patients with amyotrophic lateral sclerosis (ALS). The authors analyzed studies from 1998 to 2007 to update the 1999 practice parameter. Topics covered in this section include slowing disease progression, nutrition, and respiratory management for patients with ALS. The authors identified 8 Class I studies, 5 Class II studies, and 43 Class III studies in ALS. Important treatments are available for patients with ALS that are underutilized. Noninvasive ventilation (NIV), percutaneous endoscopic gastrostomy (PEG), and riluzole are particularly important and have the best evidence. More studies are needed to examine the best tests of respiratory function in ALS, as well as the optimal time for starting PEG, the impact of PEG on quality of life and survival, and the effect of vitamins and supplements on ALS. Riluzole should be offered to slow disease progression (Level A). PEG should be considered to stabilize weight and to prolong survival in patients with ALS (Level B). NIV should be considered to treat respiratory insufficiency in order to lengthen survival (Level B) and to slow the decline of forced vital capacity (Level B). NIV may be considered to improve quality of life (Level C) [corrected].Early initiation of NIV may increase compliance (Level C), and insufflation/exsufflation may be considered to help clear secretions (Level C).

Rare vulvar malignancies; incidence, treatment and survival in the Netherlands

NARCIS (Netherlands)

Pleunis, N.; Schuurman, M.S.; Rossum, M.M. van; Bulten, J.; Massuger, L.F.A.G.; Hullu, J.A. de; Aa, M.A. van der

2016-01-01

OBJECTIVE: To describe trends in incidence, treatment and survival of patients with basal cell carcinomas and melanomas of the vulva. Also to compare survival of vulvar and cutaneous melanoma patients. METHODS: All women with a vulvar malignancy between 1989 and 2012 were selected from the Dutch

Mecasin treatment in patients with amyotrophic lateral sclerosis: study protocol for a randomized controlled trial.

Science.gov (United States)

Kim, Sungha; Kim, Jae Kyoun; Son, Mi Ju; Kim, Dongwoung; Song, Bongkeun; Son, Ilhong; Kang, Hyung Won; Lee, Jongdeok; Kim, Sungchul

2018-04-13

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes paralysis of limb, swallowing, and breathing muscles. Riluzole, the Food and Drug Administration-approved drug for ALS, provides minimal benefit, prolonging patient life by only 2-3 months. Previous studies have found a neuro-protective and anti-neuroinflammatory effect of Mecasin, with retrospective studies providing suggestive evidence for a beneficial effect of Mecasin. The aim of this study was to develop a protocol to determine the proper dosage of Mecasin. This is a phase II-A, multi-center, randomized study with three arms. Thirty-six patients with ALS will be randomly assigned to one of three groups, each receiving the standard treatment with 100 mg of riluzole in addition to one of 1.6 g of Mecasin, 2.4 g of Mecasin, or a placebo. The Primary outcome is the Korean version of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised result after 12 weeks of treatment. Secondary outcomes include results of the Short Form Health Survey-8, Medical Research Council Scale, Visual Analogue Scale for Pain, Hamilton Rating Scale for Depression, Fatigue Severity Scale, Patient Global Impression of Change, pulmonary function test, forced expiratory volume in 1 s and its ratio to forced vital capacity, creatine kinase, and body weight. The frequencies of total adverse events and serious adverse events will be described and documented. The trial protocol has been approved by the Institutional Review Board of the Wonkwang University Gwangju and Sanbon Hospital (2016-5-4 and 2016-34-01, respectively). An Investigational New Drug status (30731) was granted by the Korea Food and Drug Administration. This trial will aim to identify the optimal dosage of Mecasin. Additionally, it will test the efficacy and safety of Mecasin in conjunction with standard treatment, riluzole, for alleviating the functional decline in patients with ALS. Korean National Clinical Trial Registry CRIS; KCT

Incidence, treatment, and survival patterns for sacral chordoma in the United States, 1974-2011

Directory of Open Access Journals (Sweden)

Esther Yu

2016-09-01

Full Text Available IntroductionSacral chordomas represent one half of all chordomas, a rare neoplasm of notochordal remnants. Current NCCN guidelines recommend surgical resection with or without adjuvant radiotherapy, or definitive radiation for unresectable cases. Recent advances in radiation for chordomas include conformal photon and proton beam radiation. We investigated incidence, treatment, and survival outcomes to observe any trends in response to improvements in surgical and radiation techniques over a near 40 year time period.Materials and Methods345 microscopically confirmed cases of sacral chordoma were identified between 1974 and 2011 from the Surveillance, Epidemiology, and End Results (SEER program of the National Cancer Institute. Cases were divided into three cohorts by calendar year, 1974-1989, 1990-1999, and 2000-2011, as well as into two groups by age less than or equal to 65 versus greater than 65 to investigate trends over time and age via Chi-square analysis. Kaplan-Meier analyses were performed to determine effects of treatment on survival. Multivariate Cox regression analysis was performed to determine predictors of overall survival.Results5-year overall survival for the entire cohort was 60.0%. Overall survival correlated significantly with treatment modality, with 44% surviving at 5 years with no treatment, 52% with radiation alone, 82% surgery alone, and 78% surgery and radiation (p<.001. Age greater than 65 was significantly associated with non-surgical management with radiation alone or no treatment (p<.001. Relatively fewer patients received radiation between 2000 and 2011 compared to prior time periods (p=.03 versus surgery, for which rates which did not vary significantly over time (p=.55. However, 5-year overall survival was not significantly different by time period. Age group and treatment modality were predictive for overall survival on multivariate analysis (p<.001. ConclusionSurgery remains an important component in the

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.

Improved survival with an innovative approach to the treatment of severely burned patients: development of a burn treatment manual.

Science.gov (United States)

Morisada, S; Nosaka, N; Tsukahara, K; Ugawa, T; Sato, K; Ujike, Y

2015-09-30

The management of severely burned patients remains a major issue worldwide as indicated by the high incidence of permanent debilitating complications and poor survival rates. In April 2012, the Advanced Emergency & Critical Care Medical Center of the Okayama University Hospital began implementing guidelines for severely burned patients, distributed as a standard burn treatment manual. The protocol, developed in-house, was validated by comparing the outcomes of patients with severe extensive burns (SEB) treated before and after implementation of these new guidelines at this institution. The patients included in this study had a burn index (BI) ≥30 or a prognostic burn index (PBI = BI + patient's age) ≥100. The survival rate of the patients with BI ≥30 was 65.2% with the traditional treatment and 100% with the new guidelines. Likewise, the survival rate of the patients with PBI ≥100 was 61.1% with the traditional treatment compared to 100% with the new guidelines. Together, these data demonstrate that the new treatment guidelines dramatically improved the treatment outcome and survival of SEB patients.

Impact of delay to treatment upon survival in 1067 patients with breast-cancer.

Science.gov (United States)

Rabinovich, M; Vallejo, C; Perez, J; Rodriguez, R; Cuevas, M; Machiavelli, M; Lacava, J; Leone, B; Romero, A; Mickiewicz, E; Chacon, R; Estevez, R

1993-02-01

The medical records of 1067 patients with breast cancer were reviewed to evaluate the influence of delay between first symptom and first treatment upon survival. Three delay intervals were considered: 6 months. At a follow-up of 120 months, survival analyses identified a statistically significant difference (p=0.029) favoring patients with 3 months delay between first symptom and first treatment. Better survival rate for patients with a short delay would obey to a greater number of patients in favorable stages and a higher proportion of women aged 50 or older in this group.

Treatment for occult hepatocellular carcinoma: does it offer survival advantages over symptom-driven treatment?

Science.gov (United States)

Kim, Kwang Min; Kim, Jiyu; Sinn, Dong Hyun; Kim, Hye Seung; Kim, Kyunga; Kang, Wonseok; Gwak, Geum-Youn; Paik, Yong-Han; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon

2018-04-03

In order to claim a benefit of screen-based diagnosis for asymptomatic individuals, treatment of occult disease needs to offer survival advantages compared to the treatment of symptomatic disease, yet information on this issue is scarce with regard to hepatocellular carcinoma (HCC) screening. A total of 3353 treatment-naïve, consecutive, newly diagnosed HCC patients [age: 57.9 ± 10.3, male: 2,689 (80.2%), hepatitis B virus: 2555 (76.2%)], diagnosed between 2010 and 2013 were analyzed. Data on the mode of detection was prospectively collected at the time of HCC diagnosis and was used to group patients into occult or symptomatic cases. Overall, 643 (19.2%) patients were symptomatic cases. The proportion of patients undergoing resection, radiofrequency ablation or transplantation were lower in symptomatic cases than occult cases (20.8 vs. 56.2%, p offered a survival benefit to patients over symptomatic cases. These data support screening practices for asymptomatic individuals to diagnose occult HCC.

Perioperative blood transfusion does not decrease survival after surgical treatment of spinal metastases

DEFF Research Database (Denmark)

Clausen, Caroline; Lönn, Lars; Morgen, Søren Schmidt

2014-01-01

PURPOSE: To assess whether perioperative allogenic blood transfusions in patients undergoing surgical treatment for spinal metastases independently influence patient survival. METHODS: A retrospective study including 170 consecutive patients undergoing surgical treatment for spinal metastases in ...... 12-month survival. Future studies should assess if a liberal transfusion regime can be applied to this group of patients; thereby, prioritizing early postoperative mobilization....

Estimating the average treatment effect on survival based on observational data and using partly conditional modeling.

Science.gov (United States)

Gong, Qi; Schaubel, Douglas E

2017-03-01

Treatments are frequently evaluated in terms of their effect on patient survival. In settings where randomization of treatment is not feasible, observational data are employed, necessitating correction for covariate imbalances. Treatments are usually compared using a hazard ratio. Most existing methods which quantify the treatment effect through the survival function are applicable to treatments assigned at time 0. In the data structure of our interest, subjects typically begin follow-up untreated; time-until-treatment, and the pretreatment death hazard are both heavily influenced by longitudinal covariates; and subjects may experience periods of treatment ineligibility. We propose semiparametric methods for estimating the average difference in restricted mean survival time attributable to a time-dependent treatment, the average effect of treatment among the treated, under current treatment assignment patterns. The pre- and posttreatment models are partly conditional, in that they use the covariate history up to the time of treatment. The pre-treatment model is estimated through recently developed landmark analysis methods. For each treated patient, fitted pre- and posttreatment survival curves are projected out, then averaged in a manner which accounts for the censoring of treatment times. Asymptotic properties are derived and evaluated through simulation. The proposed methods are applied to liver transplant data in order to estimate the effect of liver transplantation on survival among transplant recipients under current practice patterns. © 2016, The International Biometric Society.

Survival and behavior of silver catfish, Rhamdia quelen, submitted to antibiotics and sodium chloride treatments

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Andrade Luciana Segura de

2006-01-01

Full Text Available In order to evaluate the use of antibiotics and NaCl on the behavior and survival of silver catfish, Rhamdia quelen, infested by Ichthyophthirius multifiliis and infected with Aeromonas hydrophila, juveniles were treated with chloramphenicol, chloramphenicol + salt, oxytetracycline, oxytetracycline + salt and water alone (control. Fish survival in the treatments with chloramphenicol + salt and oxytetracycline + salt was significantly higher than in the other treatments. The treatment with chloramphenicol presented higher survival than the treatment with oxytetracycline and both showed significantly higher survival than control. Swimming activity was higher in the fish treated with antibiotics and salt compared to control fish. A combination of the studied antibiotics plus salt is more effective to treat both A. hydrophila infection and I. multifiliis infestation in silver catfish, but since the use of chloramphenicol is not allowed in Brazil, oxytetracycline plus salt seems to be the best treatment option.

Survival and psychomotor development with early betaine treatment in patients with severe methylenetetrahydrofolate reductase deficiency.

Science.gov (United States)

Diekman, Eugene F; de Koning, Tom J; Verhoeven-Duif, Nanda M; Rovers, Maroeska M; van Hasselt, Peter M

2014-02-01

The impact of betaine treatment on outcome in patients with severe methylenetetrahydrofolate reductase (MTHFR) deficiency is presently unclear. To investigate the effect of betaine treatment on development and survival in patients with severe MTHFR deficiency. MEDLINE, EMBASE, and Cochrane databases between January 1960 and December 2012. Studies that described patients with severe MTHFR deficiency who received betaine treatment. We identified 15 case reports and case series, totaling 36 patients. Data included the following: (1) families with 2 or more patients with severe MTHFR deficiency, of whom at least 1 received betaine, or (2) single patients with severe MTHFR deficiency treated with betaine. To define severe MTHFR deficiency, methionine, homocysteine, MTHFR enzyme activity in fibroblasts, or mutations (in the MTHFR gene) had to be described as well as the effect of treatment (survival and/or psychomotor development). We compared the outcome in treated vs untreated patients and early- vs late-treated patients. Sensitivity analysis was performed to address definition of early treatment. To further assess the impact of treatment on mortality, we performed a subanalysis in families with at least 1 untreated deceased patient. Survival and psychomotor development. Eleven of 36 patients (31%) died. All deaths occurred in patients who did not receive treatment or in patients in whom treatment was delayed. In contrast, all 5 early-treated patients survived. Subgroup analysis of patients with deceased siblings-their genotypically identical controls-revealed that betaine treatment prevented mortality (P = .002). In addition, psychomotor development in surviving patients treated with betaine was normal in all 5 early-treated patients but in none of the 19 surviving patients with delayed treatment (P psychomotor development in patients with severe MTHFR deficiency, highlighting the importance of timely recognition through newborn screening.

Survival analysis of patients with uveal melanoma after organ preserving and liquidation treatment

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E. E. Grishina

2018-01-01

Full Text Available Rationale: Uveal melanoma is the most common primary malignancy of the eye.Aim: To evaluate survival in patients with uveal melanoma stratified according to the type of treatment and to identify factors significantly associated with their survival.Materials and methods: The study was performed on the data extracted from medical files and follow-up forms of patients with uveal melanoma seen in the Ophthalmological Clinical Hospital of the Department of Healthcare, Moscow, from 1977 to 2012. Analysis of survival was used to assess the life longevity of patients with uveal melanoma. The analysis was censored at January 2013, when vital status (dead or alive of all patients was assessed. The factors included into the study analysis, were those taken from the follow-up forms. The incidence of uveal melanoma in Moscow (2012 was 0.9 per 100,000 of the population, whereas its prevalence was 11.1 per 100,000.Results: 698 patients with uveal melanoma were included into the study, among them 260 (37% men (aged from 19 to 87 years, median age 60 years and 438 (63% women (aged from 18 to 93 years, median age 63 years; therefore, the proportion of women under the follow-up monitoring was by 26% higher than that of men. The liquidation treatment (mostly enucleation was performed in 358 (51% of the patients, whereas the organ preserving treatment in 340 (49%. At 5, 7, and 10 years of the follow-up, the disease-specific survival of patients with uveal melanoma after the organ preserving treatment (median survival has not been reached and after the liquidation treatment (median, 88 months were 89 ± 2, 83 ± 3, and 75 ± 4% versus 63 ± 3, 52 ± 4, and 47 ± 5%, respectively (р = 0.001. Overall survival and disease-specific survival of the patients after the liquidation treatment were significantly lower than in the patients after the organ-preserving treatment. According to multiple regression analysis, this was associated not with the type of

Targeting Glutamatergic Signaling and the PI3 Kinase Pathway to Halt Melanoma Progression

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Stephen A. Rosenberg

2015-02-01

Full Text Available Our group has previously reported that the majority of human melanomas (>60% express the metabotropic glutamate receptor 1 (GRM1 and that the glutamate release inhibitor riluzole, a drug currently used to treat amyotrophic lateral sclerosis, can induce apoptosis in GRM1-expressing melanoma cells. Our group previously reported that in vitro riluzole treatment reduces cell growth in three-dimensional (3D soft agar colony assays by 80% in cells with wildtype phosphoinositide 3-kinase (PI3K pathway activation. However, melanoma cell lines harboring constitutive activating mutations of the PI3K pathway (PTEN and NRAS mutations showed only a 35% to 40% decrease in colony formation in soft agar in the presence of riluzole. In this study, we have continued our preclinical studies of riluzole and its effect on melanoma cells alone and in combination with inhibitors of the PI3 kinase pathway: the AKT inhibitor, API-2, and the mammalian target of rapamycin (mTOR inhibitor, rapamycin. We modeled these combinatorial therapies on various melanoma cell lines in 3D and 2D systems and in vivo. Riluzole combined with mTOR inhibition is more effective at halting melanoma anchorage-independent growth and xenograft tumor progression than either agent alone. PI3K signaling changes associated with this combinatorial treatment shows that 3D (nanoculture modeling of cell signaling more closely resembles in vivo signaling than monolayer models. Riluzole combined with mTOR inhibition is effective at halting tumor cell progression independent of BRAF mutational status. This makes this combinatorial therapy a potentially viable alternative for metastatic melanoma patients who are BRAF WT and are therefore ineligible for vemurafenib therapy.

Effect of different heat treatments and disinfectants on the survival of Prototheca zopfii.

Science.gov (United States)

Lassa, Henryka; Jagielski, Tomasz; Malinowski, Edward

2011-03-01

Bovine mastitis caused by the yeast-like alga Prototheca zopfii represents a serious veterinary problem and may result in heavy economic losses to particular dairy farms. The purpose of this study was to evaluate the survival of 50 isolates of P. zopfii in milk subjected to different heat treatments and the survival of further 106 P. zopfii isolates after exposure to three classes of teat disinfectants: iodine (Dipal), quaternary ammonium compounds (Teat), and dodecylbenzenesulphonic acid (Blu-gard). Of the 50 isolates tested for thermal tolerance, 29 (58%) survived heat treatment at 62 °C for 30 s and 13 (26% of all isolates) of those survived after heat treatment at 72 °C for 15 s. None of the 106 isolates were able to withstand the in-use concentrations of the three disinfectants tested. The highest disinfectant concentrations that permitted survival of at least one isolate were dilutions: 1:1,000 for Dipal (survival rate of 52.8-57.5%), 1:100 for Teat (88.7-90.6%), and 1:10 for Blu-gard (100%). No differences in the survival rates of P. zopfii were observed with respect to the duration of exposure to disinfectant. The results of this study support the previous findings that P. zopfii may resist high-temperature treatments, including that applied in the high-temperature, short-time (HTST) pasteurization process. The obtained data also demonstrate the efficacy of the three classes of teat disinfectants against P. zopfii, with the efficacy of iodine being most pronounced. The study emphasizes the necessity of using higher temperatures in the pasteurization of raw milk to kill the Prototheca algae, as well as the particular suitability of the iodine for the control procedures of protothecal mastitis.

Survival of Bactericidal Antibiotic Treatment by a Persister Subpopulation of Listeria monocytogenes

DEFF Research Database (Denmark)

Knudsen, Gitte Maegaard; Ng, Yin; Gram, Lone

2013-01-01

Listeria monocytogenes can cause the serious infection listeriosis, which despite antibiotic treatment has a high mortality. Understanding the response of L. monocytogenes to antibiotic exposure is therefore important to ensure treatment success. Some bacteria survive antibiotic treatment...... by formation of persisters, which are a dormant antibiotic-tolerant subpopulation. The purpose of this study was to determine whether L. monocytogenes can form persisters and how bacterial physiology affects the number of persisters in the population. A stationary-phase culture of L. monocytogenes was adjusted...... that eradication of persisters is possible. Our study adds L. monocytogenes to the list of bacterial species capable of surviving bactericidal antibiotics in a dormant stage, and this persister phenomenon should be borne in mind when developing treatment regimens....

Causal inference for long-term survival in randomised trials with treatment switching: Should re-censoring be applied when estimating counterfactual survival times?

OpenAIRE

Latimer, N.R.; White, I.R.; Abrams, K.R.; Sieburt, U.

2017-01-01

Treatment switching often has a crucial impact on estimates of effectiveness and cost-effectiveness of new oncology treatments. Rank preserving structural failure time models (RPSFTM) and two-stage estimation (TSE) methods estimate ‘counterfactual’ (i.e. had there been no switching) survival times and incorporate re-censoring to guard against informative censoring in the counterfactual dataset. However, re-censoring causes a loss of longer term survival information which is problematic when e...

Treatment strategies and survival of older breast cancer patients - an international comparison between the Netherlands and Ireland.

Science.gov (United States)

Kiderlen, Mandy; Walsh, Paul M; Bastiaannet, Esther; Kelly, Maria B; Audisio, Riccardo A; Boelens, Petra G; Brown, Chris; Dekkers, Olaf M; de Craen, Anton J M; van de Velde, Cornelis J H; Liefers, Gerrit-Jan

2015-01-01

Forty percent of breast cancers occur among older patients. Unfortunately, there is a lack of evidence for treatment guidelines for older breast cancer patients. The aim of this study is to compare treatment strategy and relative survival for operable breast cancer in the elderly between The Netherlands and Ireland. From the Dutch and Irish national cancer registries, women aged ≥65 years with non-metastatic breast cancer were included (2001-2009). Proportions of patients receiving guideline-adherent locoregional treatment, endocrine therapy, and chemotherapy were calculated and compared between the countries by stage. Secondly, 5-year relative survival was calculated by stage and compared between countries. Overall, 41,055 patients from The Netherlands and 5,826 patients from Ireland were included. Overall, more patients received guideline-adherent locoregional treatment in The Netherlands, overall (80% vs. 68%, adjusted pNetherlands. In The Netherlands, only 6% received chemotherapy, as compared 24% in Ireland. But relative survival was poorer in Ireland (5 years relative survival 89% vs. 83%), especially in stage II (87% vs. 85%) and stage III (61% vs. 58%) patients. Treatment for older breast cancer patients differed significantly on all treatment modalities between The Netherlands and Ireland. More locoregional treatment was provided in The Netherlands, and more systemic therapy was provided in Ireland. Relative survival for Irish patients was worse than for their Dutch counterparts. This finding should be a strong recommendation to study breast cancer treatment and survival internationally, with the ultimate goal to equalize the survival rates for breast cancer patients across Europe.

Socioeconomic disparities in breast cancer survival: relation to stage at diagnosis, treatment and race

Directory of Open Access Journals (Sweden)

Yu Xue

2009-10-01

Full Text Available Abstract Background Previous studies have documented lower breast cancer survival among women with lower socioeconomic status (SES in the United States. In this study, I examined the extent to which socioeconomic disparity in breast cancer survival was explained by stage at diagnosis, treatment, race and rural/urban residence using the Surveillance, Epidemiology, and End Results (SEER data. Methods Women diagnosed with breast cancer during 1998-2002 in the 13 SEER cancer registry areas were followed-up to the end of 2005. The association between an area-based measure of SES and cause-specific five-year survival was estimated using Cox regression models. Six models were used to assess the extent to which SES differences in survival were explained by clinical and demographical factors. The base model estimated the hazard ratio (HR by SES only and then additional adjustments were made sequentially for: 1 age and year of diagnosis; 2 stage at diagnosis; 3 first course treatment; 4 race; and 5 rural/urban residence. Results An inverse association was found between SES and risk of dying from breast cancer (p Conclusion Stage at diagnosis, first course treatment and race explained most of the socioeconomic disparity in breast cancer survival. Targeted interventions to increase breast cancer screening and treatment coverage in patients with lower SES could reduce much of socioeconomic disparity.

Combined treatment with atorvastatin and imipenem improves survival and vascular functions in mouse model of sepsis.

Science.gov (United States)

Choudhury, Soumen; Kannan, Kandasamy; Pule Addison, M; Darzi, Sazad A; Singh, Vishakha; Singh, Thakur Uttam; Thangamalai, Ramasamy; Dash, Jeevan Ranjan; Parida, Subhashree; Debroy, Biplab; Paul, Avishek; Mishra, Santosh Kumar

2015-08-01

We have recently reported that pre-treatment, but not the post-treatment with atorvastatin showed survival benefit and improved hemodynamic functions in cecal ligation and puncture (CLP) model of sepsis in mice. Here we examined whether combined treatment with atorvastatin and imipenem after onset of sepsis can prolong survival and improve vascular functions. At 6 and 18h after sepsis induction, treatment with atorvastatin plus imipenem, atorvastatin or imipenem alone or placebo was initiated. Ex vivo experiments were done on mouse aorta to examine the vascular reactivity to nor-adrenaline and acetylcholine and mRNA expressions of α1D AR, GRK2 and eNOS. Atorvastatin plus imipenem extended the survival time to 56.00±4.62h from 20.00±1.66h observed in CLP mice. The survival time with atorvastatin or imipenem alone was 20.50±1.89h and 27.00±4.09h, respectively. The combined treatment reversed the hyporeactivity to nor-adrenaline through preservation of α1D AR mRNA/protein expression and reversal of α1D AR desensitization mediated by GRK2/Gβγ pathway. The treatment also restored endothelium-dependent relaxation to ACh through restoration of aortic eNOS mRNA expression and NO availability. In conclusion, combined treatment with atorvastatin and imipenem exhibited survival benefit and improved vascular functions in septic mice. Copyright © 2015 Elsevier Inc. All rights reserved.

Impact of diabetes on treatment outcomes and long-term survival in multidrug-resistant tuberculosis.

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Kang, Young Ae; Kim, Song Yee; Jo, Kyung-Wook; Kim, Hee Jin; Park, Seung-Kyu; Kim, Tae-Hyung; Kim, Eun Kyung; Lee, Ki Man; Lee, Sung Soon; Park, Jae Seuk; Koh, Won-Jung; Kim, Dae Yun; Shim, Tae Sun

2013-01-01

Few studies have investigated the impact of diabetes mellitus (DM), a globally increasing metabolic disease, on treatment outcomes and long-term survival in patients with multidrug-resistant forms of tuberculosis (MDR-TB). We analyzed outcomes in a large cohort to assess the impact of DM on treatment outcomes of patients with MDR-TB. MDR-TB patients newly diagnosed or retreated between 2000 and 2002 and followed for 8-11 years were retrospectively analyzed with respect to the effect of DM as a comorbidity on their treatment outcome and long-term survival. Of 1,407 patients with MDR-TB, 239 (17.0%) had coexisting DM. The mean age and body mass index were higher in MDR-TB patients with DM [MDR-TBDM(+)] than in those without DM [MDR-TBDM(-)]. Patients with MDR-TB and a comorbidity of DM had a significantly lower treatment success rate than those without a history of DM (36.0 vs. 47.2%, p = 0.002). In addition, DM was the negative predictor for MDR-TB treatment success in multivariate analyses [odds ratio 0.51, 95% confidence interval (CI) 0.26-0.99]. Mean survival times were also lower in MDR-TBDM(+) than in MDR-TBDM(-) patients (102 vs. 114 months, p = 0.001), with DM as a significant predictor of poor long-term survival in multivariate analyses (hazard ratio 1.59, 95% CI 1.01-2.50). Among MDR-TB patients, DM was a relatively common comorbidity. In patients undergoing treatment for MDR-TB and followed for 8-11 years, it was found to be independently associated with an increased risk of both treatment failure and death. Copyright © 2013 S. Karger AG, Basel.

Glioblastoma multiforme (GBM) in the elderly: initial treatment strategy and overall survival.

Science.gov (United States)

Glaser, Scott M; Dohopolski, Michael J; Balasubramani, Goundappa K; Flickinger, John C; Beriwal, Sushil

2017-08-01

The EORTC trial which solidified the role of external beam radiotherapy (EBRT) plus temozolomide (TMZ) in the management of GBM excluded patients over age 70. Randomized studies of elderly patients showed that hypofractionated EBRT (HFRT) alone or TMZ alone was at least equivalent to conventionally fractionated EBRT (CFRT) alone. We sought to investigate the practice patterns and survival in elderly patients with GBM. We identified patients age 65-90 in the National Cancer Data Base (NCDB) with histologically confirmed GBM from 1998 to 2012 and known chemotherapy and radiotherapy status. We analyzed factors predicting treatment with EBRT alone vs. EBRT plus concurrent single-agent chemotherapy (CRT) using multivariable logistic regression. Similarly, within the EBRT alone cohort we compared CFRT (54-65 Gy at 1.7-2.1 Gy/fraction) to HFRT (34-60 Gy at 2.5-5 Gy/fraction). Multivariable Cox proportional hazards model (MVA) with propensity score adjustment was used to compare survival. A total of 38,862 patients were included. Initial treatments for 1998 versus 2012 were: EBRT alone = 50 versus 10%; CRT = 6 versus 50%; chemo alone = 1.6% (70% single-agent) versus 3.2% (94% single-agent). Among EBRT alone patients, use of HFRT (compared to CFRT) increased from 13 to 41%. Numerous factors predictive for utilization of CRT over EBRT alone and for HFRT over CFRT were identified. Median survival and 1-year overall survival were higher in the CRT versus EBRT alone group at 8.6 months vs. 5.1 months and 36.0 versus 15.7% (p GBM patients in the United States, CRT is the most common initial treatment and appears to offer a survival advantage over EBRT alone. Adoption of hypofractionation has increased over time but continues to be low.

Corticosteroid Treatment Influences TA-Proteinuria and Renal Survival in IgA Nephropathy.

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Cristina Sarcina

Full Text Available The clinical course of IgA nephropathy (IgAN and its outcome are extremely variable. Proteinuria at baseline has been considered one of the most important risk factors. More recently, mean proteinuria of follow-up (time-average proteinuria: TAp was described as a stronger marker of renal survival, suggesting to consider it as a marker of disease activity and response to treatment. We evaluated predictors of renal survival in IgAN patients with different degrees of renal dysfunction and histological lesions, focusing on the role of the therapy in influencing TAp. We performed a retrospective analysis of three prospective, randomized, clinical trials enrolling 325 IgAN patients from 1989 to 2005. Patients were divided into 5 categories according to TAp. The primary endpoint of the 100% increase of serum creatinine occurred in 54 patients (16.6% and renal survival was much better in groups having lower TAp. The median follow up was 66.6 months (range 12 to 144. The primary endpoint of the 100% increase of serum creatinine occurred in 54 patients (16,6% and renal survival was much better in groups having lower TA proteinuria. At univariate analysis plasma creatinine and 24h proteinuria, systolic (SBP and diastolic (DBP blood pressure during follow-up and treatment with either steroid (CS or steroid plus azathioprine (CS+A were the main factors associated with lower TAp and renal survival. At multivariate analysis, female gender, treatment with S or S+A, lower baseline proteinuria and SBP during follow-up remained as the only variables independently influencing TAp. In conclusion, TA-proteinuria is confirmed as one of the best outcome indicators, also in patients with a severe renal insufficiency. A 6-month course of corticosteroids seems the most effective therapy to reduce TAp.

FDG PET/CT patterns of treatment failure of malignant pleural mesothelioma: relationship to histologic type, treatment algorithm, and survival

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Gerbaudo, Victor H.; Mamede, Marcelo [Brigham and Women' s Hospital, Harvard Medical School, Division of Nuclear Medicine and Molecular Imaging, Boston, MA (United States); Trotman-Dickenson, Beatrice; Hatabu, Hiroto [Brigham and Women' s Hospital, Harvard Medical School, Division of Thoracic Radiology, Boston, MA (United States); Sugarbaker, David J. [Brigham and Women' s Hospital, Harvard Medical School, Division of Thoracic Surgery, Boston, MA (United States)

2011-05-15

This study investigated the diagnostic performance and prognostic value of fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in suspected malignant pleural mesothelioma (MPM) recurrence, in the context of patterns and intensity of FDG uptake, histologic type, and treatment algorithm. Fifty patients with MPM underwent FDG PET/CT for restaging 11 {+-} 6 months after therapy. Tumor relapse was confirmed by histopathology, and by clinical evolution and subsequent imaging. Progression-free survival was defined as the time between treatment and the earliest clinical evidence of recurrence. Survival after FDG PET/CT was defined as the time between the scan and death or last follow-up. Overall survival was defined as the time between initial treatment and death or last follow-up date. Treatment failure was confirmed in 42 patients (30 epithelial and 12 non-epithelial MPM). Sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for FDG PET/CT were 97.6, 75, 94, 86, and 95.3%, respectively. FDG PET/CT evidence of single site of recurrence was observed in the ipsilateral hemithorax in 18 patients (44%), contralaterally in 2 (5%), and in the abdomen in 1 patient (2%). Bilateral thoracic relapse was detected in three patients (7%). Simultaneous recurrence in the ipsilateral hemithorax and abdomen was observed in ten (24%) patients and in seven (17%) in all three cavities. Unsuspected distant metastases were detected in 11 patients (26%). Four patterns of uptake were observed in recurrent disease: focal, linear, mixed (focal/linear), and encasing, with a significant difference between the intensity of uptake in malignant lesions compared to benign post-therapeutic changes. Lesion uptake was lower in patients previously treated with more aggressive therapy and higher in intrathoracic lesions of patients with distant metastases. FDG PET/CT helped in the selection of 12 patients (29%) who benefited from additional previously

FDG PET/CT patterns of treatment failure of malignant pleural mesothelioma: relationship to histologic type, treatment algorithm, and survival

International Nuclear Information System (INIS)

Gerbaudo, Victor H.; Mamede, Marcelo; Trotman-Dickenson, Beatrice; Hatabu, Hiroto; Sugarbaker, David J.

2011-01-01

This study investigated the diagnostic performance and prognostic value of fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in suspected malignant pleural mesothelioma (MPM) recurrence, in the context of patterns and intensity of FDG uptake, histologic type, and treatment algorithm. Fifty patients with MPM underwent FDG PET/CT for restaging 11 ± 6 months after therapy. Tumor relapse was confirmed by histopathology, and by clinical evolution and subsequent imaging. Progression-free survival was defined as the time between treatment and the earliest clinical evidence of recurrence. Survival after FDG PET/CT was defined as the time between the scan and death or last follow-up. Overall survival was defined as the time between initial treatment and death or last follow-up date. Treatment failure was confirmed in 42 patients (30 epithelial and 12 non-epithelial MPM). Sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for FDG PET/CT were 97.6, 75, 94, 86, and 95.3%, respectively. FDG PET/CT evidence of single site of recurrence was observed in the ipsilateral hemithorax in 18 patients (44%), contralaterally in 2 (5%), and in the abdomen in 1 patient (2%). Bilateral thoracic relapse was detected in three patients (7%). Simultaneous recurrence in the ipsilateral hemithorax and abdomen was observed in ten (24%) patients and in seven (17%) in all three cavities. Unsuspected distant metastases were detected in 11 patients (26%). Four patterns of uptake were observed in recurrent disease: focal, linear, mixed (focal/linear), and encasing, with a significant difference between the intensity of uptake in malignant lesions compared to benign post-therapeutic changes. Lesion uptake was lower in patients previously treated with more aggressive therapy and higher in intrathoracic lesions of patients with distant metastases. FDG PET/CT helped in the selection of 12 patients (29%) who benefited from additional previously

Survival after treatment with phenylacetate and benzoate for urea-cycle disorders.

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Enns, Gregory M; Berry, Susan A; Berry, Gerard T; Rhead, William J; Brusilow, Saul W; Hamosh, Ada

2007-05-31

The combination of intravenous sodium phenylacetate and sodium benzoate has been shown to lower plasma ammonium levels and improve survival in small cohorts of patients with historically lethal urea-cycle enzyme defects. We report the results of a 25-year, open-label, uncontrolled study of sodium phenylacetate and sodium benzoate therapy (Ammonul, Ucyclyd Pharma) in 299 patients with urea-cycle disorders in whom there were 1181 episodes of acute hyperammonemia. Overall survival was 84% (250 of 299 patients). Ninety-six percent of the patients survived episodes of hyperammonemia (1132 of 1181 episodes). Patients over 30 days of age were more likely than neonates to survive an episode (98% vs. 73%, Purea-cycle disorder and treatment with both sodium phenylacetate and sodium benzoate, in conjunction with other therapies, such as intravenous arginine hydrochloride and the provision of adequate calories to prevent catabolism, effectively lower plasma ammonium levels and result in survival in the majority of patients. Hemodialysis may also be needed to control hyperammonemia, especially in neonates and older patients who do not have a response to intravenous sodium phenylacetate and sodium benzoate. Copyright 2007 Massachusetts Medical Society.

Cell-based neurotrophin treatment supports long-term auditory neuron survival in the deaf guinea pig.

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Gillespie, Lisa N; Zanin, Mark P; Shepherd, Robert K

2015-01-28

The cochlear implant provides auditory cues to profoundly deaf patients by electrically stimulating the primary auditory neurons (ANs) of the cochlea. However, ANs degenerate in deafness; the preservation of a robust AN target population, in combination with advances in cochlear implant technology, may provide improved hearing outcomes for cochlear implant patients. The exogenous delivery of neurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 is well known to support AN survival in deafness, and cell-based therapies provide a potential clinically viable option for delivering neurotrophins into the deaf cochlea. This study utilized cells that were genetically modified to express BDNF and encapsulated in alginate microspheres, and investigated AN survival in the deaf guinea pig following (a) cell-based neurotrophin treatment in conjunction with chronic electrical stimulation from a cochlear implant, and (b) long-term cell-based neurotrophin delivery. In comparison to deafened controls, there was significantly greater AN survival following the cell-based neurotrophin treatment, and there were ongoing survival effects for at least six months. In addition, functional benefits were observed following cell-based neurotrophin treatment and chronic electrical stimulation, with a statistically significant decrease in electrically evoked auditory brainstem response thresholds observed during the experimental period. This study demonstrates that cell-based therapies, in conjunction with a cochlear implant, shows potential as a clinically transferable means of providing neurotrophin treatment to support AN survival in deafness. This technology also has the potential to deliver other therapeutic agents, and to be used in conjunction with other biomedical devices for the treatment of a variety of neurodegenerative conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

Incidence, treatment and survival of patients with craniopharyngioma in the surveillance, epidemiology and end results program

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Zacharia, Brad E.; Bruce, Samuel S.; Goldstein, Hannah; Malone, Hani R.; Neugut, Alfred I.; Bruce, Jeffrey N.

2012-01-01

Craniopharyngioma is a rare primary central nervous system neoplasm. Our objective was to determine factors associated with incidence, treatment, and survival of craniopharyngiomas in the United States. We used the surveillance, epidemiology and end results program (SEER) database to identify patients who received a diagnosis of craniopharyngioma during 2004–2008. We analyzed clinical and demographic information, including age, race, sex, tumor histology, and treatment. Age-adjusted incidence rates and age, sex, and race-adjusted expected survival rates were calculated. We used Cox proportional hazards models to determine the association between covariates and overall survival. We identified 644 patients with a diagnosis of craniopharyngioma. Black race was associated with an age-adjusted relative risk for craniopharyngioma of 1.26 (95% confidence interval [CI], 0.98–1.59), compared with white race. One- and 3-year survival rates of 91.5% (95% CI, 88.9%–93.5%), and 86.2% (95% CI, 82.7%–89.0%) were observed for the cohort; relative survival rates were 92.1% (95% CI, 89.5%–94.0%) and 87.6% (95% CI, 84.1%–90.4%) for 1- and 3-years, respectively. In the multivariable model, factors associated with prolonged survival included younger age, smaller tumor size, subtotal resection, and radiation therapy. Black race, on the other hand, was associated with worse overall survival in the final model. We demonstrated that >85% of patients survived 3 years after diagnosis and that subtotal resection and radiation therapy were associated with prolonged survival. We also noted a higher incidence rate and worse 1- and 3-year survival rates in the black population. Future investigations should examine these racial disparities and focus on evaluating the efficacy of emerging treatment paradigms. PMID:22735773

Corticosterone, but not Glucose, Treatment Enables Fasted Adrenalectomized Rats to Survive Moderate Hemorrhage

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Darlington, Daniel N.; Chew, Gordon; Ha, Taryn; Keil, Lanny C.; Dallman, Mary F.

1990-01-01

Fed adrenalectomized rats survive the stress of hemorrhage and hypovolemia, whereas fasted adrenalectomized rats become hypotensive and hypoglycemic after the first 90 min and die within 4 hours (h). We have studied the effects of glucose and corticosterone (B) infusions after hemorrhage as well as treatment with B at the time of adrenalectomy on the capacity of chronically prepared, conscious, fasted, adrenalectomized rats to survive hemorrhage. We have also measured the magnitudes of vasoactive hormone responses to hemorrhage. Maintenance of plasma glucose concentrations did not sustain life; however, treatment of rats at the time of adrenalectomy with B allowed 100 percent survival, and acute treatment of adrenalectomized rats at the time of hemorrhage allowed about 50 percent survival during the 5-h posthemorrhage observation period. Rats in the acute B infusion group that died exhibited significantly increased plasma B and significantly decreased plasma glucose concentrations by 2 h compared to the rats that lived. Plasma vasopressin, renin, and norepinephrine responses to hemorrhage were markedly augmented in the adrenalectomized rats not treated with B, and plasma vasopressin concentrations were significantly elevated at 1 and 2 h in all of the rats that subsequently died compared to values in those that lived. We conclude that: 1) death after hemorrhage in fasted adrenalectomized rats is not a result of lack of glucose; 2) chronic and, to an extent, acute treatment of fasted adrenalectomized rats with B enables survival; 3) fasted adrenalectomized rats exhibit strong evidence of hepatic insufficiency which is not apparent in either fed adrenalectomized rats or B-treated fasted adrenalectomized rats; 4) death after hemorrhage in fasted adrenalectomized rats may result from hepatic failure as a consequence of marked splanchnic vasoconstriction mediated bv the actions of extraordinarily high levels of vasoactive hormones after hemorrhage; and 5) B appears to

The influence of cultural treatments of the long-term survival and growth of planted Quercus rubra

Science.gov (United States)

James J. Zaczek; Kim C. Steiner

2011-01-01

A northern red oak (Quercus rubra L.) plantation testing 20 nursery stock and planting methods was used to evaluate treatments 3, 6, 10, and 17 years after planting. Survival over all treatments was 92 percent at age 3 and declined to 74 percent, 56 percent, and 39 percent at ages 6, 10, and 17, respectively. At age 17, survival was highest for...

Geographical variations in the use of cancer treatments are associated with survival of lung cancer patients

DEFF Research Database (Denmark)

Møller, Henrik; Coupland, Victoria H; Tataru, Daniela

2018-01-01

INTRODUCTION: Lung cancer outcomes in England are inferior to comparable countries. Patient or disease characteristics, healthcare-seeking behaviour, diagnostic pathways, and oncology service provision may contribute. We aimed to quantify associations between geographic variations in treatment...... and survival of patients in England. METHODS: We retrieved detailed cancer registration data to analyse the variation in survival of 176,225 lung cancer patients, diagnosed 2010-2014. We used Kaplan-Meier analysis and Cox proportional hazards regression to investigate survival in the two-year period following...... diagnosis. RESULTS: Survival improved over the period studied. The use of active treatment varied between geographical areas, with inter-quintile ranges of 9%-17% for surgical resection, 4%-13% for radical radiotherapy, and 22%-35% for chemotherapy. At 2 years, there were 188 potentially avoidable deaths...

Aggressive Treatment of Patients with Metastatic Colorectal Cancer Increases Survival: A Scandinavian Single-Center Experience

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Kristoffer Watten Brudvik

2013-01-01

Full Text Available Background. We examined overall and disease-free survivals in a cohort of patients subjected to resection of liver metastasis from colorectal cancer (CRLM in a 10-year period when new treatment strategies were implemented. Methods. Data from 239 consecutive patients selected for liver resection of CRLM during the period from 2002 to 2011 at a single center were used to estimate overall and disease-free survival. The results were assessed against new treatment strategies and established risk factors. Results. The 5-year cumulative overall and disease-free survivals were 46 and 24%. The overall survival was the same after reresection, independently of the number of prior resections and irrespectively of the location of the recurrent disease. The time intervals between each recurrence were similar (11 ± 1 months. Patients with high tumor load given neoadjuvant chemotherapy had comparable survival to those with less extensive disease without neoadjuvant chemotherapy. Positive resection margin or resectable extrahepatic disease did not affect overall survival. Conclusion. Our data support that one still, and perhaps to an even greater extent, should seek an aggressive therapeutic strategy to achieve resectable status for recurrent hepatic and extrahepatic metastases. The data should be viewed in the context of recent advances in the understanding of cancer biology and the metastatic process.

Affluence and Private Health Insurance Influence Treatment and Survival in Non-Hodgkin's Lymphoma.

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Harry Comber

Full Text Available The aim of this study was to investigate inequalities in survival for non-Hodgkin's lymphoma (NHL, distinguishing between direct and indirect effects of patient, social and process-of-care factors.All cases of NHL diagnosed in Ireland in 2004-2008 were included. Variables describing patient, cancer, stage and process of care were included in a discrete-time model of survival using Structural Equation Modelling software.Emergency admissions were more common in patients with co-morbid conditions or with more aggressive cancers, and less frequent for patients from more affluent areas. Aggressive morphology, female sex, emergency admission, increasing age, comorbidity, treatment in a high caseload hospital and late stage were associated with increased hazard of mortality. Private patients had a reduced hazard of mortality, mediated by systemic therapy, admission to high caseload hospitals and fewer emergency admissions.The higher rate of emergency presentation, and consequent poorer survival, of uninsured patients, suggests they face barriers to early presentation. Social, educational and cultural factors may also discourage disadvantaged patients from consulting with early symptoms of NHL. Non-insured patients, who present later and have more emergency admissions would benefit from better access to diagnostic services. Older patients remain disadvantaged by sub-optimal treatment, treatment in non-specialist centres and emergency admission.

Racial differences in treatment and survival in older patients with diffuse large B-cell lymphoma (DLBCL)

International Nuclear Information System (INIS)

Griffiths, Robert; Gleeson, Michelle; Knopf, Kevin; Danese, Mark

2010-01-01

Diffuse large B-cell lymphoma (DLBCL) comprises 31% of lymphomas in the United States. Although it is an aggressive type of lymphoma, 40% to 50% of patients are cured with treatment. The study objectives were to identify patient factors associated with treatment and survival in DLBCL. Using Surveillance, Epidemiology, and End Results (SEER) registry data linked to Medicare claims, we identified 7,048 patients diagnosed with DLBCL between January 1, 2001 and December 31, 2005. Patients were followed from diagnosis until the end of their claims history (maximum December 31, 2007) or death. Medicare claims were used to characterize the first infused chemo-immunotherapy (C-I therapy) regimen and to identify radiation. Multivariate analyses were performed to identify patient demographic, socioeconomic, and clinical factors associated with treatment and with survival. Outcomes variables in the survival analysis were all-cause mortality, non-Hodgkin's lymphoma (NHL) mortality, and other/unknown cause mortality. Overall, 84% (n = 5,887) received C-I therapy or radiation treatment during the observation period: both, 26%; C-I therapy alone, 53%; and radiation alone, 5%. Median age at diagnosis was 77 years, 54% were female, 88% were white, and 43% had Stage III or IV disease at diagnosis. The median time to first treatment was 42 days, and 92% of these patients had received their first treatment by day 180 following diagnosis. In multivariate analysis, the treatment rate was significantly lower among patients ≥ 80 years old, blacks versus whites, those living in a census tract with ≥ 12% poverty, and extra-nodal disease. Blacks had a lower treatment rate overall (Hazard Ratio [HR] 0.77; P < 0.001), and were less likely to receive treatment within 180 days of diagnosis (Odds Ratio [OR] 0.63; P = 0.002) than whites. In multivariate survival analysis, black race was associated with higher all-cause mortality (HR 1.24; P = 0.01) and other/unknown cause mortality (HR 1

Survival and metamorphosis of low-density populations of larval sea lampreys (Petromyzon marinus) in streams following lampricide treatment

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Johnson, Nicholas S.; Swink, William D.; Brenden, Travis O.; Slade, Jeffrey W.; Steeves, Todd B.; Fodale, Michael F.; Jones, Michael L.

2014-01-01

Sea lamprey Petromyzon marinus control in the Great Lakes primarily involves application of lampricides to streams where larval production occurs to kill larvae prior to their metamorphosing and entering the lakes as parasites (juveniles). Because lampricides are not 100% effective, larvae that survive treatment maymetamorphose before streams are again treated. Larvae that survive treatment have not beenwidely studied, so their dynamics are notwell understood.Wetagged and released larvae in six Great Lake tributaries following lampricide treatment and estimated vital demographic rates using multistate tag-recovery models. Model-averaged larval survivals ranged from 56.8 to 57.6%. Model-averaged adult recovery rates, which were the product of juvenile survivals and adult capture probabilities, ranged from 6.8 to 9.3%. Using stochastic simulations, we estimated production of juvenile sea lampreys from a hypothetical population of treatment survivors under different growth conditions based on parameter estimates from this research. For fast-growing populations, juvenile production peaked 2 years after treatment. For slow-growing populations, juvenile production was approximately one-third that of fast-growing populations,with production not peaking until 4 years after treatment. Our results suggest that dynamics (i.e., survival, metamorphosis) of residual larval populations are very similar to those of untreated larval populations. Consequently, residual populations do not necessarily warrant special consideration for the purpose of sea lamprey control and can be ranked for treatment along with other populations. Consecutive lampricide treatments, which are under evaluation by the sea lamprey control program, would bemost effective for reducing juvenile production in large, fast-growing populations.

Brain tumors in children: long-term survival after radiation treatment

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Jenkin, Derek; Greenberg, Mark; Hoffman, Harold; Hendrick, Bruce; Humphreys, Robin; Vatter, Annette

1995-02-01

Purpose: To determine the cause of death in children who survive more than 5 years after radiation treatment of a brain tumor. Methods and Material: Nine hundred and twelve consecutive children with a primary brain tumor irradiated at the Princess Margaret Hospital or Toronto-Bayview Regional Cancer Center from 1958 to 1991, were evaluated for long-term outcome. Results: Overall 10- and 20-year survival rates were 44% and 37%. Subsequent survival of 377 5-year survivors was, at an additional 10 and 20 years, 78% and 67%. Most (83%) deaths that occurred more than 5 years from diagnosis were a result of relapse of the original tumor. The 10-year survival rate subsequent to relapse was 9% when the first relapse occurred less than one year from diagnosis, 17% for 1-2 years, and 31% when the time to relapse was 3 years or greater. The cumulative actuarial incidence of, and death from, second malignant tumors at 30 years from diagnosis was 18% and 13%, respectively. Conclusions: Death later than 5 years from diagnosis of a brain tumor in children is common and is usually due to progressive disease in slowly evolving low grade tumors. Death from a second malignant tumor becomes more frequent than death from the original tumor after 15 years from diagnosis.

Do patient characteristics, disease, or treatment explain social inequality in survival from colorectal cancer?

DEFF Research Database (Denmark)

Frederiksen, Birgitte Lidegaard; Osler, Merete; Harling, Henrik

2009-01-01

This paper investigates the association between individually measured socioeconomic status (SES) and all-cause survival in colorectal cancer patients, and explores whether factors related to the patient, the disease, or the surgical treatment mediate the observed social gradient. The data were...... on comorbidity from previous hospitalizations and use of medication. Only patients with colorectal cancer as their first primary tumour and those born after 1920 were included. A total of 8763 patients were included in the study. Cox proportional hazard regression models revealed a positive social gradient......, while no evidence of a mediating effect was found for disease or surgical treatment factors. This indicates that the difference in survival among colorectal cancer patients from different social groups was probably not caused by unintentional differences in treatment factors related to surgery...

Effect of integrated surgery + radiotherapy + chemotherapy treatment on survival status and serum indexes in patients with gallbladder carcinoma

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Zhi-Li Wei

2016-12-01

Full Text Available Objective: To study the effect of integrated surgery + radiotherapy + chemotherapy treatment on the survival status and serum indexes in patients with gallbladder carcinoma. Methods: A total of 68 patients with gallbladder carcinoma were divided into observation group (received integrated surgery + radiotherapy + chemotherapy treatment and control group (received surgery + radiotherapy according to different treatments. Differences in the content of tumor markers, growth factors and adhesion molecules in serum as well as the median survival time and survival rate in 5 years of follow-up were compared between the two groups 1 month after treatment. Results: Tumor markers β2-MG, CA19-9, CA242, CA125, CA724, CEA and AFP content in serum of observation group after treatment were significantly lower than those of control group; growth factors VEGF, FGF, EGFR and HER2 content in serum were significantly lower than those of control group while IGFBP-2 and IGFBP-3 content were significantly higher than those of control group; adhesion molecules E-selectin, ICAM-1, VCAM-1 and sE-Cd content in serum were significantly lower than those of control group; the median survival time of 5-year follow-up as well as 1-, 3- and 5-year survival rate were significantly greater than those of control group. Conclusions: Integrated treatment of surgery + radiotherapy + chemotherapy can optimize the short-term and long-term curative effect in patients with gallbladder carcinoma.

Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

International Nuclear Information System (INIS)

McMillan, Matthew T.; Ojerholm, Eric; Roses, Robert E.; Plastaras, John P.; Metz, James M.; Mamtani, Ronac; Karakousis, Giorgos C.; Fraker, Douglas L.; Drebin, Jeffrey A.; Stripp, Diana; Ben-Josef, Edgar; Datta, Jashodeep

2015-01-01

Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiation therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered

Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

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McMillan, Matthew T. [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Ojerholm, Eric [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Roses, Robert E., E-mail: Robert.Roses@uphs.upenn.edu [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Plastaras, John P.; Metz, James M. [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Mamtani, Ronac [Department of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Karakousis, Giorgos C.; Fraker, Douglas L.; Drebin, Jeffrey A. [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Stripp, Diana; Ben-Josef, Edgar [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Datta, Jashodeep [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States)

2015-10-01

Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiation therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered.

Trends in incidence, treatment and survival of aggressive B-cell lymphoma in the Netherlands 1989–2010

Science.gov (United States)

Issa, Djamila E.; van de Schans, Saskia A.M.; Chamuleau, Martine E.D.; Karim-Kos, Henrike E.; Wondergem, Marielle; Huijgens, Peter C.; Coebergh, Jan Willem W.; Zweegman, Sonja; Visser, Otto

2015-01-01

Only a small number of patients with aggressive B-cell lymphoma take part in clinical trials, and elderly patients in particular are under-represented. Therefore, we studied data of the population-based nationwide Netherlands Cancer Registry to determine trends in incidence, treatment and survival in an unselected patient population. We included all patients aged 15 years and older with newly diagnosed diffuse large B-cell lymphoma or Burkitt lymphoma in the period 1989–2010 and mantle cell lymphoma in the period 2001–2010, with follow up until February 2013. We examined incidence, first-line treatment and survival. We calculated annual percentage of change in incidence and carried out relative survival analyses. Incidence remained stable for diffuse large B-cell lymphoma (n=23,527), while for mantle cell lymphoma (n=1,634) and Burkitt lymphoma (n=724) incidence increased for men and remained stable for women. No increase in survival for patients with aggressive B-cell lymphoma was observed during the period 1989–1993 and the period 1994–1998 [5-year relative survival 42% (95%CI: 39%–45%) and 41% (38%–44%), respectively], but increased to 46% (43%–48%) in the period 1999–2004 and to 58% (56%–61%) in the period 2005–2010. The increase in survival was most prominent in patients under 65 years of age, while there was a smaller increase in patients over 75 years of age. However, when untreated patients were excluded, patients over 75 years of age had a similar increase in survival to younger patients. In the Netherlands, survival for patients with aggressive B-cell lymphoma increased over time, particularly in younger patients, but also in elderly patients when treatment had been initiated. The improvement in survival coincided with the introduction of rituximab therapy and stem cell transplantation into clinical practice. PMID:25512643

Biologically-equivalent dose and long-term survival time in radiation treatments

International Nuclear Information System (INIS)

Zaider, Marco; Hanin, Leonid

2007-01-01

Within the linear-quadratic model the biologically-effective dose (BED)-taken to represent treatments with an equal tumor control probability (TCP)-is commonly (and plausibly) calculated according to BED(D) = -log[S(D)]/α. We ask whether in the presence of cellular proliferation this claim is justified and examine, as a related question, the extent to which BED approximates an isoeffective dose (IED) defined, more sensibly, in terms of an equal long-term survival probability, rather than TCP. We derive, under the assumption that cellular birth and death rates are time homogeneous, exact equations for the isoeffective dose, IED. As well, we give a rigorous definition of effective long-term survival time, T eff . By using several sets of radiobiological parameters, we illustrate potential differences between BED and IED on the one hand and, on the other, between T eff calculated as suggested here or by an earlier recipe. In summary: (a) the equations currently in use for calculating the effective treatment time may underestimate the isoeffective dose and should be avoided. The same is the case for the tumor control probability (TCP), only more so; (b) for permanent implants BED may be a poor substitute for IED; (c) for a fractionated treatment schedule, interpreting the observed probability of cure in terms of a TCP formalism that refers to the end of the treatment (rather than T eff ) may result in a miscalculation (underestimation) of the initial number of clonogens

A Gene Expression Signature Associated With Overall Survival in Patients With Hepatocellular Carcinoma Suggests a New Treatment Strategy

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Gillet, Jean-Pierre; Andersen, Jesper B; Madigan, James P

2015-01-01

Despite improvements in the management of liver cancer, the survival rate for individuals with hepatocellular carcinoma (HCC) remains dismal. The survival benefit of systemic chemotherapy for the treatment of liver cancer is only marginal. Although the reasons for treatment failure...... are multifactorial, intrinsic resistance to chemotherapy plays a primary role. Here, we analyzed the expression of 377 multidrug resistance-associated genes in two independent cohorts of patients with advanced hepatocellular carcinoma, with the aim of finding ways to improve survival in this poor-prognosis cancer...

Disparities in breast cancer tumor characteristics, treatment, time to treatment, and survival probability among African American and white women.

Science.gov (United States)

Foy, Kevin Chu; Fisher, James L; Lustberg, Maryam B; Gray, Darrell M; DeGraffinreid, Cecilia R; Paskett, Electra D

2018-01-01

African American (AA) women have a 42% higher breast cancer death rate compared to white women despite recent advancements in management of the disease. We examined racial differences in clinical and tumor characteristics, treatment and survival in patients diagnosed with breast cancer between 2005 and 2014 at a single institution, the James Cancer Hospital, and who were included in the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute Cancer Registry in Columbus OH. Statistical analyses included likelihood ratio chi-square tests for differences in proportions, as well as univariate and multivariate Cox proportional hazards regressions to examine associations between race and overall and progression-free survival probabilities. AA women made up 10.2% (469 of 4593) the sample. Average time to onset of treatment after diagnosis was almost two times longer in AA women compared to white women (62.0 days vs 35.5 days, p  triple negative and late stage breast cancer, and were less likely to receive surgery, especially mastectomy and reconstruction following mastectomy. After adjustment for confounding factors (age, grade, and surgery), overall survival probability was significantly associated with race (HR = 1.33; 95% CI 1.03-1.72). These findings highlight the need for efforts focused on screening and receipt of prompt treatment among AA women diagnosed with breast cancer.

Identification of markers that functionally define a quiescent multiple myeloma cell sub-population surviving bortezomib treatment

International Nuclear Information System (INIS)

Adomako, Alfred; Calvo, Veronica; Biran, Noa; Osman, Keren; Chari, Ajai; Paton, James C; Paton, Adrienne W; Moore, Kateri; Schewe, Denis M; Aguirre-Ghiso, Julio A

2015-01-01

The mechanisms allowing residual multiple myeloma (MM) cells to persist after bortezomib (Bz) treatment remain unclear. We hypothesized that studying the biology of bortezomib-surviving cells may reveal markers to identify these cells and survival signals to target and kill residual MM cells. We used H2B-GFP label retention, biochemical tools and in vitro and in vivo experiments to characterize growth arrest and the unfolded protein responses in quiescent Bz-surviving cells. We also tested the effect of a demethylating agent, 5-Azacytidine, on Bz-induced quiescence and whether inhibiting the chaperone GRP78/BiP (henceforth GRP78) with a specific toxin induced apoptosis in Bz-surviving cells. Finally, we used MM patient samples to test whether GRP78 levels might associate with disease progression. Statistical analysis employed t-test and Mann-Whitney tests at a 95% confidence. We report that Bz-surviving MM cells in vitro and in vivo enter quiescence characterized by p21 CIP1 upregulation. Bz-surviving MM cells also downregulated CDK6, Ki67 and P-Rb. H2B-GFP label retention showed that Bz-surviving MM cells are either slow-cycling or deeply quiescent. The Bz-induced quiescence was stabilized by low dose (500nM) of 5-azacytidine (Aza) pre-treatment, which also potentiated the initial Bz-induced apoptosis. We also found that expression of GRP78, an unfolded protein response (UPR) survival factor, persisted in MM quiescent cells. Importantly, GRP78 downregulation using a specific SubAB bacterial toxin killed Bz-surviving MM cells. Finally, quantification of Grp78 high /CD138+ MM cells from patients suggested that high levels correlated with progressive disease. We conclude that Bz-surviving MM cells display a GRP78 HIGH /p21 HIGH /CDK6 LOW /P-Rb LOW profile, and these markers may identify quiescent MM cells capable of fueling recurrences. We further conclude that Aza + Bz treatment of MM may represent a novel strategy to delay recurrences by enhancing Bz

Ten-Year Effect of Six Site-Preparation Treatments on Piedmont Loblolly Pine Survival and Growth

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M. Boyd Edwards

1994-01-01

Limited information is available on growth responses to different levels of intensity for site preparation in the Piedmont. In the present study, six intensities of site preparation were compared for their effect on survival, height and diameter growth, total volume produced, and basal area per acre for the first 10 years after treatment. Rates of survival and growth...

Survival and Psychomotor Development With Early Betaine Treatment in Patients With Severe Methylenetetrahydrofolate Reductase Deficiency

NARCIS (Netherlands)

Diekman, Eugene F.; de Koning, Tom J.; Verhoeven-Duif, Nanda M.; Rovers, Maroeska M.; van Hasselt, Peter M.

IMPORTANCE The impact of betaine treatment on outcome in patients with severe methylenetetrahydrofolate reductase (MTHFR) deficiency is presently unclear. OBJECTIVE To investigate the effect of betaine treatment on development and survival in patients with severe MTHFR deficiency. DATA SOURCES

Survival and psychomotor development with early betaine treatment in patients with severe methylenetetrahydrofolate reductase deficiency

NARCIS (Netherlands)

Diekman, E.F.; Koning, T.J. de; Verhoeven-Duif, N.M.; Rovers, M.M.; Hasselt, P.M. van

2014-01-01

IMPORTANCE The impact of betaine treatment on outcome in patients with severe methylenetetrahydrofolate reductase (MTHFR) deficiency is presently unclear. OBJECTIVE To investigate the effect of betaine treatment on development and survival in patients with severe MTHFR deficiency. DATA SOURCES

Adult Rhabdomyosarcoma Survival Improved With Treatment on Multimodality Protocols

International Nuclear Information System (INIS)

Gerber, Naamit Kurshan; Wexler, Leonard H.; Singer, Samuel; Alektiar, Kaled M.; Keohan, Mary Louise; Shi, Weiji; Zhang, Zhigang; Wolden, Suzanne

2013-01-01

Purpose: Rhabdomyosarcoma (RMS) is a pediatric sarcoma rarely occurring in adults. For unknown reasons, adults with RMS have worse outcomes than do children. Methods and Materials: We analyzed data from all patients who presented to Memorial Sloan-Kettering Cancer Center between 1990 and 2011 with RMS diagnosed at age 16 or older. One hundred forty-eight patients met the study criteria. Ten were excluded for lack of adequate data. Results: The median age was 28 years. The histologic diagnoses were as follows: embryonal 54%, alveolar 33%, pleomorphic 12%, and not otherwise specified 2%. The tumor site was unfavorable in 67% of patients. Thirty-three patients (24%) were at low risk, 61 (44%) at intermediate risk, and 44 (32%) at high risk. Forty-six percent were treated on or according to a prospective RMS protocol. The 5-year rate of overall survival (OS) was 45% for patients with nonmetastatic disease. The failure rates at 5 years for patients with nonmetastatic disease were 34% for local failure and 42% for distant failure. Among patients with nonmetastatic disease (n=94), significant factors associated with OS were histologic diagnosis, site, risk group, age, and protocol treatment. On multivariate analysis, risk group and protocol treatment were significant after adjustment for age. The 5-year OS was 54% for protocol patients versus 36% for nonprotocol patients. Conclusions: Survival in adult patients with nonmetastatic disease was significantly improved for those treated on RMS protocols, most of which are now open to adults

Adult Rhabdomyosarcoma Survival Improved With Treatment on Multimodality Protocols

Energy Technology Data Exchange (ETDEWEB)

Gerber, Naamit Kurshan [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Wexler, Leonard H. [Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Singer, Samuel [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Alektiar, Kaled M. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Keohan, Mary Louise [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Shi, Weiji; Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Wolden, Suzanne, E-mail: woldens@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

2013-05-01

Purpose: Rhabdomyosarcoma (RMS) is a pediatric sarcoma rarely occurring in adults. For unknown reasons, adults with RMS have worse outcomes than do children. Methods and Materials: We analyzed data from all patients who presented to Memorial Sloan-Kettering Cancer Center between 1990 and 2011 with RMS diagnosed at age 16 or older. One hundred forty-eight patients met the study criteria. Ten were excluded for lack of adequate data. Results: The median age was 28 years. The histologic diagnoses were as follows: embryonal 54%, alveolar 33%, pleomorphic 12%, and not otherwise specified 2%. The tumor site was unfavorable in 67% of patients. Thirty-three patients (24%) were at low risk, 61 (44%) at intermediate risk, and 44 (32%) at high risk. Forty-six percent were treated on or according to a prospective RMS protocol. The 5-year rate of overall survival (OS) was 45% for patients with nonmetastatic disease. The failure rates at 5 years for patients with nonmetastatic disease were 34% for local failure and 42% for distant failure. Among patients with nonmetastatic disease (n=94), significant factors associated with OS were histologic diagnosis, site, risk group, age, and protocol treatment. On multivariate analysis, risk group and protocol treatment were significant after adjustment for age. The 5-year OS was 54% for protocol patients versus 36% for nonprotocol patients. Conclusions: Survival in adult patients with nonmetastatic disease was significantly improved for those treated on RMS protocols, most of which are now open to adults.

Geographical variations in the use of cancer treatments are associated with survival of lung cancer patients

DEFF Research Database (Denmark)

Møller, Henrik; Coupland, Victoria H; Tataru, Daniela

2018-01-01

INTRODUCTION: Lung cancer outcomes in England are inferior to comparable countries. Patient or disease characteristics, healthcare-seeking behaviour, diagnostic pathways, and oncology service provision may contribute. We aimed to quantify associations between geographic variations in treatment...... and survival of patients in England. METHODS: We retrieved detailed cancer registration data to analyse the variation in survival of 176,225 lung cancer patients, diagnosed 2010-2014. We used Kaplan-Meier analysis and Cox proportional hazards regression to investigate survival in the two-year period following...... to statistical adjustments for age, sex, socio-economic status, performance status and co-morbidity. CONCLUSION: The extent of use of different treatment modalities varies between geographical areas in England. These variations are not attributable to measurable patient and tumour characteristics, and more...

Bromocriptine Mesylate Attenuates Amyotrophic Lateral Sclerosis: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Research in Japanese Patients.

Directory of Open Access Journals (Sweden)

Eiichiro Nagata

Full Text Available Bromocriptine mesylate (BRC, a dopamine D2 receptor agonist has been shown to confer neuroprotection, sustained motor function and slowed disease progression in mouse models of amyotrophic lateral sclerosis (ALS Here we report a first in human trial in ALS.A multicenter, Riluzole add-on, randomized, double-blind, placebo controlled 102-week extension BRC clinical trial.The trial was conducted between January 2009 and March 2012 on 36 Japanese ALS patients. A 12-week treatment with Riluzole observational period was followed by combined treatment (Riluzole + BRC; n = 29 or Riluzole + placebo; n = 7. The dosing commenced at 1.25 mg/day increasing in steps at two weeks intervals to a maximum of 15 mg/day. The efficacy of BRC was evaluated by comparing BRC and placebo groups upon completion of stepwise dosing at 14 weeks 2 points (1st endpoint and upon completion or discontinuation of the study (2nd endpoint of the dosing.Statistics analyses revealed a marginal BRC treatment efficacy with P≦20%to placebo by 1st and 2nd endpoint analysis. In the 1st endpoint analysis, BRC group was significantly effective on the scores of ALSAQ40-communicaton (P = 1.2%, eating and drinking (P = 2.2%, ALSFRS-R total (P = 17.6%, grip strength (P = 19.8% compared to the placebo group. In the 2nd endpoint analysis, differences between the scores of Limb Norris Scale (P = 18.3%, ALSAQ40-communication (P = 11.9%, eating and drinking (P = 13.6%, and neck forward-bent test (P = 15.4% of BRC group were detected between the two groups. There was no significant difference between the treatment groups for adverse events or serious drug reactions incidence.BRC sustains motoneuronal function at least in part through BRC treatment. Further analysis involving a Phase 2b or 3 clinical trial is required but BRC currently shows promise for ALS treatment.UMIN Clinical Trials UMIN000008527.

Malariotherapy at Mont Park: the earliest surviving movie of psychiatric treatment in Australia.

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Kaplan, Robert M

2013-02-01

A movie on malariotherapy for neurosyphilis made at Mont Park and filmed by Reg Ellery in 1926 is believed to be the oldest surviving movie of psychiatric treatment in Australia. The objective is to review the movie and discuss the background and context of the film, which shows the conditions of patients in a psychiatric hospital in the 1920s. Movie film is a guide to a psychiatric past that is rapidly being forgotten. The Ellery movie is an incentive to collect surviving footage before it is too late.

Shifting brain inhibitory balance and connectivity of the prefrontal cortex of adults with autism spectrum disorder.

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Ajram, L A; Horder, J; Mendez, M A; Galanopoulos, A; Brennan, L P; Wichers, R H; Robertson, D M; Murphy, C M; Zinkstok, J; Ivin, G; Heasman, M; Meek, D; Tricklebank, M D; Barker, G J; Lythgoe, D J; Edden, R A E; Williams, S C; Murphy, D G M; McAlonan, G M

2017-05-23

Currently, there are no effective pharmacologic treatments for the core symptoms of autism spectrum disorder (ASD). There is, nevertheless, potential for progress. For example, recent evidence suggests that the excitatory (E) glutamate and inhibitory (I) GABA systems may be altered in ASD. However, no prior studies of ASD have examined the 'responsivity' of the E-I system to pharmacologic challenge; or whether E-I modulation alters abnormalities in functional connectivity of brain regions implicated in the disorder. Therefore, we used magnetic resonance spectroscopy ([1H]MRS) to measure prefrontal E-I flux in response to the glutamate and GABA acting drug riluzole in adult men with and without ASD. We compared the change in prefrontal 'Inhibitory Index'-the GABA fraction within the pool of glutamate plus GABA metabolites-post riluzole challenge; and the impact of riluzole on differences in resting-state functional connectivity. Despite no baseline differences in E-I balance, there was a significant group difference in response to pharmacologic challenge. Riluzole increased the prefrontal cortex inhibitory index in ASD but decreased it in controls. There was also a significant group difference in prefrontal functional connectivity at baseline, which was abolished by riluzole within the ASD group. Our results also show, for we believe the first time in ASD, that E-I flux can be 'shifted' with a pharmacologic challenge, but that responsivity is significantly different from controls. Further, our initial evidence suggests that abnormalities in functional connectivity can be 'normalised' by targeting E-I, even in adults.

Evaluation of medical treatments to increase survival of ebullism in guinea pigs

Science.gov (United States)

Stegmann, Barbara J.; Pilmanis, Andrew A.; Wolf, E. G.; Derion, Toniann; Fanton, J. W.; Davis, H.; Kemper, G. B.; Scoggins, Terrell E.

1993-01-01

Spaceflight carriers run a constant risk of exposure to vacuum. Above 63,000 ft (47 mmHg), the ambient pressure falls below the vapor pressure of water at 37 C, and tissue vaporization (ebullism) begins. Little is know about appropriate resuscitative protocols after such an ebullism exposure. This study identified injury patterns and mortality rates associated with ebullism while verifying effectiveness of traditional pulmonary resuscitative techniques. Male Hartley guinea pigs were exposed to 87,000 ft for periods of 40 to 115 sec. After descent, those animals that did not breathe spontaneously were given artificial ventilation by bag and mask for up to 15 minutes. Those animals surviving were randomly assigned to one of three treatment groups--hyperbaric oxygen (HBO), ground-level oxygen (GLO2), and ground-level air (GLAIR). The HBO group was treated on a standard treatment table 6A while the GLO2 animals received O2 for an equivalent length of time. Those animals in the GLAIR group were observed only. All surviving animals were humanely sacrified at 48 hours. Inflation of the animal's lungs after the exposure was found to be difficult and, at times, impossible. This may be due to surfactant disruption at the alveolar lining. Electron microscopy identified a disruption of the surfactant layer in animals that did not survive initial exposure. Mortality was found to increase with exposure time: 40 sec--0 percent; 60 sec--6 percent; 70 sec--40 percent; 80 sec--13 percent; 100 sec--38 percent; 110 sec--40 percent; and 115 sec--100 percent. There was no difference in the delayed mortality among the treatment groups (HBO--15 percent, GLO2--11 percent, GLAIR--11 percent). However, since resuscitation was ineffective, the effectiveness of any post-exposure treatment was severely limited. Preliminary results indicate that reuscitation of guinea pigs following ebullism exposure is difficult, and that current techniques (such as traditional CPR) may not be appropriate.

Treatment of primary liver tumors with Yttrium-90 microspheres (TheraSphere) in high risk patients: analysis of survival and toxicities.

Science.gov (United States)

Reardon, Kelli A; McIntosh, Alyson F; Shilling, A Tanner; Hagspiel, Klaus D; Al-Osaimi, Abdullah; Berg, Carl; Caldwell, Stephen H; Northup, Patrick G; Angle, Fritz; Mulder, Robert; Rich, Tyvin A

2009-02-01

This retrospective study was undertaken to obtain information regarding the survival and toxicities after Yttrium-90 microspheres treatment in patients with primary liver malignancies. Baseline, treatment, and follow-up data were collected and analyzed for 21 patients treated with Yttrium-90 microspheres. Survival analysis was then performed. The results of this study showed that median survival for all the patients was 120 days. Twenty of 21 patients were categorized as high-risk with a median survival of 114 days. It was also found that one high-risk patient has survived 858 days with no recurrence of disease. Acute grade 3-5 toxicities were recorded for nine patients and consisted of elevations in AST and bilirubin, thrombocytopenia, abdominal pain, ascites, nausea, fatigue, and death. This study concluded that Yttrium-90 is a low-toxicity, outpatient alternative for individuals with liver cancer and without many options. The maximal value, however, may lie in the treatment of low-risk patients.

The growth of Propionibacterium cyclohexanicum in fruit juices and its survival following elevated temperature treatments.

Science.gov (United States)

Walker, Michelle; Phillips, Carol A

2007-06-01

This study investigated the growth of Propionibacterium cyclohexanicum in orange juice over a temperature range from 4 to 40 degrees C and its ability to multiply in tomato, grapefruit, apple, pineapple and cranberry juices at 30 and 35 degrees C. Survival after 10 min exposure to 50, 60, 70, 80, 85, 90 and 95 degrees C in culture medium and in orange juice was also assessed. In orange juice the organism was able to multiply by 2 logs at temperatures from 4 to 35 degrees C and survived for up to 52 days. However, at 40 degrees C viable counts were reduced after 6 days and no viable cells isolated after 17 days. The optimum growth temperature in orange juice over 6 days was 25 degrees C but over 4 days it was 35 degrees C. The growth of P. cyclohexanicum was monitored in tomato, grapefruit, cranberry, pineapple and apple juices at 30 and 35 degrees C over 29 days. Cranberry, grapefruit and apple juice did not support the growth of P. cyclohexanicum. At 30 degrees C no viable cells were detected after 8 days in cranberry juice or after 22 days in grapefruit juice while at 35 degrees C no viable cells were detected after 5 and 15 days, respectively. However, in apple juice, although a 5 log reduction occurred, viable cells could be detected after 29 days. P. cyclohexanicum was able to multiply in both tomato and pineapple juices. In tomato juice, there was a 2 log increase in viable counts after 8 days at 30 degrees C but no increase at 35 degrees C, while in pineapple juice there was a 1 log increase in numbers over 29 days with no significant difference between numbers of viable cells present at 30 and 35 degrees C. The organism survived at 50 degrees C for 10 min in culture medium without a significant loss of viability while similar treatment at 60, 70 and 80 degrees C resulted in approximately a 3-4 log reduction, with no viable cells detected after treatment at 85 or 90 or 95 degrees C but, when pre-treated at intermediate temperatures before exposure to higher

Survival of localized NSCLC patients without active treatment or treated with SBRT

DEFF Research Database (Denmark)

Jeppesen, S S; Hansen, N C G; Schytte, T

2018-01-01

BACKGROUND: Little information on the natural history of patients with localized NSCLC is available since many of the studies covering the subject lack information on pathological confirmation, staging procedures and comorbidity. No randomized studies have compared SBRT with no treatment for pati......BACKGROUND: Little information on the natural history of patients with localized NSCLC is available since many of the studies covering the subject lack information on pathological confirmation, staging procedures and comorbidity. No randomized studies have compared SBRT with no treatment...... for patients with localized NSCLC. The purpose of this study was to evaluate whether SBRT has influence on overall survival for patients with localized NSCLC and investigate the effect of baseline ventilatory lung function on overall survival. MATERIAL AND METHODS: From 2007 to 2013, 136 patients treated...... with SBRT at Odense University Hospital were prospectively recorded. The thoracic SBRT consisted of three fractions of 15-22 Gy delivered in 9 days. For comparison, a national group of 73 untreated patients in the same time period was extracted from the Danish Lung Cancer Registry. All patients had...

Marital status, treatment, and survival in patients with glioblastoma multiforme: a population based study.

Science.gov (United States)

Chang, Susan M; Barker, Fred G

2005-11-01

Social factors influence cancer treatment choices, potentially affecting patient survival. In the current study, the authors studied the interrelations between marital status, treatment received, and survival in patients with glioblastoma multiforme (GM), using population-based data. The data source was the Surveillance, Epidemiology, and End Results (SEER) Public Use Database, 1988-2001, 2004 release, all registries. Multivariate logistic, ordinal, and Cox regression analyses adjusted for demographic and clinical variables were used. Of 10,987 patients with GM, 67% were married, 31% were unmarried, and 2% were of unknown marital status. Tumors were slightly larger at the time of diagnosis in unmarried patients (49% of unmarried patients had tumors larger than 45 mm vs. 45% of married patients; P = 0.004, multivariate analysis). Unmarried patients were less likely to undergo surgical resection (vs. biopsy; 75% of unmarried patients vs. 78% of married patients) and were less likely to receive postoperative radiation therapy (RT) (70% of unmarried patients vs. 79% of married patients). On multivariate analysis, the odds ratio (OR) for resection (vs. biopsy) in unmarried patients was 0.88 (95% confidence interval [95% CI], 0.79-0.98; P = 0.02), and the OR for RT in unmarried patients was 0.69 (95% CI, 0.62-0.77; P Unmarried patients more often refused both surgical resection and RT. Unmarried patients who underwent surgical resection and RT were found to have a shorter survival than similarly treated married patients (hazard ratio for unmarried patients, 1.10; P = 0.003). Unmarried patients with GM presented with larger tumors, were less likely to undergo both surgical resection and postoperative RT, and had a shorter survival after diagnosis when compared with married patients, even after adjustment for treatment and other prognostic factors. (c) 2005 American Cancer Society.

Second-line treatments: moving towards an opportunity to improve survival in advanced gastric cancer?

Science.gov (United States)

Salati, Massimiliano; Di Emidio, Katia; Tarantino, Vittoria; Cascinu, Stefano

2017-01-01

Gastric cancer is the third leading cause of cancer-related death globally with approximately 723 000 deaths every year. Most patients present with advanced unresectable or metastatic disease, only amenable to palliative systemic treatment and a median survival uncommonly exceeding 12 months. Over the last years, the efficacy of chemotherapy combination has plateaued and the introduction of the anti-human epidermal growth factor receptor 2 trastuzumab has resulted in a limited survival gain in the upfront setting. After this positive experience, first-line treatment with new targeted therapies failed to improve the outcome of advanced gastric cancer. On the contrary, second-line options, including monochemotherapy with taxanes or irinotecan and the anti-vascular endothelial growth factor receptor 2 ramucirumab, either alone or combined with paclitaxel, opened new therapeutic rooms for an ever-increasing number of patients who maintain an acceptable performance status across multiple lines. This article provides an updated overview on the current management of advanced gastric cancer and discusses how the different treatment options available may be best combined to favourably impact the outcome of patients following the logic of a treatment strategy.

Short-term azithromycin treatment promotes cornea allograft survival in the rat.

Science.gov (United States)

Wacker, Katrin; Denker, Sophy; Hildebrand, Antonia; Eberwein, Philipp; Reinhard, Thomas; Schwartzkopff, Johannes

2013-01-01

Any inflammatory response following corneal transplantation may induce rejection and irreversible graft failure. The purpose of this study is to analyze the anti-inflammatory effect of azithromycin (AZM) following experimental keratoplasty in rats. Corneal transplants were performed between Fisher-donor and Lewis-recipient rats. Recipients were postoperatively treated three times daily with AZM, miglyol, ofloxacin or dexamethasone eye drops. As an additional control, AZM was applied following syngeneic keratoplasty. Furthermore, short-term treatments with AZM for seven days perioperatively or with AZM only three days prior to the transplantation were compared to appropriate controls. All transplants were monitored clinically for opacity, edema, and vascularization. Infiltrating CD45(+), CD4(+), CD8(+), CD25(+), CD161(+) and CD163(+) cells were quantified via immunohistochemistry. AZM significantly promoted corneal graft survival compared with miglyol or ofloxacin treatment. This effect was comparable to topical dexamethasone. No adverse AZM effect was observed. Histology confirmed a significant reduction of infiltrating leukocytes. The short-term application of AZM for three days prior to transplantation or for seven days perioperatively reduced corneal graft rejection significantly compared with the controls. Along with antibiotic properties, topical AZM has a strong anti-inflammatory effect. Following keratoplasty, this effect is comparable to topical dexamethasone without the risk of steroid-induced adverse effects. Short-term treatment with AZM three days prior to the transplantation was sufficient to promote graft survival in the rat keratoplasty model. We therefore suggest further assessing the anti-inflammatory function of topical AZM following keratoplasty in humans.

Short-term azithromycin treatment promotes cornea allograft survival in the rat.

Directory of Open Access Journals (Sweden)

Katrin Wacker

Full Text Available Any inflammatory response following corneal transplantation may induce rejection and irreversible graft failure. The purpose of this study is to analyze the anti-inflammatory effect of azithromycin (AZM following experimental keratoplasty in rats.Corneal transplants were performed between Fisher-donor and Lewis-recipient rats. Recipients were postoperatively treated three times daily with AZM, miglyol, ofloxacin or dexamethasone eye drops. As an additional control, AZM was applied following syngeneic keratoplasty. Furthermore, short-term treatments with AZM for seven days perioperatively or with AZM only three days prior to the transplantation were compared to appropriate controls. All transplants were monitored clinically for opacity, edema, and vascularization. Infiltrating CD45(+, CD4(+, CD8(+, CD25(+, CD161(+ and CD163(+ cells were quantified via immunohistochemistry.AZM significantly promoted corneal graft survival compared with miglyol or ofloxacin treatment. This effect was comparable to topical dexamethasone. No adverse AZM effect was observed. Histology confirmed a significant reduction of infiltrating leukocytes. The short-term application of AZM for three days prior to transplantation or for seven days perioperatively reduced corneal graft rejection significantly compared with the controls.Along with antibiotic properties, topical AZM has a strong anti-inflammatory effect. Following keratoplasty, this effect is comparable to topical dexamethasone without the risk of steroid-induced adverse effects. Short-term treatment with AZM three days prior to the transplantation was sufficient to promote graft survival in the rat keratoplasty model. We therefore suggest further assessing the anti-inflammatory function of topical AZM following keratoplasty in humans.

Artificially regenerating longleaf pine on wet sites: preliminary analysis of effects of site preparation treatments on early survival and growth

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Benjamin O. Knapp; G. Geoff Wang; Joan L. Walker

2010-01-01

Our study, conducted over two years on poorly drained, sandy sites in Onslow County, NC, compared the effects of eight common site preparation treatments on early survival and growth of planted longleaf pine seedlings. Through two growing seasons, we found survival to be similar across all treatments (p = 0.8806), but root collar diameter was greatest with combinations...

Development of a cell-based treatment for long-term neurotrophin expression and spiral ganglion neuron survival.

Science.gov (United States)

Zanin, M P; Hellström, M; Shepherd, R K; Harvey, A R; Gillespie, L N

2014-09-26

Spiral ganglion neurons (SGNs), the target cells of the cochlear implant, undergo gradual degeneration following loss of the sensory epithelium in deafness. The preservation of a viable population of SGNs in deafness can be achieved in animal models with exogenous application of neurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3. For translation into clinical application, a suitable delivery strategy that provides ongoing neurotrophic support and promotes long-term SGN survival is required. Cell-based neurotrophin treatment has the potential to meet the specific requirements for clinical application, and we have previously reported that Schwann cells genetically modified to express BDNF can support SGN survival in deafness for 4 weeks. This study aimed to investigate various parameters important for the development of a long-term cell-based neurotrophin treatment to support SGN survival. Specifically, we investigated different (i) cell types, (ii) gene transfer methods and (iii) neurotrophins, in order to determine which variables may provide long-term neurotrophin expression and which, therefore, may be the most effective for supporting long-term SGN survival in vivo. We found that fibroblasts that were nucleofected to express BDNF provided the most sustained neurotrophin expression, with ongoing BDNF expression for at least 30 weeks. In addition, the secreted neurotrophin was biologically active and elicited survival effects on SGNs in vitro. Nucleofected fibroblasts may therefore represent a method for safe, long-term delivery of neurotrophins to the deafened cochlea to support SGN survival in deafness. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Evaluation of Treatment Patterns and Survival Outcomes in Elderly Pancreatic Cancer Patients: A Surveillance, Epidemiology, and End Results-Medicare Analysis.

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Shaib, Walid L; Jones, Jeb S; Goodman, Michael; Sarmiento, Juan M; Maithel, Shishir K; Cardona, Kenneth; Kane, Sujata; Wu, Christina; Alese, Olatunji B; El-Rayes, Bassel F

2018-02-14

Management of pancreatic cancer (PC) in elderly patients is unknown; clinical trials exclude patients with comorbidities and those of extreme age. This study evaluated treatment patterns and survival outcomes in elderly PC patients using linked Surveillance, Epidemiology, and End Results (SEER) and Medicare data. Histology codes 8140, 8500, 8010, 8560, 8490, 8000, 8260, 8255, 8261, 8263, 8020, 8050, 8141, 8144, 8210, 8211, or 8262 in Medicare Parts A and B were identified. Data regarding demographic, characteristics, treatments, and vital status between 1998 and 2009 were collected from the SEER. Determinants of treatment receipt and overall survival were examined using logistic regression and Cox proportional hazards models, respectively. A total of 5,975 patients met inclusion. The majority of patients were non-Hispanic whites (85%) and female (55%). Most cases presented with locoregional stage disease (74%); 41% received only chemotherapy, 30% chemotherapy and surgery, 10% surgery alone, 3% radiation, and 16% no cancer-directed therapy. Patients with more advanced cancer, older age, and those residing in areas of poverty were more likely to receive no treatment. Among patients 66-74 years of age with locoregional disease, surgery alone (hazard ratio [HR] = 0.54; 95% confidence interval [CI]: 0.39-0.74) and surgery in combination with chemotherapy (HR = 0.69; 95% CI: 0.53-0.91) showed survival benefit as compared with the no treatment group. Among patients ≥75 years of age with locoregional disease, surgery alone (HR = 2.04; 95% CI: 0.87-4.8) or in combination with chemotherapy (HR = 1.59; 95% CI: 0.87-2.91) was not associated with better survival. Treatment modality and survival differs by age and stage. Low socioeconomic status appears to be a major barrier to the receipt of PC therapy among Medicare patients. Elderly patients with cancer are under-represented on clinical trials and usually have comorbid illnesses. The management of elderly

Colorectal cancer in Slovenia – differences in surgical treatment and patient survival

Directory of Open Access Journals (Sweden)

Gregor Norčič

2005-12-01

Full Text Available Background: Colorectal cancer (CRC is one of the most frequent malignant diseases in Slovenia. Its incidence rises constantly in the last years while the outcome of treatment is poorer than in other developed countries.Methods: In a retrospective study we analysed 940 colorectal cancer patients diagnosed in Slovenia in 1997.Results: Differences in outcome between the Slovenian institutions are due to different stage-distributions and differences in surgical radicality. Differences in pathohistological staging and medical oncological treatment are probably less important. The same can be said regarding some of the examples from abroad.Conclusions: With constant and objective auditing, the improvement of all aspects of treatment can be achieved, resulting in better survival of all Slovenian colorectal cancer patients.

Tumour vasculature immaturity, oxidative damage and systemic inflammation stratify survival of colorectal cancer patients on bevacizumab treatment

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Martin, Petra; Biniecka, Monika; Ó'Meachair, Shane; Maguire, Aoife; Tosetto, Miriam; Nolan, Blathnaid; Hyland, John; Sheahan, Kieran; O'Donoghue, Diarmuid; Mulcahy, Hugh; Fennelly, David; O'Sullivan, Jacintha

2018-01-01

Despite treatment of patients with metastatic colorectal cancer (mCRC) with bevacizumab plus chemotherapy, response rates are modest and there are no biomarkers available that will predict response. The aim of this study was to assess if markers associated with three interconnected cancer-associated biological processes, specifically angiogenesis, inflammation and oxidative damage, could stratify the survival outcome of this cohort. Levels of angiogenesis, inflammation and oxidative damage markers were assessed in pre-bevacizumab resected tumour and serum samples of mCRC patients by dual immunofluorescence, immunohistochemistry and ELISA. This study identified that specific markers of angiogenesis, inflammation and oxidative damage stratify survival of patients on this anti-angiogenic treatment. Biomarkers of immature tumour vasculature (% IMM, p=0.026, n=80), high levels of oxidative damage in the tumour epithelium (intensity of 8-oxo-dG in nuclear and cytoplasmic compartments, p=0.042 and 0.038 respectively, n=75) and lower systemic pro-inflammatory cytokines (IL6 and IL8, p=0.053 and 0.049 respectively, n=61) significantly stratify with median overall survival (OS). In summary, screening for a panel of biomarkers for high levels of immature tumour vasculature, high levels of oxidative DNA damage and low levels of systemic pro-inflammatory cytokines may be beneficial in predicting enhanced survival outcome following bevacizumab treatment for mCRC. PMID:29535825

Solitary plasmacytoma: population-based analysis of survival trends and effect of various treatment modalities in the USA.

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Thumallapally, Nishitha; Meshref, Ahmed; Mousa, Mohammed; Terjanian, Terenig

2017-01-05

Solitary plasmacytoma (SP) is a localized neoplastic plasma cell disorder with an annual incidence of less than 450 cases. Given the rarity of this disorder, it is difficult to conduct large-scale population studies. Consequently, very limited information on the disorder is available, making it difficult to estimate the incidence and survival rates. Furthermore, limited information is available on the efficacy of various treatment modalities in relation to primary tumor sites. The data for this retrospective study were drawn from the Surveillance, Epidemiology and End Results (SEER) database, which comprises 18 registries; patient demographics, treatment modalities and survival rates were obtained for those diagnosed with SP from 1998 to 2007. Various prognostic factors were analyzed via Kaplan-Meier analysis and log-rank test, with 5-year relative survival rate defined as the primary outcome of interest. Cox regression analysis was employed in the multivariate analysis. The SEER search from 1998 to 2007 yielded records for 1691 SP patients. The median age at diagnosis was 63 years. The patient cohort was 62.4% male, 37.6% female, 80% Caucasian, 14.6% African American and 5.4% other races. Additionally, 57.8% had osseous plasmacytoma, and 31.9% had extraosseous involvement. Unspecified plasmacytoma was noted in 10.2% of patients. The most common treatment modalities were radiotherapy (RT) (48.8%), followed by combination surgery with RT (21.2%) and surgery alone (11.6%). Univariate analysis of prognostic factors revealed that the survival outcomes were better for younger male patients who received RT with surgery (p multiple myeloma (MM) was noted in 551 patients. Age >60 years was associated with a lower 5-year survival in patients who progressed to MM compared to those who were diagnosed initially with MM (15.1 vs 16.6%). Finally, those who received RT and progressed to MM still had a higher chance of survival than those who were diagnosed with MM initially and

Survival of patients with non-small cell lung cancer without treatment: a systematic review and meta-analysis

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Wao Hesborn

2013-02-01

Full Text Available Abstract Background Lung cancer is considered a terminal illness with a five-year survival rate of about 16%. Informed decision-making related to the management of a disease requires accurate prognosis of the disease with or without treatment. Despite the significance of disease prognosis in clinical decision-making, systematic assessment of prognosis in patients with lung cancer without treatment has not been performed. We conducted a systematic review and meta-analysis of the natural history of patients with confirmed diagnosis of lung cancer without active treatment, to provide evidence-based recommendations for practitioners on management decisions related to the disease. Specifically, we estimated overall survival when no anticancer therapy is provided. Methods Relevant studies were identified by search of electronic databases and abstract proceedings, review of bibliographies of included articles, and contacting experts in the field. All prospective or retrospective studies assessing prognosis of lung cancer patients without treatment were eligible for inclusion. Data on mortality was extracted from all included studies. Pooled proportion of mortality was calculated as a back-transform of the weighted mean of the transformed proportions using the random-effects model. To perform meta-analysis of median survival, published methods were used to pool the estimates as mean and standard error under the random-effects model. Methodological quality of the studies was examined. Results Seven cohort studies (4,418 patients and 15 randomized controlled trials (1,031 patients were included in the meta-analysis. All studies assessed mortality without treatment in patients with non-small cell lung cancer (NSCLC. The pooled proportion of mortality without treatment in cohort studies was 0.97 (95% CI: 0.96 to 0.99 and 0.96 in randomized controlled trials (95% CI: 0.94 to 0.98 over median study periods of eight and three years, respectively. When data

Depression and Liver Transplant Survival.

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Meller, William; Welle, Nicole; Sutley, Kristen; Thurber, Steven

Patients who underwent liver transplantation and experienced clinical depression have heretofore evinced lower survival rates when compared to nondepressed counterparts. To investigate the hypothesis that transplant patients who seek and obtain medical treatment for depression would circumvent the prior reduced survival findings. A total of 765 patients with liver transplants were scrutinized for complications following transplantation. Further, 104 patients experienced posttransplant depression as manifested by diagnosis and treatment by medical personnel. Survival analyses were conducted comparing hazard and survival curves for these selected individuals and the remainder of transplant patients. Contrary to prior data and consistent with the aforementioned hypothesis, median survival durations, survival curves, and hazard functions (controlling for age and prolonged posttransplant survival for the depressed patients were better. The improved survival for the depressed patients may simply be related to an amelioration of depressed symptoms via antidepressant medications. However, this interpretation would only be congruent with reduced hazard, not elevated survival, beyond the norm (median) for other transplant participants. Assuming the reliability and generalization of our findings, perhaps a reasonable and compelling interpretation is that combined with the effectiveness of antidepressant medications, the seeking and receiving treatment for depression is a type of proxy measure of a more global pattern of adherence to recommended posttransplant medical regimens. Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

The statistical treatment of cell survival data

International Nuclear Information System (INIS)

Boag, J.W.

1975-01-01

The paper considers the sources of experimental error in cell survival experiments and discusses in simple terms how these combine to influence the accuracy of single points and the parameters of complete survival curves. Cell sampling and medium-dilution errors are discussed at length and one way of minimizing the former is examined. The Monte-Carlo method of estimating the distribution of derived parameters in small samples is recommended and illustrated. (author)

Potential North American Clinical Trials Network (NACTN) for Treatment of Spinal Cord Injury: A Consortium of Military, Veterans Administration, and Civilian Hospitals

National Research Council Canada - National Science Library

Grossman, Robert G

2008-01-01

.... In anticipation of approval, all NACTN personnel met in February 2008 to discuss the riluzole protocol/safety study, and the centers are working with local IRBs and ORP to fulfill all regulatory...

Overtreatment of young adults with colon cancer: more intense treatments with unmatched survival gains.

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Kneuertz, Peter J; Chang, George J; Hu, Chung-Yuan; Rodriguez-Bigas, Miguel A; Eng, Cathy; Vilar, Eduardo; Skibber, John M; Feig, Barry W; Cormier, Janice N; You, Y Nancy

2015-05-01

Colon cancer is increasing among adults younger than 50 years. However, the prognosis of young-onset colon cancer remains poorly defined given significant age-related demographic, disease, and treatment differences. To define stage-specific treatments and prognosis of colon cancer diagnosed in young adults (ages 18-49 years) vs older adults (ages 65-75 years) outside of the clinical trial setting while accounting for real-world age-related variations in patient, tumor, and treatment factors. A nationwide cohort study was conducted among US hospitals accredited by the American College of Surgeons Commission on Cancer. Participants were 13 102 patients diagnosed as having young-onset colon adenocarcinoma aged 18 to 49 years and 37 007 patients diagnosed as having later-onset colon adenocarcinoma aged 65 to 75 years treated between January 1, 2003, and December 31, 2005, and reported to the National Cancer Data Base. Patients who underwent surgical resection and postoperative systemic chemotherapy of curative intent. The primary end point was stage-specific relative survival, an objective measure of survival among patients with cancer, adjusting for baseline mortality rates and independent of the data on cause of death. The secondary end point was stage-specific likelihood of receiving postoperative systemic chemotherapy. Most young-onset colon cancer was initially seen at advanced stages (61.8% had stage III or IV). After adjusting for patient-related and tumor-related factors, young patients were more likely to receive systemic chemotherapy, particularly multiagent regimens, at all stages relative to those with later-onset disease. These odds ratios were 2.88 (95% CI, 2.21-3.77) for stage I, 3.93 (95% CI, 3.58-4.31) for stage II, 2.42 (95% CI, 2.18-2.68) for stage III, and 2.74 (95% CI, 2.44-3.07) for stage IV. The significantly more intense treatments received by younger patients were unmatched by any survival gain, which was nil for stage II (relative risk, 0

Improved Survival and Cure Rates With Concurrent Treatment for Multidrug-Resistant Tuberculosis-Human Immunodeficiency Virus Coinfection in South Africa.

Science.gov (United States)

Brust, James C M; Shah, N Sarita; Mlisana, Koleka; Moodley, Pravi; Allana, Salim; Campbell, Angela; Johnson, Brent A; Master, Iqbal; Mthiyane, Thuli; Lachman, Simlatha; Larkan, Lee-Megan; Ning, Yuming; Malik, Amyn; Smith, Jonathan P; Gandhi, Neel R

2018-04-03

Mortality in multidrug-resistant (MDR) tuberculosis-human immunodeficiency virus (HIV) coinfection has historically been high, but most studies predated the availability of antiretroviral therapy (ART). We prospectively compared survival and treatment outcomes in MDR tuberculosis-HIV-coinfected patients on ART to those in patients with MDR tuberculosis alone. This observational study enrolled culture-confirmed MDR tuberculosis patients with and without HIV in South Africa between 2011 and 2013. Participants received standardized MDR tuberculosis and HIV regimens and were followed monthly for treatment response, adverse events, and adherence. The primary outcome was survival. Among 206 participants, 150 were HIV infected, 131 (64%) were female, and the median age was 33 years (interquartile range [IQR], 26-41). Of the 191 participants with a final MDR tuberculosis outcome, 130 (73%) were cured or completed treatment, which did not differ by HIV status (P = .50). After 2 years, CD4 count increased a median of 140 cells/mm3 (P = .005), and 64% had an undetectable HIV viral load. HIV-infected and HIV-uninfected participants had high rates of survival (86% and 94%, respectively; P = .34). The strongest risk factor for mortality was having a CD4 count ≤100 cells/mm3 (adjusted hazards ratio, 15.6; 95% confidence interval, 4.4-55.6). Survival and treatment outcomes among MDR tuberculosis-HIV individuals receiving concurrent ART approached those of HIV-uninfected patients. The greatest risk of death was among HIV-infected individuals with CD4 counts ≤100 cells/mm3. These findings provide critical evidence to support concurrent treatment of MDR tuberculosis and HIV.

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

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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.

Amyotrophic lateral sclerosis and the clinical potential of dexpramipexole

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Corcia P

2012-08-01

Full Text Available Philippe Corcia,1 Paul H Gordon21Centre SLA, CHRU de Tours, Tours, France; UMR INSERM U930, Université François Rabelais de Tours (PC, Tours, France; 2AP-HP, Hôpital de la Pitié-Salpêtrière, Département des Maladies du Système Nerveux (PHG, Paris, FranceAbstract: Amyotrophic lateral sclerosis (ALS is a neurodegenerative disorder that leads to progressive weakness from loss of motor neurons and death on average in less than 3 years after symptom onset. No clear causes have been found and just one medication, riluzole, extends survival. Researchers have identified some of the cellular processes that occur after disease onset, including mitochondrial dysfunction, protein aggregation, oxidative stress, excitotoxicity, inflammation, and apoptosis. Mitochondrial disease may be a primary event in neurodegeneration or occur secondary to other cellular processes, and may itself contribute to oxidative stress, excitotoxicity, and apoptosis. Clinical trials currently aim to slow disease progression by testing drugs that impact one or more of these pathways. While every agent tested in the 18 years after the approval of riluzole has been ineffective, basic and clinical research methods in ALS have become dramatically more sophisticated. Dexpramipexole (RPPX, the R(+ enantiomer of pramiprexole, which is approved for symptomatic treatment of Parkinson disease, carries perhaps the currently largest body of pre- and early clinical data that support testing in ALS. The neuroprotective properties of RPPX in various models of neurodegeneration, including the ALS murine model, may be produced through protective actions on mitochondria. Early phase trials in human ALS suggest that the drug can be taken safely by patients in doses that provide neuroprotection in preclinical models. A Phase III trial to test the efficacy of RPPX in ALS is underway.Keywords: dexpramipexole, amyotrophic lateral sclerosis, survival, clinical trials, neurodegeneration

Therapeutic neuroprotective agents for amyotrophic lateral sclerosis

Science.gov (United States)

Pandya, Rachna S.; Zhu, Haining; Li, Wei; Bowser, Robert; Friedlander, Robert M.

2014-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal chronic neurodegenerative disease whose hallmark is proteinaceous, ubiquitinated, cytoplasmic inclusions in motor neurons and surrounding cells. Multiple mechanisms proposed as responsible for ALS pathogenesis include dysfunction of protein degradation, glutamate excitotoxicity, mitochondrial dysfunction, apoptosis, oxidative stress, and inflammation. It is therefore essential to gain a better understanding of the underlying disease etiology and search for neuroprotective agents that might delay disease onset, slow progression, prolong survival, and ultimately reduce the burden of disease. Because riluzole, the only Food and Drug Administration (FDA)-approved treatment, prolongs the ALS patient’s life by only 3 months, new therapeutic agents are urgently needed. In this review, we focus on studies of various small pharmacological compounds targeting the proposed pathogenic mechanisms of ALS and discuss their impact on disease progression. PMID:23864030

Addition of immunosuppressive treatment to hemoperfusion is associated with improved survival after paraquat poisoning: a nationwide study.

Science.gov (United States)

Wu, Wen-Pyng; Lai, Ming-Nan; Lin, Ching-Heng; Li, Yu-Fen; Lin, Ching-Yuang; Wu, Ming-Ju

2014-01-01

Paraquat poisoning associates very high mortality rate. Early treatment with hemoperfusion is strongly suggested by animal and human studies. Although the survival benefit of additional immunosuppressive treatment (IST) in combination with hemoperfusion is also reported since 1971, the large-scale randomized control trials to confirm the effects of IST is difficult to be executed. Therefore, we designed this nationwide large-scale population-based retrospective cohort study to investigate the outcome of paraquat poisoning with hemoperfusion and the additional effects of IST combined with hemoperfusion. This nationwide retrospective cohort study utilized data retrieved from the National Health Insurance Research Database (NHIRD) of Taiwan. A total of 1811 hospitalized patients with a diagnosis of paraquat poisoning who received hemoperfusion between 1997 and 2009 were enrolled. The mean age of all 1811 study subjects was 47.3 years. 70% was male. The overall survival rate was only 26.4%. Respiratory failure and renal failure were diagnosed in 56.2% and 36% patients. The average frequency of hemoperfusion was twice. IST was added in 42.2% patients. IST significantly increases survival rate (from 24.3% to 29.3%, Ppoisoned patients. The best survival effect of IST is the combination of methylprednisolone, cyclophosphamide and daily dexamethasone, especially in patients with younger age.

Addition of immunosuppressive treatment to hemoperfusion is associated with improved survival after paraquat poisoning: a nationwide study.

Directory of Open Access Journals (Sweden)

Wen-Pyng Wu

Full Text Available Paraquat poisoning associates very high mortality rate. Early treatment with hemoperfusion is strongly suggested by animal and human studies. Although the survival benefit of additional immunosuppressive treatment (IST in combination with hemoperfusion is also reported since 1971, the large-scale randomized control trials to confirm the effects of IST is difficult to be executed. Therefore, we designed this nationwide large-scale population-based retrospective cohort study to investigate the outcome of paraquat poisoning with hemoperfusion and the additional effects of IST combined with hemoperfusion. This nationwide retrospective cohort study utilized data retrieved from the National Health Insurance Research Database (NHIRD of Taiwan. A total of 1811 hospitalized patients with a diagnosis of paraquat poisoning who received hemoperfusion between 1997 and 2009 were enrolled. The mean age of all 1811 study subjects was 47.3 years. 70% was male. The overall survival rate was only 26.4%. Respiratory failure and renal failure were diagnosed in 56.2% and 36% patients. The average frequency of hemoperfusion was twice. IST was added in 42.2% patients. IST significantly increases survival rate (from 24.3% to 29.3%, P<0.001. The combined IST with methylprednisolone, cyclophosphamide and dexamethasone associates with the highest survival rate (48%, P<0.001. Moreover, patients younger than 45 years of age in the IST group had the best survival (41.0% vs. 33.7%, p<0.001. Our results support the use of IST with hemoperfusion for paraquat-poisoned patients. The best survival effect of IST is the combination of methylprednisolone, cyclophosphamide and daily dexamethasone, especially in patients with younger age.

Survival of Primates in Lethal Septic Shock Following Delayed Treatment with Steroid.

Science.gov (United States)

1981-02-26

TECHNICAL REPORT NO. 142 SURVIVAL OF PRIMATES IN LETHAL SEPTIC SHOCK FOLLOWING DELAYED TREAMENT WIn STEROID L. B. Hinshaw, L. T. Archer, B. K. Belier ...2. Schumer W: Steroids in the treatment of clinical septic shock. Ann Surg 184:333-341, 1976. 3. Hinshaw LB, Belier PK, Archer LT, Flournoy DJ, White...not preventable by antibiotic alone. Infect Immun ZS:538-5)7, 1979. 6. Hinshaw LB, Archer LT, Belier -Todd BK, Coalson .JJ, Flournoy DL, Passey R

Radiotherapy Is Associated With Improved Survival in Adjuvant and Palliative Treatment of Extrahepatic Cholangiocarcinomas

International Nuclear Information System (INIS)

Shinohara, Eric T.; Mitra, Nandita; Guo Mengye; Metz, James M.

2009-01-01

Purpose: Extrahepatic cholangiocarcinomas (EHC) are rare tumors of the biliary tree because of their low incidence, large randomized studies examining radiotherapy (RT) for EHC have not been performed. The purpose of this study was to examine the role of adjuvant and palliative RT in the treatment of EHC in a large patient population. Methods and Materials: This was a retrospective analysis of 4,758 patients with EHC collected from the Surveillance, Epidemiology, and End Results database. The primary endpoint was overall survival. Results: Patients underwent surgery (28.8%), RT (10.0%), surgery and RT (14.7%), or no RT or surgery (46.4%). The median age of the patient population was 73 years (range, 23-104), 52.5% were men, and 80.7% were white. The median overall survival time was 16 months (95% confidence interval [CI] 15-17), 9 months (95% CI 9-11), 9 months (95% CI 9-10), and 4 months (95% CI 3-4) for surgery and RT, surgery, RT, and no RT or surgery, respectively. The overall survival was significantly different between the surgery and surgery and RT groups (p < .0001) and RT and no RT or surgery groups (p < .0001) on the log-rank test. The propensity score-adjusted analyses of surgery and RT vs. surgery (hazard ratio, 0.94; 95% CI, 0.84-1.05) were not significantly different, but that for RT vs. no RT or surgery (hazard ratio, 0.61; 95% CI, 0.54-0.70) was significantly different. Conclusion: These results suggest that palliative RT prolongs survival in patients with EHC. The benefit associated with surgery and RT was significant on univariate analysis but not after controlling for potential confounders using the propensity score. Future studies should evaluate the addition of chemotherapy and biologic agents for the treatment of EHC.

Treatment and survival outcomes of small cell carcinoma of the esophagus: an analysis of the National Cancer Data Base.

Science.gov (United States)

Wong, Andrew T; Shao, Meng; Rineer, Justin; Osborn, Virginia; Schwartz, David; Schreiber, David

2017-02-01

Given the paucity of esophageal small cell carcinoma (SCC) cases, there are few large studies evaluating this disease. In this study, the National Cancer Data Base (NCDB) was utilized to analyze the clinical features, treatment, and survival of patients with esophageal SCC in a large, population-based dataset. We selected patients diagnosed with esophageal SCC from 1998 to 2011. Patients were identified as having no treatment, chemotherapy alone, radiation ± sequential chemotherapy, concurrent chemoradiation, and esophagectomy ± chemotherapy and/or radiation. Overall survival (OS) was analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis was conducted to identify factors associated with OS. A total of 583 patients were identified. Most patients had stage IV disease (41.7%). Regarding treatment selection, chemoradiation was the most commonly utilized for patients with nonmetasatic disease, whereas chemotherapy alone was most common for metastatic patients. Esophagectomy (median survival 44.9 months with 3 year OS 50.5%) was associated with the best OS for patients with localized (node-negative) disease compared with chemotherapy alone (p < 0.001) or chemoradiation (p = 0.01). For locoregional (node-positive) disease, treatment with chemoradiation resulted in a median survival of 17.8 months and a 3 year OS 31.6%. On multivariate analysis, treatment with chemotherapy alone (p = 0.003) was associated with worse OS while esophagectomy (p = 0.04) was associated with improved OS compared to chemoradiation. Esophageal SCC is an aggressive malignancy with most patients presenting with metastatic disease. Either esophagectomy or chemoradiation as part of multimodality treatment appear to improve OS for selected patients with nonmetastatic disease. © 2016 International Society for Diseases of the Esophagus.

Estimating quality adjusted progression free survival of first-line treatments for EGFR mutation positive non small cell lung cancer patients in The Netherlands

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Verduyn S

2012-09-01

Full Text Available Abstract Background Gefitinib, a tyrosine kinase inhibitor, is an effective treatment in advanced non-small cell lung cancer (NSCLC patients with an activating mutation in the epidermal growth factor receptor (EGFR. Randomised clinical trials showed a benefit in progression free survival for gefitinib versus doublet chemotherapy regimens in patients with an activated EGFR mutation (EGFR M+. From a patient perspective, progression free survival is important, but so is health-related quality of life. Therefore, this analysis evaluates the Quality Adjusted progression free survival of gefitinib versus three relevant doublet chemotherapies (gemcitabine/cisplatin (Gem/Cis; pemetrexed/cisplatin (Pem/Cis; paclitaxel/carboplatin (Pac/Carb in a Dutch health care setting in patients with EGFR M+ stage IIIB/IV NSCLC. This study uses progression free survival rather than overall survival for its time frame in order to better compare the treatments and to account for the influence that subsequent treatment lines would have on overall survival analysis. Methods Mean progression free survival for Pac/Carb was obtained by extrapolating the median progression free survival as reported in the Iressa-Pan-Asia Study (IPASS. Data from a network meta-analysis was used to estimate the mean progression free survival for therapies of interest relative to Pac/Carb. Adjustment for health-related quality of life was done by incorporating utilities for the Dutch population, obtained by converting FACT-L data (from IPASS to utility values and multiplying these with the mean progression free survival for each treatment arm to determine the Quality Adjusted progression free survival. Probabilistic sensitivity analysis was carried out to determine 95% credibility intervals. Results The Quality Adjusted progression free survival (PFS (mean, (95% credibility interval was 5.2 months (4.5; 5.8 for Gem/Cis, 5.3 months (4.6; 6.1 for Pem/Cis; 4.9 months (4.4; 5.5 for Pac/Carb and 8

Clinical profile, treatment and survival outcomes of peadiatric germ cell tumours: A Pakistani perspective.

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Islam Nasir, Irfan Ul; Ashraf, Muhammad Ijaz; Ahmed, Nouman; Shah, Muhammad Fahd; Pirzada, Muhammad Taqi; Syed, Amir Ali; Qazi, Abid Quddus

2016-10-01

Germ Cell Tumours (GCTs) are rare tumours. Generally 80% are benign and 20% malignant with a bimodal age distribution. The retrospective study was conducted at Shaukat Khanum Cancer Hospital, Lahore, Pakistan, and comprised all paediatric patients below 18 years of age who received treatment for histology-proven GCT from 2006 to 2014. Of the 207 patients, 98(42.3%) were males and 109(52.7%) were females. The most common GCT was yolk sac tumour in 90(43.5%) children followed by mixed GCT in 40(19.3%) and dysgerminoma in 34(16.4%). Gonads were most commonly involved in 165(79.7%) patients with metastasis in 24(11.6%) at presentation and recurrence in 26(12.5%) patients. Overall, 133(64.3%) patients are well and followed up at regular intervals and 55(26.5%) have been lost to follow-up with an expected overall 5-year median survival of 45%. Despite the distinct clinical profile of paediatric GCT, survival can be improved by early diagnosis, regimented treatment according to set guidelines, protocols and by improving follow-up.

The impact of bevacizumab treatment on survival and quality of life in newly diagnosed glioblastoma patients

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Poulsen, Hans Skovgaard; Urup, Thomas; Michaelsen, Signe Regner; Staberg, Mikkel; Villingshøj, Mette; Lassen, Ulrik

2014-01-01

Glioblastoma multiforme (GBM) remains one of the most devastating tumors, and patients have a median survival of 15 months despite aggressive local and systemic therapy, including maximal surgical resection, radiation therapy, and concomitant and adjuvant temozolomide. The purpose of antineoplastic treatment is therefore to prolong life, with a maintenance or improvement of quality of life. GBM is a highly vascular tumor and overexpresses the vascular endothelial growth factor A, which promotes angiogenesis. Preclinical data have suggested that anti-angiogenic treatment efficiently inhibits tumor growth. Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor A, and treatment has shown impressive response rates in recurrent GBM. In addition, it has been shown that response is correlated to prolonged survival and improved quality of life. Several investigations in newly diagnosed GBM patients have been performed during recent years to test the hypothesis that newly diagnosed GBM patients should be treated with standard multimodality treatment, in combination with bevacizumab, in order to prolong life and maintain or improve quality of life. The results of these studies along with relevant preclinical data will be described, and pitfalls in clinical and paraclinical endpoints will be discussed

Treatment algorithm based on the multivariate survival analyses in patients with advanced hepatocellular carcinoma treated with trans-arterial chemoembolization.

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Hasmukh J Prajapati

Full Text Available To develop the treatment algorithm from multivariate survival analyses (MVA in patients with Barcelona clinic liver cancer (BCLC C (advanced Hepatocellular carcinoma (HCC patients treated with Trans-arterial Chemoembolization (TACE.Consecutive unresectable and non-tranplantable patients with advanced HCC, who received DEB TACE were studied. A total of 238 patients (mean age, 62.4yrs was included in the study. Survivals were analyzed according to different parameters from the time of the 1st DEB TACE. Kaplan Meier and Cox Proportional Hazard model were used for survival analysis. The SS was constructed from MVA and named BCLC C HCC Prognostic (BCHP staging system (SS.Overall median survival (OS was 16.2 months. In HCC patients with venous thrombosis (VT of large vein [main portal vein (PV, right or left PV, hepatic vein, inferior vena cava] (22.7% versus small vein (segmental/subsegmental PV (9.7% versus no VT had OSs of 6.4 months versus 20 months versus 22.8 months respectively (p<0.001. On MVA, the significant independent prognostic factors (PFs of survival were CP class, eastern cooperative oncology group (ECOG performance status (PS, single HCC<5 cm, site of VT, metastases, serum creatinine and serum alpha-feto protein. Based on these PFs, the BCHP staging system was constructed. The OSs of stages I, II and III were 28.4 months, 11.8 months and 2.4 months accordingly (p<0.001. The treatment plan was proposed according to the different stages.On MVA of patients with advanced HCC treated with TACE, significant independent prognostic factors (PFs of survival were CP class, ECOG PS, single HCC<5 cm or others, site of VT, metastases, serum creatinine and serum alpha-feto protein. New BCHP SS was proposed based on MVA data to identify the suitable advanced HCC patients for TACE treatments.

Global variations in cancer survival. Study Group on Cancer Survival in Developing Countries.

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Sankaranarayanan, R; Swaminathan, R; Black, R J

1996-12-15

Population-based cancer registries from Algeria, China, Costa Rica, Cuba, India, the Philippines, and Thailand are collaborating with the International Agency for Research on Cancer in a study of cancer survival in developing countries. Comparisons with the SEER program results of the National Cancer Institute in the United States, and the EUROCARE study of survival in European countries revealed considerable differences in the survival of patients with certain tumors associated with intensive chemotherapeutic treatment regimes (Hodgkin's disease and testicular tumors), more modest differences in the survival of patients with tumors for which early diagnosis and treatment confer an improved prognosis (carcinomas of the large bowel, breast, and cervix), and only slight differences for tumors associated with poor prognosis (carcinomas of the stomach, pancreas, and lung). With limited resources to meet the challenge of the increasing incidence of cancer expected in the next few decades, health authorities in developing countries should be aware of the importance of investing in a range of cancer control activities, including primary prevention and early detection programs as well as treatment.

Treatment outcomes and survival in patients with primary central nervous system lymphomas treated between 1995 and 2010 – a single centre report

International Nuclear Information System (INIS)

Jezersek Novakovic, Barbara

2012-01-01

Primary central nervous system lymphomas (PCNSL) are rare variants of extranodal non-Hodgkin’s lymphomas that are nowadays primarily treated with high-dose methotrexate or methotrexate-based chemotherapy with or without radiation therapy. The optimal treatment of PCNSL is still unknown and there are differences in clinical practice. With a retrospective research we evaluated our series of patients with PCNSL in regards to the patient’s characteristics, treatment results, disease specific survival and overall survival. Fifty nine patients who attended the Institute of Oncology Ljubljana between 1995 and 2010 were treated according to the protocol that was valid at the time of the patient’s admission. Between 1995 and 1999, the systemic treatment was classical CHOP (cyclophosphamide, doxorubicin, vincristine, steroids) chemotherapy, and later on high-dose methotrexate either alone or in combination with other agents. From 1999 onwards, radiation therapy was applied according to the patient’s age and response to chemotherapy, prior to that all patients treated with CHOP were also irradiated. Patients ineligible for the systemic treatment were treated with sole radiation therapy. There was a strong female predominance in our series and the median age at diagnosis was 59.8 years. Patients had predominantly aggressive B cell lymphomas (69.5%), one patient had marginal cell lymphoma and two patients T cell lymphoma. In total, 20.3% of patients were treated just with chemotherapy, 33.9% with combined therapy and 42.4% with sole radiation therapy. The overall response rate to the primary treatment in patients treated with sole chemotherapy was 33.3%, in patients treated with combined therapy 65% and in patients treated only with radiation therapy 56%, respectively. In terms of response duration, significantly better results were achieved with combined therapy or radiation therapy alone compared to sole chemotherapy (p<0.0006). The median overall survival of the

Improved survival with an innovative approach to the treatment of severely burned patients: development of a burn treatment manual

OpenAIRE

Morisada, S.; Nosaka, N.; Tsukahara, K.; Ugawa, T.; Sato, K.; Ujike, Y.

2015-01-01

The management of severely burned patients remains a major issue worldwide as indicated by the high incidence of permanent debilitating complications and poor survival rates. In April 2012, the Advanced Emergency & Critical Care Medical Center of the Okayama University Hospital began implementing guidelines for severely burned patients, distributed as a standard burn treatment manual. The protocol, developed in-house, was validated by comparing the outcomes of patients with severe extensive b...

Clinical care of patients with amyotrophic lateral sclerosis.

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Radunović, Aleksandar; Mitsumoto, Hiroshi; Leigh, P Nigel

2007-10-01

Although amyotrophic lateral sclerosis and its variants are readily recognised by neurologists, about 10% of patients are misdiagnosed, and delays in diagnosis are common. Prompt diagnosis, sensitive communication of the diagnosis, the involvement of the patient and their family, and a positive care plan are prerequisites for good clinical management. A multidisciplinary, palliative approach can prolong survival and maintain quality of life. Treatment with riluzole improves survival but has a marginal effect on the rate of functional deterioration, whereas non-invasive ventilation prolongs survival and improves or maintains quality of life. In this Review, we discuss the diagnosis, management, and how to cope with impaired function and end of life on the basis of our experience, the opinions of experts, existing guidelines, and clinical trials. We highlight the need for research on the effectiveness of gastrostomy, access to non-invasive ventilation and palliative care, communication between the care team, the patient and his or her family, and recognition of the clinical and social effects of cognitive impairment. We recommend that the plethora of evidence-based guidelines should be compiled into an internationally agreed guideline of best practice.

Reduced-intensity allogeneic hematopoietic stem cell transplantation combined with imatinib has comparable event-free survival and overall survival to long-term imatinib treatment in young patients with chronic myeloid leukemia.

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Zhao, Yanmin; Wang, Jiasheng; Luo, Yi; Shi, Jimin; Zheng, Weiyan; Tan, Yamin; Cai, Zhen; Huang, He

2017-08-01

The relative merits of reduced intensity hematopoietic stem cell transplantation (RIST) for chronic myeloid leukemia (CML) in the first chronic phase (CP) in imatinib era have not been evaluated. The study was designed to compare the outcomes of combination therapy of RIST plus imatinib (RIST + IM) vs. imatinib (IM) alone for young patients with early CP (ECP) and late CP (LCP). Of the patients, 130 were non-randomly assigned to treatment with IM alone (n = 88) or RIST + IM (n = 42). The 10-year overall survival (OS) and event-free survival (EFS) were comparable between RIST + IM and IM groups. LCP, high Sokal score, and no complete cytogenetic response at 3 months were adverse prognostic factors for survival, but only the time from diagnosis to IM was an independent predictor after multivariate analysis. For ECP, IM was similar to RIST + IM, with 10-year EFS rates of 77.2 vs. 81.6% (p = 0.876) and OS rates of 93.8 vs. 87.9% (p = 0.102), respectively. For LCP, both treatments resulted in similar survival, but more patients in the imatinib group experienced events (10-year EFS 40.8 vs. 66.7%, p = 0.047). The patients with higher EBMT risk scores had an inferior survival than those with lower scores (69.2 vs. 92.9%, p = 0.04). We concluded that RIST + IM was comparable to IM in terms of OS and EFS. However, RIST + IM was more affordable than IM alone in a 10-year scale. Thus, RIST + IM could be considered as an alternative treatment option, especially when the patients have low EBMT risk scores and demand a definite cure for CML.

[Treatment outcome, survival and their risk factors among new tuberculosis patients co-infected with HIV during the Ebola outbreak in Conakry].

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Camara, A; Sow, M S; Touré, A; Diallo, O H; Kaba, I; Bah, B; Diallo, T H; Diallo, M S; Guilavogui, T; Sow, O Y

2017-11-01

Mortality among TB/HIV co-infected patients remains high in Africa. The study aimed to estimate survival and associated factors in a cohort of TB/HIV co-infected patients who started tuberculosis treatment during the Ebola outbreak in Conakry, Guinea. A prospective cohort study was conducted from April 2014 to December 2015. TB patients with HIV co-infection were enrolled at the University Hospital of Conakry. Survival and risk factors were analyzed according to Kaplan-Meier's method, log-rank test and Cox's regression. Data from 573 patients were analyzed. From these, 86 (15.0%) died before the end of treatment, 52% occurring within eight weeks of treatment onset. Survival at 4, 12 and 24 weeks after the beginning of the TB treatment was 92%, 86% and 83%, respectively. Independent risk factors associated with death were in the cell CD4 <200 cells/mm 3 [adjusted hazard ratio (AHR): 2.25; 95% CI (confidence intervals): 1.16-4.37], opportunistic infections other than TB [AHR: 2.89; 95% CI: 1.39-6.02], and comorbidities [AHR: 4.12; 95% CI: 2.10-8.10]. An increase of one unit in hemoglobin [AHR: 0.81; 95% CI: 0.75-0.91] was protective of death. TB/HIV co-infected patients had a higher fatality rate during treatment of tuberculosis. Prevention of opportunistic infections, anemia and proper management of tuberculosis treatment in early comorbidities may improve survival for TB/HIV co-infected patients in restoring immune function. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Adherence to treatment guidelines and survival for older patients with stage II or III colon cancer in Texas from 2001 through 2011.

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Zhao, Hui; Zhang, Ning; Ho, Vivian; Ding, Minming; He, Weiguo; Niu, Jiangong; Yang, Ming; Du, Xianglin L; Zorzi, Daria; Chavez-MacGregor, Mariana; Giordano, Sharon H

2018-02-15

Treatment guidelines for colon cancer recommend colectomy with lymphadenectomy of at least 12 lymph nodes for patients with stage I to stage III disease as surgery adherence (SA) and adjuvant chemotherapy for individuals with stage III disease. Herein, the authors evaluated adherence to these guidelines among older patients in Texas with colon cancer and the associated survival outcomes. Using Texas Cancer Registry data linked with Medicare data, the authors included patients with AJCC stage II and III colon cancer who were aged ≥66 years and diagnosed between 2001 and 2011. SA and adjuvant chemotherapy adherence rates to treatment guidelines were estimated. The chi-square test, general linear regression, survival probability, and Cox regression were used to identify factors associated with adherence and survival. The rate of SA increased from 47.2% to 84% among 6029 patients with stage II or stage III disease from 2001 to 2011, and the rate of adjuvant chemotherapy increased from 48.9% to 53.1% for patients with stage III disease during the same time period. SA was associated with marital status, tumor size, surgeon specialty, and year of diagnosis. Patient age, sex, marital status, Medicare state buy-in status, comorbidity status, and year of diagnosis were found to be associated with adjuvant chemotherapy. The 5-year survival probability for patients receiving guideline-concordant treatment was the highest at 87% for patients with stage II disease and was 73% for those with stage III disease. After adjusting for demographic and tumor characteristics, improved cancer cause-specific survival was associated with the receipt of stage-specific, guideline-concordant treatment for patients with stage II or stage III disease. The adherence to guideline-concordant treatment among older patients with colon cancer residing in Texas improved over time, and was associated with better survival outcomes. Future studies should be focused on identifying interventions to

Clinical efficacy of edaravone for the treatment of amyotrophic lateral sclerosis.

Science.gov (United States)

Sawada, Hideyuki

2017-05-01

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disease. Although the pathogenesis remains unresolved, oxidative stress is known to play a pivotal role. Edaravone works in the central nervous system as a potent scavenger of oxygen radicals. In ALS mouse models, edaravone suppresses motor functional decline and nitration of tyrosine residues in the cerebrospinal fluid. Areas covered: Three clinical trials, one phase II open-label trial, and two phase III placebo-control randomized trials were reviewed. In all trials, the primary outcome measure was the changes in scores on the revised ALS functional rating scale (ALSFRS-R) to evaluate motor function of patients. Expert opinion: The phase II open label trial suggested that edaravone is safe and effective in ALS, markedly reducing 3-nitrotyrosine levels in the cerebrospinal fluid. One of the two randomized controlled trials showed beneficial effects in ALSFRS-R, although the differences were not significant. The last trial demonstrated that edaravone provided significant efficacy in ALSFRS-R scores over 24 weeks where concomitant use of riluzole was permitted. Eligibility was restricted to patients with a relatively short disease duration and preserved vital capacity. Therefore, combination therapy with edaravone and riluzole should be considered earlier.

Prolonged survival of patients with non-small-cell lung cancer with leptomeningeal carcinomatosis in the modern treatment era.

Science.gov (United States)

Riess, Jonathan W; Nagpal, Seema; Iv, Michael; Zeineh, Michael; Gubens, Matthew A; Ramchandran, Kavitha; Neal, Joel W; Wakelee, Heather A

2014-05-01

Leptomeningeal carcinomatosis (LM) is a severe complication of non-small-cell lung cancer (NSCLC) historically associated with poor prognosis. New chemotherapeutic and targeted treatments could potentially affect the natural history of LM. Patients with a pathologic diagnosis of NSCLC with LM treated at Stanford between 2003 and 2011 were identified via institutional databases and medical records. LM was defined by cerebrospinal fluid (CSF) that was positive for malignant cells or by LM enhancement on magnetic resonance imaging with gadolinium contrast. Retrospective, landmark analyses were performed to estimate survival. Statistical analyses were performed using SAS Enterprise Guide, version 4.3. LM was identified in 30 patients. All cases were adenocarcinoma; 60% of patients had a known or suspected driver mutation. The mean age was 58 years. Of the 30 patients, 67% were women; 70% were nonsmokers; 27% initially presented with LM; 84% received systemic treatment at or after development of LM; and 53% of these patients received modern systemic therapy for their LM, defined as a regimen containing pemetrexed, bevacizumab, or a tyrosine kinase inhibitor. Mean overall survival after LM diagnosis was 6 months (95% CI, 3-12). Patients who received modern systemic therapy for LM had decreased hazard of death (hazard ratio [HR], 0.24; P = .007). In this retrospective, single-institution analysis, median survival with LM was higher compared with historical experience. Patients who received modern systemic therapy for their LM had particularly good outcomes. These data provide evidence for improving survival outcomes in the modern treatment era for this difficult-to-treat complication. Copyright © 2014 Elsevier Inc. All rights reserved.

Post-treatment changes of tumour perfusion parameters can help to predict survival in patients with high-grade astrocytoma

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Sanz-Requena, Roberto; Marti-Bonmati, Luis [Hospital Quironsalud Valencia, Radiology Department, Valencia (Spain); Hospital Universitari i Politecnic La Fe, Grupo de Investigacion Biomedica en Imagen, Valencia (Spain); Revert-Ventura, Antonio J.; Salame-Gamarra, Fares [Hospital de Manises, Radiology Department, Manises (Spain); Garcia-Marti, Gracian [Hospital Quironsalud Valencia, Radiology Department, Valencia (Spain); Hospital Universitari i Politecnic La Fe, Grupo de Investigacion Biomedica en Imagen, Valencia (Spain); CIBER-SAM, Instituto de Salud Carlos III, Madrid (Spain); Perez-Girbes, Alexandre [Hospital Universitari i Politecnic La Fe, Grupo de Investigacion Biomedica en Imagen, Valencia (Spain); Molla-Olmos, Enrique [Hospital La Ribera, Radiology Department, Alzira (Spain)

2017-08-15

Vascular characteristics of tumour and peritumoral volumes of high-grade gliomas change with treatment. This work evaluates the variations of T2*-weighted perfusion parameters as overall survival (OS) predictors. Forty-five patients with histologically confirmed high-grade astrocytoma (8 grade III and 37 grade IV) were included. All patients underwent pre- and post-treatment T2*-weighted contrast-enhanced magnetic resonance (MR) imaging. Tumour, peritumoral and control volumes were segmented. Relative variations of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), K{sup trans-T2*}, k{sub ep-T2*}, v{sub e-T2*} and v{sub p-T2*} were calculated. Differences regarding tumour grade and surgical resection extension were evaluated with ANOVA tests. For each parameter, two groups were defined by non-supervised clusterisation. Survival analysis were performed on these groups. For the tumour region, the 90th percentile increase or stagnation of CBV was associated with shorter survival, while a decrease related to longer survival (393 ± 189 vs 594 ± 294 days; log-rank p = 0.019; Cox hazard-ratio, 2.31; 95% confidence interval [CI], 1.12-4.74). K{sup trans-T2*} showed similar results (414 ± 177 vs 553 ± 312 days; log-rank p = 0.037; hazard-ratio, 2.19; 95% CI, 1.03-4.65). The peritumoral area values showed no relationship with OS. Post-treatment variations of the highest CBV and K{sup trans-T2*} values in the tumour volume are predictive factors of OS in patients with high-grade gliomas. (orig.)

Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants.

Science.gov (United States)

Hehlmann, R; Lauseker, M; Saußele, S; Pfirrmann, M; Krause, S; Kolb, H J; Neubauer, A; Hossfeld, D K; Nerl, C; Gratwohl, A; Baerlocher, G M; Heim, D; Brümmendorf, T H; Fabarius, A; Haferlach, C; Schlegelberger, B; Müller, M C; Jeromin, S; Proetel, U; Kohlbrenner, K; Voskanyan, A; Rinaldetti, S; Seifarth, W; Spieß, B; Balleisen, L; Goebeler, M C; Hänel, M; Ho, A; Dengler, J; Falge, C; Kanz, L; Kremers, S; Burchert, A; Kneba, M; Stegelmann, F; Köhne, C A; Lindemann, H W; Waller, C F; Pfreundschuh, M; Spiekermann, K; Berdel, W E; Müller, L; Edinger, M; Mayer, J; Beelen, D W; Bentz, M; Link, H; Hertenstein, B; Fuchs, R; Wernli, M; Schlegel, F; Schlag, R; de Wit, M; Trümper, L; Hebart, H; Hahn, M; Thomalla, J; Scheid, C; Schafhausen, P; Verbeek, W; Eckart, M J; Gassmann, W; Pezzutto, A; Schenk, M; Brossart, P; Geer, T; Bildat, S; Schäfer, E; Hochhaus, A; Hasford, J

2017-11-01

Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400 mg/day (n=400) could be optimized by doubling the dose (n=420), adding interferon (IFN) (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival was 80% and 10-year relative survival was 92%. Survival between IM400 mg and any experimental arm was not different. In a multivariate analysis, risk group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs other) influenced survival significantly, but not any form of treatment optimization. Patients reaching the molecular response milestones at 3, 6 and 12 months had a significant survival advantage. For responders, monotherapy with IM400 mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients' and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease, more life-time can currently be gained by carefully addressing non-CML determinants of survival.

Clinical Outcomes of Volume-Modulated Arc Therapy in 205 Patients with Nasopharyngeal Carcinoma: An Analysis of Survival and Treatment Toxicities.

Directory of Open Access Journals (Sweden)

Rui Guo

Full Text Available To investigate the clinical efficacy and treatment toxicity of volume-modulated arc therapy (VMAT for nasopharyngeal carcinoma (NPC.205 VMAT-treated NPC patients from our cancer center were prospectively entrolled. All patients received 68-70 Gy irradiation based on the planning target volume of the primary gross tumor volume. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group Late Radiation Morbidity Scoring Criteria.The median follow-up period was 37.3 months (range, 6.3-45.1 months. The 3-year estimated local failure-free survival, regional failure-free survival, locoregional failure-free survival, distant metastasis-free survival, disease-free survival and overall survival were 95.5%, 97.0%, 94.0%, 92.1%, 86.8% and 97.0%, respectively. Cox regression analysis showed primary gross tumor volume, N stage and EBV-DNA to be independent predictors of VMAT outcomes (P < 0.05. The most common acute and late side effects were grade 2-3 mucositis (78% and xerostomia (83%, 61%, 34%, and 9% at 3, 6, 12 and 24 months after VMAT, respectively.VMAT for the primary treatment of NPC achieved very high locoregional control with a favorable toxicity profile. The time-saving benefit of VMAT will enable more patients to receive precision radiotherapy.

Do stage of disease, comorbidity or access to treatment explain socioeconomic differences in survival after ovarian cancer?

DEFF Research Database (Denmark)

Ibfelt, Else Helene; Dalton, Susanne Oksbjerg; Høgdall, Claus

2015-01-01

educated women. After adjustment for comorbid conditions, cancer stage, tumour histology, operation status and lifestyle factors, socioeconomic differences in survival persisted. CONCLUSIONS: Socioeconomic disparities in survival after ovarian cancer were to some extent, but not fully explained...... we retrieved information on prognostic factors, treatment information and lifestyle factors. Age, vital status, comorbidity, education, income and cohabitation status were ascertained from nationwide administrative registers. Associations were analyzed with logistic regression and Cox regression...... models. RESULTS: Educational level was weakly associated with cancer stage. Short education, lower income and living without a partner were related to poorer survival after ovarian cancer. Among women with early cancer stage, HR (95% CI) for death was 1.75 (1.20-2.54) in shorter compared to longer...

Overall survival after immunotherapy, tyrosine kinase inhibitors and surgery in treatment of metastatic renal cell cancer

DEFF Research Database (Denmark)

de Lichtenberg, Trine Honnens; Hermann, Gregers G.; Rorth, Mikael

2014-01-01

Abstract Objective. The aim of this study was to evaluate overall survival (OS) after treatment of metastatic renal cell carcinoma (mRCC) following the introduction of tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors. Material and methods. One-hundred and forty...

Brain metastases of solid tumour. Treatment distribution and analysis of survival in the period 1/01/2004 to 31/12/2008

International Nuclear Information System (INIS)

Xavier, F.; Rodriguez, R.; Lima, R.; Rios, A.; Mara, C.

2010-01-01

Objective: To retrospectively analyze the characteristics, treatments and survival analysis in patients with solid tumors with brain metastases (E IV) assisted in Unit Neuro-Oncology over a period of five years. Patients and methods: The records of patients (pts) with diagnosis of brain metastases from solid tumors assisted in Neuro-Oncology Unit, from 1/01/2004 and 31/12/2008. Results: 51 new patients carriers of brain metastases were treated with solid tumors. The median age at diagnosis was 57 years, ranging from 30 to 75. They corresponded to the male 37 and female 14 ratio 2.5 / 1. The majority was presented as metastases 31/51. The location was in the supratentorial region in 27 cases, posterior fossa in 11 and 13 were supra and infratentorial. In only 5 patients cranial MRI was performed in only one case and it changed the therapeutical strategy. In 35 patients he corresponded to the lung primary tumor (CBP), following cancer renal (5/51). Within the CBP, the most common histologic subtypes were to large cells and adenocarcinomas, 11 and 10, respectively. In 32 patients were not found dissemination elsewhere. Surgery + RT was performed in 30 cases, in 11 exclusive RT, exclusive surgery in 4 and 3 patients symptomatic treatment. In 39 cases did not Systemic treatment diagnosis. When a progression was only diagnosed It could make systemic treatment 5 pts. The median survival was 15.4 weeks (1-301 weeks). Conclusions: Lung cancer is the most common source of metastases brain, with a poor survival. The results of other characteristics patients, systemic treatments performed and survival according to the treatments performed will be presented during the congresss

Comparison of survival rates among different treatment methods of transcatheter hepatic arterial chemoembolization for hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Shim, Yong Woon; Lee, Jong Tae; Yoo, Hyung Sik; Lee, Do Yun; Jun, Pyoung Jun; Chang, So Yong [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

1996-06-01

To compare the survival rates of patients with hepatoma using different methods of transcatheter arterial chemoemblization(THAE). Four hundred and eighty three patients with hepatoma diagnosed by biopsy, serum alpha-fetoprotein, abdominal CT scan, abdominal ultrasonography or hepatic angiography were included, but not all had received surgical treatment. They were divided onto two groups according to Child's classification and into subgroups according to different methods of THAE. Five-tear survival rates among these groups were retrospectively compared. The patients were aged between 24 and 85(mean, 58) ; male to female ratio was 324 : 61 for those who received THAE (369 : 87 when only hepatic angiography was considered.). In the group with more than a single episode of chemoembolization, regardless of Child's classification, a better survival rate compared to the other groups with or without concommitant radiotherapy or without chemoembolization was noted. There was no difference in the survival rate of patients with multiple chemoembolization. moreover, no difference in this rate was observed no matter what chemotherapeutic agents, including Adriamycin, Cis-Diaminedichloroplatinum of I-131-Lipiodol, were used. Amortization by gelfoam in conjuction with Adriamycin resulted in no difference in survival rate regardless of frequency of chemoembolization. An improved survival rate was seen when multiple episodes of chemoembolization were applied, but no difference was seen when there was concomitant application of either gelfoam or radiotherapy. Two different chemotherapeutic agents, Adriamycin and Cis-Diaminedichloroplatinum, were used, but there was no difference between them in their effect on survival rates.

ALS (Amyotrophic Lateral Sclerosis)

Science.gov (United States)

... FDA) has approved the drugs riluzole (Rilutek) and edaravone (Radicava) to treat ALS. Riluzole is believed to ... reverse the damage already done to motor neurons. Edaravone has been shown to slow the decline in ...

Effects of site preparation treatments on early growth and survival of planted longleaf pine (Pinus palustris Mill.) seedlings in North Carolina

Science.gov (United States)

Benjamin O. Knapp; G. Geoff Wang; Joan L. Walker; Susan Cohen

2006-01-01

We tested the effects of eight site preparation treatments on early growth and survival of container-grown longleaf pine (Pinus palustris Mill.) seedlings. Treatments included an untreated check, six combinations of two initial vegetation control treatments (chopping or herbicide) with three planting site conditions (flat [no additional treatment],...

Longitudinal, population-based study of racial/ethnic differences in colorectal cancer survival: impact of neighborhood socioeconomic status, treatment and comorbidity

International Nuclear Information System (INIS)

Gomez, Scarlett Lin; O'Malley, Cynthia D; Stroup, Antoinette; Shema, Sarah J; Satariano, William A

2007-01-01

Colorectal cancer, if detected early, has greater than 90% 5-year survival. However, survival has been shown to vary across racial/ethnic groups in the United States, despite the availability of early detection methods. This study evaluated the joint effects of sociodemographic factors, tumor characteristics, census-based socioeconomic status (SES), treatment, and comorbidities on survival after colorectal cancer among and within racial/ethnic groups, using the SEER-Medicare database for patients diagnosed in 1992–1996, and followed through 1999. Unadjusted colorectal cancer-specific mortality rates were higher among Blacks and Hispanic males than whites (relative rates (95% confidence intervals) = 1.34 (1.26–1.42) and 1.16 (1.04–1.29), respectively), and lower among Japanese (0.78 (0.70–0.88)). These patterns were evident for all-cause mortality, although the magnitude of the disparity was larger for colorectal cancer mortality. Adjustment for stage accounted for the higher rate among Hispanic males and most of the lower rate among Japanese. Among Blacks, stage and SES accounted for about half of the higher rate relative to Whites, and within stage III colon and stages II/III rectal cancer, SES completely accounted for the small differentials in survival between Blacks and Whites. Comorbidity did not appear to explain the Black-White differentials in colorectal-specific nor all-cause mortality, beyond stage, and treatment (surgery, radiation, chemotherapy) explained a very small proportion of the Black-White difference. The fully-adjusted relative mortality rates comparing Blacks to Whites was 1.14 (1.09–1.20) for all-cause mortality and 1.21 (1.14–1.29) for colorectal cancer specific mortality. The sociodemographic, tumor, and treatment characteristics also had different impacts on mortality within racial/ethnic groups. In this comprehensive analysis, race/ethnic-specific models revealed differential effects of covariates on survival after colorectal

The effectiveness of RECIST on survival in patients with NSCLC receiving chemotherapy with or without target agents as first-line treatment.

Science.gov (United States)

Zhou, Ting; Zheng, Lie; Hu, Zhihuang; Zhang, Yang; Fang, Wenfeng; Zhao, Yuanyuan; Ge, Jieying; Zhao, Hongyun; Zhang, Li

2015-01-08

We analyzed the correlation between survival and antitumor effect evaluated by RECIST in advanced NSCLC patients with chemotherapy plus target therapy or not as first-line treatment, to examine the applicability of RECIST in this population. The patients were screened from 4 clinical trials (12621, 12006, FASTACT-I, and FASTACT-II), and those who received chemotherapy plus target therapy or chemotherapy alone were eligible. Among the 59 enrolled patients, 29 received combination therapy, while the other 30 received chemotherapy only. In the combination therapy group, patients with PR or SD had longer overall survival (OS) than those with PD (P chemotherapy alone group, compared with PD patients, either PR or SD group had no significant overall survival benefit (P = 0.690 and P = 0.528, respectively). In summary, for advanced NSCLC patients receiving chemotherapy plus target therapy as first-line treatment and evaluated by RECIST criteria, SD has the same overall survival benefit as PR, suggesting that antitumor effective evaluation by RECIST criteria cannot be translated to overall survival benefit especially for this kind of patients. Therefore, developing a more comprehensive evaluation method to perfect RECIST criteria is thus warranted for patients received target therapy in NSCLC.

Promotion of Metastasis-associated Gene Expression in Survived PANC-1 Cells Following Trichostatin A Treatment.

Science.gov (United States)

Chen, Zongjing; Yang, Yunxiu; Liu, Biao; Wang, Benquan; Sun, Meng; Zhang, Ling; Chen, Bicheng; You, Heyi; Zhou, Mengtao

2015-01-01

Histone deacetylase inhibitors represent a promising class of potential anticancer agents for the treatment of human malignancies. In this study, the effects of trichostatin A (TSA) on apoptosis, metastasis-associated gene expression, and activation of the Notch pathway in human pancreatic cancer cell lines were investigated. After treatment with TSA, cell viability and apoptosis were evaluated using the MTT [3-(4,5-dimethylthia-zol-2-yl)-2,5-diphenyltetrazolium bromide] assay, Hoechst 33258 staining, and flow cytometry. Moreover, RT-PCR and western blot analyses were performed to measure the expression levels of apoptosis-associated genes (Bcl-2, Bax, and caspase-3), metastasis-associated genes (E-cadherin, vimentin, and matrix metalloproteinases), and Notch pathway activation (Notch intracellular domain, NICD). The levels of matrix metalloproteinase 2 and NICD were also semi-quantified by immunoassay. Following treatment with TSA for 24 h, PANC-1, SW1990, and MIATACA-2 cells exhibited cell death. The MTT assay revealed that TSA significantly decreased cell viability in a dose-dependent manner in PANC-1 cells. The Hoechst 33258 staining and flow cytometry results evidenced a significant increase in PANC-1 cell apoptosis following TSA treatment. The expression levels of Bax and caspase-3 were increased significantly, whereas Bcl-2 was down-regulated after TSA treatment. In the PANC-1 cells that survived after TSA treatment, the expression levels of vimentin, E-cadherin, and MMP genes were altered by the promotion of potential metastasis and increased expression of NICD. TSA can induce apoptosis of pancreatic cancer cells. In addition, the up-regulation of metastasis-related genes and the activation of the Notch pathway in the survived PANC-1 cells may be associated with a too-low level of TSA or resistance to TSA.

Prolonged Minocycline Treatment Impairs Motor Neuronal Survival and Glial Function in Organotypic Rat Spinal Cord Cultures

Science.gov (United States)

Pinkernelle, Josephine; Fansa, Hisham; Ebmeyer, Uwe; Keilhoff, Gerburg

2013-01-01

Background Minocycline, a second-generation tetracycline antibiotic, exhibits anti-inflammatory and neuroprotective effects in various experimental models of neurological diseases, such as stroke, Alzheimer’s disease, amyotrophic lateral sclerosis and spinal cord injury. However, conflicting results have prompted a debate regarding the beneficial effects of minocycline. Methods In this study, we analyzed minocycline treatment in organotypic spinal cord cultures of neonatal rats as a model of motor neuron survival and regeneration after injury. Minocycline was administered in 2 different concentrations (10 and 100 µM) at various time points in culture and fixed after 1 week. Results Prolonged minocycline administration decreased the survival of motor neurons in the organotypic cultures. This effect was strongly enhanced with higher concentrations of minocycline. High concentrations of minocycline reduced the number of DAPI-positive cell nuclei in organotypic cultures and simultaneously inhibited microglial activation. Astrocytes, which covered the surface of the control organotypic cultures, revealed a peripheral distribution after early minocycline treatment. Thus, we further analyzed the effects of 100 µM minocycline on the viability and migration ability of dispersed primary glial cell cultures. We found that minocycline reduced cell viability, delayed wound closure in a scratch migration assay and increased connexin 43 protein levels in these cultures. Conclusions The administration of high doses of minocycline was deleterious for motor neuron survival. In addition, it inhibited microglial activation and impaired glial viability and migration. These data suggest that especially high doses of minocycline might have undesired affects in treatment of spinal cord injury. Further experiments are required to determine the conditions for the safe clinical administration of minocycline in spinal cord injured patients. PMID:23967343

Insurance Status and Differences in Treatment and Survival of Testicular Cancer Patients.

Science.gov (United States)

Kamel, Mohamed H; Elfaramawi, Mohammed; Jadhav, Supriya; Saafan, Ahmed; Raheem, Omer A; Davis, Rodney

2016-01-01

To explore the relationship between insurance status and differences in treatment and survival of testicular cancer patients. The Surveillance, Epidemiology, and End Results (SEER) database was utilized for this study. Between 2007 and 2011, 5986 testicular cancer patients were included in the SEER database. Patients were classified into nonseminoma and seminoma groups. We compared mortality rates, metastasis (M+) at diagnosis, and rates of adjuvant treatments between the uninsured (UI) and insured (I) populations. Overall, 2.64% of UI vs 1.36% of I died from testicular cancer (P = .025) and 16.73% of UI vs 10.52% of I had M+ at diagnosis (P testicular cancer (P = .326) and 25.92% of UI vs 18.46% of I had M+ at diagnosis (P = .0007). Also 17.28% of UI vs 20.88% of I had retroperitoneal lymph node dissection (RPLND; P = .1). In the seminoma group, 1.06% of UI vs 0.33% of I died from testicular cancer (P = .030) and 7.43% of UI vs 4.81% of I had M+ at diagnosis (P = .029). Also 34.75% of UI vs 48.4% of I received adjuvant radiation (P = .0083). The lack of health insurance predicted poor survival after adjusting for tumor stage, receiving adjuvant radiation or RPLND. UI testicular cancer patients present with more advanced cancer stages and have higher mortality rates than I patients. UI seminoma patients received less adjuvant radiation. This may be related to lack of access to care or more advanced cancer stage at diagnosis. Copyright © 2016. Published by Elsevier Inc.

Improved Survival Endpoints With Adjuvant Radiation Treatment in Patients With High-Risk Early-Stage Endometrial Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Elshaikh, Mohamed A., E-mail: melshai1@hfhs.org [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Vance, Sean; Suri, Jaipreet S. [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Mahan, Meredith [Public Health Science, Henry Ford Hospital, Detroit, Michigan (United States); Munkarah, Adnan [Division of Gynecologic Oncology, Department of Women' s Health Services, Henry Ford Hospital, Detroit, Michigan (United States)

2014-02-01

Purpose/Objective(s): To determine the impact of adjuvant radiation treatment (RT) on recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in patients with high-risk 2009 International Federation of Gynecology and Obstetrics stage I-II endometrial carcinoma. Methods and Materials: We identified 382 patients with high-risk EC who underwent hysterectomy. RFS, DSS, and OS were calculated from the date of hysterectomy by use of the Kaplan-Meier method. Cox regression modeling was used to explore the risks associated with various factors on survival endpoints. Results: The median follow-up time for the study cohort was 5.4 years. The median age was 71 years. All patients underwent hysterectomy and salpingo-oophorectomy, 93% had peritoneal cytology, and 85% underwent lymphadenectomy. Patients with endometrioid histology constituted 72% of the study cohort, serous in 16%, clear cell in 7%, and mixed histology in 4%. Twenty-three percent of patients had stage II disease. Adjuvant management included RT alone in 220 patients (57%), chemotherapy alone in 25 patients (7%), and chemoradiation therapy in 27 patients (7%); 110 patients (29%) were treated with close surveillance. The 5-year RFS, DSS, and OS were 76%, 88%, and 73%, respectively. On multivariate analysis, adjuvant RT was a significant predictor of RFS (P<.001) DSS (P<.001), and OS (P=.017). Lymphovascular space involvement was a significant predictor of RFS and DSS (P<.001). High tumor grade was a significant predictor for RFS (P=.038) and DSS (P=.025). Involvement of the lower uterine segment was also a predictor of RFS (P=.049). Age at diagnosis and lymphovascular space involvement were significant predictors of OS: P<.001 and P=.002, respectively. Conclusion: In the treatment of patients with high-risk features, our study suggests that adjuvant RT significantly improves recurrence-free, disease-specific, and overall survival in patients with early-stage endometrial carcinoma

Coyote removal, understory cover, and survival of white-tailed deer neonates: Coyote Control and Fawn Survival

Energy Technology Data Exchange (ETDEWEB)

Kilgo, John C. [USDA Forest Service; Southern Research Station, New Ellenton, SC (United States); Vukovich, Mark [USDA Forest Service; Southern Research Station, New Ellenton, SC (United States); Ray, H. Scott [USDA Forest Service, Savannah River; New Ellenton, SC (United States); Shaw, Christopher E. [USDA Forest Service; Southern Research Station, New Ellenton, SC (United States); Ruth, Charles [South Carolina Dept. of Natural Resources, Columbia, SC (United States)

2014-09-01

Predation by coyotes (Canis latrans) on white-tailed deer (Odocoileus virginianus) neonates has led to reduced recruitment in many deer populations in southeastern North America. This low recruitment combined with liberal antlerless deer harvest has resulted in declines in some deer populations, and consequently, increased interest in coyote population control. We investigated whether neonate survival increased after coyote removal, whether coyote predation on neonates was additive to other mortality sources, and whether understory vegetation density affected neonate survival. We monitored neonate survival for 4 years prior to (2006–2009) and 3 years during (2010–2012) intensive coyote removal on 3 32-km² units on the United States Department of Energy’s Savannah River Site, South Carolina. We removed 474 coyotes (1.63 coyotes/km² per unit per year), reducing coyote abundance by 78% from pre-removal levels. The best model (w_i = 0.927) describing survival probability among 216 radio-collared neonates included a within-year quadratic time trend variable, date of birth, removal treatment, and a varying removal year effect. Under this model, survival differed between pre-treatment and removal periods and it differed among years during the removal period, being >100% greater than pre-treatment survival (0.228) during the first removal year (0.513), similar to pre-treatment survival during the second removal year (0.202), and intermediate during the third removal year (0.431). Despite an initial increase, the overall effect of coyote removal on neonate survival was modest. Mortality rate attributable to coyote predation was lowest during the first removal year (0.357) when survival was greatest, but the mortality rate from all other causes did not differ between the pretreatment period and any year during removals, indicating that coyote predation acted as an additive source of mortality. Survival probability was not related to

A retrospective analysis of the results of p(65) + Be neutron therapy for the treatment of prostate adenocarcinoma at the cyclotron of Louvain-la-Neuve. Part I: survival and progression-free survival

International Nuclear Information System (INIS)

Scalliet, P.G.M.; Remouchamps, V.; Wambersie, A.; Richard, F.; Lhoas, F.; Van Glabbeke, M.; Curran, D.; Van Cangh, P.; Ledent, T.

2001-01-01

Purpose. -To retrospectively evaluate survival, progression free survival (PFS) and biological response in a series of patients irradiated with mixed neutron/photon beams for locally advanced prostate cancer in our institution. Patients and methods. - Three hundred and eight patients were treated between January 1990 and December 1996. Fifty-five of these were recruited for pT3 or pN1 tumors after radical prostatectomy. Neo-adjuvant androgen deprivation was given in 106 patients. The treatment protocol consisted of a mixed photon/neutron irradiation in a two-to-three proportion, up to a total equivalent dose of 66 Gy (assuming a clinical RBE value of 2.8). Pre- and post-treatment PSA determinations were available in practically all cases. Study endpoints were overall survival (OAS) and progression-free survival (PFS). The Cox proportional hazard regression model was used to investigate the prognostic value of baseline characteristics on survival and progression-free survival were a progression was defined as local, regional, metastatic or biological progression. Mean age was 69 years (49-86); mean pretreatment PSA was 15 (0.5-330) in all patients and 14 (0.5-160) in those receiving neo-adjuvant hormonotherapy; seven patients only had an initial PSA S 4 ng/mL; 15% were T1, 46% were T2, 28% were T3 or pT3 and 4% were T4 (7% unspecified); WHO grade of differentiation was I in 38%, II in 38% and III in 14% (5% unspecified). Results. -The median follow-up was 2.8 years (0-7.8). Five year overall survival (OAS) was 79% (95% CI: 71-87%) and 5-year progression-free survival (PFS) was 64% (95% Cl: 54-74%) for the entire series. PFS in patients with an initial PSA >- 20 ng/mL was the same. PFS could be predicted by two optimal Cox regression models, one including histological grade (p = 0.003) and initial PSA (p = 0.0009) as cofactors, the other including histological grade (p = 0.003) and T stage (p = 0.02). The main prognostic factors for overall survival were PSA and age

Effect of changes in treatment practice on survival for cervical cancer: results from a population-based study in Manitoba, Canada

International Nuclear Information System (INIS)

Kang, Yoon-Jung; O’Connell, Dianne L.; Lotocki, Robert; Kliewer, Erich V.; Goldsbury, David E.; Demers, Alain A.; Canfell, Karen

2015-01-01

Results from clinical trials in the 1990s led to changes in the recommended treatment for the standard therapy for stage IIB-IVA cervical cancer from radiotherapy alone to chemo-radiotherapy. We conducted the first population-based study in Canada to investigate temporal treatment patterns for cervical cancer and long-term survival in relation to these changes in the treatment guidelines. Detailed information on stage and treatment for 1085 patients diagnosed with cervical cancer in 1984–2008 and identified from the population-based Manitoba Cancer Registry (MCR) in Canada was obtained from clinical chart review and the MCR. Factors associated with receiving guideline treatment were identified using logistic regression. All cause and cervical cancer specific survival were compared in patients who were and were not treated as recommended in the guidelines, using Cox proportional hazards models. The median follow-up time was 6.4 years (range: 0.05–26.5 years). The proportion of women who received guideline treatment was 79 % (95 % confidence interval [CI]: 76–81 %). However, the likelihood of being treated according to the guidelines over time was modified by age (p < 0.0001) and tumour stage at diagnosis (p = 0.002). Women who were treated according to the guidelines after the change in recommended clinical practice (1999–2008) had a significantly lower risk of death from all causes and from cervical cancer. This was driven by lower mortality rates in cases with stage IIB-IVA tumours (all causes of death: hazard ratio [HR] = 0.60, 95 % CI: 0.43–0.82, p = 0.002; cervical cancer related death: HR = 0.64, 95 % CI: 0.44–0.93, p = 0.02). The management of cervical cancer patients in Manitoba, Canada was in good agreement with treatment guidelines although reasons for departure from the guideline recommendations could not be examined further due to lack of data. Treatment of stage IIB-IVA cervical cancers with recommended concurrent chemo-radiotherapy, which

Overstory removal and residue treatments affect soil surface, air, and soil temperature: implications for seedling survival

Science.gov (United States)

Roger D. Hungerford; Ronald E. Babbitt

1987-01-01

Potentially lethal ground surface temperatures were measured at three locations in the Northern Rocky Mountains but occurred more frequently under treatments with greater overstory removal. Observed maximum and minimum temperatures of exposed surfaces are directly related to the thermal properties of the surface materials. Survival of planted seedlings was consistent...

Simvastatin Treatment Improves Survival in a Murine Model of Burn Sepsis

Science.gov (United States)

Beffa, David C; Fischman, Alan J.; Fagan, Shawn P.; Hamrahi, Victoria F.; Kaneki, Masao; Yu, Yong-Ming; Tompkins, Ronald G.; Carter, Edward A.

2014-01-01

Infection is the most common and most serious complication of a major burn injury related to burn size. Despite improvements in antimicrobial therapies sepsis still accounts for 50–60% of deaths in burn patients. Given the acute onset and unpredictable nature of sepsis, primary prevention was rarely attempted in its management. However, recent studies have demonstrated that statin treatment can decrease mortality is a murine model of sepsis by preservation of cardiac function and reversal of inflammatory alterations. In addition, it has been shown that treatment with statins is associated with reduced incidence of sepsis in human patients. In the current study groups of CD1 male mice (n=12) were anesthetized and subjected to a dorsal 30% TBSA scald burn injury. Starting 2 hours post burn, the animals were divided into a treatment group receiving 0.2 µ/g simvastatin or a sham group receiving placebo. Simvastatin and placebo were administered by intraperitoneal injection with two dosing regimens; once daily and every 12 hours. On Post burn day 7 cecal ligation and puncture with a 21-gauge needle was performed under ketamine/xylazine anesthesia and the two different dosing schedules were continued. A simvastatin dose dependant improvement in survival was observed in the burn sepsis model. PMID:21145172

Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma.

Science.gov (United States)

Facon, Thierry; Dimopoulos, Meletios A; Dispenzieri, Angela; Catalano, John V; Belch, Andrew; Cavo, Michele; Pinto, Antonello; Weisel, Katja; Ludwig, Heinz; Bahlis, Nizar J; Banos, Anne; Tiab, Mourad; Delforge, Michel; Cavenagh, Jamie D; Geraldes, Catarina; Lee, Je-Jung; Chen, Christine; Oriol, Albert; De La Rubia, Javier; White, Darrell; Binder, Daniel; Lu, Jin; Anderson, Kenneth C; Moreau, Philippe; Attal, Michel; Perrot, Aurore; Arnulf, Bertrand; Qiu, Lugui; Roussel, Murielle; Boyle, Eileen; Manier, Salomon; Mohty, Mohamad; Avet-Loiseau, Herve; Leleu, Xavier; Ervin-Haynes, Annette; Chen, Guang; Houck, Vanessa; Benboubker, Lotfi; Hulin, Cyrille

2018-01-18

This FIRST trial final analysis examined survival outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) treated with lenalidomide and low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks). The primary endpoint was progression-free survival (PFS; primary comparison: Rd continuous vs MPT). Overall survival (OS) was a key secondary endpoint (final analysis prespecified ≥60 months' follow-up). Patients were randomized to Rd continuous (n = 535), Rd18 (n = 541), or MPT (n = 547). At a median follow-up of 67 months, PFS was significantly longer with Rd continuous vs MPT (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.59-0.79; P < .00001) and was similarly extended vs Rd18. Median OS was 10 months longer with Rd continuous vs MPT (59.1 vs 49.1 months; HR, 0.78; 95% CI, 0.67-0.92; P = .0023), and similar with Rd18 (62.3 months). In patients achieving complete or very good partial responses, Rd continuous had an ≈30-month longer median time to next treatment vs Rd18 (69.5 vs 39.9 months). Over half of all patients who received second-line treatment were given a bortezomib-based therapy. Second-line outcomes were improved in patients receiving bortezomib after Rd continuous and Rd18 vs after MPT. No new safety concerns, including risk for secondary malignancies, were observed. Treatment with Rd continuous significantly improved survival outcomes vs MPT, supporting Rd continuous as a standard of care for patients with transplant-ineligible NDMM. This trial was registered at www.clinicaltrials.gov as #NCT00689936 and EudraCT as 2007-004823-39. © 2018 by The American Society of Hematology.

Survival after stereotactic biopsy of malignant gliomas

International Nuclear Information System (INIS)

Coffey, R.J.; Lunsford, L.D.; Taylor, F.H.

1988-01-01

For many patients with malignant gliomas in inaccessible or functionally important locations, stereotactic biopsy followed by radiation therapy (RT) may be a more appropriate initial treatment than craniotomy and tumor resection. We studied the long term survival in 91 consecutive patients with malignant gliomas diagnosed by stereotactic biopsy: 64 had glioblastoma multiforme (GBM) and 27 had anaplastic astrocytoma (AA). Sixty-four per cent of the GBMs and 33% of the AAs involved deep or midline cerebral structures. The treatment prescribed after biopsy, the tumor location, the histological findings, and the patient's age at presentation (for AAs) were statistically important factors determining patient survival. If adequate RT (tumor dose of 5000 to 6000 cGy) was not prescribed, the median survival was less than or equal to 11 weeks regardless of tumor histology or location. The median survival for patients with deep or midline tumors who completed RT was similar in AA (19.4 weeks) and GBM (27 weeks) cases. Histology was an important predictor of survival only for patients with adequately treated lobar tumors. The median survival in lobar GBM patients who completed RT was 46.9 weeks, and that in lobar AA patients who completed RT was 129 weeks. Cytoreductive surgery had no statistically significant effect on survival. Among the clinical factors examined, age of less than 40 years at presentation was associated with prolonged survival only in AA patients. Constellations of clinical features, tumor location, histological diagnosis, and treatment prescribed were related to survival time

Contribution of FKBP5 genetic variation to gemcitabine treatment and survival in pancreatic adenocarcinoma.

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Katarzyna A Ellsworth

Full Text Available FKBP51, (FKBP5, is a negative regulator of Akt. Variability in FKBP5 expression level is a major factor contributing to variation in response to chemotherapeutic agents including gemcitabine, a first line treatment for pancreatic cancer. Genetic variation in FKBP5 could influence its function and, ultimately, treatment response of pancreatic cancer.We set out to comprehensively study the role of genetic variation in FKBP5 identified by Next Generation DNA resequencing on response to gemcitabine treatment of pancreatic cancer by utilizing both tumor and germline DNA samples from 43 pancreatic cancer patients, including 19 paired normal-tumor samples. Next, genotype-phenotype association studies were performed with overall survival as well as with FKBP5 gene expression in tumor using the same samples in which resequencing had been performed, followed by functional genomics studies.In-depth resequencing identified 404 FKBP5 single nucleotide polymorphisms (SNPs in normal and tumor DNA. SNPs with the strongest associations with survival or FKBP5 expression were subjected to functional genomic study. Electromobility shift assay showed that the rs73748206 "A(T" SNP altered DNA-protein binding patterns, consistent with significantly increased reporter gene activity, possibly through its increased binding to Glucocorticoid Receptor (GR. The effect of rs73748206 was confirmed on the basis of its association with FKBP5 expression by affecting the binding to GR in lymphoblastoid cell lines derived from the same patients for whom DNA was used for resequencing.This comprehensive FKBP5 resequencing study provides insights into the role of genetic variation in variation of gemcitabine response.

Survival and breast relapse in 3834 patients with T1-T2 breast cancer after conserving surgery and adjuvant treatment

International Nuclear Information System (INIS)

Livi, Lorenzo; Paiar, Fabiola; Saieva, Calogero; Scoccianti, Silvia; Dicosmo, Dora; Borghesi, Simona; Agresti, Benedetta; Nosi, Fabiano; Orzalesi, Lorenzo; Santini, Roberto; Barca, Raffaella; Biti, Giampaolo P.

2007-01-01

Purpose: The aim of the present analysis is to determine the long-term results in terms of breast relapse and specific survival in patients treated with conserving surgery and adjuvant treatment for early breast cancer. Methods: From January 1980 to December 2001, 3834 patients with pT1-T2 breast cancer were treated consecutively at the University of Florence. The median age of the patient population was 55 years (range 30-80). All patients were followed for a median of 7.4 years (range 0.6 year to 22.5 years). The crude probability of survival (or local recurrence) was estimated by using Kaplan-Meier method, and survival (or local recurrence) comparisons were carried out using Cox proportional hazard regression models. Results: The Cox regression model by stepwise selection showed some parameters, such as chemotherapy (HR 1.53; CI 1.19-1.95), pT status (HR 1.62, CI 1.31-2.01), positive axillary lymph nodes (HR 1.92, CI 1.66-2.22), and local recurrence (HR 4.58; CI 3.66-5.73), as independent prognostic factors for breast cancer death. Moreover, we found lower rate survival among patients treated before 1991 in comparison to women treated after 1991 (p = 0.0001) probably due to inadequate treatment. For local disease free survival, age at presentation (HR 0.47; CI 0.35-0.63), use of tamoxifen (HR 0.42; CI 0.25-0.71), surgical margins (HR 2.00; CI 1.21-3.30), and chemotherapy (HR 0.53; CI 0.31-0.91) emerged by multivariate analyses as significant breast relapse predictors. Conclusion: In our experience breast conserving surgery followed by adjuvant radiotherapy treatment gives high rates of local control in women with early breast cancer. The use of routinely adjuvant chemotherapy and hormone therapy lowered the local recurrence and probably the modification of therapeutic approach in the last decades also improved the specific survival

Regional variations in cancer survival: Impact of tumour stage, socioeconomic status, comorbidity and type of treatment in Norway.

Science.gov (United States)

Skyrud, Katrine Damgaard; Bray, Freddie; Eriksen, Morten Tandberg; Nilssen, Yngvar; Møller, Bjørn

2016-05-01

Cancer survival varies by place of residence, but it remains uncertain whether this reflects differences in tumour, patient and treatment characteristics (including tumour stage, indicators of socioeconomic status (SES), comorbidity and information on received surgery and radiotherapy) or possibly regional differences in the quality of delivered health care. National population-based data from the Cancer Registry of Norway were used to identify cancer patients diagnosed in 2002-2011 (n = 258,675). We investigated survival from any type of cancer (all cancer sites combined), as well as for the six most common cancers. The effect of adjusting for prognostic factors on regional variations in cancer survival was examined by calculating the mean deviation, defined by the mean absolute deviation of the relative excess risks across health services regions. For prostate cancer, the mean deviation across regions was 1.78 when adjusting for age and sex only, but decreased to 1.27 after further adjustment for tumour stage. For breast cancer, the corresponding mean deviations were 1.34 and 1.27. Additional adjustment for other prognostic factors did not materially change the regional variation in any of the other sites. Adjustment for tumour stage explained most of the regional variations in prostate cancer survival, but had little impact for other sites. Unexplained regional variations after adjusting for tumour stage, SES indicators, comorbidity and type of treatment in Norway may be related to regional inequalities in the quality of cancer care. © 2015 UICC.

Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin's lymphoma: a systematic review

DEFF Research Database (Denmark)

Herbst, Christine; Rehan, Fareed A; Brillant, Corinne

2010-01-01

as well as conference proceedings from January 1980 to February 2009 for randomized controlled trials comparing chemotherapy alone versus the same chemotherapy regimen plus radiotherapy. Progression free survival and similar outcomes were analyzed together as tumor control. Effect measures used were......Combined modality treatment (CMT) of chemotherapy followed by localized radiotherapy is standard treatment for patients with early stage Hodgkin's lymphoma. However, the role of radiotherapy has been questioned recently and some clinical study groups advocate chemotherapy only for this indication....... We thus performed a systematic review with meta-analysis of randomized controlled trials comparing chemotherapy alone with CMT in patients with early stage Hodgkin's lymphoma with respect to response rate, tumor control and overall survival (OS). We searched Medline, EMBASE and the Cochrane Library...

Adherence to treatment guidelines for primary sarcomas affects patient survival: a side study of the European CONnective TIssue CAncer NETwork (CONTICANET).

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Rossi, C R; Vecchiato, A; Mastrangelo, G; Montesco, M C; Russano, F; Mocellin, S; Pasquali, S; Scarzello, G; Basso, U; Frasson, A; Pilati, P; Nitti, D; Lurkin, A; Ray-Coquard, I

2013-06-01

The impact of adherence to clinical practice guidelines (CPGs) for loco-regional treatment (i.e. surgery and radiotherapy) and chemotherapy on local disease control and survival in sarcoma patients was investigated in a European study conducted in an Italian region (Veneto). The completeness of the adherence to the Italian CPGs for sarcomas treatment was assessed by comparing the patient's charts and the CPGs. Propensity score-adjusted multivariate survival analysis was used to assess the impact of CPGs adherence on patient clinical outcomes. A total of 151 patients were included. Adherence to CPGs for loco-regional therapy and chemotherapy was observed in 106 out of 147 (70.2%) and 129 out of 139 (85.4%) patients, respectively. Non-adherence to CPGs for loco-regional treatment was independently associated with AJCC stage III disease [odds ratio (OR) 1.77, P = 0.011] and tumor-positive excision margin (OR 3.55, P = 0.003). Patients not treated according to the CPGs were at a higher risk of local recurrence [hazard ratio (HR) 5.4, P < 0.001] and had a shorter sarcoma-specific survival (HR 4.05, P < 0.001), independently of tumor stage. Incomplete adherence to CPGs for loco-regional treatment of sarcomas was associated with worse prognosis in patients with non-metastatic tumors.

Robust estimation of the expected survival probabilities from high-dimensional Cox models with biomarker-by-treatment interactions in randomized clinical trials

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Nils Ternès

2017-05-01

Full Text Available Abstract Background Thanks to the advances in genomics and targeted treatments, more and more prediction models based on biomarkers are being developed to predict potential benefit from treatments in a randomized clinical trial. Despite the methodological framework for the development and validation of prediction models in a high-dimensional setting is getting more and more established, no clear guidance exists yet on how to estimate expected survival probabilities in a penalized model with biomarker-by-treatment interactions. Methods Based on a parsimonious biomarker selection in a penalized high-dimensional Cox model (lasso or adaptive lasso, we propose a unified framework to: estimate internally the predictive accuracy metrics of the developed model (using double cross-validation; estimate the individual survival probabilities at a given timepoint; construct confidence intervals thereof (analytical or bootstrap; and visualize them graphically (pointwise or smoothed with spline. We compared these strategies through a simulation study covering scenarios with or without biomarker effects. We applied the strategies to a large randomized phase III clinical trial that evaluated the effect of adding trastuzumab to chemotherapy in 1574 early breast cancer patients, for which the expression of 462 genes was measured. Results In our simulations, penalized regression models using the adaptive lasso estimated the survival probability of new patients with low bias and standard error; bootstrapped confidence intervals had empirical coverage probability close to the nominal level across very different scenarios. The double cross-validation performed on the training data set closely mimicked the predictive accuracy of the selected models in external validation data. We also propose a useful visual representation of the expected survival probabilities using splines. In the breast cancer trial, the adaptive lasso penalty selected a prediction model with 4

Estimation of age- and stage-specific Catalan breast cancer survival functions using US and Catalan survival data

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2009-01-01

Background During the last part of the 1990s the chance of surviving breast cancer increased. Changes in survival functions reflect a mixture of effects. Both, the introduction of adjuvant treatments and early screening with mammography played a role in the decline in mortality. Evaluating the contribution of these interventions using mathematical models requires survival functions before and after their introduction. Furthermore, required survival functions may be different by age groups and are related to disease stage at diagnosis. Sometimes detailed information is not available, as was the case for the region of Catalonia (Spain). Then one may derive the functions using information from other geographical areas. This work presents the methodology used to estimate age- and stage-specific Catalan breast cancer survival functions from scarce Catalan survival data by adapting the age- and stage-specific US functions. Methods Cubic splines were used to smooth data and obtain continuous hazard rate functions. After, we fitted a Poisson model to derive hazard ratios. The model included time as a covariate. Then the hazard ratios were applied to US survival functions detailed by age and stage to obtain Catalan estimations. Results We started estimating the hazard ratios for Catalonia versus the USA before and after the introduction of screening. The hazard ratios were then multiplied by the age- and stage-specific breast cancer hazard rates from the USA to obtain the Catalan hazard rates. We also compared breast cancer survival in Catalonia and the USA in two time periods, before cancer control interventions (USA 1975–79, Catalonia 1980–89) and after (USA and Catalonia 1990–2001). Survival in Catalonia in the 1980–89 period was worse than in the USA during 1975–79, but the differences disappeared in 1990–2001. Conclusion Our results suggest that access to better treatments and quality of care contributed to large improvements in survival in Catalonia. On

A Pilot Trial of Pioglitazone HCl and Tretinoin in ALS: Cerebrospinal Fluid Biomarkers to Monitor Drug Efficacy and Predict Rate of Disease Progression

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Todd D. Levine

2012-01-01

Full Text Available Objectives. To determine if therapy with pioglitazone HCl and tretinoin could slow disease progression in patients with ALS. Levels of tau and pNFH in the cerebrospinal fluid were measured to see if they could serve as prognostic indicators. Methods. 27 subjects on stable doses of riluzole were enrolled. Subjects were randomized to receive pioglitazone 30 mg/d and tretinoin 10 mg/BID for six months or two matching placebos. ALSFRS-R scores were followed monthly. At baseline and at the final visit, lumbar punctures (LPs were performed to measure cerebrospinal fluid (CSF biomarker levels. Results. Subjects treated with tretinoin, pioglitazone, and riluzole had an average rate of decline on the ALSFRS-R scale of −1.02 points per month; subjects treated with placebo and riluzole had a rate of decline of -.86 (P=.18. Over six months of therapy, CSF tau levels decreased in subjects randomized to active treatment and increased in subjects on placebo. Further higher levels of pNF-H at baseline correlated with a faster rate of progression. Conclusion. ALS patients who were treated with tretinoin and pioglitazone demonstrated no slowing on their disease progression. Interestingly, the rate of disease progression was strongly correlated with levels of pNFH in the CSF at baseline.

Survival among children and adults with sickle cell disease in Belgium: Benefit from hydroxyurea treatment.

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Lê, Phu Quoc; Gulbis, Béatrice; Dedeken, Laurence; Dupont, Sophie; Vanderfaeillie, Anna; Heijmans, Catherine; Huybrechts, Sophie; Devalck, Christine; Efira, André; Dresse, Marie-Françoise; Rozen, Laurence; Benghiat, Fleur Samantha; Ferster, Alina

2015-11-01

To evaluate the survival of patients with sickle cell disease (SCD) recorded in the Belgian SCD Registry and to assess the impact of disease-modifying treatments (DMT). The Registry created in 2008 included patients of eight centers. All available data in 2008 were retrospectively encoded in the database. After 2008 and until 2012, all data were recorded prospectively for already registered patients as well as newly diagnosed subjects. Data were registered from neonatal screening or from diagnosis (first contact) until last follow-up or death. Data included diagnosis, demography, and outcome data. We collected data from 469 patients over a 5,110 patient years (PY) follow-up period. The global mortality rate was low (0.25/100 PY), although 13 patients died (2.8%) and was similar between children, adolescents (10-18 years), and young adults (P = 0.76). Out of the cohort, 185 patients received hydroxyurea at last follow-up (median duration of treatment: 10.3 years), 90 underwent hematopoietic stem cell transplantation (HSCT), 24 were chronically transfused, and 170 had never had any DMT. Hydroxyurea showed significant benefit on patients outcome as reflected by a lower mortality rate compared to transplanted individuals or people without DMT (0.14, 0.36, and 0.38 per 100 PY, respectively) and by higher Kaplan-Meier estimates of 15 year survival (99.4%) compared to HSCT (93.8%; P = 0.01) or no DMT groups (95.4%; P = 0.04). SCD mortality in Belgium is low with no increase observed in young adults. Patients treated with hydroxyurea demonstrate a significant benefit in survival when compared to those without DMT or transplanted. © 2015 Wiley Periodicals, Inc.

Neurogenesis and Increase in Differentiated Neural Cell Survival via Phosphorylation of Akt1 after Fluoxetine Treatment of Stem Cells

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Anahita Rahmani

2013-01-01

Full Text Available Fluoxetine (FLX is a selective serotonin reuptake inhibitor (SSRI. Its action is possibly through an increase in neural cell survival. The mechanism of improved survival rate of neurons by FLX may relate to the overexpression of some kinases such as Akt protein. Akt1 (a serine/threonine kinase plays a key role in the modulation of cell proliferation and survival. Our study evaluated the effects of FLX on mesenchymal stem cell (MSC fate and Akt1 phosphorylation levels in MSCs. Evaluation tests included reverse transcriptase polymerase chain reaction, western blot, and immunocytochemistry assays. Nestin, MAP-2, and β-tubulin were detected after neurogenesis as neural markers. Ten μM of FLX upregulated phosphorylation of Akt1 protein in induced hEnSC significantly. Also FLX did increase viability of these MSCs. Continuous FLX treatment after neurogenesis elevated the survival rate of differentiated neural cells probably by enhanced induction of Akt1 phosphorylation. This study addresses a novel role of FLX in neurogenesis and differentiated neural cell survival that may contribute to explaining the therapeutic action of fluoxetine in regenerative pharmacology.

The impact of bevacizumab treatment on survival and quality of life in newly diagnosed glioblastoma patients

DEFF Research Database (Denmark)

Poulsen, Hans Skovgaard; Urup, Thomas; Michaelsen, Signe Regner

2014-01-01

in newly diagnosed GBM patients have been performed during recent years to test the hypothesis that newly diagnosed GBM patients should be treated with standard multimodality treatment, in combination with bevacizumab, in order to prolong life and maintain or improve quality of life. The results...... treatment is therefore to prolong life, with a maintenance or improvement of quality of life. GBM is a highly vascular tumor and overexpresses the vascular endothelial growth factor A, which promotes angiogenesis. Preclinical data have suggested that anti-angiogenic treatment efficiently inhibits tumor...... growth. Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor A, and treatment has shown impressive response rates in recurrent GBM. In addition, it has been shown that response is correlated to prolonged survival and improved quality of life. Several investigations...

Daily clinical practice and patterns of care in upper gastrointestinal cancer treatment : Toxicity, quality of life and survival

NARCIS (Netherlands)

Haj Mohammad, N.

2016-01-01

Upper gastrointestinal (GI) cancers - esophageal, gastric and pancreatic cancer - have a dismal prognosis. Despite treatment with curative intent, randomized clinical trials report 5-year survival rates of only 47% in esophageal cancer, 36 % in gastric cancer and 21% in pancreatic cancer. In

Current view and perspectives in amyotrophic lateral sclerosis

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Stéphane Mathis

2017-01-01

Full Text Available Amyotrophic lateral sclerosis (ALS, identified as a distinct clinical entity by Charcot since the end of the nineteenth century, is a devastating and fatal neurodegenerative disorder that affects motor neurons in the brain, brainstem and spinal cord. Survival of patients with ALS is associated with several factors such as clinical phenotype, age at onset, gender, early presence of respiratory failure, weight loss and treatment with Riluzole (the only disease-modifying drug approved for this disease. Nowadays, there is still no curative treatment for ALS: palliative care and symptomatic treatment are therefore essential components in the management of these patients. Nevertheless, the scientific knowledge in the field of ALS motor neuron degeneration is growing, with the prospect of new treatments. Based on this physiopathological knowledge, several new therapeutic targets are being studied, involving various mechanisms such as excitotoxicity, neuroinflammation, mitochondrial dysfunction, oxidative stress, RNA metabolism and other attractive concepts. Moreover, it is also important to identify reliable biomarkers that will be essential components for future therapeutic development and study design in ALS. In this review, we present the main recent advances and promising therapeutics and biomarkers in the field of ALS.

Early post-treatment FDG PET predicts survival after {sup 90}Y microsphere radioembolization in liver-dominant metastatic colorectal cancer

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Sabet, Amir; Aouf, Anas; Sabet, Amin; Ghamari, Shahab; Biersack, Hans-Juergen [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Meyer, Carsten; Pieper, Claus C. [University Hospital, Department of Radiology, Bonn (Germany); Mayer, Karin [University Hospital, Department of Medicine and Oncology, Bonn (Germany); Ezziddin, Samer [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Saarland University, Department of Nuclear Medicine, Homburg (Germany)

2014-10-29

The aim of this study was to evaluate the predictive value of early metabolic response 4 weeks post-treatment using {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with unresectable hepatic metastases of colorectal cancer (CRC) undergoing radioembolization (RE) with {sup 90}Y-labelled microspheres. A total of 51 consecutive patients with liver-dominant metastases of CRC were treated with RE and underwent {sup 18}F-FDG PET/CT at baseline and 4 weeks after RE. In each patient, three hepatic metastases with the highest maximum standardized uptake value (SUV{sub max}) were selected as target lesions. Metabolic response was defined as >50 % reduction of tumour to liver ratios. Survival analyses using Kaplan-Meier and multivariate analyses were performed to identify prognostic factors for overall survival (OS). Investigated baseline characteristics included age (>60 years), performance status (Eastern Cooperative Oncology Group >1), bilirubin (>1.0 mg/dl), hepatic tumour burden (>25 %) and presence of extrahepatic disease. The median OS after RE was 7 months [95 % confidence interval (CI) 5-8]; early metabolic responders (n = 33) survived longer than non-responders (p < 0.001) with a median OS of 10 months (95 % CI 3-16) versus 4 months (95 % CI 2-6). Hepatic tumour burden also had significant impact on treatment outcome (p < 0.001) with a median OS of 5 months (95 % CI, 3-7) for patients with >25 % metastatic liver replacement vs 14 months (95 % CI 6-22) for the less advanced patients. Both factors (early metabolic response and low hepatic tumour burden) remained as independent predictors of improved survival on multivariate analysis. These are the first findings to show that molecular response assessment in CRC using {sup 18}F-FDG PET/CT appears feasible as early as 4 weeks post-RE, allowing risk stratification and potentially facilitating early response-adapted treatment strategies. (orig.)

Improved survival with combined modality treatment for Stage IV breast cancer

International Nuclear Information System (INIS)

Nervi, C.; Arcangeli, G.; Concolino, F.; Cortese, M.

1979-01-01

Between 1974 and 1977, 85 patients with breast cancer at first postmastectomy relapse were irradiated (Radiation 3500 to 6000 rad--3/5 weeks) to all clinically evident lesions. Radiation fields were properly shaped to include a maximum 40% active bone marrow. After 3 to 4 weeks rest, chemotherapy was started as adjuvant therapy for residual or subclinical disease (ADR 30 mg/M 2 Day 1 and 8, 5-FU 400 mg/M 2 Day 1 and 8, CY 100 mg/M 2 Day 1 through 14: repeated after 14 days). ADR was discontinued at 500/M 2 and substituted by MTX 30 mg/M 2 Day 1 and 8 for a total of 2 years. Irradiated sites were chest wall in 35, supraclavicular and internal mammary nodes in 22, bone in 56, single lung lesions in 12, brain in 24. Controls were 52 comparable but non-randomized patients treated with chemotherapy only. Forty days after x-irradiation 68 patients (80%) were free of disease (NED) while in 17 cases (20%) some residual was still present (RED). In 28 of 68 cases (41%) NED after x-irradiation and 13 of 17 (76%) in RED group developed second relapse after a median interval of 26 and 20 mos., respectively. Four of 52 patients (8%) in the control group had complete regression with a median interval to second relapse of 7 mos. Median survival was 30 mos., 24 mos., and 13 mos., respectively, for NED, RED and chemotherapy only. Eighteen patients (26%) are free of disease after 36 to 48 mos. in the combined modality group; none in the chemotherapy group. Combined treatment cases did not show untolerable myelodepression. In 10 long-surviving patients a marked subcutaneous and skin fibrosis developed because of drug additive effect. Stage IV breast cancers rendered clinically free of disease with x-irradiation and subsequently treated with chemotherapy survive significantly longer than with chemotherapy alone

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

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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

High-dose melphalan and autologous stem cell transplantation for AL amyloidosis: recent trends in treatment-related mortality and 1-year survival at a single institution

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Seldin, D. C.; Andrea, N.; Berenbaum, I.; Berk, J. L.; Connors, L.; Dember, L. M.; Doros, G.; Fennessey, S.; Finn, K.; Girnius, S.; Lerner, A.; Libbey, C.; Meier-Ewert, H. K.; O’Connell, R.; O’Hara, C.; Quillen, K.; Ruberg, F. L.; Sam, F.; Segal, A.; Shelton, A.; Skinner, M.; Sloan, J. M.; Wiesman, J. F.; Sanchorawala, V.

2017-01-01

Treatment with high-dose melphalan chemotherapy supported by hematopoietic rescue with autologous stem cells produces high rates of hematologic responses and improvement in survival and organ function for patients with AL amyloidosis. Ongoing clinical trials explore pre-transplant induction regimens, post-transplant consolidation or maintenance approaches, and compare transplant to non-transplant regimens. To put these studies into context, we reviewed our recent experience with transplant for AL amyloidosis in the Amyloid Treatment and Research Program at Boston Medical Center and Boston University School of Medicine. Over the past 10 years, there was a steady reduction in rates of treatment-related mortality and improvement in 1-year survival, now approximately 5% and 90%, respectively, based upon an intention-to-treat analysis. Median overall survival of patients treated with this approach at our center exceeds 7.5 years. PMID:21838459

Comparison of three radiotherapy modalities on biochemical control and overall survival for the treatment of prostate cancer: A systematic review

International Nuclear Information System (INIS)

Pieters, Bradley R.; Back, Djuna Z. de; Koning, Caro C.E.; Zwinderman, Aeilko H.

2009-01-01

Background and Purpose: For the radiation treatment of prostate cancer high dose should be delivered for optimal biochemical control. Treatment can be given by dose-escalated external beam radiotherapy (EBRT) or external beam radiotherapy combined with a radioactive seed implantation (EBSeeds) or high-dose rate (HDR) brachytherapy (EBTI). Differences in outcome between the modalities were assessed by a systematic review. Materials and methods: A systematic search was performed resulting in 40 articles to be used. Data were extracted on biochemical control and overall survival at 3, 5, and 8 years and other time points mentioned in the articles. Also known prognostic parameters were noted. Comparison of the modalities was done by a Weibull survival analysis and estimation of Hazard Ratio's (HR) was done with 95% confidence intervals (95% CIs). Results: The HR for biochemical recurrence was 1.40 (95% CI 1.31-1.51) for EBRT relative to EBTI, and was 1.37 (95% CI 1.26-1.49) for EBSeeds relative to EBTI. The HR for overall survival was 1.50 (95% CI 1.29-1.73) for EBRT relative to EBTI, and was 2.33 (95% CI 2.04-2.66) for EBSeeds relative to EBTI. Conclusion: The combination of external beam radiotherapy and HDR brachytherapy results in a superior biochemical control and overall survival found in a systematic review on radiotherapy for prostate cancer.

Pathogenic Dermatophytes Survive in Nail Lesions During Oral Terbinafine Treatment for Tinea Unguium.

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Iwanaga, Tomoyuki; Ushigami, Tsuyoshi; Anzawa, Kazushi; Mochizuki, Takashi

2017-08-01

Tinea unguium caused by dermatophyte species are usually treated with oral antimycotic, terbinafine (TBF). To understand the mechanisms of improvement and recalcitrance of tinea unguium by oral TBF treatment, a method of quantifying dermatophyte viability in the nail was developed, and the viability of dermatophytes was analyzed in toenail lesions of 14 patients with KOH-positive tinea unguium treated with oral TBF 125 mg/day for up to 16 weeks. Mycological tests, including KOH examination and fungal culture, and targeted quantitative real-time PCR for internal transcribed spacer (ITS) region, including rRNA, were demonstrated at the initial visit and after 8 and 16 weeks of treatment. Assays in eight patients showed that average ITS DNA amount significantly decreased, to 44% at 8 weeks and 36% at 16 weeks compared with 100% at initial visit. No significant difference was observed between at 8 and 16 weeks, despite the TBF concentration in the nail supposedly more than 10-fold higher than the minimum fungicidal concentration for dermatophytes. This finding suggests the pathogenic dermatophytes in nail lesions could survive in a dormant form, such as arthroconidia, during oral TBF treatment. Both antimycotic activity and nail growth are important factors in treatment of tinea unguium.

Helplessness/hopelessness, minimization and optimism predict survival in women with invasive ovarian cancer: a role for targeted support during initial treatment decision-making?

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Price, Melanie A; Butow, Phyllis N; Bell, Melanie L; deFazio, Anna; Friedlander, Michael; Fardell, Joanna E; Protani, Melinda M; Webb, Penelope M

2016-06-01

Women with advanced ovarian cancer generally have a poor prognosis but there is significant variability in survival despite similar disease characteristics and treatment regimens. The aim of this study was to determine whether psychosocial factors predict survival in women with ovarian cancer, controlling for potential confounders. The sample comprised 798 women with invasive ovarian cancer recruited into the Australian Ovarian Cancer Study and a subsequent quality of life study. Validated measures of depression, optimism, minimization, helplessness/hopelessness, and social support were completed 3-6 monthly for up to 2 years. Four hundred nineteen women (52.5 %) died over the follow-up period. Associations between time-varying psychosocial variables and survival were tested using adjusted Cox proportional hazard models. There was a significant interaction of psychosocial variables measured prior to first progression and overall survival, with higher optimism (adjusted hazard ratio per 1 standard deviation (HR) = 0.80, 95 % confidence interval (CI) 0.65-0.97), higher minimization (HR = 0.79, CI 0.66-0.94), and lower helplessness/hopelessness (HR = 1.40, CI 1.15-1.71) associated with longer survival. After disease progression, these variables were not associated with survival (optimism HR = 1.10, CI 0.95-1.27; minimization HR = 1.12, CI 0.95-1.31; and helplessness/hopelessness HR = 0.86, CI 0.74-1.00). Depression and social support were not associated with survival. In women with invasive ovarian cancer, psychosocial variables prior to disease progression appear to impact on overall survival, suggesting a preventive rather than modifying role. Addressing psychosocial responses to cancer and their potential impact on treatment decision-making early in the disease trajectory may benefit survival and quality of life.

Changing Pattern in Malignant Mesothelioma Survival

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Jennifer Faig

2015-02-01

Full Text Available Survival for mesothelioma has been shown to be poor, with marginal improvement over time. Recent advances in the understanding of pathophysiology and treatment of mesothelioma may impact therapy to improve survival that may not be evident from available clinical trials that are often small and not randomized. Therapies may affect survival differently based on mesothelioma location (pleural vs peritoneal. Data are conflicting regarding the effect of asbestos exposure on mesothelioma location. OBJECTIVES: We examined survival in a large cohort of mesothelioma subjects analyzed by tumor location and presence and mode of asbestos exposure. METHODS: Data were analyzed from cases (n = 380 diagnosed with mesothelioma from 1992 to 2012. Cases were either drawn from treatment referrals, independent medical evaluation for medical legal purposes, or volunteers who were diagnosed with mesothelioma. Subjects completed an occupational medical questionnaire, personal interview with the examining physician, and physician review of the medical record. RESULTS: This study reports better survival for mesothelioma than historical reports. Survival for peritoneal mesothelioma was longer than that for pleural mesothelioma (hazard ratio = 0.36, 95% confidence interval = 0.24-0.54, P < .001 after adjusting for gender and age at diagnosis. Non-occupational cases were more likely to be 1 diagnosed with peritoneal mesothelioma, 2 female, 3 exposed, and 4 diagnosed at a younger age and to have a 5 shorter latency compared to occupational cases (P < .001. CONCLUSION: Peritoneal mesothelioma was more likely associated with non-occupational exposure, thus emphasizing the importance of exposure history in enhancing early diagnosis and treatment impact.

Revascularization and cardioprotective drug treatment in myocardial infarction patients: how do they impact on patients' survival when delivered as usual care

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Courteau Josiane

2006-05-01

Full Text Available Abstract Background Randomized clinical trials showed the benefit of pharmacological and revascularization treatments in secondary prevention of myocardial infarction (MI, in selected population with highly controlled interventions. The objective of this study is to measure these treatments' impact on the cardiovascular (CV mortality rate among patients receiving usual care in the province of Quebec. Methods The study population consisted of a "naturalistic" cohort of all patients ≥ 65 years old living in the Quebec province, who survived a MI (ICD-9: 410 in 1998. The studied dependant variable was time to death from a CV disease. Independent variables were revascularization procedure and cardioprotective drugs. Death from a non CV disease was also studied for comparison. Revascularization procedure was defined as percutaneous transluminal coronary angioplasty (PTCA or coronary artery bypass graft (CABG. The exposure to cardioprotective drugs was defined as the number of cardioprotective drug classes (Acetylsalicylic Acid (ASA, Beta-Blockers, Angiotensin-Converting Enzyme (ACE Inhibitors, Statins claimed within the index period (first 30 days after the index hospitalization. Age, gender and a comorbidity index were used as covariates. Kaplan-Meier survival curves, Cox proportional hazard models, logistic regressions and regression trees were used. Results The study population totaled 5596 patients (3206 men; 2390 women. We observed 1128 deaths (20% within two years following index hospitalization, of them 603 from CV disease. The CV survival rate at two years is much greater for patients with revascularization, regardless of pharmacological treatments. For patients without revascularization, the CV survival rate increases with the number of cardioprotective drug classes claimed. Finally, Cox proportional hazard models, regression tree and logistic regression analyses all revealed that the absence of revascularization and, to a lower extent

Long-term survival of indirect pulp treatment performed in primary and permanent teeth with clinically diagnosed deep carious lesions

NARCIS (Netherlands)

Gruythuysen, R.; van Strijp, G.; Wu, M.K.

2010-01-01

Introduction: This retrospective study examined clinically and radiographically the 3-year survival of teeth treated with indirect pulp treatment (IPT) performed between 2000 and 2004. Methods: Sixty-six uncooperative children (4-18 years old) with at least one tooth with clinically diagnosed deep

Factors associated with initial treatment and survival for clinically localized prostate cancer: results from the CDC-NPCR Patterns of Care Study (PoC1)

International Nuclear Information System (INIS)

Schymura, Maria J; Kahn, Amy R; German, Robert R; Hsieh, Mei-Chin; Cress, Rosemary D; Finch, Jack L; Fulton, John P; Shen, Tiefu; Stuckart, Erik

2010-01-01

Despite the large number of men diagnosed with localized prostate cancer, there is as yet no consensus concerning appropriate treatment. The purpose of this study was to describe the initial treatment patterns for localized prostate cancer in a population-based sample and to determine the clinical and patient characteristics associated with initial treatment and overall survival. The analysis included 3,300 patients from seven states, diagnosed with clinically localized prostate cancer in 1997. We examined the association of sociodemographic and clinical characteristics with four treatment options: radical prostatectomy, radiation therapy, hormone therapy, and watchful waiting. Diagnostic and treatment information was abstracted from medical records. Socioeconomic measures were derived from the 2000 Census based on the patient's residence at time of diagnosis. Vital status through December 31, 2002, was obtained from medical records and linkages to state vital statistics files and the National Death Index. Multiple logistic regression analysis and Cox proportional hazards models identified factors associated with initial treatment and overall survival, respectively. Patients with clinically localized prostate cancer received the following treatments: radical prostatectomy (39.7%), radiation therapy (31.4%), hormone therapy (10.3%), or watchful waiting (18.6%). After multivariable adjustment, the following variables were associated with conservative treatment (hormone therapy or watchful waiting): older age, black race, being unmarried, having public insurance, having non-screen detected cancer, having normal digital rectal exam results, PSA values above 20, low Gleason score (2-4), comorbidity, and state of residence. Among patients receiving definitive treatment (radical prostatectomy or radiation therapy), older age, being unmarried, PSA values above 10, unknown Gleason score, state of residence, as well as black race in patients under 60 years of age, were

Factors associated with initial treatment and survival for clinically localized prostate cancer: results from the CDC-NPCR Patterns of Care Study (PoC1

Directory of Open Access Journals (Sweden)

Fulton John P

2010-04-01

Full Text Available Abstract Background Despite the large number of men diagnosed with localized prostate cancer, there is as yet no consensus concerning appropriate treatment. The purpose of this study was to describe the initial treatment patterns for localized prostate cancer in a population-based sample and to determine the clinical and patient characteristics associated with initial treatment and overall survival. Methods The analysis included 3,300 patients from seven states, diagnosed with clinically localized prostate cancer in 1997. We examined the association of sociodemographic and clinical characteristics with four treatment options: radical prostatectomy, radiation therapy, hormone therapy, and watchful waiting. Diagnostic and treatment information was abstracted from medical records. Socioeconomic measures were derived from the 2000 Census based on the patient's residence at time of diagnosis. Vital status through December 31, 2002, was obtained from medical records and linkages to state vital statistics files and the National Death Index. Multiple logistic regression analysis and Cox proportional hazards models identified factors associated with initial treatment and overall survival, respectively. Results Patients with clinically localized prostate cancer received the following treatments: radical prostatectomy (39.7%, radiation therapy (31.4%, hormone therapy (10.3%, or watchful waiting (18.6%. After multivariable adjustment, the following variables were associated with conservative treatment (hormone therapy or watchful waiting: older age, black race, being unmarried, having public insurance, having non-screen detected cancer, having normal digital rectal exam results, PSA values above 20, low Gleason score (2-4, comorbidity, and state of residence. Among patients receiving definitive treatment (radical prostatectomy or radiation therapy, older age, being unmarried, PSA values above 10, unknown Gleason score, state of residence, as well as black

Methamphetamine and dopamine neurotoxicity: differential effects of agents interfering with glutamatergic transmission.

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Boireau, A; Bordier, F; Dubédat, P; Doble, A

1995-07-28

The effects of riluzole and lamotrigine, two agents which interfere with the release of glutamate (GLU), and MK-801, a blocker of N-methyl-D-aspartate (NMDA) receptors, were compared in the model of methamphetamine-induced depletion of dopamine (DA) levels in mice. Repeated injections with methamphetamine (4 x 5 mg/kg i.p.) markedly decreased levels of DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels. When mice were treated with riluzole (2 x 10 mg/kg p.o.), no protection was observed against the decrease in DA and the two metabolites. Lamotrigine (2 x 10 mg/kg p.o.) was also inactive. Treatment with MK-801 (2 x 2.5 mg/kg i.p.) antagonized the decrease in DA, DOPAC and HVA levels induced by the neurotoxin. Thus, unlike an NMDA blocker, drugs that interfere with GLU release did not antagonize the methamphetamine-induced DA neurotoxicity in mice. The consequences of this inactivity are discussed in terms of the reliability of this model to test new drugs with putative efficacy in the treatment of Parkinson's disease.

Symptomatic treatments for amyotrophic lateral sclerosis/motor neuron disease.

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Ng, Louisa; Khan, Fary; Young, Carolyn A; Galea, Mary

2017-01-10

Motor neuron disease (MND), which is also known as amyotrophic lateral sclerosis (ALS), causes a wide range of symptoms but the evidence base for the effectiveness of the symptomatic treatment therapies is limited. To summarise the evidence from Cochrane Systematic Reviews of all symptomatic treatments for MND. We searched the Cochrane Database of Systematic Reviews (CDSR) on 15 November 2016 for systematic reviews of symptomatic treatments for MND. We assessed the methodological quality of the included reviews using the Assessment of Multiple Systematic Reviews (AMSTAR) tool and the GRADE approach. We followed standard Cochrane study (review) selection and data extraction procedures. We reported findings narratively and in tables. We included nine Cochrane Systematic Reviews of interventions to treat symptoms in people with MND. Three were empty reviews with no included randomised controlled trials (RCTs); however, all three reported on non-RCT evidence and the remaining six included mostly one or two studies. We deemed all of the included reviews of high methodological quality. Drug therapy for painThere is no RCT evidence in a Cochrane Systematic Review exploring the efficacy of drug therapy for pain in MND. Treatment for crampsThere is evidence (13 RCTs, N = 4012) that for the treatment of cramps in MND, compared to placebo:- memantine and tetrahydrocannabinol (THC) are probably ineffective (moderate-quality evidence);- vitamin E may have little or no effect (low-quality evidence); and- the effects of L-threonine, gabapentin, xaliproden, riluzole, and baclofen are uncertain as the evidence is either very low quality or the trial specified the outcome but did not report numerical data.The review reported adverse effects of riluzole, but it is not clear whether other interventions had adverse effects. Treatment for spasticityIt is uncertain whether an endurance-based exercise programme improved spasticity or quality of life, measured at three months after the

Systemic treatment after whole-brain radiotherapy may improve survival in RPA class II/III breast cancer patients with brain metastasis.

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Zhang, Qian; Chen, Jian; Yu, Xiaoli; Ma, Jinli; Cai, Gang; Yang, Zhaozhi; Cao, Lu; Chen, Xingxing; Guo, Xiaomao; Chen, Jiayi

2013-09-01

Whole brain radiotherapy (WBRT) is the most widely used treatment for brain metastasis (BM), especially for patients with multiple intracranial lesions. The purpose of this study was to examine the efficacy of systemic treatments following WBRT in breast cancer patients with BM who had different clinical characteristics, based on the classification of the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) and the breast cancer-specific Graded Prognostic Assessment (Breast-GPA). One hundred and one breast cancer patients with BM treated between 2006 and 2010 were analyzed. The median interval between breast cancer diagnosis and identification of BM in the triple-negative patients was shorter than in the luminal A subtype (26 vs. 36 months, respectively; P = 0.021). Univariate analysis indicated that age at BM diagnosis, Karnofsky performance status/recursive partitioning analysis (KPS/RPA) classes, number of BMs, primary tumor control, extracranial metastases and systemic treatment following WBRT were significant prognostic factors for overall survival (OS) (P RPA classes and systemic treatments following WBRT remained the significant prognostic factors for OS. For RPA class I, the median survival with and without systemic treatments following WBRT was 25 and 22 months, respectively (P = 0.819), while for RPA class II/III systemic treatments significantly improved OS from 7 and 2 months to 11 and 5 months, respectively (P RPA class II/III patients.

Survival effect of first- and second-line treatments for patients with primary glioblastoma: a cohort study from a prospective registry, 1997-2010.

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Nava, Francesca; Tramacere, Irene; Fittipaldo, Andrea; Bruzzone, Maria Grazia; Dimeco, Francesco; Fariselli, Laura; Finocchiaro, Gaetano; Pollo, Bianca; Salmaggi, Andrea; Silvani, Antonio; Farinotti, Mariangela; Filippini, Graziella

2014-05-01

Prospective follow-up studies of large cohorts of patients with glioblastoma (GBM) are needed to assess the effectiveness of conventional treatments in clinical practice. We report GBM survival data from the Brain Cancer Register of the Fondazione Istituto Neurologico Carlo Besta (INCB) in Milan, Italy, which collected longitudinal data for all consecutive patients with GBM from 1997 to 2010. Survival data were obtained from 764 patients (aged>16 years) with histologically confirmed primary GBM who were diagnosed and treated over a 7-year period (2004-2010) with follow-up to April 2012 (cohort II). Equivalent data from 490 GBM patients diagnosed and treated over the preceding 7 years (1997-2003) with follow-up to April 2005 (cohort I) were available for comparison. Progression-free survival (PFS) was available from 361 and 219 patients actively followed up at INCB in cohorts II and I, respectively. Survival probabilities were 54% at 1 year, 21% at 2 years, and 11% at 3 years, respectively, in cohort II compared with 47%, 11%, and 5%, respectively, in cohort I. PFS was 22% and 12% at 1 year in cohorts II and I. Better survival and PFS in cohort II was significantly associated with introduction of the Stupp protocol into clinical practice, with adjusted hazard ratios (HRs) of 0.78 for survival and 0.73 for PFS, or a 22% relative decrease in the risk of death and a 27% relative decrease in the risk of recurrence. After recurrence, reoperation was performed in one-fifth of cohort I and in one-third of cohort II but was not effective (HR, 1.05 in cohort I and 1.02 in cohort II). Second-line chemotherapy, mainly consisting of nitrosourea-based chemotherapy, temozolomide, mitoxantrone, fotemustine, and bevacizumab, improved survival in both cohorts (HR, 0.57 in cohort I and 0.74 in cohort II). Radiosurgery was also effective (HR, 0.52 in cohort II). We found a significant increase in overall survival, PFS, and survival after recurrence after 2004, likely due to

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

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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)

Circulating HER2 DNA after trastuzumab treatment predicts survival and response in breast cancer

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Sorensen, Boe S; Mortensen, Lise S; Andersen, Jørn

2010-01-01

BACKGROUND: Only a subset of breast cancer patients responds to the HER2 inhibitor trastuzumab, and methods to identify responders are needed. PATIENTS AND METHODS: We studied 28 patients with metastatic breast cancer that had amplified human epidermal growth factor receptor 2 (HER2) genes...... in their primary tumour and were treated with a combination of trastuzumab and chemotherapy. Plasma was collected and amplification of the HER2 gene in circulating DNA and the amounts of the extracellular domain (ECD) of HER2 were measured just before first treatment (n=28) and just before second treatment three...... response (p=0.02), and overall survival (p=0.05). HER2 ECD kinetics did not correlate to clinical data. CONCLUSION: We suggest that a decrease in HER2 gene amplification in the plasma predicts a more favourable response to trastuzumab....

Incidence and survival from lung cancer in Greenland is comparable to survival in the Nordic countries

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Gelvan, Allan; Risum, Signe; Langer, Seppo W

2015-01-01

INTRODUCTION: Oncological treatment of lung cancer has been available in Greenland since 2004. We evaluated patient characteristics and survival rates for the first six years of local lung cancer treatment. METHODS: From September 2004 to August 2010, a total of 173 patients with lung cancer were...... referred to treatment at Queen Ingrid's Hospital. On 1 February 2014, treatment results, survival, and prognostic variables were analysed. RESULTS: The mean age at diagnosis was 63 years. Non-small cell lung cancer (NSCLC) was diagnosed in 145 patients (84%); 56% had squamous cell carcinoma, 34% had...... adenocarcinoma, 2% had large cell carcinoma and 8% had NSCLC not otherwise specified (NOS). In all, 28 (16%) had small cell lung cancer. A total of 142 patients (82%) received treatment; 20 underwent surgery (ten stage Ib, one stage IIa, five stage IIb, four stage IIIa); palliative chemotherapy was given to 122...

Treatment factors influencing survival in pancreatic carcinoma; Der Einfluss der Therapie auf das Ueberleben von Patienten mit Pankreaskarzinom. Eine Analyse von Einzelfaktoren

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Warszawski, N.; Warszawski, A.; Schneider, B.M.; Roettinger, E.M. [Ulm Univ. (Germany). Abt. Radiologie 2 (Strahlentherapie); Link, K.H.; Gansauge, F. [Ulm Univ. (Germany). Abt. fuer Allgemeinchirurgie; Lutz, M.P. [Ulm Univ. (Germany). Abt. Innere Medizin 1

1999-07-01

Purpose: To identify the impact of treatment factors on overall survival in patients with pancreatic carcinoma. Patients and methods: We performed a follow-up study on 38 patients with adenocarcinoma of the pancreas treated from 1984 to 1998. 18/38 patients were resected. Irradiated volume included the primary tumor (or tumor bed) and regional lymph nodes. Thirty-seven patients received in addition chemotherapy consisting of mitoxantrone, 5-fluorouracil and cis-platin, either i.v. (14/38) or i.a. (23/38). The influence of treatment related factors on the overall survival was tested. Biologically effective dose was calculated by the linear-quadratic model ({alpha}/{beta}=25 Gy) and by losing 0.85 Gy per day starting accelerated repopulation at day 28. Results: Treatment factors influencing overall survival were resection (p=0.02), overall treatment time (p=0.03) and biologically effective dose (p<0.002). Total dose and kind of chemotherapy had no significant influence. Treatment volume had a negative correlation (r=-0.5, p=0.06) with overall survival, without any correlation between tumor size, tumor stage, and treatment volume. In multivariate analysis only biologically effective dose remained significant (p=0.02). Conclusions: Among with surgery, biologically effective dose strongly influences overall survival in patients treated for pancreatic carcinoma. Treatment volume should be kept as small as possible and all efforts should be made to avoid treatments splits in radiation therapy. (orig.) [Deutsch] Ziel: Behandlungsfaktoren zu identifizieren, die einen Einfluss auf das Ueberleben von Patienten mit Pankreaskarzinom haben. Patienten und Methode: In einer nichtrandomisierten Studie wurden 38 Patienten ausgewertet, die von 1984 bis 1998 wegen eines Adenokarzinoms des Pankreas behandelt worden waren. Bei 18/38 Patienten war eine Resektion vorgenommen worden. Das Bestrahlungsvolumen beinhaltete den Primaertumor bzw. das Tumorbett und die regionaeren Lymphknoten

Presymptomatic Treatment with Acetylcholinesterase Antisense Oligonucleotides Prolongs Survival in ALS (G93A-SOD1 Mice

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Gotkine Marc

2013-01-01

Full Text Available Objective. Previous research suggests that acetylcholinesterase (AChE may be involved in ALS pathogenesis. AChE enzyme inhibitors can upregulate AChE transcription which in certain contexts can have deleterious (noncatalytic effects, making them theoretically harmful in ALS, whilst AChE antisense-oligonucleotides (mEN101, which downregulate AChE may be beneficial. Our aim was to investigate whether downregulation of AChE using mEN101 is beneficial in an ALS mouse model. Methods. ALS (G93A-SOD1 mice received saline, mEN101, inverse-EN101, or neostigmine. Treatments were administered from 5 weeks. Disease-onset and survival were recorded. Additional mice were sacrificed for pathological analysis at 15 weeks of age. In a follow-up experiment treatment was started at the symptomatic stage at a higher dose. Results. mEN101 given at the presymptomatic (but not symptomatic stage prolonged survival and attenuated motor-neuron loss in ALS mice. In contrast, neostigmine exacerbated the clinical parameters. Conclusions. These results suggest that AChE may be involved in ALS pathogenesis. The accelerated disease course with neostigmine suggests that any beneficial effects of mEN101 occur through a non-catalytic rather than cholinergic mechanism.

Comparison of continuous versus categorical tumor measurement-based metrics to predict overall survival in cancer treatment trials

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An, Ming-Wen; Mandrekar, Sumithra J.; Branda, Megan E.; Hillman, Shauna L.; Adjei, Alex A.; Pitot, Henry; Goldberg, Richard M.; Sargent, Daniel J.

2011-01-01

Purpose The categorical definition of response assessed via the Response Evaluation Criteria in Solid Tumors has documented limitations. We sought to identify alternative metrics for tumor response that improve prediction of overall survival. Experimental Design Individual patient data from three North Central Cancer Treatment Group trials (N0026, n=117; N9741, n=1109; N9841, n=332) were used. Continuous metrics of tumor size based on longitudinal tumor measurements were considered in addition to a trichotomized response (TriTR: Response vs. Stable vs. Progression). Cox proportional hazards models, adjusted for treatment arm and baseline tumor burden, were used to assess the impact of the metrics on subsequent overall survival, using a landmark analysis approach at 12-, 16- and 24-weeks post baseline. Model discrimination was evaluated using the concordance (c) index. Results The overall best response rates for the three trials were 26%, 45%, and 25% respectively. While nearly all metrics were statistically significantly associated with overall survival at the different landmark time points, the c-indices for the traditional response metrics ranged from 0.59-0.65; for the continuous metrics from 0.60-0.66 and for the TriTR metrics from 0.64-0.69. The c-indices for TriTR at 12-weeks were comparable to those at 16- and 24-weeks. Conclusions Continuous tumor-measurement-based metrics provided no predictive improvement over traditional response based metrics or TriTR; TriTR had better predictive ability than best TriTR or confirmed response. If confirmed, TriTR represents a promising endpoint for future Phase II trials. PMID:21880789

Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival.

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Salem, Riad; Lewandowski, Robert J; Atassi, Bassel; Gordon, Stuart C; Gates, Vanessa L; Barakat, Omar; Sergie, Ziad; Wong, Ching-Yee O; Thurston, Kenneth G

2005-12-01

To present safety and efficacy results obtained in treatment of a cohort of patients with unresectable hepatocellular carcinoma (HCC) with use of 90Y microspheres (TheraSphere). Forty-three consecutive patients with HCC were treated with 90Y microspheres over a 4-year period. Patients were treated by liver segment or lobe on one or more occasions based on tumor distribution, liver function, and vascular flow dynamics. Patients were followed for adverse events, objective tumor response, and survival. Patients were stratified into three risk groups according to method of treatment and risk stratification (group 0, segmental; group 1, lobar low-risk; group 2, lobar high-risk) and Okuda and Child-Pugh scoring systems. Based on follow-up data from 43 treated patients, 20 patients (47%) had an objective tumor response based on percent reduction in tumor size and 34 patients (79%) had a tumor response when percent reduction and/or tumor necrosis were used as a composite measure of tumor response. There was no statistical difference among the three risk groups with respect to tumor response. Survival times from date of diagnosis were different among the risk groups (P TheraSpheres) provides a safe and effective method of treatment for a broad spectrum of patients presenting with unresectable HCC. Further investigation is warranted.

Long-term survival in laparoscopic vs open resection for colorectal liver metastases: inverse probability of treatment weighting using propensity scores.

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Lewin, Joel W; O'Rourke, Nicholas A; Chiow, Adrian K H; Bryant, Richard; Martin, Ian; Nathanson, Leslie K; Cavallucci, David J

2016-02-01

This study compares long-term outcomes between intention-to-treat laparoscopic and open approaches to colorectal liver metastases (CLM), using inverse probability of treatment weighting (IPTW) based on propensity scores to control for selection bias. Patients undergoing liver resection for CLM by 5 surgeons at 3 institutions from 2000 to early 2014 were analysed. IPTW based on propensity scores were generated and used to assess the marginal treatment effect of the laparoscopic approach via a weighted Cox proportional hazards model. A total of 298 operations were performed in 256 patients. 7 patients with planned two-stage resections were excluded leaving 284 operations in 249 patients for analysis. After IPTW, the population was well balanced. With a median follow up of 36 months, 5-year overall survival (OS) and recurrence-free survival (RFS) for the cohort were 59% and 38%. 146 laparoscopic procedures were performed in 140 patients, with weighted 5-year OS and RFS of 54% and 36% respectively. In the open group, 138 procedures were performed in 122 patients, with a weighted 5-year OS and RFS of 63% and 38% respectively. There was no significant difference between the two groups in terms of OS or RFS. In the Brisbane experience, after accounting for bias in treatment assignment, long term survival after LLR for CLM is equivalent to outcomes in open surgery. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

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

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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

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

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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.

Progression-free Survival Following Stereotactic Body Radiotherapy for Oligometastatic Prostate Cancer Treatment-naive Recurrence: A Multi-institutional Analysis.

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Ost, Piet; Jereczek-Fossa, Barbara Alicja; As, Nicholas Van; Zilli, Thomas; Muacevic, Alexander; Olivier, Kenneth; Henderson, Daniel; Casamassima, Franco; Orecchia, Roberto; Surgo, Alessia; Brown, Lindsay; Tree, Alison; Miralbell, Raymond; De Meerleer, Gert

2016-01-01

The literature on metastasis-directed therapy for oligometastatic prostate cancer (PCa) recurrence consists of small heterogeneous studies. This study aimed to reduce the heterogeneity by pooling individual patient data from different institutions treating oligometastatic PCa recurrence with stereotactic body radiotherapy (SBRT). We focussed on patients who were treatment naive, with the aim of determining if SBRT could delay disease progression. We included patients with three or fewer metastases. The Kaplan-Meier method was used to estimate distant progression-free survival (DPFS) and local progression-free survival (LPFS). Toxicity was scored using the Common Terminology Criteria for Adverse Events. In total, 163 metastases were treated in 119 patients. The median DPFS was 21 mo (95% confidence interval, 15-26 mo). A lower radiotherapy dose predicted a higher local recurrence rate with a 3-yr LPFS of 79% for patients treated with a biologically effective dose ≤100Gy versus 99% for patients treated with >100Gy (p=0.01). Seventeen patients (14%) developed toxicity classified as grade 1, and three patients (3%) developed grade 2 toxicity. No grade ≥3 toxicity occurred. These results should serve as a benchmark for future prospective trials. This multi-institutional study pools all of the available data on the use of stereotactic body radiotherapy for limited prostate cancer metastases. We concluded that this approach is safe and associated with a prolonged treatment progression-free survival. Copyright © 2015. Published by Elsevier B.V.

Systemic treatment with CAR-engineered T cells against PSCA delays subcutaneous tumor growth and prolongs survival of mice

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Hillerdal, Victoria; Ramachandran, Mohanraj; Leja, Justyna; Essand, Magnus

2014-01-01

Adoptive transfer of T cells genetically engineered with a chimeric antigen receptor (CAR) has successfully been used to treat both chronic and acute lymphocytic leukemia as well as other hematological cancers. Experimental therapy with CAR-engineered T cells has also shown promising results on solid tumors. The prostate stem cell antigen (PSCA) is a protein expressed on the surface of prostate epithelial cells as well as in primary and metastatic prostate cancer cells and therefore a promising target for immunotherapy of prostate cancer. We developed a third-generation CAR against PSCA including the CD28, OX-40 and CD3 ζ signaling domains. T cells were transduced with a lentivirus encoding the PSCA-CAR and evaluated for cytokine production (paired Student’s t-test), proliferation (paired Student’s t-test), CD107a expression (paired Student’s t-test) and target cell killing in vitro and tumor growth and survival in vivo (Log-rank test comparing Kaplan-Meier survival curves). PSCA-CAR T cells exhibit specific interferon (IFN)-γ and interleukin (IL)-2 secretion and specific proliferation in response to PSCA-expressing target cells. Furthermore, the PSCA-CAR-engineered T cells efficiently kill PSCA-expressing tumor cells in vitro and systemic treatment with PSCA-CAR-engineered T cells significantly delays subcutaneous tumor growth and prolongs survival of mice. Our data confirms that PSCA-CAR T cells may be developed for treatment of prostate cancer

Survival, reproduction, growth, and parasite resistance of aquatic organisms exposed on-site to wastewater treated by advanced treatment processes.

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Schlüter-Vorberg, Lisa; Knopp, Gregor; Cornel, Peter; Ternes, Thomas; Coors, Anja

2017-05-01

Advanced wastewater treatment technologies are generally known to be an effective tool for reducing micropollutant discharge into the aquatic environment. Nevertheless, some processes such as ozonation result in stable transformation products with often unknown toxicity. In the present study, whole effluents originating from nine different steps of advanced treatment combinations were compared for their aquatic toxicity. Assessed endpoints were survival, growth and reproduction of Lumbriculus variegatus, Daphnia magna and Lemna minor chronically exposed in on-site flow-through tests based on standard guidelines. The treatment combinations were activated sludge treatment followed by ozonation with subsequent filtration by granular activated carbon or biofilters and membrane bioreactor treatment of raw wastewater followed by ozonation. Additionally, the impact of treated wastewater on the immune response of invertebrates was investigated by challenging D. magna with a bacterial endoparasite. Conventionally treated wastewater reduced reproduction of L. variegatus by up to 46%, but did not affect D. magna and L. minor with regard to survival, growth, reproduction and parasite resistance. Instead, parasite susceptibility was significantly reduced in D. magna exposed to conventionally treated as well as ozonated wastewater in comparison to D. magna exposed to the medium control. None of the three test organisms provided clear evidence that wastewater ozonation leads to increased aquatic toxicity. Rather than to the presence of toxic transformation products, the affected performance of L. variegatus could be linked to elevated concentrations of ammonium and nitrite that likely resulted from treatment failures. Copyright © 2017 Elsevier B.V. All rights reserved.

Cluster-randomized study of intermittent preventive treatment for malaria in infants (IPTi in southern Tanzania: evaluation of impact on survival

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Schellenberg Joanna

2011-12-01

Full Text Available Abstract Background Intermittent Preventive Treatment for malaria control in infants (IPTi consists of the administration of a treatment dose of an anti-malarial drug, usually sulphadoxine-pyrimethamine, at scheduled intervals, regardless of the presence of Plasmodium falciparum infection. A pooled analysis of individually randomized trials reported that IPTi reduced clinical episodes by 30%. This study evaluated the effect of IPTi on child survival in the context of a five-district implementation project in southern Tanzania. [Trial registration: clinical trials.gov NCT00152204]. Methods After baseline household and health facility surveys in 2004, five districts comprising 24 divisions were randomly assigned either to receive IPTi (n = 12 or not (n = 12. Implementation started in March 2005, led by routine health services with support from the research team. In 2007, a large household survey was undertaken to assess the impact of IPTi on survival in infants aged two-11 months through birth history interviews with all women aged 13-49 years. The analysis is based on an "intention-to-treat" ecological design, with survival outcomes analysed according to the cluster in which the mothers lived. Results Survival in infants aged two-11 months was comparable in IPTi and comparison areas at baseline. In intervention areas in 2007, 48% of children aged 12-23 months had documented evidence of receiving three doses of IPTi, compared to 2% in comparison areas (P P = 0.31. Conclusion The lack of evidence of an effect of IPTi on survival could be a false negative result due to a lack of power or imbalance of unmeasured confounders. Alternatively, there could be no mortality impact of IPTi due to low coverage, late administration, drug resistance, decreased malaria transmission or improvements in vector control and case management. This study raises important questions for programme evaluation design.

Survival analysis of a treatment data for cancer of the larynx

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Khan, K.

2002-01-01

In this paper a survival analysis of the survival time is done. The Cox regression model is fitted to the survival time with the assumption of proportional hazard. A model is selected after inclusion and exclusion of factors and variables as explanatory variables. The assumption of proportional hazards is tested in the manner suggested by Harrell (1986). The assumption of proportional hazards is supported by these tests. However the plot of Schoenfeld residuals against dose gave a little evidence of non validity of the proportional hazard assumption. The assumption seems to be satisfied for variable time. The martingale residuals suggest no pattern for variable age. The functional form of dose is not linear. Hence the quadratic dose is used as an explanatory variable. A comparison of logistic regression analysis and survival analysis is also made in this paper. It can be concluded that Cox proportional hazards model is a better model than the logistic model as it is more parsimonious and utilizes more information. (author)

Survival analysis of patients with clinical stages I or II Hodgkin's disease who have relapsed after initial treatment with radiotherapy alone

DEFF Research Database (Denmark)

Horwich, A.; Specht, L.; Ashley, S.

1997-01-01

relapse included initial stage, age, sex, histology, number of involved areas, mediastinal involvement, E-lesions, B-symptoms, erythrocyte sedimentation rate, alkaline phosphatase, serum albumin and haemoglobin. As well as presentation variables, we analysed the disease-free interval after initial......To aid treatment choice in early stage of Hodgkin's disease, we analysed patients registered in the IDHD Database with clinical stages I or II Hodgkin's disease who were not staged with laparotomy and whose initial treatment was with radiotherapy alone. The factors analysed for outcome after first...... radiotherapy and the extent of disease at relapse. A total of 1364 patients with clinical stage I or II Hodgkin's disease were treated with initial radiotherapy, of whom 473 relapsed. The probability of survival 10 years after relapse was 63%. For cause-specific survival (CSS), both multivariate and univariate...

Health-related quality of life for nasopharyngeal carcinoma patients with cancer-free survival after treatment

International Nuclear Information System (INIS)

Fang, F.-M.; Chiu, H.-C.; Kuo, W.-R.; Wang, C.-J.; Leung, Stephen W.; Chen, H.-C.; Sun, L.-M.; Hsu, H.-C.

2002-01-01

Purpose: To evaluate the health-related quality of life (HR-QOL) of nasopharyngeal cancer (NPC) patients with cancer-free survival after treatment and to investigate the factors correlated with their HR-QOL. Methods and Materials: One hundred eighty-two NPC patients with cancer-free survival of more than 2 years after treatment were enrolled in the study. Data from the same number of people without a history of cancer, who had come to the hospital for health checkups, were also collected for comparison. The Chinese SF-36 questionnaire and nine items about head-and-neck functional impairments (HNFI) were self-reported by all participants at the clinics. Data relating to sociodemographic factors, cancer stage, and treatment of NPC survivors were analyzed. Results: Psychometric tests revealed the excellent internal reliability (Cronbach's α: 0.87-0.96) and discriminative validity of the Chinese SF-36 used in Taiwan. Most functional domains of the Chinese SF-36 and all nine HNFI items were significantly worse in NPC survivors than in control subjects. No cancer or treatment-related variables significantly correlated with any functional domains of SF-36 or any items of HNFI for NPC survivors. Economic status, educational level, occupational status, and the number of comorbidities were the variables that significantly correlated with most functional domains of SF-36 for NPC survivors. Patients with more sufficient economic status, higher educational levels, with employment, or without comorbidity tended to enjoy better HR-QOL as detected by the SF-36. Salivation, hearing, and swallowing dysfunctions were the top three HNFI that disturbed NPC survivors. Economic status remained the most significant variable correlated with HNFI, including salivation, swallowing, neck stiffness, taste, and phonation. Survivors with better economic status reported less severe HNFI. Conclusions: NPC survivors had worse HR-QOL than healthy control subjects in the study. Socioeconomic status

Impact of plant extracts tested in attention-deficit/hyperactivity disorder treatment on cell survival and energy metabolism in human neuroblastoma SH-SY5Y cells.

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Schmidt, Andreas Johannes; Krieg, Jürgen-Christian; Hemmeter, Ulrich Michael; Kircher, Tilo; Schulz, Eberhard; Clement, Hans-Willi; Heiser, Philip

2010-10-01

Plant extracts such as Hypericum perforatum and Pycnogenol have been tested as alternatives to the classical ADHD drugs. It has been possible to describe neuroprotective effects of such plant extracts. A reduction of ADHD symptoms could be shown in clinical studies after the application of Pycnogenol, which is a pine bark extract. The impacts of the standardized herbal extracts Hypericum perforatum, Pycnogenol and Enzogenol up to a concentration of 5000 ng/mL on cell survival and energy metabolism in human SH-SY5Y neuroblastoma cells has been investigated in the present examination. Hypericum perforatum significantly decreased the survival of cells after treatment with a concentration of 5000 ng/mL, whereas lower concentrations exerted no significant effects. Pycnogenol( induced a significant increase of cell survival after incubation with a concentration of 32.25 ng/mL and a concentration of 250 ng/mL. Other applied concentrations of Pycnogenol failed to exert significant effects. Treatment with Enzogenol did not lead to significant changes in cell survival.Concerning energy metabolism, the treatment of cells with a concentration of 5000 ng/mL Hypericum perforatum led to a significant increase of ATP levels, whereas treatment with a concentration of 500 ng/mL had no significant effect. Incubation of cells with Pycnogenol and Enzogenol exerted no significant effects.None of the tested substances caused any cytotoxic effect when used in therapeutically relevant concentrations. Copyright © 2010 John Wiley & Sons, Ltd.

Locally Applied Valproate Enhances Survival in Rats after Neocortical Treatment with Tetanus Toxin and Cobalt Chloride

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Dirk-Matthias Altenmüller

2013-01-01

Full Text Available Purpose. In neocortical epilepsies not satisfactorily responsive to systemic antiepileptic drug therapy, local application of antiepileptic agents onto the epileptic focus may enhance treatment efficacy and tolerability. We describe the effects of focally applied valproate (VPA in a newly emerging rat model of neocortical epilepsy induced by tetanus toxin (TeT plus cobalt chloride (CoCl2. Methods. In rats, VPA ( or sodium chloride (NaCl ( containing polycaprolactone (PCL implants were applied onto the right motor cortex treated before with a triple injection of 75 ng TeT plus 15 mg CoCl2. Video-EEG monitoring was performed with intracortical depth electrodes. Results. All rats randomized to the NaCl group died within one week after surgery. In contrast, the rats treated with local VPA survived significantly longer (. In both groups, witnessed deaths occurred in the context of seizures. At least of the rats surviving the first postoperative day developed neocortical epilepsy with recurrent spontaneous seizures. Conclusions. The novel TeT/CoCl2 approach targets at a new model of neocortical epilepsy in rats and allows the investigation of local epilepsy therapy strategies. In this vehicle-controlled study, local application of VPA significantly enhanced survival in rats, possibly by focal antiepileptic or antiepileptogenic mechanisms.

Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression : a pilot randomized, placebo-controlled continuation trial

NARCIS (Netherlands)

Mathew, S.J.; Murrough, J.W.; Aan het Rot, M.; Collins, K.A.; Reich, D.L.; Charney, D.S.

2010-01-01

The N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine may have rapid, albeit transient, antidepressant properties. This study in patients with treatment-resistant major depression (TRD) aimed to (1) replicate the acute efficacy of single-close intravenous (i.v.) ketamine; (2) test

Early survival factor deprivation in the olfactory epithelium enhances activity-dependent survival

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Adrien eFrançois

2013-12-01

Full Text Available The neuronal olfactory epithelium undergoes permanent renewal because of environmental aggression. This renewal is partly regulated by factors modulating the level of neuronal apoptosis. Among them, we had previously characterized endothelin as neuroprotective. In this study, we explored the effect of cell survival factor deprivation in the olfactory epithelium by intranasal delivery of endothelin receptors antagonists to rat pups. This treatment induced an overall increase of apoptosis in the olfactory epithelium. The responses to odorants recorded by electroolfactogram were decreased in treated animal, a result consistent with a loss of olfactory sensory neurons (OSNs. However, the treated animal performed better in an olfactory orientation test based on maternal odor compared to non-treated littermates. This improved performance could be due to activity-dependent neuronal survival of OSNs in the context of increased apoptosis level. In order to demonstrate it, we odorized pups with octanal, a known ligand for the rI7 olfactory receptor (Olr226. We quantified the number of OSN expressing rI7 by RT-qPCR and whole mount in situ hybridization. While this number was reduced by the survival factor removal treatment, this reduction was abolished by the presence of its ligand. This improved survival was optimal for low concentration of odorant and was specific for rI7-expressing OSNs. Meanwhile, the number of rI7-expressing OSNs was not affected by the odorization in non-treated littermates; showing that the activity-dependant survival of OSNs did not affect the OSN population during the 10 days of odorization in control conditions. Overall, our study shows that when apoptosis is promoted in the olfactory mucosa, the activity-dependent neuronal plasticity allows faster tuning of the olfactory sensory neuron population towards detection of environmental odorants.

Key factors influencing lung cancer survival in northern Italy.

Science.gov (United States)

Mangone, Lucia; Minicozzi, Pamela; Vicentini, Massimo; Giacomin, Adriano; Caldarella, Adele; Cirilli, Claudia; Falcini, Fabio; Giorgi Rossi, Paolo; Sant, Milena

2013-06-01

Lung cancer is a major cause of cancer death worldwide. The aims of this study were to analyze presentation, treatment and survival for lung cancer in northern Italy, and identify factors influencing survival. A total of 1180 lung cancer cases diagnosed in four north Italian cancer registries (Biella, Modena, Reggio Emilia, Romagna) in 2003-2005 were analyzed. Information on morphology, stage, diagnostic examinations, chemotherapy, radiotherapy, and surgical treatment was collected from clinical records. Three-year relative survival and relative excess risks of death were estimated. Overall, 10% of cases were stage I, 50% stage IV, and 12% stage unknown. Romagna - where sophisticated diagnostic examinations were performed more often - had proportionately more microscopically verified cases and resected cases than Biella. Romagna had also high proportions of cases given chemotherapy and radiotherapy. Three-year survival was 14%, range 10% (Biella) to 19% (Romagna); 69% for stage I, 3% for stage IV. Stage I survival was higher in Romagna (82%) than Reggio Emilia and Biella (60-61%) but for operated stage I cases, survival was similar (88%) in Romagna and Biella. The fully adjusted model showed a higher risk of death in Biella (1.23, 95%CI 1.02-1.48) than Modena (reference). Stage and surgery are key factors influencing survival. Centralizing lung cancer treatment to improve diagnostic work-up may improve outcomes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Two-year survival rates of proximal atraumatic restorative treatment restorations in relation to glass ionomer cements and postrestoration meals consumed

NARCIS (Netherlands)

Kemoli, A.M.; Opinya, G.N.; van Amerongen, W.E.; Mwalili, S.M.

2011-01-01

Purpose: The purpose of this study was to investigate the influence of 3 glass ionomer cement (GIC) brands and the postrestoration meal consumed on the survival rate of proximal atraumatic restorative treatment (ART) restorations. Methods: A total of 804 proximal restorations were placed in primary

Assessment of the Survival of Dental Implants in Irradiated Jaws Following Treatment of Oral Cancer: A Retrospective Study

Science.gov (United States)

Rana, Meenakshi Chauhan; Solanki, Swati; Pujari, Sudarshan C; Shaw, Eisha; Sharma, Swati; Anand, Abhishek; Singh, Harkanwal Preet

2016-01-01

Background: In patients undergoing head and neck surgery for various pathologic conditions, implants are one of the best restorative options and are increasing widely used. Therefore, we evaluated the success of dental implants in the irradiated jaws of patients following treatment of oral cancer oral cancer treated patients. Materials and Methods: Data of oral cancer treated patients was collected retrospectively from 2002 to 2008. We took 46 oral cancer treated patients in which implants were placed in irradiated jaws for rehabilitation. Results: It was found that out of 162 dental implants placed, 52 failed. Furthermore, there was no variation in the implant survival rate in between both the jaws. Radiation dose of <50 Gy units also showed significantly increased amount of implant survival rate. Conclusions: Implant survival is multifactorial and depends upon a number of factors like level of radiation exposure in that area, time gap between last radiation doses etc., Further research is required in this field to improve the esthetics and quality of life of cancer treated patients. PMID:27843270

Assessment of the survival of dental implants in irradiated jaws following treatment of oral cancer: A retrospective study

Directory of Open Access Journals (Sweden)

Meenakshi Chauhan Rana

2016-01-01

Full Text Available Background: In patients undergoing head and neck surgery for various pathologic conditions, implants are one of the best restorative options and are increasing widely used. Therefore, we evaluated the success of dental implants in the irradiated jaws of patients following treatment of oral cancer oral cancer treated patients. Materials and Methods: Data of oral cancer treated patients was collected retrospectively from 2002 to 2008. We took 46 oral cancer treated patients in which implants were placed in irradiated jaws for rehabilitation. Results: It was found that out of 162 dental implants placed, 52 failed. Furthermore, there was no variation in the implant survival rate in between both the jaws. Radiation dose of <50 Gy units also showed significantly increased amount of implant survival rate. Conclusions: Implant survival is multifactorial and depends upon a number of factors like level of radiation exposure in that area, time gap between last radiation doses etc., Further research is required in this field to improve the esthetics and quality of life of cancer treated patients.

Predicting Structure-Function Relations and Survival following Surgical and Bronchoscopic Lung Volume Reduction Treatment of Emphysema.

Science.gov (United States)

Mondoñedo, Jarred R; Suki, Béla

2017-02-01

Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (bLVR) are palliative treatments aimed at reducing hyperinflation in advanced emphysema. Previous work has evaluated functional improvements and survival advantage for these techniques, although their effects on the micromechanical environment in the lung have yet to be determined. Here, we introduce a computational model to simulate a force-based destruction of elastic networks representing emphysema progression, which we use to track the response to lung volume reduction via LVRS and bLVR. We find that (1) LVRS efficacy can be predicted based on pre-surgical network structure; (2) macroscopic functional improvements following bLVR are related to microscopic changes in mechanical force heterogeneity; and (3) both techniques improve aspects of survival and quality of life influenced by lung compliance, albeit while accelerating disease progression. Our model predictions yield unique insights into the microscopic origins underlying emphysema progression before and after lung volume reduction.

Acid and low temperature treatments on Salmonella Enteritidis inoculated in pork and its subsequent survival in simulated gastric fluid

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Simone Quintão Silva

2016-03-01

Full Text Available ABSTRACT: The objective of this study was to evaluate the acid resistance of Salmonella enterica serovar Enteritidis (S. Enteritidis in stored pork and in simulated gastric fluid (SGF. A culture of S. Enteritidis was subjected to acid treatment prior to inoculation into pork, stored under refrigeration at frozen temperatures and exposed to SGF. The S. Enteritidis CCS3 and ATCC 13076 strains previously subjected to acid treatment (at pH 4.0-5.0 were inoculated in pork and stored at 4°C and -18°C. Storage at 4ºC did not affect the populations of both S. Enteritidis strains. After 84 days at -18°C, the mean population of both CCS3 and ATCC strains were reduced by 0.8 and 1.5 log cycles, respectively. Prior acid treatment did not enhance the survival of both strains at low temperatures. After acid treatment and low temperature storage, S. Enteritidis ATCC 13076 lost culturability after being exposed to SGF for 10 minutes. In contrast, S. Enteritidis CCS3 was tolerant until three hours of SGF exposure. S. Enteritidis CCS3 submitted to pH 4.0 was more tolerant to SGF exposure than when submitted to pH 4.5, 5.0 and without acid treatment. Therefore, this study indicates that exposure to an acidic and cold environment during processing enhanced the ability of S. Enteritidis to survive in the gastric environment of the human stomach, possibly increasing the risk of a Salmonella infection after consumption of pork.

Anti-asialo GM1 antiserum treatment of lethally irradiated recipients before bone marrow transplantation: Evidence that recipient natural killer depletion enhances survival, engraftment, and hematopoietic recovery

International Nuclear Information System (INIS)

Tiberghien, P.; Longo, D.L.; Wine, J.W.; Alvord, W.G.; Reynolds, C.W.

1990-01-01

Natural killer (NK) cells are reported to have an important role in the resistance of lethally irradiated recipients to bone marrow transplantation (BMT). Therefore, we investigated the effects of recipient NK depletion on survival, chimerism, and hematopoietic reconstitution after lethal irradiation and the transplantation of limiting amounts of T-cell-deficient bone marrow (BM). When administered before BMT, anti-asialo GM1 (ASGM1) antiserum treatment, effective in depleting in vivo NK activity, was associated with a marked increase in survival in 3 of 3 allogeneic combinations (BALB/c into C3H/HeN, C57B1/6, or C3B6F1). This enhanced survival was independent of the susceptibility of each recipient strain to accept BALB/c BM. Moreover, recipient anti-ASGM1 treatment was also effective in increasing survival in recipients of syngeneic BM, suggesting that NK cells can adversely affect engraftment independent of genetically controlled polymorphic cell surface determinants. Analysis of chimerism in surviving animals 2 months post-BMT showed that recipient NK depletion significantly increased the level of donor engraftment when high doses of BM were transplanted. These studies also demonstrated that anti-ASGM1 pretreatment mainly resulted in an increase in extramedullary hematopoiesis in the second and third week after irradiation. Anti-ASGM1 treatment also dramatically accelerated the rate of appearance of donor-derived cells with a higher level of donor-cell engraftment apparent at a time when the differences in survival between NK-depleted and control BMT recipients became significant. Peripheral cell counts were also affected by NK depletion, with significantly enhanced platelet and red blood cell recovery and a moderate increase in granulocyte recovery

Anti-asialo GM1 antiserum treatment of lethally irradiated recipients before bone marrow transplantation: Evidence that recipient natural killer depletion enhances survival, engraftment, and hematopoietic recovery

Energy Technology Data Exchange (ETDEWEB)

Tiberghien, P.; Longo, D.L.; Wine, J.W.; Alvord, W.G.; Reynolds, C.W. (Program Resources, Inc., Frederick, MD (USA))

1990-10-01

Natural killer (NK) cells are reported to have an important role in the resistance of lethally irradiated recipients to bone marrow transplantation (BMT). Therefore, we investigated the effects of recipient NK depletion on survival, chimerism, and hematopoietic reconstitution after lethal irradiation and the transplantation of limiting amounts of T-cell-deficient bone marrow (BM). When administered before BMT, anti-asialo GM1 (ASGM1) antiserum treatment, effective in depleting in vivo NK activity, was associated with a marked increase in survival in 3 of 3 allogeneic combinations (BALB/c into C3H/HeN, C57B1/6, or C3B6F1). This enhanced survival was independent of the susceptibility of each recipient strain to accept BALB/c BM. Moreover, recipient anti-ASGM1 treatment was also effective in increasing survival in recipients of syngeneic BM, suggesting that NK cells can adversely affect engraftment independent of genetically controlled polymorphic cell surface determinants. Analysis of chimerism in surviving animals 2 months post-BMT showed that recipient NK depletion significantly increased the level of donor engraftment when high doses of BM were transplanted. These studies also demonstrated that anti-ASGM1 pretreatment mainly resulted in an increase in extramedullary hematopoiesis in the second and third week after irradiation. Anti-ASGM1 treatment also dramatically accelerated the rate of appearance of donor-derived cells with a higher level of donor-cell engraftment apparent at a time when the differences in survival between NK-depleted and control BMT recipients became significant. Peripheral cell counts were also affected by NK depletion, with significantly enhanced platelet and red blood cell recovery and a moderate increase in granulocyte recovery.

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

Decreased survival of prostate cancer cells in vitro by combined treatment of heat and an antioxidant inhibitor diethyldithiocarbamate (DDC).

Science.gov (United States)

Moriyama-Gonda, Nobuko; Igawa, Mikio; Shiina, Hiroaki; Urakami, Shinji; Terashima, Masaharu

2003-11-01

The aim of this study was to examine a modulation of thermotolerance by treatment with combination of heat and the antioxidant inhibitor diethyldithiocarbamate (DDC) of the PC-3 prostate cancer cells. To determine thermotolerance, cells were heated once or twice. Two 1 h exposures at 43 degrees C, with a recovery period in between, revealed better survival/recovery of cells after the second exposure than after the first (fig. 1A + 1B). Additional experiments were performed, heating cells twice (fig. 1B + 1C). First, cells were heated at 43 degrees C for 1 h and, after various recovery times (intervals) at 37 degree C, subsequently reheated at 44 degrees C for 1 h. To ensure effective cell killing, efficiency of the combined treatments of 1 mM DDC and heating at 43 or 44 degrees C for 1 h was estimated by measuring cell survival, reactive oxygen species (ROS) generation, superoxide dismutase (SOD) activity and heat shock protein 70 (hsp 70) expression. To obtain a more effective method for subsequent heat exposure, cells were heated twice after a 24 h interval in the presence or absence of 1 mM DDC. ROS generation and SOD activity immediately increased correlating with duration of heating, but their levels gently decreased with time after discontinuation of heating. On the other hand, hsp 70 levels slowly increased, also correlating with duration of heating but continued to increase with time after discontinuation of heating for a certain period. DDC administration coupled with heating at 43 or 44 degrees C significantly decreased cell survival compared to heating alone (p DDC as compared to heat alone at 43 and 44 degrees C (p DDC could have potential benefits in the treatment of prostate cancer.

Chordomas of the Skull Base, Mobile Spine, and Sacrum: An Epidemiologic Investigation of Presentation, Treatment, and Survival.

Science.gov (United States)

Zuckerman, Scott L; Bilsky, Mark H; Laufer, Ilya

2018-05-01

Chordomas are rare primary bone tumors that arise from the axial skeleton. Our objective was to analyze trends in radiation and surgery over time and determine location-based survival predictors for chordomas of the skull base, mobile spine, and sacrum. A retrospective cohort study of the SEER (Surveillance Epidemiology and End Results) database from 1973 to 2013 was conducted. All patients had histologically confirmed chordomas. The principal outcome measure was overall survival (OS). The cohort included 1616 patients: skull base (664), mobile spine (444), and sacrum (508). Skull base tumors presented earliest in life (47.4 years) and sacral tumors presented latest (62.7 years). Rates of radiation remained stable for skull base and mobile spine tumors but declined for sacral tumors (P = 0.006). Rates of surgical resection remained stable for skull base and sacral tumors but declined for mobile spine tumors (P = 0.046). Skull base chordomas had the longest median survival (162 months) compared with mobile spine (94 months) and sacral tumors (87 months). Being married was independently associated with improved OS for skull base tumors (hazard ratio, 0.73; 95% confidence interval, 0.53-0.99; P = 0.044). Surgical resection was independently associated with improved OS for sacral chordomas (hazard ratio, 0.48; 95% confidence interval, 0.34-0.69; P mobile spine chordomas and radiation for sacral chordomas decreased over time. Patients with skull base tumors survived longer than did patients with mobile spine and sacral chordomas, and surgical resection was associated with improved survival in sacral chordomas only. Understanding the behavior of these tumors can help cranial and spinal surgeons improve treatment in this patient population. Copyright © 2018 Elsevier Inc. All rights reserved.

Increased Survival after Gemfibrozil Treatment of Severe Mouse Influenza▿

Science.gov (United States)

Budd, Alison; Alleva, Lisa; Alsharifi, Mohammed; Koskinen, Aulikki; Smythe, Victoria; Müllbacher, Arno; Wood, Jeff; Clark, Ian

2007-01-01

Gemfibrozil, an agent that inhibits production of proinflammatory cytokines in addition to its clinically useful lipid-lowering activity, increased survival in BALB/c mice that were already ill from infection by influenza virus A/Japan/305/57 (H2N2). Gemfibrozil was administered intraperitoneally once daily from days 4 to 10 after intranasal exposure to the virus. Survival increased from 26% in vehicle-treated mice (n = 50) to 52% in mice given gemfibrozil at 60 mg/kg/day (n = 46) (P = 0.0026). If this principle translates to patients, a drug already approved for human use, albeit by a different route for another purpose, might be adapted relatively fast for use against influenza, conceivably including human infection with a derivative of the avian H5N1 strain. PMID:17562808

Spinal Cord Injury in the Geriatric Population: Risk Factors, Treatment Options, and Long-Term Management.

Science.gov (United States)

Ikpeze, Tochukwu C; Mesfin, Addisu

2017-06-01

Spinal cord injuries (SCIs) are sustained by more than 12 500 patients per year in the United States and more globally. The SCIs disproportionately affect the elderly, especially men. Approximately 60% of these injuries are sustained traumatically through falls, but nontraumatic causes including infections, tumors, and medication-related epidural bleeding have also been documented. Preexisting conditions such as ankylosing spondylitis and diffuse idiopathic skeletal hyperostosis can render the spine stiff and are risk factors as well as cervical spondylosis and ensuing cervical stenosis. Treatment options vary depending on the severity, location, and complexity of the injury. Surgical management has been growing in popularity over the years and remains an option as it helps reduce spinal cord compression and alleviate pain. Elevating mean arterial pressures to prevent spinal cord ischemia and avoiding the second hit of SCI have become more common as opposed to high dose steroids. Ongoing clinical trials with pharmacological agents such as minocycline and riluzole have shown early, promising results in their ability to reduce cellular damage and facilitate recovery. Though SCI can be life changing, the available treatment options have aimed to reduce pain and minimize complications and maintain quality of life alongside rehabilitative services.

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.

Socioeconomic position and survival after lung cancer

DEFF Research Database (Denmark)

Dalton, Susanne O; Steding-Jessen, Marianne; Jakobsen, Erik

2015-01-01

BACKGROUND: To address social inequality in survival after lung cancer, it is important to consider how socioeconomic position (SEP) influences prognosis. We investigated whether SEP influenced receipt of first-line treatment and whether socioeconomic differences in survival could be explained...... by differences in stage, treatment and comorbidity. MATERIAL AND METHODS: In the Danish Lung Cancer Register, we identified 13 045 patients with lung cancer diagnosed in 2004-2010, with information on stage, histology, performance status and first-line treatment. We obtained age, gender, vital status, comorbid...... with stepwise inclusion of possible mediators. RESULTS: For both low- and high-stage lung cancer, adjusted ORs for first-line treatment were reduced in patients with short education and low income, although the OR for education did not reach statistical significance in men with high-stage disease. Patients...

Socioeconomic position and survival after cervical cancer

DEFF Research Database (Denmark)

Ibfelt, E H; Kjær, S K; Høgdall, C

2013-01-01

In an attempt to decrease social disparities in cancer survival, it is important to consider the mechanisms by which socioeconomic position influences cancer prognosis. We aimed to investigate whether any associations between socioeconomic factors and survival after cervical cancer could...... be explained by socioeconomic differences in cancer stage, comorbidity, lifestyle factors or treatment....

Survival effect of first- and second-line treatments for patients with primary glioblastoma: a cohort study from a prospective registry, 1997–2010

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Nava, Francesca; Tramacere, Irene; Fittipaldo, Andrea; Bruzzone, Maria Grazia; DiMeco, Francesco; Fariselli, Laura; Finocchiaro, Gaetano; Pollo, Bianca; Salmaggi, Andrea; Silvani, Antonio; Farinotti, Mariangela; Filippini, Graziella

2014-01-01

Background Prospective follow-up studies of large cohorts of patients with glioblastoma (GBM) are needed to assess the effectiveness of conventional treatments in clinical practice. We report GBM survival data from the Brain Cancer Register of the Fondazione Istituto Neurologico Carlo Besta (INCB) in Milan, Italy, which collected longitudinal data for all consecutive patients with GBM from 1997 to 2010. Methods Survival data were obtained from 764 patients (aged>16 years) with histologically confirmed primary GBM who were diagnosed and treated over a 7-year period (2004–2010) with follow-up to April 2012 (cohort II). Equivalent data from 490 GBM patients diagnosed and treated over the preceding 7 years (1997–2003) with follow-up to April 2005 (cohort I) were available for comparison. Progression-free survival (PFS) was available from 361 and 219 patients actively followed up at INCB in cohorts II and I, respectively. Results Survival probabilities were 54% at 1 year, 21% at 2 years, and 11% at 3 years, respectively, in cohort II compared with 47%, 11%, and 5%, respectively, in cohort I. PFS was 22% and 12% at 1 year in cohorts II and I. Better survival and PFS in cohort II was significantly associated with introduction of the Stupp protocol into clinical practice, with adjusted hazard ratios (HRs) of 0.78 for survival and 0.73 for PFS, or a 22% relative decrease in the risk of death and a 27% relative decrease in the risk of recurrence. After recurrence, reoperation was performed in one-fifth of cohort I and in one-third of cohort II but was not effective (HR, 1.05 in cohort I and 1.02 in cohort II). Second-line chemotherapy, mainly consisting of nitrosourea-based chemotherapy, temozolomide, mitoxantrone, fotemustine, and bevacizumab, improved survival in both cohorts (HR, 0.57 in cohort I and 0.74 in cohort II). Radiosurgery was also effective (HR, 0.52 in cohort II). Conclusions We found a significant increase in overall survival, PFS, and survival after

Breast cancer survival studies in India: a review

OpenAIRE

Jignasa Sathwara; Saurabh Bobdey; Ganesh B.

2016-01-01

Length of survival of cancer patients is an important indicator for knowing the outcome of treatment in any study. Epidemiological features and biological profile of breast cancer appear to be different in developing countries as compared to Western countries. Knowing the factors that influence survival rates among women with breast cancer may help define early detection actions, and improve treatment and care proposals in all the areas of health. Therefore, this study aims to identify, the p...

Immunological and biological changes during ipilimumab treatment and their potential correlation with clinical response and survival in patients with advanced melanoma.

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Simeone, Ester; Gentilcore, Giusy; Giannarelli, Diana; Grimaldi, Antonio M; Caracò, Corrado; Curvietto, Marcello; Esposito, Assunta; Paone, Miriam; Palla, Marco; Cavalcanti, Ernesta; Sandomenico, Fabio; Petrillo, Antonella; Botti, Gerardo; Fulciniti, Franco; Palmieri, Giuseppe; Queirolo, Paola; Marchetti, Paolo; Ferraresi, Virginia; Rinaldi, Gaetana; Pistillo, Maria Pia; Ciliberto, Gennaro; Mozzillo, Nicola; Ascierto, Paolo A

2014-07-01

Ipilimumab can induce durable disease control and long-term survival in patients with metastatic melanoma. Identification of a biomarker that correlates with clinical benefit and potentially provides an early marker of response is an active area of research. Ipilimumab was available upon physician request for patients aged ≥16 years with stage III (unresectable) or IV cutaneous, ocular or mucosal melanoma, who had failed or did not tolerate previous treatments and had no other therapeutic option available. Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. Tumour assessments were conducted at baseline, Week 12 and Week 24 using immune-related response criteria. Patients were monitored continuously for adverse events (AEs), including immune-related AEs. Candidate immunological markers were evaluated in peripheral blood and sera samples collected at baseline and Weeks 4, 7, 10 and 12. Among 95 patients treated with ipilimumab 3 mg/kg, the immune-related disease control rate at Week 24 was 38 %. With a median follow-up of 24 months, median overall survival was 9.6 months. Both disease control and survival were significantly associated with decreasing levels of lactate dehydrogenase, C-reactive protein and FoxP3/regulatory T cells, and increasing absolute lymphocyte count, between baseline and the end of dosing (Week 12). Ipilimumab is a feasible treatment option for heavily pretreated patients with metastatic melanoma. Changes in some immunological markers between baseline and the fourth ipilimumab infusion appear to be associated with disease control and survival, but verification in prospective clinical trials is required.

The influence of marital status on the stage at diagnosis, treatment, and survival of adult patients with gastric cancer: a population-based study

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Zhang, Jieyun; Gan, Lu; Wu, Zhenhua; Yan, Shican; Liu, Xiyu; Guo, Weijian

2016-01-01

Background & Aims Marital status was reported as a prognostic factor in many cancers. However, its role in gastric cancer (GC) hasn't been thoroughly explored. In this study, we aimed to investigate the effect of marital status on survival, stage, treatment, and survival in subgroups. Methods We used the Surveillance, Epidemiology and End Results (SEER) database and identified 16910 GC patients. These patients were categorized into married (58.44%) and unmarred (41.56%) groups. Pearson chi-sq...

Locally advanced pancreatic cancer: association between prolonged preoperative treatment and lymph-node negativity and overall survival.

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Kadera, Brian E; Sunjaya, Dharma B; Isacoff, William H; Li, Luyi; Hines, O Joe; Tomlinson, James S; Dawson, David W; Rochefort, Matthew M; Donald, Graham W; Clerkin, Barbara M; Reber, Howard A; Donahue, Timothy R

2014-02-01

Treatment of patients with locally advanced/borderline resectable (LA/BR) pancreatic ductal adenocarcinoma (PDAC) is not standardized. To (1) perform a detailed survival analysis of our institution's experience with patients with LA/BR PDAC who were downstaged and underwent surgical resection and (2) identify prognostic biomarkers that may help to guide a decision for the use of adjuvant therapy in this patient subgroup. Retrospective observational study of 49 consecutive patients from a single institution during 1992-2011 with American Joint Committee on Cancer stage III LA/BR PDAC who were initially unresectable, as determined by staging computed tomography and/or surgical exploration, and who were treated and then surgically resected. Clinicopathologic variables and prognostic biomarkers SMAD4, S100A2, and microRNA-21 were correlated with survival by univariate and multivariate Cox proportional hazard modeling. All 49 patients were deemed initially unresectable owing to vascular involvement. After completing preoperative chemotherapy for a median of 7.1 months (range, 5.4-9.6 months), most (75.5%) underwent a pylorus-preserving Whipple operation; 3 patients (6.1%) had a vascular resection. Strikingly, 37 of 49 patients were lymph-node (LN) negative (75.5%) and 42 (85.7%) had negative margins; 45.8% of evaluable patients achieved a complete histopathologic (HP) response. The median overall survival (OS) was 40.1 months (range, 22.7-65.9 months). A univariate analysis of HP prognostic biomarkers revealed that perineural invasion (hazard ratio, 5.5; P=.007) and HP treatment response (hazard ratio, 9.0; P=.009) were most significant. Lymph-node involvement, as a marker of systemic disease, was also significant on univariate analysis (P=.05). Patients with no LN involvement had longer OS (44.4 vs 23.2 months, P=.04) than LN-positive patients. The candidate prognostic biomarkers, SMAD4 protein loss (P=.01) in tumor cells and microRNA-21 expression in the stroma (P=.05

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

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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.

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

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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.

Mesothelioma: treatment and survival of a patient population and review of the literature.

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Stathopoulos, John; Antoniou, Dimosthenis; Stathopoulos, George P; Rigatos, Sotiris K; Dimitroulis, John; Koutandos, John; Michalopoulou, Pinelopi; Athanasiades, Athanasios; Veslemes, Marinos

2005-01-01

Our purpose was to evaluate the survival of patients with pleural and intraperitoneal malignant mesothelioma and, particularly, to estimate the efficacy of chemotherapy as well as radiotherapy and surgery. A review of the literature with respect to these parameters is included. Thirty-five patients with malignant mesothelioma (28 with pleural and 7 with intraperitoneal) were enrolled. Twenty-eight patients underwent chemotherapy, 7/35 radiation and 9/35 surgery (2 with pleural and 7 with abdominal disease). Combination chemotherapy included cisplatin-gemcitabine, cisplatin (or carboplatin) with premetrexed and doxorubicin-cyclophosphamide. In 2/28 patients with pleural mesothelioma the tumor was excised and in 7 with intraperitoneal disease, surgical therapy was palliative and there was survival prolongation. Radiotherapy was only palliative. Chemotherapy produced a very low response: 2/28 (7.14%) patients achieved a partial response. The median survival was 17 months, 4-year survival, 24.4% and 5-year survival, 12.12%. No serious toxicity was observed. Malignant mesothelioma of the pleura and intraperitoneum is a slow-growing disease which is indicated by the long survival, despite the failure of chemotherapy, radiation therapy and surgery.

Stereotactic Radiosurgery in the Management of Brain Metastases: An Institutional Retrospective Analysis of Survival

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Frazier, James L.; Batra, Sachin; Kapor, Sumit; Vellimana, Ananth; Gandhi, Rahul; Carson, Kathryn A.; Shokek, Ori; Lim, Michael; Kleinberg, Lawrence; Rigamonti, Daniele

2010-01-01

Purpose: The objective of this study was to report our experience with stereotactic radiosurgery performed with the Gamma Knife (GK) in the treatment of patients with brain metastases and to compare survival for those treated with radiosurgery alone with survival for those treated with radiosurgery and whole-brain radiotherapy. Methods and Materials: Prospectively collected demographic and clinical characteristics and treatment and survival data on 237 patients with intracranial metastases who underwent radiosurgery with the GK between 2003 and 2007 were reviewed. Kaplan-Meier and Cox proportional hazards regression analyses were used to compare survival by demographic and clinical characteristics and treatment. Results: The mean age of the patient population was 56 years. The most common tumor histologies were non-small-cell lung carcinoma (34.2%) and breast cancer (13.9%). The median overall survival time was 8.5 months from the time of treatment. The median survival times for patients with one, two/three, and four or more brain metastases were 8.5, 9.4, and 6.7 months, respectively. Patients aged 65 years or greater and those aged less than 65 years had median survival times of 7.8 and 9 months, respectively (p = 0.008). The Karnofsky Performance Score (KPS) at the time of treatment was a significant predictor of survival: those patients with a KPS of 70 or less had a median survival of 2.9 months compared with 10.3 months (p = 0.034) for those with a KPS of 80 or greater. There was no statistically significant difference in survival between patients treated with radiosurgery alone and those treated with radiosurgery plus whole-brain radiotherapy. Conclusions: Radiosurgery with the GK is an efficacious treatment modality for brain metastases. A KPS greater than 70, histology of breast cancer, smaller tumor volume, and age less than 65 years were associated with a longer median survival in our study.

Swedish National Registry of Urinary Bladder Cancer: No difference in relative survival over time despite more aggressive treatment.

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Jahnson, Staffan; Hosseini Aliabad, Abolfazl; Holmäng, Sten; Jancke, Georg; Liedberg, Fredrik; Ljungberg, Börje; Malmström, Per-Uno; Rosell, Johan

2016-01-01

The aim of this study was to use the Swedish National Registry of Urinary Bladder Cancer (SNRUBC) to investigate changes in patient and tumour characteristics, management and survival in bladder cancer cases over a period of 15 years. All patients with newly detected bladder cancer reported to the SNRUBC during 1997-2011 were included in the study. The cohort was divided into three groups, each representing 5 years of the 15 year study period. The study included 31,266 patients (74% men, 26% women) with a mean age of 72 years. Mean age was 71.7 years in the first subperiod (1997-2001) and 72.5 years in the last subperiod (2007-2011). Clinical T categorization changed from the first to the last subperiod: Ta from 45% to 48%, T1 from 21.6% to 22.4%, and T2-T4 from 27% to 25%. Also from the first to the last subperiod, intravesical treatment after transurethral resection for T1G2 and T1G3 tumours increased from 15% to 40% and from 30% to 50%, respectively, and cystectomy for T2-T4 tumours increased from 30% to 40%. No differences between the analysed subperiods were found regarding relative survival in patients with T1 or T2-T4 tumours, or in the whole cohort. This investigation based on a national bladder cancer registry showed that the age of the patients at diagnosis increased, and the proportion of muscle-invasive tumours decreased. The treatment of all tumour stages became more aggressive but relative survival showed no statistically significant change over time.

Combination of Pre-Treatment DWI-Signal Intensity and S-1 Treatment: A Predictor of Survival in Patients with Locally Advanced Pancreatic Cancer Receiving Stereotactic Body Radiation Therapy and Sequential S-1

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Yu Zhang

2018-04-01

Full Text Available OBJECTIVE: To identify whether the combination of pre-treatment radiological and clinical factors can predict the overall survival (OS in patients with locally advanced pancreatic cancer (LAPC treated with stereotactic body radiation and sequential S-1 (a prodrug of 5-FU combined with two modulators therapy with improved accuracy compared with that of established clinical and radiologic risk models. METHODS: Patients admitted with LAPC underwent diffusion weighted imaging (DWI scan at 3.0-T (b = 600 s/mm2. The mean signal intensity (SIb = 600 of region-of-interest (ROI was measured. The Log-rank test was done for tumor location, biliary stent, S-1, and other treatments and the Cox regression analysis was done to identify independent prognostic factors for OS. Prediction error curves (PEC were used to assess potential errors in prediction of survival. The accuracy of prediction was evaluated by Integrated Brier Score (IBS and C index. RESULTS: 41 patients were included in this study. The median OS was 11.7 months (2.8-23.23 months. The 1-year OS was 46%. Multivariate analysis showed that pre-treatment SIb = 600 value and administration of S-1 were independent predictors for OS. The performance of pre-treatment SIb = 600 and S-1 treatment in combination was better than that of SIb = 600 or S-1 treatment alone. CONCLUSION: The combination of pre-treatment SIb = 600 and S-1 treatment could predict the OS in patients with LAPC undergoing SBRT and sequential S-1 therapy with improved accuracy compared with that of established clinical and radiologic risk models.

The Impact of Continuous Medicaid Enrollment on Diagnosis, Treatment, and Survival in Six Surgical Cancers

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Dawes, Aaron J; Louie, Rachel; Nguyen, David K; Maggard-Gibbons, Melinda; Parikh, Punam; Ettner, Susan L; Ko, Clifford Y; Zingmond, David S

2014-01-01

Objective To examine the effect of Medicaid enrollment on the diagnosis, treatment, and survival of six surgically relevant cancers among poor and underserved Californians. Data Sources California Cancer Registry (CCR), California's Patient Discharge Database (PDD), and state Medicaid enrollment files between 2002 and 2008. Study Design We linked clinical and administrative records to differentiate patients continuously enrolled in Medicaid from those receiving coverage at the time of their cancer diagnosis. We developed multivariate logistic regression models to predict death within 1 year for each cancer after controlling for sociodemographic and clinical variables. Data Collection/Extraction Methods All incident cases of six cancers (colon, esophageal, lung, pancreas, stomach, and ovarian) were identified from CCR. CCR records were linked to hospitalizations (PDD) and monthly Medicaid enrollment. Principal Findings Continuous enrollment in Medicaid for at least 6 months prior to diagnosis improves survival in three surgically relevant cancers. Discontinuous Medicaid patients have higher stage tumors, undergo fewer definitive operations, and are more likely to die even after risk adjustment. Conclusions Expansion of continuous insurance coverage under the Affordable Care Act is likely to improve both access and clinical outcomes for cancer patients in California. PMID:25256223

Neuro-peptide treatment with Cerebrolysin improves the survival of neural stem cell grafts in an APP transgenic model of Alzheimer disease

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Edward Rockenstein

2015-07-01

Full Text Available Neural stem cells (NSCs have been considered as potential therapy in Alzheimer's disease (AD but their use is hampered by the poor survival of grafted cells. Supply of neurotrophic factors to the grafted cells has been proposed as a way to augment survival of the stem cells. In this context, we investigated the utility of Cerebrolysin (CBL, a peptidergic mixture with neurotrophic-like properties, as an adjunct to stem cell therapy in an APP transgenic (tg model of AD. We grafted murine NSCs into the hippocampus of non-tg and APP tg that were treated systemically with CBL and analyzed after 1, 3, 6 and 9 months post grafting. Compared to vehicle-treated non-tg mice, in the vehicle-treated APP tg mice there was considerable reduction in the survival of the grafted NSCs. Whereas, CBL treatment enhanced the survival of NSCs in both non-tg and APP tg with the majority of the surviving NSCs remaining as neuroblasts. The NSCs of the CBL treated mice displayed reduced numbers of caspase-3 and TUNEL positive cells and increased brain derived neurotrophic factor (BDNF and furin immunoreactivity. These results suggest that CBL might protect grafted NSCs and as such be a potential adjuvant therapy when combined with grafting.

Long-term Survival of Personalized Surgical Treatment of Locally Advanced Non-small Cell Lung Cancer Based on Molecular Staging

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Qinghua ZHOU

2011-02-01

Full Text Available Background and objective Approximately 35%-40% of patients with newly diagnosed non-small cell Lung cancer have locally advanced disease. The average survival time of these patients only have 6-8 months with chemotherapy. The aim of this study is to explore and summarize the probability of detection of micrometastasis in peripheral blood for molecular staging, and for selection of indication of surgical treatment, and beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in locally advanced lung cancer; to summarize the long-time survival result of personalized surgical treatment of 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods. Methods CK19 mRNA expression of peripheral blood samples was detected in 516 lung cancer patients by RT-PCR before operation for molecular diagnosis of micrometastasis, personalized molecular staging, and for selection of indication of surgical treatment and the beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in patients with locally advanced nonsmall cell lung cancer invaded heart, great vessels or both. The long-term survival result of personalized surgical treatment was retrospectively analyzed in 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods. Results There were 322 patients with squamous cell carcinoma and 194 cases with adenocarcinoma in the series of 516 patients with locally advanced lung cancer involved heart, great vessels or both. There were 112 patients with IIIA disease and 404 cases with IIIB disease according to P-TNM staging. There were 97 patients with M-IIIA disease, 278 cases with M-IIIB disease and 141 cases with III disease according to our personalized molecular staging. Of the 516 patients, bronchoplastic procedures and pulmonary artery reconstruction was carried out in 256 cases; lobectomy combined with resection and reconstruction of partial left

Lung cancer survival in Norway, 1997-2011: from nihilism to optimism.

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Nilssen, Yngvar; Strand, Trond Eirik; Fjellbirkeland, Lars; Bartnes, Kristian; Møller, Bjørn

2016-01-01

We examine changes in survival and patient-, tumour- and treatment-related factors among resected and nonresected lung cancer patients, and identify subgroups with the largest and smallest survival improvements.National population-based data from the Cancer Registry of Norway, Statistics Norway and the Norwegian Patient Register were linked for lung cancer patients diagnosed during 1997-2011. The 1- and 5-year relative survival were estimated, and Cox proportional hazard regression, adjusted for selected patient characteristics, was used to assess prognostic factors for survival in lung cancer patients overall and stratified by resection status.We identified 34 157 patients with lung cancer. The proportion of histological diagnoses accompanied by molecular genetics testing increased from 0% to 26%, while those accompanied by immunohistochemistry increased from 8% to 26%. The 1-year relative survival among nonresected and resected patients increased from 21.7% to 34.2% and 75.4% to 91.5%, respectively. The improved survival remained significant after adjustment for age, sex, stage and histology. The largest improvements in survival occurred among resected and adenocarcinoma patients, while patients ≥80 years experienced the smallest increase.Lung cancer survival has increased considerably in Norway. The explanation is probably multifactorial, including improved attitude towards diagnostic work-up and treatment, and more accurate diagnostic testing that allows for improved selection for resection and improved treatment options. Copyright ©ERS 2016.

High risk bladder cancer: current management and survival

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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.

Illness perceptions predict survival in haemodialysis patients.

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Chilcot, Joseph; Wellsted, David; Farrington, Ken

2011-01-01

Illness perceptions have been shown to be important determinants of functional and psychosocial outcomes, including quality of life and treatment adherence in end-stage renal disease patients. The aim of this prospective study was to determine whether haemodialysis patients' illness perceptions impact upon survival. Haemodialysis patients from a UK renal service completed the Revised Illness Perception Questionnaire. Over the study period (May 2007 to December 2010), all-cause mortality was recorded as the endpoint. 223 patients were followed up for a median of 15.9 months (min. 10 days, max. 42.7 months). The median dialysis vintage was 17.6 months (min. 4 days, max. 391.3 months). Treatment control perceptions demonstrated a significant association with mortality (HR = 0.91, 95% CI: 0.83-0.99, p = 0.03). After controlling for covariates, including age, albumin, extra renal comorbidity and depression scores, perception of treatment control remained a significant predictor of mortality (HR = 0.89, 95% CI: 0.80-0.99, p = 0.03). Patients' perceptions of treatment control (dialysis therapy) predict survival independently of survival risk factors, including comorbidity. Studies are required to test whether psychological interventions designed to modify maladaptive illness perceptions influence clinical outcomes in this patient setting. Copyright © 2011 S. Karger AG, Basel.

Neuropeptide Treatment with Cerebrolysin Enhances the Survival of Grafted Neural Stem Cell in an α-Synuclein Transgenic Model of Parkinson's Disease

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Edward Rockenstein

2015-01-01

Full Text Available Neuronal stem cell (NSC grafts have been investigated as a potential neuro-restorative therapy in Parkinson's disease (PD but their use is compromised by the death of grafted cells. We investigated the use of Cerebrolysin (CBL, a neurotrophic peptide mixture, as an adjunct to NSC therapy in the α-synuclein (α-syn transgenic (tg model of PD. In vehicle-treated α-syn tg mice, there was decreased survival of NSCs. In contrast, CBL treatment enhanced the survival of NSCs in α-syn tg groups and ameliorated behavioral deficits. The grafted NSCs showed lower levels of terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells in the CBL-treated mice when compared with vehicle-treated α-syn tg mice. No evidence of tumor growth was detected. Levels of α-syn were similar in the vehicle in CBL-treated tg mice. In conclusion, CBL treatment might be a potential adjuvant for therapeutic NSC grafting in PD.

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

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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.

Body mass index does not influence post-treatment survival in early stage endometrial cancer: results from the MRC ASTEC trial.

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Crosbie, Emma J; Roberts, Chris; Qian, Wendi; Swart, Ann Marie; Kitchener, Henry C; Renehan, Andrew G

2012-04-01

Body mass index (BMI) is a major risk factor for endometrial cancer incidence but its impact on post-treatment survival is unclear. We investigated the relationships of BMI (categorised using the WHO definitions) with clinico-pathological characteristics and outcome in women treated within the MRC ASTEC randomised trial, which provides data from patients who received standardised allocated treatments and therefore reduces biases. The impact of BMI on both recurrence-free survival (RFS) and overall survival (OS) was analysed using the Cox regression models. An apriori framework of evaluating potential biases was explored. From 1408 participants, there were 1070 women with determinable BMI (median=29.1 kg/m(2)). Histological types were endometrioid (type 1) in 893 and non-endometrioid (type 2) in 146 women; the proportion of the latter decreasing with increasing BMI (8% versus 19% for obese III WHO category versus normal weight, p(trend)=0.003). For type 1 carcinomas, increasing BMI was associated with less aggressive histopathological features (depth of invasion, p=0.006; tumour grade, p=0.015). With a median follow-up of 34.3 months, there was no influence of BMI on RFS - adjusted HRs per 5 kg/m(2) were 0.98 (95% CI 0.86, 1.13) and 0.95 (0.74, 1.24), for type 1 and 2 carcinomas; and no influence on OS - adjusted HRs per 5 kg/m(2) were 0.96 (0.81, 1.14) and 0.92 (0.70, 1.23), respectively. These findings demonstrate an important principle: that an established link between an exposure (here, obesity) and increased incident cancer risk, does not necessarily translate into an inferior outcome following treatment for that cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.

Long term (five-year survival following radical surgical treatment plus adjuvant chemotherapy (FAM in advanced gastric cancer: a controlled study

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Bresciani Cláudio

2000-01-01

Full Text Available Several drugs and their associations are being used for adjuvant or complementary chemotherapy with the aim of improving results of gastric cancer treatment. The objective of this study was to verify the impact of these drugs on nutrition and on survival rate after radical treatment of 53 patients with gastric cancer in stage III of the TNM classification. A control group including 28 patients who had only undergone radical resection was compared to a group of 25 patients who underwent the same operative technique followed by adjuvant polychemotherapy with FAM (5-fluorouracil, Adriamycin, and mitomycin C. In this latter group, chemotherapy toxicity in relation to hepatic, renal, cardiologic, neurological, hematologic, gastrointestinal, and dermatological functions was also studied. There was no significant difference on admission between both groups in relation to gender, race, macroscopic tumoral type of tumor according to the Borrmann classification, location of the tumor in the stomach, length of the gastric resection, or response to cutaneous tests on delayed sensitivity. Chemotherapy was started on average, 2.3 months following surgical treatment. Clinical and laboratory follow-up of all patients continued for 5 years. The following conclusions were reached: 1 The nutritional status and incidence of gastrointestinal manifestation were similar in both groups; 2 There was no occurrence of cardiac, renal, neurological, or hepatic toxicity or death due to the chemotherapeutic method per se; 3 Dermatological alterations and hematological toxicity occurred exclusively in patients who underwent polychemotherapy; 4 There was no significant difference between the rate and site of tumoral recurrence, the disease-free interval, or the survival rate of both study groups; 5 Therefore, we concluded, after a 5-year follow-up, chemotherapy with the FAM regimen did not increase the survival rate.

Effect of systemic piracetam treatment on flap survival and vascular endothelial growth factor expression after ischemia-reperfusion injury.

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Tuncer, Serhan; Ayhan, Suhan; Findikcioglu, Kemal; Ergun, Hakan; Tuncer, Ilhan

2011-09-01

The effects of piracetam on flap survival, ischemia-reperfusion (I/R) injury, and vascular endothelial growth factor (VEGF) expression were evaluated in this study. Unipedicled epigastric flap model was used in 36 rats and was evaluated within 4 groups. The flap was elevated and untreated in Group 1. Postoperative piracetam treatment was given for 7 days in Group 2. In Group 3, 4 hours of ischemia and 2 hours of reperfusion were applied. I/R was applied to Group 4 and piracetam was given 30 minutes before reperfusion and postoperatively for 7 days. Laser Doppler flowmetry was used to measure blood flow changes. VEGF expression was determined using immunohistochemical methods on tissue samples taken after the completion of 2 hours reperfusion in groups 3 and 4. Flap necrosis was measured on the day 7 in all groups. Blood flow rates did not show significant difference between piracetam treated and untreated I/R groups. Piracetam significantly reduced necrosis area both in ischemic and nonischemic flaps ( P piracetam-treated Group 4 compared with Group 3 ( P = 0.005). This experimental study demonstrates that systemic piracetam treatment improves survival of pedicled flaps, reduces necrosis amounts, and increases VEGF expression in I/R induced flaps. © Thieme Medical Publishers.

Therapeutic opportunities and challenges of induced pluripotent stem cells-derived motor neurons for treatment of amyotrophic lateral sclerosis and motor neuron disease

Institute of Scientific and Technical Information of China (English)

Manoj Kumar Jaiswal

2017-01-01

Amyotrophic lateral sclerosis (ALS) and motor neuron diseases (MNDs) are progressive neurodegenera-tive diseases that affect nerve cells in the brain affecting upper and lower motor neurons (UMNs/LMNs), brain stem and spinal cord.The clinical phenotype is characterized by loss of motor neurons (MNs), mus-cular weakness and atrophy eventually leading to paralysis and death due to respiratory failure within 3–5 years after disease onset. No effective treatment or cure is currently available that halts or reverses ALS and MND except FDA approved drug riluzole that only modestly slows the progression of ALS in some patients. Recent advances in human derived induced pluripotent stem cells have made it possible for the first time to obtain substantial amounts of human cells to recapitulate in vitro"disease in dish"and test some of the underlying pathogenetic mechanisms involved in ALS and MNDs. In this review, I discussed the opportunities and challenges of induced pluropotent stem cells-derived motor neurons for treatment of ALS and MND patients with special emphasis on their implications in finding a cure for ALS and MNDs.

Therapeutic opportunities and challenges of induced pluripotent stem cells-derived motor neurons for treatment of amyotrophic lateral sclerosis and motor neuron disease.

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Jaiswal, Manoj Kumar

2017-05-01

Amyotrophic lateral sclerosis (ALS) and motor neuron diseases (MNDs) are progressive neurodegenerative diseases that affect nerve cells in the brain affecting upper and lower motor neurons (UMNs/LMNs), brain stem and spinal cord. The clinical phenotype is characterized by loss of motor neurons (MNs), muscular weakness and atrophy eventually leading to paralysis and death due to respiratory failure within 3-5 years after disease onset. No effective treatment or cure is currently available that halts or reverses ALS and MND except FDA approved drug riluzole that only modestly slows the progression of ALS in some patients. Recent advances in human derived induced pluripotent stem cells have made it possible for the first time to obtain substantial amounts of human cells to recapitulate in vitro " disease in dish " and test some of the underlying pathogenetic mechanisms involved in ALS and MNDs. In this review, I discussed the opportunities and challenges of induced pluropotent stem cells-derived motor neurons for treatment of ALS and MND patients with special emphasis on their implications in finding a cure for ALS and MNDs.

A randomized controlled clinical trial of growth hormone in amyotrophic lateral sclerosis: clinical, neuroimaging, and hormonal results.

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Saccà, Francesco; Quarantelli, Mario; Rinaldi, Carlo; Tucci, Tecla; Piro, Raffaele; Perrotta, Gaetano; Carotenuto, Barbara; Marsili, Angela; Palma, Vincenzo; De Michele, Giuseppe; Brunetti, Arturo; Brescia Morra, Vincenzo; Filla, Alessandro; Salvatore, Marco

2012-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease with motor neuron degeneration. Riluzole is the only available treatment. Two-thirds of ALS patients present with growth hormone (GH) deficiency. The aim of this study is to determine if add-on of GH to riluzole, with an individually regulated dose based on Insulin-like growth factor 1 (IGF-I) production, was able to reduce neuronal loss in the motor cortex, reduce mortality, and improve motor function of ALS patients. Patients with definite/probable ALS, in treatment with riluzole, aged 40-85 years, and with disease duration ≤3 years were enrolled. The study was randomized, placebo controlled, and double blind. Before treatment, patients were tested with a GH releasing hormone (GHRH) + arginine test. The initial dose of GH was 2 IU s.c. every other day, and was progressively increased to a maximum of 8 IU. Primary endpoint was N-acetylaspartate/(creatine + choline) (NAA/Cre + Cho) ratio in motor cortex assessed by magnetic resonance spectroscopy performed at months 0, 6, and 12. Secondary endpoints were mortality and ALS functional rating scale revised (ALSFRS-R). The NAA/(Cre + Cho) ratio decreased in all patients who completed the trial. No significant difference was noted between treated and placebo group. At baseline, although IGF-I levels were within the normal range, 73% of patients had GH deficiency, being severe in half of them. Compared with bulbar onset, spinal-onset patients showed more depressed GH response to the GHRH + arginine stimulation test (10.4 ± 7.0 versus 15.5 ± 8.1 ng/mL; p growth factor (IGF) binding protein 3 (IGFBP-3) decreased from 8,435 ± 4,477 ng/mL at baseline to 3,250 ± 1,780 ng/mL at 12 months (p deficit, with higher levels in the bulbar-onset group. During follow-up, patients showed progressive increase in HOMA-IR and decrease in IGFBP-3 levels.

Treatment, therapy results and survival for non-small cell lung cancer in a period of new therapeutic modalities and cytotoxic substances

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Treff, J.

2002-09-01

During the last years considerable changes have been made in the treatment of non-small cell lung cancer. This retrospective study analyzed besides the common characteristics the treatment, response rates and overall survival of patients with non-small cell lung cancer in a central internistical and oncological outpatient department. 328 patients treated at the haematology-oncology outpatient department were included in this study. Requirements have been patients with histologically or cytologically verified non-small cell lung cancer, diagnosis between 1989 and 2001 and comprehensible courses of disease and treatment. Results: Most of the patients were men (72 %) and only 28 % were women. Median age at diagnosis was 61 years; 8.8 % of the patients were aged under 45 years. Adenocarcinoma (46 %) and squamous cell carcinoma (36 %) were the most frequent histologic types. At time of diagnosis 68 % of the patients have been in an already advanced stage IIIB or IV. Surprisingly the diagnosis resulted for 25 % of the patients by chance, 75 % of the patients were diagnosed due to symptoms. Only 8 % of the patients did not receive a specific therapy (surgery, radiation therapy, chemotherapy) due to their advanced disease. 21 patients were treated in a neoadjuvant setting and for 10 (48 %) surgery with curative intention could be performed. The most frequently given chemotherapy in the first-line palliative therapy were Cis-, Carboplatin/VP 16 (40 %) and Cis-, Carboplatin/Navelbine (27 %). The response rate was poor - six complete responses (2.5 %) and 34 (14.3 %) partial responses. 107 patients received a second-line chemotherapy. The overall median survival of all patients was 13.5 months. The stage at time of diagnosis was the most important prognostic factor. Interestingly enough also a survival benefit for women could be demonstrated (15.5 months vs. 13 months). The common characteristics of the analyzed patients correspond to the typical collective of patients in a

Effecst of Patho- Biological Factors on the Survival of Recurrent Breast Cancer Cases

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Akbari, Mohammad Esmaeil; Rohani- Rasaf, Marzieh; Nafissi, Nahid; Akbari, Atieh; Shojaee, Leyla

2018-04-25

Background: Recurrence of breast cancer after treatment is generally due to loco-regional invasion or distant metastasis. Although patients with metastasis are considered incurable, existing treatments might prolong a patient’s life while also improving its quality. Choice of approach for individual patients requires identification of relevant survival factors. This study concerns factors influencing survival after recurrence in Iranian breast cancer patients. Methods: This study was performed on 442 recurrent breast cancer patients referred to the Cancer Research Center of Shahid Beheshti University between 1985 and 2015. After confirming recurrence as a distant metastasis or loco-regional invasion, the effects of demographic, clinic-pathologic, biological, type of surgery and type of adjuvant treatment on survival were evaluated using univariate and multivariate stratified Cox models. Results: The mean survival after recurrence was 18 months (5 days to 13 years), 219 patients (70.42%) survived two years, 75 patients (24.12%) survived from 2 to 5 years, and 17 patients (5.47%) survived more than 5 years. In this study, it was found through univariate analysis that the factors of age, lymph node status, DFI, place of recurrence and nodal ratio demonstrated greatest influence on survival after recurrence. On multivariate analysis, the most important factors influencing survival were the place of recurrence and the lymph node status. Conclusion: The results of this study enhance our knowledge of effects of different factors on survival of patients after breast cancer recurrence. Thus, they may be used to inform treatment choice. Creative Commons Attribution License

Times of analgesic efficacy of two drugs in the treatment of patients with renal-ureteral colic compared by survival models

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Luis Reyes Velázquez

2015-01-01

Full Text Available Renourethral colic is a very painful clinical situation that requires a quick diagnosis and treatment. A study was done with patients who were administered two types of analgesics, and whose pain was measured through a visual analogue scale. Censored data results were obtained, considering the time when the pain disappeared as the random variable. Maximum likelihood and survival analysis give useful methods to estimate the distribution and parametric functions for this variable. This study will allow a more effective, timely, lower cost and suitable medical treatment for patients.

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...

Comparison of cancer survival in New Zealand and Australia, 2006-2010.

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Aye, Phyu S; Elwood, J Mark; Stevanovic, Vladimir

2014-12-19

Previous studies have shown substantially higher mortality rates from cancer in New Zealand compared to Australia, but these studies have not included data on patient survival. This study compares the survival of cancer patients diagnosed in 2006-10 in the whole populations of New Zealand and Australia. Identical period survival methods were used to calculate relative survival ratios for all cancers combined, and for 18 cancers each accounting for more than 50 deaths per year in New Zealand, from 1 to 10 years from diagnosis. Cancer survival was lower in New Zealand, with 5-year relative survival being 4.2% lower in women, and 3.8% lower in men for all cancers combined. Of 18 cancers, 14 showed lower survival in New Zealand; the exceptions, with similar survival in each country, being melanoma, myeloma, mesothelioma, and cervical cancer. For most cancers, the differences in survival were maximum at 1 year after diagnosis, becoming smaller later; however, for breast cancer, the survival difference increased with time after diagnosis. The lower survival in New Zealand, and the higher mortality rates shown earlier, suggest that further improvements in recognition, diagnosis, and treatment of cancer in New Zealand should be possible. As the survival differences are seen soon after diagnosis, issues of early management in primary care and time intervals to diagnosis and treatment may be particularly important.

Improved survival for elderly married glioblastoma patients. Better treatment delivery, less toxicity, and fewer disease complications

International Nuclear Information System (INIS)

Putz, Florian; Goerig, Nicole; Knippen, Stefan; Gryc, Thomas; Semrau, Sabine; Lettmaier, Sebastian; Fietkau, Rainer; Putz, Tobias; Eyuepoglu, Ilker; Roessler, Karl

2016-01-01

Marital status is a well-described prognostic factor in patients with gliomas but the observed survival difference is unexplained in the available population-based studies. A series of 57 elderly glioblastoma patients (≥70 years) were analyzed retrospectively. Patients received radiotherapy or chemoradiation with temozolomide. The prognostic significance of marital status was assessed. Disease complications, toxicity, and treatment delivery were evaluated in detail. Overall survival was significantly higher in married than in unmarried patients (median, 7.9 vs. 4.0 months; p = 0.006). The prognostic significance of marital status was preserved in the multivariate analysis (HR, 0.41; p = 0.011). Married patients could receive significantly higher daily temozolomide doses (mean, 53.7 mg/m"2 vs. 33.1 mg/m"2; p = 0.020), were more likely to receive maintenance temozolomide (45.7 % vs. 11.8 %; p = 0.016), and had to be hospitalized less frequently during radiotherapy (55.0 % vs. 88.2 %; p = 0.016). Of the patients receiving temozolomide, married patients showed significantly lower rates of hematologic and liver toxicity. Most complications were infectious or neurologic in nature. Complications of any grade were more frequent in unmarried patients (58.8 % vs. 30.0 %; p = 0.041) with the incidence of grade 3-5 complications being particularly elevated (47.1 % vs. 15.0 %; p = 0.004). We found poorer treatment delivery as well as an unexpected severe increase in toxicity and disease complications in elderly unmarried glioblastoma patients. Marital status may be an important predictive factor for clinical decision-making and should be addressed in further studies. (orig.) [de

The influence of marital status on the stage at diagnosis, treatment, and survival of adult patients with gastric cancer: a population-based study.

Science.gov (United States)

Zhang, Jieyun; Gan, Lu; Wu, Zhenhua; Yan, Shican; Liu, Xiyu; Guo, Weijian

2017-04-04

Marital status was reported as a prognostic factor in many cancers. However, its role in gastric cancer (GC) hasn't been thoroughly explored. In this study, we aimed to investigate the effect of marital status on survival, stage, treatment, and survival in subgroups. We used the Surveillance, Epidemiology and End Results (SEER) database and identified 16910 GC patients. These patients were categorized into married (58.44%) and unmarred (41.56%) groups. Pearson chi-square, Wilcoxon-Mann-Whitney, Log-rank, multivariate Cox regression, univariate and multivariate binomial or multinomial logistic regression analysis were used in our analysis. Subgroup analyses of married versus unmarried patients were summarized in a forest plot. Married patients had better 5-year overall survival (OS) (32.09% VS 24.61%, PVS 32.79%, Punmarried ones. Then we studied several underlying mechanisms. Firstly, married patients weren't in earlier stage at diagnosis (P=0.159). Secondly, married patients were more likely to receive surgery (P unmarried. Thirdly, in subgroup analyses, married patients still had survival advantage in subgroups with stage II-IV and no radiotherapy. These results showed that marital status was an independently prognostic factor for both OS and CSS in GC patients. Undertreatment and lack of social support in unmarried patients were potential explanations. With the knowledge of heterogeneous effects of marriage in subgroups, we can target unmarried patients with better social support, especially who are diagnosed at late stage and undergo no treatment.

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

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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.

PROGNOSTIC FACTORS OF SURVIVAL IN RENAL CANCER

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A. V. Seriogin

2014-08-01

Full Text Available The purpose of the study was to reveal the independent anatomic, histological, and clinical factors of cancer-specific survival in patients with renal-cell carcinoma (RCC. For this, the authors retrospectively analyzed their experience with radical surgical treatments in 73 RCC patients operated on at the Department of Urology and Surgical Andrology, Russian Medical Academy of Postgraduate Education, from January 1, 1999 to December 31, 2004; their outcomes have become known by the present time. There was a statistically significant correlation of cancer-specific survival with its parameters, such as pathological stage of a tumor, its maximum pathological size, differentiation grade, involvement of regional lymph nodes, venous tumor thrombosis, level of thrombocytosis, and degree of the clinical symptoms of the disease. Multivariate analysis of survival in RCC in relation to the prognostic factors could reveal odd ratios for the limit values of significant prognostic factors. The statistically significant prognostic values established in the present study, as well as the molecular factors the implication of which is being now investigated can become in future an effective addition to the TNM staging system to define indications for certain treatments and to predict survival in RCC  

PROGNOSTIC FACTORS OF SURVIVAL IN RENAL CANCER

Directory of Open Access Journals (Sweden)

A. V. Seriogin

2009-01-01

Full Text Available The purpose of the study was to reveal the independent anatomic, histological, and clinical factors of cancer-specific survival in patients with renal-cell carcinoma (RCC. For this, the authors retrospectively analyzed their experience with radical surgical treatments in 73 RCC patients operated on at the Department of Urology and Surgical Andrology, Russian Medical Academy of Postgraduate Education, from January 1, 1999 to December 31, 2004; their outcomes have become known by the present time. There was a statistically significant correlation of cancer-specific survival with its parameters, such as pathological stage of a tumor, its maximum pathological size, differentiation grade, involvement of regional lymph nodes, venous tumor thrombosis, level of thrombocytosis, and degree of the clinical symptoms of the disease. Multivariate analysis of survival in RCC in relation to the prognostic factors could reveal odd ratios for the limit values of significant prognostic factors. The statistically significant prognostic values established in the present study, as well as the molecular factors the implication of which is being now investigated can become in future an effective addition to the TNM staging system to define indications for certain treatments and to predict survival in RCC  

Progression-free survival: gaining on overall survival as a gold standard and accelerating drug development.

Science.gov (United States)

Lebwohl, David; Kay, Andrea; Berg, William; Baladi, Jean Francois; Zheng, Ji

2009-01-01

In clinical trials of oncology drugs, overall survival (OS) is a direct measure of clinical efficacy and is considered the gold standard primary efficacy end point. The purpose of this study was to discuss the difficulties in using OS as a primary efficacy end point in the setting of evolving cancer therapies. We suggest that progression-free survival is an appropriate efficacy end point in many types of cancer, specifically those for which OS is expected to be prolonged and for which subsequent treatments are expected to affect OS.

A Validated Prediction Model for Overall Survival From Stage III Non-Small Cell Lung Cancer: Toward Survival Prediction for Individual Patients

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Oberije, Cary, E-mail: cary.oberije@maastro.nl [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); De Ruysscher, Dirk [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); Universitaire Ziekenhuizen Leuven, KU Leuven (Belgium); Houben, Ruud [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); Heuvel, Michel van de; Uyterlinde, Wilma [Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Deasy, Joseph O. [Memorial Sloan Kettering Cancer Center, New York (United States); Belderbos, Jose [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Dingemans, Anne-Marie C. [Department of Pulmonology, University Hospital Maastricht, Research Institute GROW of Oncology, Maastricht (Netherlands); Rimner, Andreas; Din, Shaun [Memorial Sloan Kettering Cancer Center, New York (United States); Lambin, Philippe [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands)

2015-07-15

Purpose: Although patients with stage III non-small cell lung cancer (NSCLC) are homogeneous according to the TNM staging system, they form a heterogeneous group, which is reflected in the survival outcome. The increasing amount of information for an individual patient and the growing number of treatment options facilitate personalized treatment, but they also complicate treatment decision making. Decision support systems (DSS), which provide individualized prognostic information, can overcome this but are currently lacking. A DSS for stage III NSCLC requires the development and integration of multiple models. The current study takes the first step in this process by developing and validating a model that can provide physicians with a survival probability for an individual NSCLC patient. Methods and Materials: Data from 548 patients with stage III NSCLC were available to enable the development of a prediction model, using stratified Cox regression. Variables were selected by using a bootstrap procedure. Performance of the model was expressed as the c statistic, assessed internally and on 2 external data sets (n=174 and n=130). Results: The final multivariate model, stratified for treatment, consisted of age, gender, World Health Organization performance status, overall treatment time, equivalent radiation dose, number of positive lymph node stations, and gross tumor volume. The bootstrapped c statistic was 0.62. The model could identify risk groups in external data sets. Nomograms were constructed to predict an individual patient's survival probability ( (www.predictcancer.org)). The data set can be downloaded at (https://www.cancerdata.org/10.1016/j.ijrobp.2015.02.048). Conclusions: The prediction model for overall survival of patients with stage III NSCLC highlights the importance of combining patient, clinical, and treatment variables. Nomograms were developed and validated. This tool could be used as a first building block for a decision support system.

[Impact of the chemotherapy protocols for metastatic breast cancer on the treatment cost and the survival time of 371 patients treated in three hospitals of the Rhone-Alpes region].

Science.gov (United States)

Paviot, B Trombert; Bachelot, T; Clavreul, G; Jacquin, J-P; Mille, D; Rodrigues, J-M

2009-10-01

The chemotherapy of the metastatic breast cancer is characterized by the diversity of the treatment protocols and the utilisation of new expensive molecules posing the double problem of outcomes for the patients and financial effects for the hospitals. This survey describes the different chemotherapy treatments prescribed in the metastatic breast cancer and the direct costs supported by the hospitals according to the patient survival time. A cohort of 371 patients treated for a metastatic breast cancer was followed in three hospitals of the Rhone-Alpes region between 2001 and 2006. The detail of their different antineoplasic treatments, as well as the purchase cost of the drugs and their cost of hospital administration, the cost of the other hospital stays are presented in relation with the survival. The median survival time (35,8 months; CI 95%: [31.7-39.1]) since the first metastasis does not differ significantly according to the hospital. Ninety-three different chemotherapy protocols are observed combining from one to five molecules. Thirty-two different molecules are identified. In first line treatment, there is a significant difference in the use of the new molecules according to hospital (Chi(2) test; P cost of a chemotherapy treatment is 3,919 euro (+/- 8,069 euro), the higher cost is observed for trastuzumab (23,443 euro). The average time period before the beginning of a new chemotherapy line is 212 days (+/- 237 days) and the mean cost of hospital stay during this period is 3,903 euro (+/- 4,097 euro). If no impact of the chemotherapy treatment strategy is observed on the survival time of the patient, it is the opposite for the hospital treatment cost. These results are asking for a better control system of the authorization procedure of new molecules marketing and the harmonization of the practices.

Breast cancer laterality among Egyptian patients and its association with treatments and survival

International Nuclear Information System (INIS)

Zeeneldin, A.A.; Diaa, A.; Mosaad, E.; Ramadan, M.; Elmashad, N.; Fakhr, I.

2013-01-01

Background and aim: Breast cancers (BCs) involve the left side (LS) more than the right side (RS). Among the Egyptians, neither BC laterality nor its association with demographic factors, tumor locations, treatments and outcomes were previously reported. Patients and methods: Laterality was analyzed among 5459 BCs from the Gharbiah population- based cancer registry covering > 5% of the Egyptian population. Cox proportional model was used to assess the independent effect of stage, ER, and laterality on overall survival (OS). Results: In Egypt, BCs involve LS more than RS with LS-to-RS ratio (LRR) of 1.16. LS predominance was evident among men and women and both younger (< 45 years) and older patients. HER2 over-expression and ductal cancers were significantly more in RSBCs while lobular cancers were significantly more in LSBCs. There were no significant differences in localization within the breast between LSBCs and RSBCs (p = 0.51). LS predominance was noticed across all subgroups except in patients with HER2 positive tumors (LRR = 0.63; p = 0.02). OS was significantly better in stage II and ER positive tumors than stage III and ER negative tumors. Despite OS of LSBCs being generally lower than RSBCs, this was not statistically significant. The significant impact of stage on OS was lost in LSBCs. ConclTusions: Among Egyptian patients, the left breast is at greater risk of cancer than the right one. Despite right-sided tumors seemed more aggressive, Left-sided ones tend to confer worse survival than right-sided tumors.

A comparative study of survival rates after treatment with induction chemotherapy or concurrent chemoradiotherapy in locoregionally advanced head and neck squamous cell carcinoma

International Nuclear Information System (INIS)

Hiraga, Yukihiro; Kou, Junichi

2012-01-01

Since 1989 our treatment approach for head and neck squamous cell carcinoma (HNSCC) has involved comprehensive treatment with chemotherapy, radiation followed by surgery, if needed. Between 1989 and 2005 chemotherapy using fluorouracil and carboplatin div was administered as induction chemotherapy (ICT), and concurrent chemoradiotherapy (CCRT) was administered more recently between 2006 and 2011. In this study we compared the statistical difference in 3-year survival rates between the ICT group and CCRT group. The number of target patients was 137, all of which were previously untreated and suffered from locoregionally advanced HNSCC: 52 with Stage III, 78 with Stage IVA, 7 with Stage IVB. In the ICT and CCRT groups, 3-year cause-specific survival rates were 68.2% and 76.3% respectively, both of which were statistically not recessive compared to those in the other issues. Furthermore, the rate between the two groups was identified as significant for Stage III and not significant for Stage IV. In conclusion, the addition of new modalities for the treatment of far-advanced HNSCC should be mandatory. (author)

Measuring survival time: a probability-based approach useful in healthcare decision-making.

Science.gov (United States)

2011-01-01

In some clinical situations, the choice between treatment options takes into account their impact on patient survival time. Due to practical constraints (such as loss to follow-up), survival time is usually estimated using a probability calculation based on data obtained in clinical studies or trials. The two techniques most commonly used to estimate survival times are the Kaplan-Meier method and the actuarial method. Despite their limitations, they provide useful information when choosing between treatment options.

Cancer survival among Alaska Native people.

Science.gov (United States)

Nash, Sarah H; Meisner, Angela L W; Zimpelman, Garrett L; Barry, Marc; Wiggins, Charles L

2018-03-26

Recent cancer survival trends among American Indian and Alaska Native (AN) people are not well understood; survival has not been reported among AN people since 2001. This study examined cause-specific survival among AN cancer patients for lung, colorectal, female breast, prostate, and kidney cancers. It evaluated whether survival differed between cancers diagnosed in 1992-2002 (the earlier period) and cancers diagnosed in 2003-2013 (the later period) and by the age at diagnosis (<65 vs ≥65 years), stage at diagnosis (local or regional/distant/unknown), and sex. Kaplan-Meier and Cox proportional hazards models were used to estimate univariate and multivariate-adjusted cause-specific survival for each cancer. An improvement was observed in 5-year survival over time from lung cancer (hazard ratio [HR] for the later period vs the earlier period, 0.83; 95% confidence interval [CI], 0.72-0.97), and a marginally nonsignificant improvement was observed for colorectal cancer (HR, 0.81; 95% CI, 0.66-1.01). Site-specific differences in survival were observed by age and stage at diagnosis. This study presents the first data on cancer survival among AN people in almost 2 decades. During this time, AN people have experienced improvements in survival from lung and colorectal cancers. The reasons for these improvements may include increased access to care (including screening) as well as improvements in treatment. Improving cancer survival should be a priority for reducing the burden of cancer among AN people and eliminating cancer disparities. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

ZTI-01 Treatment Improves Survival of Animals Infected with Multidrug Resistant Pseudomonas aeruginosa

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Lawrenz, Matthew B; denDekker, Ashley Eb; Cramer, Daniel E; Gabbard, Jon D; Lafoe, Kathryn M; Pfeffer, Tia L; Sotsky, Julie B; Vanover, Carol D; Ellis-Grosse, Evelyn J; Warawa, Jonathan M

2017-01-01

Abstract Background ZTI-01 (fosfomycin, FOS, for injection) is currently under US development to treat complicated urinary tract infections. ZTI-01 is unique compared with other antimicrobials in that it inhibits an early step in cell wall synthesis via covalent binding to MurA. ZTI-01 demonstrates broad in vitro activity against Gram-negative (GN) and -positive (GP) bacteria, including multidrug-resistant (MDR) organisms. Our study goals were to determine the efficacy of ZTI-01 as a monotherapy or in combination with meropenem against MDR Pseudomonas aeruginosa in a preclinical model of pulmonary infection. Methods 8 week old neutropenic mice were infected with a MDR strain of P. aeruginosa via intubation-mediated intratracheal (IMIT) instillation. 3 hours after instillation, mice received treatment with ZTI-01, meropenem, or ZTI-01 plus meropenem (combination therapy) q8h for 5 days. Mice were monitored every 8 hours for 7 days for development of disease and moribund animals were humanely euthanized. Lungs and spleens were harvested at euthanasia, or at 7 days for survivors, and processed for bacterial enumeration and development of pathology. Results Mice were challenged with a lethal dose of P. aeruginosa UNC-D. Mock treated animals succumbed to infection within 36 hours post-infection. Animals that received 6 g/kg/day ZTI-01 showed an increase in the MTD (52 hours) and 25% of the cohort were protected from lethal disease. Combining ZTI-01 with meropenem resulted in a significant increase in survival (≥75% of cohorts survived infection). Combination therapy also significantly decreased bacterial numbers in the lungs and inhibited dissemination to the spleens. Furthermore, animals receiving combination therapy were protected from significant inflammation in the lungs and the development of pneumonia. Conclusion Here we report that combination therapy with ZTI-01 and meropenem provides significant improvements in all disease manifestations over treatment with

Conventional chemotherapy and long-term survival in multiple myeloma patients

International Nuclear Information System (INIS)

Kraj, M; Poglod, R.; Sokolowska, U.; Kruk, B.; Maj, S.

2010-01-01

Objectives. The study was especially focused on the estimation of real frequency of long-term survivals in patients with multiple myeloma and finding common clinical and laboratory features present in long-term surviving patients as possible good prognostic factors. Material and methods. The survey was carried out on 600 multiple myeloma patients diagnosed before the year 2000 and treated with conventional chemotherapy in the Institute of Hematology and Transfusion Medicine in Warsaw in the years 1962-2009. All patients who had fulfilled the requirement of more than seven years of survival from the diagnosis and beginning of treatment for myeloma were included into the study group. Results. Out of 600 studied patients with multiple myeloma 88 (14.7%) survived over 7 years including 45 (7.5%) over 10 years, 11 (1.8 %) over 15 years and 7 (1.1%) over 20 years from the disease diagnosis and beginning of antitumor treatment. Patients with long survival were younger (median age 55 years) at the time of diagnosis than the whole studied group and had normal serum creatinine, calcium and beta2-microglobulin levels. Sixty eight percent of these patients had stage I or II clinical progression, 60% presented with IgG monoclonal protein and 58% with osteolysis. Treatment with melphalan only was given to 18 patients, 30 were treated with melphalan, followed by vincristine, cyclophosphamide, BCNU, doxorubicin and prednisone or dexamethasone. Polychemotherapy was given from the time of the diagnosis to 16 patients, 15 received radiotherapy or 60C o irradiation besides chemotherapy and 9 received new agents: thalidomide, bortezomib, lenalidomide. In 66% of the evaluated cases response to treatment was good and in another 34% stabilization of the proliferative process was achieved. The mean duration of treatment till the achievement of partial response was 10 months, range: 2 - 89 months. The mean duration of good therapeutic response was 70 months. Twelve patients are alive and

Survival chance in papillary thyroid cancer in Hungary: individual survival probability estimation using the Markov method

International Nuclear Information System (INIS)

Esik, Olga; Tusnady, Gabor; Daubner, Kornel; Nemeth, Gyoergy; Fuezy, Marton; Szentirmay, Zoltan

1997-01-01

Purpose: The typically benign, but occasionally rapidly fatal clinical course of papillary thyroid cancer has raised the need for individual survival probability estimation, to tailor the treatment strategy exclusively to a given patient. Materials and methods: A retrospective study was performed on 400 papillary thyroid cancer patients with a median follow-up time of 7.1 years to establish a clinical database for uni- and multivariate analysis of the prognostic factors related to survival (Kaplan-Meier product limit method and Cox regression). For a more precise prognosis estimation, the effect of the most important clinical events were then investigated on the basis of a Markov renewal model. The basic concept of this approach is that each patient has an individual disease course which (besides the initial clinical categories) is affected by special events, e.g. internal covariates (local/regional/distant relapses). On the supposition that these events and the cause-specific death are influenced by the same biological processes, the parameters of transient survival probability characterizing the speed of the course of the disease for each clinical event and their sequence were determined. The individual survival curves for each patient were calculated by using these parameters and the independent significant clinical variables selected from multivariate studies, summation of which resulted in a mean cause-specific survival function valid for the entire group. On the basis of this Markov model, prediction of the cause-specific survival probability is possible for extrastudy cases, if it is supposed that the clinical events occur within new patients in the same manner and with the similar probability as within the study population. Results: The patient's age, a distant metastasis at presentation, the extent of the surgical intervention, the primary tumor size and extent (pT), the external irradiation dosage and the degree of TSH suppression proved to be

A Cystine-Rich Whey Supplement (Immunocal® Delays Disease Onset and Prevents Spinal Cord Glutathione Depletion in the hSOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis

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Erika K. Ross

2014-12-01

Full Text Available Depletion of the endogenous antioxidant, glutathione (GSH, underlies progression of the devastating neurodegenerative disease, amyotrophic lateral sclerosis (ALS. Thus, strategies aimed at elevating GSH may yield new therapeutics for ALS. Here, we investigated the effects of a unique non-denatured whey protein supplement, Immunocal®, in the transgenic Gly position 93 to Ala (G93A mutant hSOD1 (hSOD1G93A mouse model of ALS. Immunocal® is rich in the GSH precursor, cystine, and is therefore capable of bolstering GSH content. Transgenic hSOD1G93A mice receiving Immunocal® displayed a significant delay in disease onset compared to untreated hSOD1G93A controls. Additionally, Immunocal® treatment significantly decreased the rate of decline in grip strength and prevented disease-associated reductions in whole blood and spinal cord tissue GSH levels in end-stage hSOD1G93A mice. However, Immunocal® did not extend survival, likely due to its inability to preserve the mitochondrial GSH pool in spinal cord. Combination treatment with Immunocal® and the anti-glutamatergic compound, riluzole, delayed disease onset and extended survival in hSOD1G93A mice. These findings demonstrate that sustaining tissue GSH with Immunocal® only modestly delays disease onset and slows the loss of skeletal muscle strength in hSOD1G93A mice. Moreover, the inability of Immunocal® to rescue mitochondrial GSH in spinal cord provides a possible mechanism for its lack of effect on survival and is a limiting factor in the potential utility of this supplement as a therapeutic for ALS.

Progression-free survival, post-progression survival, and tumor response as surrogate markers for overall survival in patients with extensive small cell lung cancer

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Hisao Imai

2015-01-01

Full Text Available Objectives: The effects of first-line chemotherapy on overall survival (OS might be confounded by subsequent therapies in patients with small cell lung cancer (SCLC. We examined whether progression-free survival (PFS, post-progression survival (PPS, and tumor response could be valid surrogate endpoints for OS after first-line chemotherapies for patients with extensive SCLC using individual-level data. Methods: Between September 2002 and November 2012, we analyzed 49 cases of patients with extensive SCLC who were treated with cisplatin and irinotecan as first-line chemotherapy. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level. Results: Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.97, p < 0.05, R 2 = 0.94, PFS was moderately correlated with OS (r = 0.58, p < 0.05, R 2 = 0.24, and tumor shrinkage was weakly correlated with OS (r = 0.37, p < 0.05, R 2 = 0.13. The best response to second-line treatment, and the number of regimens employed after progression beyond first-line chemotherapy were both significantly associated with PPS ( p ≤ 0.05. Conclusion: PPS is a potential surrogate for OS in patients with extensive SCLC. Our findings also suggest that subsequent treatment after disease progression following first-line chemotherapy may greatly influence OS.

Long-term survival of patients with primary oral squamous cell carcinoma. Comparison of two treatment protocols in a prospective study; 5-Jahres-Ueberlebenswahrscheinlichkeit von Patienten mit primaeren Plattenepithelkarzinomen der Mundhoehle. Vergleich von zwei Behandlungsstrategien in einer prospektiven Studie

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Kessler, P.; Bloch-Birkholz, A.; Neukam, F.W. [Erlangen-Nuernberg Univ., Erlangen (Germany). Klinik und Poliklinik fuer Mund-, Kiefer-, Gesichtschirurgie; Grabenbauer, G.; Sauer, R. [Erlangen-Nuernberg Univ., Erlangen (Germany). Klinik und Poliklinik fuer Strahlentherapie; Leher, A. [Erlangen-Nuernberg Univ., Erlangen (Germany). Inst. fuer Medizininformatik, Biometrie und Epidemiologie; Vairaktaris, E. [Univ. of Athens Medical School (Greece). Dept. of Maxillofacial Surgery

2007-04-15

Background and Purpose: In recent years, different concepts for the treatment of oral squamous cell carcinomas (OSCC) have been developed; these include preoperative simultaneous neoadjuvant radiochemotherapy and one-stage surgery with tumor ablation and reconstruction. When considering long-term survival, there is substantial evidence that multimodality treatment based on a neoadjuvant radiochemotherapy is superior to adjuvant therapy concepts based on a surgical approach with postoperative irradiation. The aim of this study was to discuss the 5-year survival rate in a neoadjuvant and an adjuvant combination treatment in patients with primary OSCC. Patients and Methods: This nonrandomized longitudinal study prospectively evaluates the long-term tumor-free survival in 128 patients with oral cancer. Two groups consisting of 74 neoadjuvantly and 54 primarily surgically treated patients were formed. 99 patients suffered from stage III and IV disease according to the UICC criteria. Long-term survival was estimated according to the Kaplan-Meier assumption. Results: The neoadjuvant treatment increases the prospect of a long-term tumor-free survival. According to Kaplan-Meier assumption the estimation for a 5-year tumor-free survival in OSCC in category T1 is 83.1% in neoadjuvant, and 70.1% in adjuvant treatment, in T2 79.6% and 57.7%, in T3 68.2% and 33.2%, in T4 51.4% and 30.5%, respectively. Significance (p < 0.05) could be proven for T1 (p = 0.002), T2 (p = 0.028), and T4 (p < 0.0001) tumors. The effectiveness of the preoperative radiochemotherapy was demonstrated in the pathohistological result of tumor-free resection specimens in 28 patients of the neoadjuvant treatment group (37.8%). On the other hand, four patients died during the preoperative combination therapy. 64.8% of the patients in the adjuvant and 71.6% in the neoadjuvant treatment group survived the observation period. Conclusion: Neoadjuvant therapy is highly effective and results in a better 5-year

MEDI4893* Promotes Survival and Extends the Antibiotic Treatment Window in a Staphylococcus aureus Immunocompromised Pneumonia Model.

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Hua, L; Cohen, T S; Shi, Y; Datta, V; Hilliard, J J; Tkaczyk, C; Suzich, J; Stover, C K; Sellman, B R

2015-08-01

Immunocompromised individuals are at increased risk of Staphylococcus aureus pneumonia. Neutralization of alpha-toxin (AT) with the monoclonal antibody (MAb) MEDI4893* protects normal mice from S. aureus pneumonia; however, the effects of the MAb in immunocompromised mice have not been reported. In this study, passive immunization with MEDI4893* increased survival rates and reduced bacterial numbers in the lungs in an immunocompromised murine S. aureus pneumonia model. Lungs from infected mice exhibited alveolar epithelial damage, protein leakage, and bacterial overgrowth, whereas lungs from mice passively immunized with MEDI4893* retained a healthy architecture, with an intact epithelial barrier. Adjunctive therapy or prophylaxis with a subtherapeutic MEDI4893* dose combined with subtherapeutic doses of vancomycin or linezolid improved survival rates, compared with the monotherapies. Furthermore, coadministration of MEDI4893* with vancomycin or linezolid extended the antibiotic treatment window. These data suggest that MAb-mediated neutralization of AT holds promise in strategies for prevention and adjunctive therapy among immunocompromised patients. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Influence of beta blockers on survival in dogs with severe subaortic stenosis.

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Eason, B D; Fine, D M; Leeder, D; Stauthammer, C; Lamb, K; Tobias, A H

2014-01-01

Subaortic stenosis (SAS) is one of the most common congenital cardiac defects in dogs. Severe SAS frequently is treated with a beta adrenergic receptor blocker (beta blocker), but this approach largely is empirical. To determine the influence of beta blocker treatment on survival time in dogs with severe SAS. Retrospective review of medical records of dogs diagnosed with severe, uncomplicated SAS (pressure gradient [PG] ≥80 mmHg) between 1999 and 2011. Fifty dogs met the inclusion criteria. Twenty-seven dogs were treated with a beta blocker and 23 received no treatment. Median age at diagnosis was significantly greater in the untreated group (1.2 versus 0.6 years, respectively; P = .03). Median PG at diagnosis did not differ between the treated and untreated groups (127 versus 121 mmHg, respectively; P = .2). Cox proportional hazards regression was used to identify the influence of PG at diagnosis, age at diagnosis, and beta blocker treatment on survival. In the all-cause multivariate mortality analysis, only age at diagnosis (P = .02) and PG at diagnosis (P = .03) affected survival time. In the cardiac mortality analysis, only PG influenced survival time (P = .03). Treatment with a beta blocker did not influence survival time in either the all-cause (P = .93) or cardiac-cause (P = .97) mortality analyses. Beta blocker treatment did not influence survival in dogs with severe SAS in our study, and a higher PG at diagnosis was associated with increased risk of death. Copyright © 2014 by the American College of Veterinary Internal Medicine.

Impact of experimental habitat manipulation on northern bobwhite survival

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Peters, David C.; Brooke, Jarred M.; Tanner, Evan P.; Unger, Ashley M.; Keyser, Patrick D.; Harper, Craig A.; Clark, Joseph D.; Morgan, John J.

2015-01-01

Habitat management for northern bobwhite (Colinus virginianus) should affect vital rates, but direct linkages with survival are not well documented; therefore, we implemented an experiment to evaluate those responses. We conducted our experiment on a reclaimed surface mine, a novel landscape where conditions were considered sub-optimal because of the dominance of non-native vegetation, such as sericea lespedeza (Lespedeza cuneata), which has been reported to provide marginal habitat for northern bobwhite and may negatively affect survival. Nonetheless, these areas have great potential for contributing to bobwhite conservation because of the amount of early successional cover they provide. Our study site, a 3,330-ha reclaimed surface mine in western Kentucky, consisted of 2 tracts (Sinclair and Ken, 1,471 ha and 1,853 ha, respectively) that served as replicates with each randomly divided into a treatment (i.e., habitat manipulation through a combination of disking, burning, and herbicide application) and an undisturbed control (n = 4 experimental units). Habitat treatments were applied October 2009 to September 2013. We used radio telemetry to monitor northern bobwhite (n = 1,198) during summer (1 Apr–30 Sep) and winter (1 Oct–31 Mar), 2009–2013. We used the known-fate model in Program MARK to evaluate treatment effects on seasonal survival rates. We included biological, home-range, landscape, and microhabitat metrics as covariates to help improve model sensitivity and further elucidate experimental impacts. Survival varied annually, ranging from 0.139 (SE = 0.031) to 0.301 (SE = 0.032), and seasonally (summer, 0.148 [SE = 0.015]; winter, 0.281 [SE = 0.022]). We found a treatment effect (β = 0.256, 95% CI = 0.057–0.456) with a seasonal interaction (β  = −0.598, 95% CI = −0.898 to −0.298) with survival being higher in summer (0.179 [SE = 0.022] vs. 0.109 [SE = 0.019]) and lower in winter (0.233 [SE�

Impact of treatment in long-term survival patients with follicular lymphoma: A Spanish Lymphoma Oncology Group registry

Science.gov (United States)

Provencio, Mariano; Sabín, Pilar; Gomez-Codina, Jose; Calvo, Virginia; Llanos, Marta; Gumá, Josep; Quero, Cristina; Blasco, Ana; Cruz, Miguel Angel; Aguiar, David; García-Arroyo, Francisco; Lavernia, Javier; Martinez, Natividad; Morales, Manuel; Saez-Cusi, Alvaro; Rodriguez, Delvys; de la Cruz, Luis; Sanchez, Jose Javier; Rueda, Antonio

2017-01-01

Background Follicular lymphoma is the second most common non-Hodgkin lymphoma in the United States and Europe. However, most of the prospective randomized studies have very little follow-up compared to the long natural history of the disease. The primary aim of this study was to investigate the long-term survival of our series of patients with follicular lymphoma. Patients and methods A total of 1074 patients with newly diagnosed FL were enrolled. Patients diagnosed were prospectively enrolled from 1980 to 2013. Results Median follow-up was 54.9 months and median overall survival is over 20 years in our series. We analyzed the patients who are still alive beyond 10 years from diagnosis in order to fully assess the prognostic factors that condition this group. Out of 166 patients who are still alive after more than 10 years of follow-up, 118 of them (73%) are free of evident clinical disease. Variables significantly associated with survival at 10 years were stage < II (p <0.03), age < 60 years (p <0.0001), low FLIPI (p <0.002), normal β2 microglobulin (p <0.005), no B symptoms upon diagnosis (p <0.02), Performance Status 0–1 (p <0.03) and treatment with anthracyclines and rituximab (p <0.001), or rituximab (p <0.0001). Conclusions A longer follow-up and a large series demonstrated a substantial population of patients with follicular lymphoma free of disease for more than 10 years. PMID:28493986

Conditional survival is greater than overall survival at diagnosis in patients with osteosarcoma and Ewing's sarcoma.

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Miller, Benjamin J; Lynch, Charles F; Buckwalter, Joseph A

2013-11-01

Conditional survival is a measure of the risk of mortality given that a patient has survived a defined period of time. These estimates are clinically helpful, but have not been reported previously for osteosarcoma or Ewing's sarcoma. We determined the conditional survival of patients with osteosarcoma and Ewing's sarcoma given survival of 1 or more years. We used the Surveillance, Epidemiology, and End Results (SEER) Program database to investigate cases of osteosarcoma and Ewing's sarcoma in patients younger than 40 years from 1973 to 2009. The SEER Program is managed by the National Cancer Institute and provides survival data gathered from population-based cancer registries. We used an actuarial life table analysis to determine any cancer cause-specific 5-year survival estimates conditional on 1 to 5 years of survival after diagnosis. We performed a similar analysis to determine 20-year survival from the time of diagnosis. The estimated 5-year survival improved each year after diagnosis. For local/regional osteosarcoma, the 5-year survival improved from 74.8% at baseline to 91.4% at 5 years-meaning that if a patient with localized osteosarcoma lives for 5 years, the chance of living for another 5 years is 91.4%. Similarly, the 5-year survivals for local/regional Ewing's sarcoma improved from 72.9% at baseline to 92.5% at 5 years, for metastatic osteosarcoma 35.5% at baseline to 85.4% at 5 years, and for metastatic Ewing's sarcoma 31.7% at baseline to 83.6% at 5 years. The likelihood of 20-year cause-specific survival from the time of diagnosis in osteosarcoma and Ewing's sarcoma was almost 90% or greater after 10 years of survival, suggesting that while most patients will remain disease-free indefinitely, some experience cancer-related complications years after presumed eradication. The 5-year survival estimates of osteosarcoma and Ewing's sarcoma improve with each additional year of patient survival. Knowledge of a changing risk profile is useful in counseling

Effect of ponderosa pine needle litter on grass seedling survival.

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Burt R. McConnell; Justin G. Smith

1971-01-01

Hard fescue survival rates were followed for 6 years on four different pine needle treatment plots. Needle litter had a significant effect on initial survival of fescue seedlings, but subsequent losses undoubtedly resulted from the interaction of many factors.

Building Infrastructure to Accelerate Transfer of Basic Research in Spinal Cord Injury (SCI) to Clinical Practice: North American Clinical Trials Network

Science.gov (United States)

2013-08-01

that may emerge and longer term lifestyle and caregiving issues). A recent Lancet publication (Freund et al) reports on the use of MRI to track the...hours of injury. Riluzole, 50 mg, was administered enterally ( tablet form) every 12 hours for 14 days. At the successful conclusion of the Riluzole...report. • Michael Fehlings, MD, PhD, University Health Network (University of Toronto) (NOA5-2011-MF) for “The use of MRI characteristics to predict

Partitioning of excess mortality in population-based cancer patient survival studies using flexible parametric survival models

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Eloranta Sandra

2012-06-01

Full Text Available Abstract Background Relative survival is commonly used for studying survival of cancer patients as it captures both the direct and indirect contribution of a cancer diagnosis on mortality by comparing the observed survival of the patients to the expected survival in a comparable cancer-free population. However, existing methods do not allow estimation of the impact of isolated conditions (e.g., excess cardiovascular mortality on the total excess mortality. For this purpose we extend flexible parametric survival models for relative survival, which use restricted cubic splines for the baseline cumulative excess hazard and for any time-dependent effects. Methods In the extended model we partition the excess mortality associated with a diagnosis of cancer through estimating a separate baseline excess hazard function for the outcomes under investigation. This is done by incorporating mutually exclusive background mortality rates, stratified by the underlying causes of death reported in the Swedish population, and by introducing cause of death as a time-dependent effect in the extended model. This approach thereby enables modeling of temporal trends in e.g., excess cardiovascular mortality and remaining cancer excess mortality simultaneously. Furthermore, we illustrate how the results from the proposed model can be used to derive crude probabilities of death due to the component parts, i.e., probabilities estimated in the presence of competing causes of death. Results The method is illustrated with examples where the total excess mortality experienced by patients diagnosed with breast cancer is partitioned into excess cardiovascular mortality and remaining cancer excess mortality. Conclusions The proposed method can be used to simultaneously study disease patterns and temporal trends for various causes of cancer-consequent deaths. Such information should be of interest for patients and clinicians as one way of improving prognosis after cancer is

Gastric Malignancy Survival in Zambia, Southern Africa: A Two Year ...

African Journals Online (AJOL)

Esem

numbers provided at time of enrollment. Corresponding author: ... duration of symptoms, treatment (surgery, chemotherapy, ... Zambia and no studies about management survival out comes. ... evaluated risk factors associated with gastric cancer survival in ... patients because patient financial limitations precluded testing for ...

Survival of Patients with Stomach Cancer and its Determinants in Kurdistan.

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Moradi, Ghobad; Karimi, Kohsar; Esmailnasab, Nader; Roshani, Daem

2016-01-01

Stomach cancer is the fourth most common cancer and the second leading cause of death from cancer in the world. In Iran, this type of cancer has high rates of incidence and mortality. This study aimed to assess the survival rate of patients with stomach cancer and its determinants in Kurdistan, a province with one of the highest incidence rates of stomach cancer in the country. We studied a total of 202 patients with stomach cancer who were admitted to Tohid Hospital in Sanandaj from 2009 to 2013. Using KaplanMeier nonparametric methods the survival rate of patients was calculated in terms of different levels of age at diagnosis, gender, education, residential area, occupation, underweight, and clinical variables including tumor histology, site of tumor, disease stage, and type of treatment. In addition, we compared the survival rates using the logrank test. Finally, Cox proportional hazards regression was applied using Stata 12 and R 3.1.0 software. The significance level was set at 0.05. The mean age at diagnosis was 64.7 ± 12.0 years. The survival rate of patients with stomach cancer was 43.9% and 7% at the first and the fifth year after diagnosis, respectively. The results of logrank test showed significant relationships between survival and age at diagnosis, education, disease stage, type of treatment, and degree of being underweight (P<0.05). Moreover, according to the results of Cox proportional hazards regression model, the variables of education, disease stage, and type of treatment were associated with patient survival (P<0.05). The survival rate of patients with stomach cancer is low and the prognosis is very poor. Given the poor prognosis of the patients, it is critical to find ways for early diagnosis and facilitating timely access to effective treatment methods.

Trastuzumab and survival of patients with metastatic breast cancer.

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Kast, Karin; Schoffer, Olaf; Link, Theresa; Forberger, Almuth; Petzold, Andrea; Niedostatek, Antje; Werner, Carmen; Klug, Stefanie J; Werner, Andreas; Gatzweiler, Axel; Richter, Barbara; Baretton, Gustavo; Wimberger, Pauline

2017-08-01

Prognosis of Her2-positive breast cancer has changed since the introduction of trastuzumab for treatment in metastatic and early breast cancer. It was described to be even better compared to prognosis of Her2-negative metastatic breast cancer. The purpose of this study was to evaluate the effect of trastuzumab in our cohort. Besides the effect of adjuvant pretreatment with trastuzumab on survival of patients with metastatic Her2-positive breast cancer was analyzed. All patients with primary breast cancer of the Regional Breast Cancer Center Dresden diagnosed during the years 2001-2013 were analyzed for treatment with or without trastuzumab in the adjuvant and in the metastatic treatment setting using Kaplan-Meier survival estimation and Cox regression. Age and tumor stage at time of first diagnosis of breast cancer as well as hormone receptor status, grading, time, and site of metastasis at first diagnosis of distant metastatic disease were analyzed. Of 4.481 female patients with primary breast cancer, 643 presented with metastatic disease. Her2-positive status was documented in 465 patients, including 116 patients with primary or secondary metastases. Median survival of patients with Her2-positive primary metastatic disease was 3.0 years (95% CI 2.3-4.0). After adjustment for other factors, survival was better in patients with Her2-positive breast cancer with trastuzumab therapy compared to Her2-negative metastatic disease (HR 2.10; 95% CI 1.58-2.79). Analysis of influence of adjuvant therapy with and without trastuzumab by Kaplan-Meier showed a trend for better survival in not pretreated patients. Median survival was highest in hormone receptor-positive Her2-positive (triple-positive) primary metastatic breast cancer patients with 3.3 years (95% CI 2.3-4.6). Prognosis of patients with Her2-positive metastatic breast cancer after trastuzumab treatment is more favorable than for Her2-negative breast cancer. The role of adjuvant chemotherapy with or without

Optimal fractionation for the radiotherapy of tumour cells possessing wide-shouldered survival curves

International Nuclear Information System (INIS)

Wheldon, T.E.

1979-01-01

A recent publication (Zeitz, L., and McDonald, J.M., 1978, Br. J. Radiol., vol. 51, 637) has considered the use of in vitro survival curves in the evaluation of different treatment schedules. Several studies of oxygenated melanoma cell have demonstrated a wider than average shoulder width for the survival curves. It is possible that hypoxia reduces the width of this shoulder. Theoretical cell survival probabilities were calculated for each of the four treatment schedules considered by Zeitz and McDonald. The calculations were based on hypothetical survival curves for anoxic melanoma cells with the shoulder either fully retained or completely abolished. No allowance was made for either re-population or re-oxygenation. The advantage of small doses per fraction was demonstrated for both types of survival curve. Re-oxygenation during therapy could therefore mean that a non-uniform treatment schedule is the appropriate choice for this type of tumour. (U.K.)

Factors influencing survival and mark retention in postmetamorphic boreal chorus frogs

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Swanson, Jennifer E; Bailey, Larissa L.; Muths, Erin L.; Funk, W. Chris

2013-01-01

The ability to track individual animals is crucial in many field studies and often requires applying marks to captured individuals. Toe clipping has historically been a standard marking method for wild amphibian populations, but more recent marking methods include visual implant elastomer and photo identification. Unfortunately, few studies have investigated the influence and effectiveness of marking methods for recently metamorphosed individuals and as a result little is known about this life-history phase for most amphibians. Our focus was to explore survival probabilities, mark retention, and mark migration in postmetamorphic Boreal Chorus Frogs (Psuedacris maculata) in a laboratory setting. One hundred forty-seven individuals were assigned randomly to two treatment groups or a control group. Frogs in the first treatment group were marked with visual implant elastomer, while frogs in the second treatment group were toe clipped. Growth and mortality were recorded for one year and resulting data were analyzed using known-fate models in Program MARK. Model selection results suggested that survival probabilities of frogs varied with time and showed some variation among marking treatments. We found that frogs with multiple toes clipped on the same foot had lower survival probabilities than individuals in other treatments, but individuals can be marked by clipping a single toe on two different feet without any mark loss or negative survival effects. Individuals treated with visual implant elastomer had a mark migration rate of 4% and mark loss rate of 6%, and also showed very little negative survival impacts relative to control individuals.

Survival outcome of malignant minor salivary tumors in Pakistani population

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Hassan Iqbal

2014-01-01

Full Text Available Objective: Malignant tumors of minor salivary glands (MSG are rare. Survival outcome in Pakistani population with malignant MSG tumors remains to be defined. The objective of this study was to report the clinical presentation, treatment modalities, and survival outcome of radically treated malignant tumors of MSG in Pakistani population. Materials and Methods: Between April 2003 and March 2011, 45 patients with malignant tumors of MSG were treated at Shaukat Khanum Cancer Hospital and included in the study. Patient characteristics and treatment modalities were assessed and local, regional, and distant failures determined. Relapse-free (RFS and overall survival (OS was calculated using Kaplan-Meier curves, and log-rank test was used to determine significance. Results: Median age was 40 (17-83 years. Male to female ratio was 1.25:1. Most common site was hard palate in 31 (69% patients. Adenoid cystic carcinoma (51% was the most common histological diagnosis. Nine patients (20% underwent surgery as the only treatment modality, six patients received (13% radiotherapy alone, and 30 patients (67% had surgery followed by adjuvant radiotherapy. Eight patients developed recurrence (four local, two regional, one locoregional, and one distant. The 5-year actuarial overall OS and RFS was 77 and 66%, respectively. Age, T-stage, and treatment modality were significant for RFS, whereas T-stage and treatment modality were significant factors for OS. Conclusion: Surgery as single modality or combined with radiation therapy resulted in acceptable survival in Pakistani population with malignant minor salivary tumors.

New graphic AUC-based method to estimate overall survival benefit: pomalidomide reanalysis.

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Fenix-Caballero, S; Diaz-Navarro, J; Prieto-Callejero, B; Rios-Sanchez, E; Alegre-del Rey, E J; Borrero-Rubio, J M

2016-02-01

Difference in median survival is an erratic measure and sometimes does not provide a good assessment of survival benefit. The aim of this study was to reanalyse the overall survival benefit of pomalidomide from pivotal clinical trial using a new area under curve (AUC)-based method. In the pivotal trial, pomalidomide plus low-dose dexamethasone showed a significant survival benefit over high-dose dexamethasone, with a difference between medians of 4.6 months. The new AUC method applied to the survival curves, obtained an overall survival benefit of 2.6 months for the pomalidomide treatment. This average difference in OS was calculated for the 61.5% of patients for whom the time to event is reliable enough. This 2-month differential would have major clinical and pharmacoeconomic implications, on both cost-effectiveness studies and on the willingness of the healthcare systems to pay for this treatment. © 2015 John Wiley & Sons Ltd.

Factors of influence upon overall survival in the treatment of intracranial MPNSTs. Review of the literature and report of a case

International Nuclear Information System (INIS)

Gousias, Konstantinos; Boström, Jan; Kovacs, Attila; Niehusmann, Pitt; Wagner, Ingo; Kristof, Rudolf

2010-01-01

Intracranial malignant peripheral nerve sheath tumors are rare entities that carry a poor prognosis. To date, there are no established therapeutic strategies for these tumors. We review the present treatment modalities and present the current therapeutic dilemmas. We perform a statistical analysis to evaluate the prognostic factors for Overall Survival of these patients. Additionally, we present our experience with a 64-year-old man with a MPNST of the left cerebellopontine angle. To our best knowledge, forty three patients with intracranial MPNSTs, including our case, have been published in the international literature. Our analysis showed gross total resection, radiotherapy and female gender to be beneficial prognostic factors of survival in the univariate analysis. Gross total resection was recognized as the only independent predictor of prolonged Overall Survival. In our case, we performed a gross total resection followed for the first time by stereotactically guided radiotherapy. Considering the results of the statistical analysis and the known advantages of the stereotaxy, we suggest aggressive surgery followed by stereotactically guided radiotherapy as therapy of choice

Hepatorenal Syndrome: Outcome of Response to Therapy and Predictors of Survival

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Jan Heidemann

2015-01-01

Full Text Available Aim. Treatment of hepatorenal syndrome (HRS in patients with liver cirrhosis is still challenging and characterized by a very high mortality. This study aimed to delineate treatment patterns and clinical outcomes of patients with HRS intravenously treated with terlipressin. Methods. In this retrospective single-center cohort study, 119 patients (median [IQR]; 56.50 [50.75–63.00] years of age with HRS were included. All patients were treated with terlipressin and human albumin intravenously. Those with response to treatment (n=65 were compared to the patient cohort without improvement (n=54. Patient characteristics and clinical parameters (Child stage, ascites, hepatic encephalopathy, HRS type I/II, and initial MELD score were retrieved. Univariate analysis of factors influencing the success of terlipressin therapy and Cox regression analysis of factors influencing survival was carried out. Results. One-month survival was significantly longer in the group of responders (p=0.048. Cox regression analysis identified age [Hazard ratio, 95% confidence interval (CI; 1.05, 1.01–1.09, resp.], alcohol abuse [HR 3.05, 95% CI 1.11–8.38], duration of treatment [HR 0.92, 95% CI 0.88–0.96], and MELD score [HR 1.08, 95% CI 1.02–1.14] to be independent predictors of survival. Conclusions. Survival of HRS patients after treatment depends on age, etiology of liver disease, and the duration of treatment.

Predicting treatment effect from surrogate endpoints and historical trials: an extrapolation involving probabilities of a binary outcome or survival to a specific time.

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Baker, Stuart G; Sargent, Daniel J; Buyse, Marc; Burzykowski, Tomasz

2012-03-01

Using multiple historical trials with surrogate and true endpoints, we consider various models to predict the effect of treatment on a true endpoint in a target trial in which only a surrogate endpoint is observed. This predicted result is computed using (1) a prediction model (mixture, linear, or principal stratification) estimated from historical trials and the surrogate endpoint of the target trial and (2) a random extrapolation error estimated from successively leaving out each trial among the historical trials. The method applies to either binary outcomes or survival to a particular time that is computed from censored survival data. We compute a 95% confidence interval for the predicted result and validate its coverage using simulation. To summarize the additional uncertainty from using a predicted instead of true result for the estimated treatment effect, we compute its multiplier of standard error. Software is available for download. © 2011, The International Biometric Society No claim to original US government works.

Pre-treatment hemodynamic features involved with long-term survival of cirrhotic patients after embolization of gastric fundal varices

International Nuclear Information System (INIS)

Maruyama, Hitoshi; Okugawa, Hidehiro; Kobayashi, Satoshi; Yoshizumi, Hiroaki; Yokosuka, Osamu

2010-01-01

Purpose: To clarify the pre-treatment hemodynamic features involved in the long-term survival of cirrhotic patients with gastric fundal varices (FV) after balloon-occluded retrograde transvenous obliteration (B-RTO). Materials and methods: Eighty-one cirrhotic patients with medium- or large-grade FV treated by B-RTO were enrolled in this retrospective study. Pre-treatment flow volume ratio between gastric vein and portal trunk (GP-R) was obtained by Doppler ultrasound. Results: The cumulative survival rate was 90% at 1 year, 74.8% at 3 years, 57.2% at 5 years, and 45.8% at 7 years without recurrence in a median period of 1148.5 days The survival was poorer in patients with HCC (47% at 3 years, 9.4% at 5 years, p < 0.0001) than without (89.2% at 3 years, 81.9% at 5 years, 67.5% at 7 years), in patients with Child B/C (57.7% at 3 years, 42.1% at 5 years, 28.1% at 7 years, p = 0.0016) than with Child A (91.8% at 3 years, 71.5% at 5 years, 62.1% at 7 years), and in patients with GP-R ≥ 1.0 (58.9% at 3 years, p = 0.0485) than with GP-R < 1.0 (76.3% at 3 years, 62% at 5 years, 49.6% at 7 years). Multivariate analysis identified the presence of HCC (hazard ratio, 12.486; 95% CI, 4.08-38.216; p < 0.0001), Child B/C (hazard ratio, 3.41; 95% CI, 1.594-7.15; p = 0.0051) and GP-R ≥ 1.0 (hazard ratio, 2.701; 95% CI, 1.07-6.15; p = 0.0221) as independent factors for poor prognosis. Conclusion: GP-R ≥ 1.0 on Doppler ultrasound before B-RTO may be a predictive indicator for poor prognosis in cirrhotic patients with FV after B-RTO, in addition to the presence of HCC and severe liver damage.

Pre-treatment hemodynamic features involved with long-term survival of cirrhotic patients after embolization of gastric fundal varices

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Maruyama, Hitoshi, E-mail: maru-cib@umin.ac.j [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670 (Japan); Okugawa, Hidehiro, E-mail: hideun@yahoo.co.j [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670 (Japan); Kobayashi, Satoshi, E-mail: kobakobakopa@yahoo.co.j [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670 (Japan); Yoshizumi, Hiroaki, E-mail: yossih04@yahoo.co.j [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670 (Japan); Yokosuka, Osamu, E-mail: yokosukao@faculty.chiba-u.j [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670 (Japan)

2010-08-15

Purpose: To clarify the pre-treatment hemodynamic features involved in the long-term survival of cirrhotic patients with gastric fundal varices (FV) after balloon-occluded retrograde transvenous obliteration (B-RTO). Materials and methods: Eighty-one cirrhotic patients with medium- or large-grade FV treated by B-RTO were enrolled in this retrospective study. Pre-treatment flow volume ratio between gastric vein and portal trunk (GP-R) was obtained by Doppler ultrasound. Results: The cumulative survival rate was 90% at 1 year, 74.8% at 3 years, 57.2% at 5 years, and 45.8% at 7 years without recurrence in a median period of 1148.5 days The survival was poorer in patients with HCC (47% at 3 years, 9.4% at 5 years, p < 0.0001) than without (89.2% at 3 years, 81.9% at 5 years, 67.5% at 7 years), in patients with Child B/C (57.7% at 3 years, 42.1% at 5 years, 28.1% at 7 years, p = 0.0016) than with Child A (91.8% at 3 years, 71.5% at 5 years, 62.1% at 7 years), and in patients with GP-R {>=} 1.0 (58.9% at 3 years, p = 0.0485) than with GP-R < 1.0 (76.3% at 3 years, 62% at 5 years, 49.6% at 7 years). Multivariate analysis identified the presence of HCC (hazard ratio, 12.486; 95% CI, 4.08-38.216; p < 0.0001), Child B/C (hazard ratio, 3.41; 95% CI, 1.594-7.15; p = 0.0051) and GP-R {>=} 1.0 (hazard ratio, 2.701; 95% CI, 1.07-6.15; p = 0.0221) as independent factors for poor prognosis. Conclusion: GP-R {>=} 1.0 on Doppler ultrasound before B-RTO may be a predictive indicator for poor prognosis in cirrhotic patients with FV after B-RTO, in addition to the presence of HCC and severe liver damage.

Survival and Growth of Cottonwood Clones After Angle Planting and Base Angle Treatments

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W.K. Randall; Harvey E. Kennedy

1976-01-01

Presently, commercial cottonwood plantations in the lower Mississippi Valley are established using vertically planted, unrooted cuttings with a flat (90°) base. Neither survival nor first-year growth of a group of six Stoneville clones was improved by angle planting or cutting base angles diagonally. For one clone, survival was significantly better when base angle was...

Concurrent Chemoradiotherapy Improves Survival in Patients With Hypopharyngeal Cancer

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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.

Ten-year survival rates of teeth adjacent to treated and untreated posterior bounded edentulous spaces.

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Aquilino, S A; Shugars, D A; Bader, J D; White, B A

2001-05-01

Failure to replace a single missing posterior tooth may lead to a variety of dental problems, which may ultimately result in tooth loss. However, little is known about the fate of the adjacent teeth if a missing posterior tooth is not replaced. This retrospective study evaluated the survival of teeth adjacent to treated and untreated posterior bounded edentulous spaces. Data were obtained from electronic treatment records from the Kaiser Permanente Dental Care Program, Portland, Ore. A final sample of 317 patients who met the study inclusion criteria was identified. Each bounded edentulous space was placed in 1 of 3 treatment categories: untreated, restored with a fixed partial denture, or restored with a removable partial denture. Subsequent treatment and the status of the teeth adjacent to the bounded edentulous space were followed through December 1999. Ten-year Kaplan-Meier survival estimates were generated for each treatment group, and differences in survival were evaluated with the log-rank chi-square test (alpha=.05). There was a significant difference in survival among the 3 treatment categories (P=.005). Spaces restored with a fixed partial denture had longer 10-year survival estimates (92%) than those that remained untreated (81%). Spaces restored with a removable partial denture had the poorest 10-year survival rate (56%). Under the conditions and selection bias associated with this retrospective study, the survival of teeth adjacent to a single posterior edentulous space was negatively associated with removable partial denture placement compared with no treatment or the use of a fixed partial denture.

Calculating the 30-day survival rate in acute myocardial infarction: should we use the treatment chain or the hospital catchment model?

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Jan Norum

2017-12-01

Full Text Available Introduction: Acute myocardial infarction (AMI is a potentially deadly disease and significant efforts have been concentrated on improving hospital performance. A 30-day survival rate has become a key quality of care indicator. In Northern Norway, some patients undergoing AMI are directly transferred to the Regional Cardiac Intervention Center at the University Hospital of North Norway in Tromsø. Here, coronary angiography and percutaneous coronary intervention is performed. Consequently, local hospitals may be bypassed in the treatment chain, generating differences in case mix, and making the treatment chain model difficult to interpret. We aimed to compare the treatment chain model with an alternative based on patients’ place of living. Methods: Between 2013 and 2015, a total of 3,155 patients were registered in the Norwegian Patient Registry database. All patients were categorized according to their local hospital’s catchment area. The method of Guo-Romano, with an indifference interval of 0.02, was used to test whether a hospital was an outlier or not. We adjusted for age, sex, comorbidity, and number of prior hospitalizations. Conclusions: We revealed the 30-day AMI survival figure ranging between 88.0% and 93.5% (absolute difference 5.5% using the hospital catchment method. The treatment chain rate ranged between 86.0% and 94.0% (absolute difference 8.0%. The latter figure is the one published as the National Quality of Care Measure in Norway. Local hospitals may get negative attention even though their catchment area is well served. We recommend the hospital catchment method as the first choice when measuring equality of care.

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

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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

Kaempferol and Chrysin Synergies to Improve Septic Mice Survival.

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Harasstani, Omar A; Tham, Chau Ling; Israf, Daud A

2017-01-06

Previously, we reported the role of synergy between two flavonoids-namely, chrysin and kaempferol-in inhibiting the secretion of a few major proinflammatory mediators such as tumor necrosis factor -alpha (TNF-α), prostaglandin E₂ (PGE₂) , and nitric oxide (NO) from lipopolysaccharide (LPS)-induced RAW 264.7 cells. The present study aims to evaluate the effects of this combination on a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Severe sepsis was induced in male ICR mice ( n = 7) via the CLP procedure. The effects of chrysin and kaempferol combination treatment on septic mice were investigated using a 7-day survival study. The levels of key proinflammatory mediators and markers-such as aspartate aminotransferase (AST), TNF-α, and NO-in the sera samples of the septic mice were determined via ELISA and fluorescence determination at different time point intervals post-CLP challenge. Liver tissue samples from septic mice were harvested to measure myeloperoxidase (MPO) levels using a spectrophotometer. Moreover, intraperitoneal fluid (IPF) bacterial clearance and total leukocyte count were also assessed to detect any antibacterial effects exerted by chrysin and kaempferol, individually and in combination. Kaempferol treatment improved the survival rate of CLP-challenged mice by up to 16%. During this treatment, kaempferol expressed antibacterial, antiapoptotic and antioxidant activities through the attenuation of bacterial forming units, AST and NO levels, and increased polymorphonuclear leukocyte (PMN) count in the IPF. On the other hand, the chrysin treatment significantly reduced serum TNF-α levels. However, it failed to significantly improve the survival rate of the CLP-challenged mice. Subsequently, the kaempferol/chrysin combination treatment significantly improved the overall 7-day survival rate by 2-fold-up to 29%. Kaempferol and chrysin revealed some synergistic effects by acting individually upon multiple

When palliative treatment achieves more than palliation: Instances of long-term survival after palliative radiotherapy

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Madhup Rastogi

2012-01-01

Full Text Available Context: Palliative radiotherapy aims at symptom alleviation and improvement of quality of life. It may be effective in conferring a reasonable quantum of local control, as well as possibly prolonging survival on the short term. However, there can be rare instances where long-term survival, or even cure, results from palliative radiotherapy, which mostly uses sub-therapeutic doses. Aim: To categorize and characterize the patients with long-term survival and/or cure after palliative radiotherapy. Materials and Methods: This study is a retrospective analysis of hospital records of patients treated with palliative radiotherapy from 2001 to 2006 at the Regional Cancer Centre, Shimla. Results: Of the analyzed 963 patients who received palliative radiotherapy, 2.4% (n = 23 survived at least 5 years, with a large majority of these surviving patients (73.9%, n = 17 being free of disease. Conclusions: In addition to providing valuable symptom relief, palliative radiotherapy utilizing sub-therapeutic doses may, in a small proportion of patients, bestow long-term survival, and possibly cure. Rationally, such a favorable, but rare outcome cannot be expected with supportive care alone.

Improved survival for elderly married glioblastoma patients : Better treatment delivery, less toxicity, and fewer disease complications.

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Putz, Florian; Putz, Tobias; Goerig, Nicole; Knippen, Stefan; Gryc, Thomas; Eyüpoglu, Ilker; Rössler, Karl; Semrau, Sabine; Lettmaier, Sebastian; Fietkau, Rainer

2016-11-01

Marital status is a well-described prognostic factor in patients with gliomas but the observed survival difference is unexplained in the available population-based studies. A series of 57 elderly glioblastoma patients (≥70 years) were analyzed retrospectively. Patients received radiotherapy or chemoradiation with temozolomide. The prognostic significance of marital status was assessed. Disease complications, toxicity, and treatment delivery were evaluated in detail. Overall survival was significantly higher in married than in unmarried patients (median, 7.9 vs. 4.0 months; p = 0.006). The prognostic significance of marital status was preserved in the multivariate analysis (HR, 0.41; p = 0.011). Married patients could receive significantly higher daily temozolomide doses (mean, 53.7 mg/m² vs. 33.1 mg/m²; p = 0.020), were more likely to receive maintenance temozolomide (45.7 % vs. 11.8 %; p = 0.016), and had to be hospitalized less frequently during radiotherapy (55.0 % vs. 88.2 %; p = 0.016). Of the patients receiving temozolomide, married patients showed significantly lower rates of hematologic and liver toxicity. Most complications were infectious or neurologic in nature. Complications of any grade were more frequent in unmarried patients (58.8 % vs. 30.0 %; p = 0.041) with the incidence of grade 3-5 complications being particularly elevated (47.1 % vs. 15.0 %; p = 0.004). We found poorer treatment delivery as well as an unexpected severe increase in toxicity and disease complications in elderly unmarried glioblastoma patients. Marital status may be an important predictive factor for clinical decision-making and should be addressed in further studies.

Survival and kinetics of Chinese hamster ovary cell subpopulations induced by Adriamycin and radiation

International Nuclear Information System (INIS)

Schneiderman, M.H.

1979-01-01

Mitotic selection of Chinese hamster ovary (CHO) cells, at 10 min intervals after the initiation of Adriamycin and/or x-ray treatment was used to measure the kinetics and survival of cells which progressed without delay, the ''refractory'' cells, the cells that reached mitosis only after recovery from the treatment-induced delay, the ''recovered'' cells, and the survival of the cells remaining attached to the flask 5 h after treatment. The cell kinetics were determined from the rate at which cells entered mitosis, and the reproductive integrity from the survival of the selected refractory, recovered and remaining (unselected) cells

Conditional survival of patients with diffuse large B-cell lymphoma

DEFF Research Database (Denmark)

Møller, Michael Boe; Pedersen, Niels Tinggaard; Christensen, Bjarne E

2006-01-01

BACKGROUND: Prognosis of lymphoma patients is usually estimated at the time of diagnosis and the estimates are guided by the International Prognostic Index (IPI). However, conditional survival estimates are more informative clinically, as they consider those patients only who have already survive...... survival probability provides more accurate prognostic information than the conventional survival rate estimated from the time of diagnosis.......BACKGROUND: Prognosis of lymphoma patients is usually estimated at the time of diagnosis and the estimates are guided by the International Prognostic Index (IPI). However, conditional survival estimates are more informative clinically, as they consider those patients only who have already survived...... a period of time after treatment. Conditional survival data have not been reported for lymphoma patients. METHODS: Conditional survival was estimated for 1209 patients with diffuse large B-cell lymphoma (DLBCL) from the population-based LYFO registry of the Danish Lymphoma Group. The Kaplan-Meier method...

Association Between Treatment at a High-Volume Facility and Improved Survival for Radiation-Treated Men With High-Risk Prostate Cancer

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Chen, Yu-Wei [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Mahal, Brandon A. [Department of Medicine, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Muralidhar, Vinayak [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Nezolosky, Michelle [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Beard, Clair J. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Den, Robert B. [Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Feng, Felix Y. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Hoffman, Karen E. [Department of Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Martin, Neil E.; Orio, Peter F. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Nguyen, Paul L., E-mail: pnguyen@LROC.harvard.edu [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States)

2016-03-15

Purpose: Although the association between higher hospital volume and improved outcomes has been well-documented in surgery, there is little data about whether this effect exists for radiation-treated patients. We investigated whether treatment at a radiation facility that treats a high volume of prostate cancer patients is associated with improved survival for men with high-risk prostate cancer. Methods and Materials: We used the National Cancer Database (NCDB) to identity patients diagnosed with prostate cancer from 2004 to 2006. The radiation case volume (RCV) of each hospital was based on its number of radiation-treated prostate cancer patients. We used propensity-score based analysis to compare the overall survival (OS) of high-risk prostate cancer patients in high versus low RCV hospitals. Primary endpoint is overall survival. Covariates adjusted for were tumor characteristics, sociodemographic factors, radiation type, and use of androgen deprivation therapy (ADT). Results: A total of 19,565 radiation-treated high-risk patients were identified. Median follow-up was 81.0 months (range: 1-108 months). When RCV was coded as a continuous variable, each increment of 100 radiation-managed patients was associated with improved OS (adjusted hazard ratio [AHR]: 0.97; 95% confidence interval [CI]: 0.95-0.98; P<.0001) after adjusting for known confounders. For illustrative purposes, when RCV was dichotomized at the 80th percentile (43 patients/year), high RCV was associated with improved OS (7-year overall survival 76% vs 74%, log-rank test P=.0005; AHR: 0.91, 95% CI: 0.86-0.96, P=.0005). This association remained significant when RCV was dichotomized at 75th (37 patients/year), 90th (60 patients/year), and 95th (84 patients/year) percentiles but not the 50th (19 patients/year). Conclusions: Our results suggest that treatment at centers with higher prostate cancer radiation case volume is associated with improved OS for radiation-treated men with high-risk prostate

Cancer survival for Aboriginal and Torres Strait Islander Australians: a national study of survival rates and excess mortality.

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Condon, John R; Zhang, Xiaohua; Baade, Peter; Griffiths, Kalinda; Cunningham, Joan; Roder, David M; Coory, Michael; Jelfs, Paul L; Threlfall, Tim

2014-01-31

National cancer survival statistics are available for the total Australian population but not Indigenous Australians, although their cancer mortality rates are known to be higher than those of other Australians. We aimed to validate analysis methods and report cancer survival rates for Indigenous Australians as the basis for regular national reporting. We used national cancer registrations data to calculate all-cancer and site-specific relative survival for Indigenous Australians (compared with non-Indigenous Australians) diagnosed in 2001-2005. Because of limited availability of Indigenous life tables, we validated and used cause-specific survival (rather than relative survival) for proportional hazards regression to analyze time trends and regional variation in all-cancer survival between 1991 and 2005. Survival was lower for Indigenous than non-Indigenous Australians for all cancers combined and for many cancer sites. The excess mortality of Indigenous people with cancer was restricted to the first three years after diagnosis, and greatest in the first year. Survival was lower for rural and remote than urban residents; this disparity was much greater for Indigenous people. Survival improved between 1991 and 2005 for non-Indigenous people (mortality decreased by 28%), but to a much lesser extent for Indigenous people (11%) and only for those in remote areas; cancer survival did not improve for urban Indigenous residents. Cancer survival is lower for Indigenous than other Australians, for all cancers combined and many individual cancer sites, although more accurate recording of Indigenous status by cancer registers is required before the extent of this disadvantage can be known with certainty. Cancer care for Indigenous Australians needs to be considerably improved; cancer diagnosis, treatment, and support services need to be redesigned specifically to be accessible and acceptable to Indigenous people.

Cell Survival Signaling in Neuroblastoma

Science.gov (United States)

Megison, Michael L.; Gillory, Lauren A.; Beierle, Elizabeth A.

2013-01-01

Neuroblastoma is the most common extracranial solid tumor of childhood and is responsible for over 15% of pediatric cancer deaths. Neuroblastoma tumorigenesis and malignant transformation is driven by overexpression and dominance of cell survival pathways and a lack of normal cellular senescence or apoptosis. Therefore, manipulation of cell survival pathways may decrease the malignant potential of these tumors and provide avenues for the development of novel therapeutics. This review focuses on several facets of cell survival pathways including protein kinases (PI3K, AKT, ALK, and FAK), transcription factors (NF-κB, MYCN and p53), and growth factors (IGF, EGF, PDGF, and VEGF). Modulation of each of these factors decreases the growth or otherwise hinders the malignant potential of neuroblastoma, and many therapeutics targeting these pathways are already in the clinical trial phase of development. Continued research and discovery of effective modulators of these pathways will revolutionize the treatment of neuroblastoma. PMID:22934706

Survival of Root-filled Teeth in the Swedish Adult Population

DEFF Research Database (Denmark)

Fransson, Helena; Dawson, Victoria S; Frisk, Fredrik

2016-01-01

INTRODUCTION: The aim was to assess survival in the Swedish population of teeth treated by nonsurgical root canal treatment during 2009. METHODS: Data from the Swedish Social Insurance Agency were analyzed by Kaplan-Meier analysis to assess cumulative tooth survival during a period of 5-6 years o...

Socioeconomic position, treatment, and survival of non-Hodgkin lymphoma in Denmark--a nationwide study

DEFF Research Database (Denmark)

Frederiksen, Birgitte Lidegaard; Dalton, Susanne Oksbjerg; Osler, Merete

2012-01-01

Not all patients have benefited equally from the advances in non-Hodgkin lymphoma (NHL) survival. This study investigates several individual-level markers of socioeconomic position (SEP) in relation to NHL survival, and explores whether any social differences could be attributed to comorbidity...

Nogo-receptor 1 antagonization in combination with neurotrophin-4/5 is not superior to single factor treatment in promoting survival and morphological complexity of cultured dopaminergic neurons.

Science.gov (United States)

Seiler, Stefanie; Di Santo, Stefano; Sahli, Sebastian; Andereggen, Lukas; Widmer, Hans Rudolf

2017-08-01

Cell transplantation using ventral mesencephalic tissue is an experimental approach to treat Parkinson's disease. This approach is limited by poor survival of the transplants and the high number of dopaminergic neurons needed for grafting. Increasing the yield of dopaminergic neurons in donor tissue is of great importance. We have previously shown that antagonization of the Nogo-receptor 1 by NEP1-40 promoted survival of cultured dopaminergic neurons and exposure to neurotrophin-4/5 increased dopaminergic cell densities in organotypic midbrain cultures. We investigated whether a combination of both treatments offers a novel tool to further improve dopaminergic neuron survival. Rat embryonic ventral mesencephalic neurons grown as organotypic free-floating roller tube or primary dissociated cultures were exposed to neurotrophin-4/5 and NEP1-40. The combined and single factor treatment resulted in significantly higher numbers of tyrosine hydroxylase positive neurons compared to controls. Significantly stronger tyrosine hydroxylase signal intensity was detected by Western blotting in the combination-treated cultures compared to controls but not compared to single factor treatments. Neurotrophin-4/5 and the combined treatment showed significantly higher signals for the neuronal marker microtubule-associated protein 2 in Western blots compared to control while no effects were observed for the astroglial marker glial fibrillary acidic protein between groups, suggesting that neurotrophin-4/5 targets mainly neuronal cells. Finally, NEP1-40 and the combined treatment significantly augmented tyrosine hydroxylase positive neurite length. Summarizing, our findings substantiate that antagonization of the Nogo-receptor 1 promotes dopaminergic neurons but does not further increase the yield of dopaminergic neurons and their morphological complexity when combined with neurotrophin-4/5 hinting to the idea that these treatments might exert their effects by activating common

Treatment outcome and prognostic variables for local control and survival in patients receiving radical radiotherapy for urinary bladder cancer

Energy Technology Data Exchange (ETDEWEB)

Fokdal, Lars; Hoeyer, Morten; Maase, Hans von der [Aarhus Univ. Hospital (Denmark). Dept. of Oncology

2004-12-01

The aim of this retrospective study was to analyze the outcome of radical radiotherapy in 292 patients with bladder cancer and to identify prognostic factors for local control and survival. Median age was 72.3 years (range 45-83 years). Median follow up was 66 months (range 18-121 months). All patients were treated by use of a standard 3-field technique with 60 Gy in 30 fractions to the tumor and the bladder. The elective lymph nodes were treated with doses in the range from 46 Gy to 60 Gy. Complete response was obtained in 52% of the patients at 3-month control. However, 41% of all patients with an initial CR developed recurrence during follow-up. The 3-year and 5-year overall survival rate was 31% and 21%, respectively. Performance status, T-stage, macroscopic complete TURB, hydronephrosis, and serum creatinine were independent prognostic factors for overall survival and, thus, important for the selection of patients for curative intended radiotherapy. During radiotherapy acute transient side effects were recorded in 78% of the patients; severe bowel complications were recorded in 9 patients (3%). Following radiotherapy, 10 patients (3%) developed intestinal reactions requiring surgery. Three patients (1%) were cystectomized because of severe radiation reactions in the bladder. At 5-year follow-up, the actuarial risk of complications requiring surgery was 15%. Treatment-related mortality was 2%.

Survival of patients with hepatocellular carcinoma in the San Joaquin Valley: a comparison with California Cancer Registry data.

Science.gov (United States)

Atla, Pradeep R; Sheikh, Muhammad Y; Mascarenhas, Ranjan; Choudhury, Jayanta; Mills, Paul

2012-01-01

Variation in the survival of patients with hepatocellular carcinoma (HCC) is related to racial differences, socioeconomic disparities and treatment options among different populations. A retrospective review of the data from medical records of patients diagnosed with HCC were analyzed at an urban tertiary referral teaching hospital and compared to patients in the California Cancer Registry (CCR) - a participant in the Survival Epidemiology and End Results (SEER)program of the National Cancer Institute (NCI). The main outcome measure was overall survival rates. 160 patients with the diagnosis of HCC (M/F=127/33), mean age 59.7±10 years, 32% white, 49% Hispanic, 12% Asian and 6% African American. Multivariate analysis identified tumor size, model for end-stage liver disease (MELD) score, portal vein invasion and treatment offered as the independent predictors of survival (p <0.05). Survival rates across racial groups were not statistically significant. 5.6% received curative treatments (orthotopic liver transplantation, resection, rediofrequency ablation) (median survival 69 months), 34.4% received nonsurgical treatments (trans-arterial chemoembolization, systemic chemotherapy) (median survival 9 months), while 60% received palliative or no treatment (median survival 3 months) (p <0.001). There was decreased survival in our patient population with HCC beyond 2 years. 60% of our study population received only palliative or no treatment suggesting a possible lack of awareness of chronic liver disease as well as access to appropriate surveillance modalities. Ethnic disparities such as Hispanic predominance in this study in contrast to the CCR/SEER database may have been a contributing factor for poorer outcome.

National incidence, management and survival of urachal carcinoma

Directory of Open Access Journals (Sweden)

Dearbhaile C. Collins

2016-10-01

Full Text Available Urachal carcinoma is an uncommon cancer whose rarity has precluded its study and evidence-based management strategies are lacking. This study assessed all urachal carcinomas in Ireland and clinical parameters in order to improve understanding. Urachal carcinomas diagnosed from 1994 to 2011 were identified from the National Cancer Registry in Ireland. Data obtained included patient age, gender, diagnostic year, pathology, tumor stage, patient treatment strategies and survival. Twenty-six urachal carcinomas were identified, the majority being adenocarcinoma. This comprised 0.3% of all invasive bladder tumors. Patients were predominantly male (62% and over 50 years of age (58%. Twenty-two patients (85% underwent surgery, with only six (23% undergoing chemotherapy. On average, median overall survival was 2.6 years (range 0-15.2 yrs. Survival was longer in women (5 vs. 1.9 yrs, patients under 50 years of age (3.6 vs. 1.9 yrs, those without confirmed metastasis (4.1 vs. 0.7 yrs and those who received chemotherapy (3.6 vs. 2.6 yrs. The overall survival of urachal carcinoma in Ireland is less than expected from published literature. This study highlights the need for centralization of rare tumors with international collaboration to identify the optimal treatment strategy and improve outcome.

Understanding survival analysis: Kaplan-Meier estimate.

Science.gov (United States)

Goel, Manish Kumar; Khanna, Pardeep; Kishore, Jugal

2010-10-01

Kaplan-Meier estimate is one of the best options to be used to measure the fraction of subjects living for a certain amount of time after treatment. In clinical trials or community trials, the effect of an intervention is assessed by measuring the number of subjects survived or saved after that intervention over a period of time. The time starting from a defined point to the occurrence of a given event, for example death is called as survival time and the analysis of group data as survival analysis. This can be affected by subjects under study that are uncooperative and refused to be remained in the study or when some of the subjects may not experience the event or death before the end of the study, although they would have experienced or died if observation continued, or we lose touch with them midway in the study. We label these situations as censored observations. The Kaplan-Meier estimate is the simplest way of computing the survival over time in spite of all these difficulties associated with subjects or situations. The survival curve can be created assuming various situations. It involves computing of probabilities of occurrence of event at a certain point of time and multiplying these successive probabilities by any earlier computed probabilities to get the final estimate. This can be calculated for two groups of subjects and also their statistical difference in the survivals. This can be used in Ayurveda research when they are comparing two drugs and looking for survival of subjects.

Proliferation kinetics and survival of mammal cells after treatment with radiation of various ionization densities and with hyperthermia

International Nuclear Information System (INIS)

Schlag, H.

1977-01-01

Survival and proliferation kinetics of chinese hamster cells after Co-γ-, π - -meson irradiation, hyperthermia (40 - 43 0 C), and a combination of Co-γ irradiation and hyperthermia were studied in this paper. After γ-irradiation, exponential-phase and stationary-phase cells showed equal survival rates for equal doses. Cytofluorometric analysis showed that there was a dose-dependent delay in the synthesis phase with subsequent cell blocking in the G 2 +M phase. After irradiation with π - mesons, there is a dose-dependent accumulation in the G 2 +M phase, with a RBE of 2.2. The different response of S-phase cells to radiations of different LET may be explained with the inactivation kinetics typical of each type of radiation. The effectiveness of hyperthermal treatment depends on the stage of growth of the cells. A temperature of 40 0 C does not induce cell killing, not even after prolonged exposure. After 7 hours' exposure to 41 0 C, on the other hand, 80% of the cells are killed after blocking in G 2 +M. Exposure to 42 0 C for 1-2 h induces a synchronisation effect which is induced by a block in S and G 2 +M. After exposure to 42 0 C for 4 h, however, the cells blocked in S are killed in this phase. Combination of Co-γ radiation leads to increased cells killing and also to sensitization, especially of cells in the exponential growth stage. The proliferation kinetics effects of this combined treatment are the same as after pion irradiation. (orig.) [de

ABO blood type correlates with survival on prostate cancer vaccine therapy.

Science.gov (United States)

Muthana, Saddam M; Gulley, James L; Hodge, James W; Schlom, Jeffrey; Gildersleeve, Jeffrey C

2015-10-13

Immunotherapies for cancer are transforming patient care, but clinical responses vary considerably from patient to patient. Simple, inexpensive strategies to target treatment to likely responders could substantially improve efficacy while simultaneously reducing health care costs, but identification of reliable biomarkers has proven challenging. Previously, we found that pre-treatment serum IgM to blood group A (BG-A) correlated with survival for patients treated with PROSTVAC-VF, a therapeutic cancer vaccine in phase III clinical trials for the treatment of prostate cancer. These results suggested that ABO blood type might influence efficacy. Unfortunately, blood types were not available in the clinical records for all but 8 patients and insufficient amounts of sera were left for standard blood typing methods. To test the hypothesis, therefore, we developed a new glycan microarray-based method for determining ABO blood type. The method requires only 4 μL of serum, provides 97% accuracy, and allows simultaneous profiling of many other serum anti-glycan antibodies. After validation with 220 healthy subjects of known blood type, the method was then applied to 74 PROSTVAC-VF patients and 37 control patients from a phase II trial. In this retrospective study, we found that type B and O PROSTVAC-VF patients demonstrated markedly improved clinical outcomes relative to A and AB patients, including longer median survival, longer median survival relative to Halabi predicted survival, and improved overall survival via Kaplan-Meier survival analysis (p = 0.006). Consequently, blood type may provide an inexpensive screen to pre-select patients likely to benefit from PROSTVAC-VF therapy.

A retrospective analysis of the impact of treatments and blood counts on survival and the risk of vascular events during the course of polycythaemia vera

DEFF Research Database (Denmark)

Enblom-Larsson, Anneli; Girodon, Francois; Bak, Marie

2017-01-01

Vascular and non-vascular complications are common in patients with polycythaemia vera. This retrospective study of 217 patients with polycythaemia vera aimed to determine whether blood counts with respect to different treatments influenced the complication rate and survival. We found that 78 (36...

Linking Costs and Survival in the Treatment of Older Adults With Chronic Myeloid Leukemia: An Analysis of SEER-Medicare Data From 1995 to 2007.

Science.gov (United States)

Lin, Pei-Jung; Winn, Aaron N; Parsons, Susan K; Neumann, Peter J; Weiss, Elisa S; Cohen, Joshua T

2016-04-01

The high prices of chronic myeloid leukemia (CML) therapy are well recognized, but less discussion has focused on the value of health care spending on the disease. This study examined whether the added costs have been "worth" the benefits among older adults with CML. We analyzed trends in health care costs and survival over time of 2164 CML patients over age 65 using the Surveillance, Epidemiology and End Results-Medicare-linked database. We estimated life expectancy over a 15-year duration after diagnosis using a Weibull survival model and projected the corresponding costs using a 2-part model, adjusting for patient characteristics. We estimated population-level survival, total health care costs, and incremental cost-effectiveness ratios (expressed as cost per life year gained) over the period of 1995-2007. We found that therapeutic improvements in the treatment of CML have been associated with survival gains among older adults. Mean life expectancy was 2.2 years in 1995 and increased to 4.2 years in 2007. During the same timeframe, CML care costs have increased, from $127,000 in 1995 to $278,000 in 2007 (2010 dollars), mostly due to increasing tyrosine kinase inhibitor costs. The aggregated incremental cost-effectiveness ratio was $74,000/life year gained. Our findings showed that, despite high costs, CML care may provide reasonable value for money among older patients between 1995-2007. Our study sheds light on the value of health care spending on CML by considering both the costs and the benefits. Future research should investigate strategies to improve treatment adherence to maximize the value of CML care.

Relationship Between Radiation Treatment Time and Overall Survival After Induction Chemotherapy for Locally Advanced Head-and-Neck Carcinoma: A Subset Analysis of TAX 324

International Nuclear Information System (INIS)

Sher, David J.; Posner, Marshall R.; Tishler, Roy B.; Sarlis, Nicholas J.; Haddad, Robert I.; Holupka, Edward J.; Devlin, Phillip M.

2011-01-01

Purpose: To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). Methods and Materials: TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of ≥ 70 Gy. Radiotherapy treatment time was analyzed as binary (≤ 8 weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). Results: A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p = 0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p = 0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. Conclusions: In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential

Relationship Between Radiation Treatment Time and Overall Survival After Induction Chemotherapy for Locally Advanced Head-and-Neck Carcinoma: A Subset Analysis of TAX 324

Energy Technology Data Exchange (ETDEWEB)

Sher, David J., E-mail: dsher@partners.org [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, MA (United States); Posner, Marshall R. [Division of Hematology/Oncology, Mount Sinai School of Medicine, New York, NY (United States); Tishler, Roy B. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, MA (United States); Sarlis, Nicholas J. [Sanofi-Aventis US, Bridgewater, NJ (United States); Haddad, Robert I. [Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women' s Hospital, Boston, MA (United States); Holupka, Edward J. [Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA (Israel); Devlin, Phillip M. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, MA (United States)

2011-12-01

Purpose: To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). Methods and Materials: TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of {>=} 70 Gy. Radiotherapy treatment time was analyzed as binary ({<=} 8 weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). Results: A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p = 0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p = 0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. Conclusions: In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential

Relationship between radiation treatment time and overall survival after induction chemotherapy for locally advanced head-and-neck carcinoma: a subset analysis of TAX 324.

Science.gov (United States)

Sher, David J; Posner, Marshall R; Tishler, Roy B; Sarlis, Nicholas J; Haddad, Robert I; Holupka, Edward J; Devlin, Phillip M

2011-12-01

To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of ≥70 Gy. Radiotherapy treatment time was analyzed as binary (≤8 weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p=0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p=0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential for optimizing OS in LAHNC. Copyright © 2011 Elsevier Inc

The Effect of Biologically Effective Dose and Radiation Treatment Schedule on Overall Survival in Stage I Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Stahl, John M. [Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States); Ross, Rudi [21st Century Oncology, Fort Myers, Florida (United States); Harder, Eileen M.; Mancini, Brandon R. [Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States); Soulos, Pamela R. [Cancer Outcomes, Public Policy and Effectiveness Research (COPPER) Center, Yale School of Medicine, New Haven, Connecticut (United States); Finkelstein, Steven E.; Shafman, Timothy D.; Dosoretz, Arie P. [21st Century Oncology, Fort Myers, Florida (United States); Evans, Suzanne B.; Husain, Zain A.; Yu, James B. [Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States); Gross, Cary P. [Cancer Outcomes, Public Policy and Effectiveness Research (COPPER) Center, Yale School of Medicine, New Haven, Connecticut (United States); Decker, Roy H., E-mail: roy.decker@yale.edu [Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States)

2016-12-01

Purpose: To determine the effect of biologically effective dose (BED{sub 10}) and radiation treatment schedule on overall survival (OS) in patients with early-stage non-small cell lung cancer (NSCLC) undergoing stereotactic body radiation therapy (SBRT). Methods and Materials: Using data from 65 treatment centers in the United States, we retrospectively reviewed the records of T1-2 N0 NSCLC patients undergoing SBRT alone from 2006 to 2014. Biologically relevant covariates, including dose per fraction, number of fractions, and time between fractions, were used to quantify BED{sub 10} and radiation treatment schedule. The linear-quadratic equation was used to calculate BED{sub 10} and to generate a dichotomous dose variable of <105 Gy versus ≥105 Gy BED{sub 10}. The primary outcome was OS. We used the Kaplan-Meier method, the log–rank test, and Cox proportional hazards regression with propensity score matching to determine whether prescription BED{sub 10} was associated with OS. Results: We identified 747 patients who met inclusion criteria. The median BED{sub 10} was 132 Gy, and 59 (7.7%) had consecutive-day fractions. Median follow-up was 41 months, and 452 patients (60.5%) had died by the conclusion of the study. The 581 patients receiving ≥105 Gy BED{sub 10} had a median survival of 28 months, whereas the 166 patients receiving <105 Gy BED{sub 10} had a median survival of 22 months (log–rank, P=.01). Radiation treatment schedule was not a significant predictor of OS on univariable analysis. After adjusting for T stage, sex, tumor histology, and Eastern Cooperative Oncology Group performance status, BED{sub 10} ≥105 Gy versus <105 Gy remained significantly associated with improved OS (hazard ratio 0.78, 95% confidence interval 0.62-0.98, P=.03). Propensity score matching on imbalanced variables within high- and low-dose cohorts confirmed a survival benefit with higher prescription dose. Conclusions: We found that dose escalation to 105 Gy BED

Changes in growth, survival and digestive enzyme activities of Asian ...

African Journals Online (AJOL)

A study was conducted to determine the effects of different dietary treatments on the growth, survival and digestive enzyme activities of Mystus nemurus larvae. Newly hatched larvae were reared for 14 days in twelve 15 L glass aquaria (for growth and survival) and eight 300 L fiberglass tanks (for enzyme samples) at a ...

Survival after early-stage breast cancer of women previously treated for depression

DEFF Research Database (Denmark)

Suppli, Nis Frederik Palm; Johansen, Christoffer; Kessing, Lars Vedel

2017-01-01

treatment of depression and risk of receiving nonguideline treatment of breast cancer were assessed in multivariable logistic regression analyses. We compared the overall survival, breast cancer-specific survival, and risk of death by suicide of women who were and were not treated for depression before......Purpose The aim of this nationwide, register-based cohort study was to determine whether women treated for depression before primary early-stage breast cancer are at increased risk for receiving treatment that is not in accordance with national guidelines and for poorer survival. Material...... and Methods We identified 45,325 women with early breast cancer diagnosed in Denmark from 1998 to 2011. Of these, 744 women (2%) had had a previous hospital contact (as an inpatient or outpatient) for depression and another 6,068 (13%) had been treated with antidepressants. Associations between previous...

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

Plasmodium Parasitemia Associated With Increased Survival in Ebola Virus–Infected Patients

Science.gov (United States)

Rosenke, Kyle; Adjemian, Jennifer; Munster, Vincent J.; Marzi, Andrea; Falzarano, Darryl; Onyango, Clayton O.; Ochieng, Melvin; Juma, Bonventure; Fischer, Robert J.; Prescott, Joseph B.; Safronetz, David; Omballa, Victor; Owuor, Collins; Hoenen, Thomas; Groseth, Allison; Martellaro, Cynthia; van Doremalen, Neeltje; Zemtsova, Galina; Self, Joshua; Bushmaker, Trenton; McNally, Kristin; Rowe, Thomas; Emery, Shannon L.; Feldmann, Friederike; Williamson, Brandi N.; Best, Sonja M.; Nyenswah, Tolbert G.; Grolla, Allen; Strong, James E.; Kobinger, Gary; Bolay, Fatorma K.; Zoon, Kathryn C.; Stassijns, Jorgen; Giuliani, Ruggero; de Smet, Martin; Nichol, Stuart T.; Fields, Barry; Sprecher, Armand; Massaquoi, Moses; Feldmann, Heinz; de Wit, Emmie

2016-01-01

Background. The ongoing Ebola outbreak in West Africa has resulted in 28 646 suspected, probable, and confirmed Ebola virus infections. Nevertheless, malaria remains a large public health burden in the region affected by the outbreak. A joint Centers for Disease Control and Prevention/National Institutes of Health diagnostic laboratory was established in Monrovia, Liberia, in August 2014, to provide laboratory diagnostics for Ebola virus. Methods. All blood samples from suspected Ebola virus–infected patients admitted to the Médecins Sans Frontières ELWA3 Ebola treatment unit in Monrovia were tested by quantitative real-time polymerase chain reaction for the presence of Ebola virus and Plasmodium species RNA. Clinical outcome in laboratory-confirmed Ebola virus–infected patients was analyzed as a function of age, sex, Ebola viremia, and Plasmodium species parasitemia. Results. The case fatality rate of 1182 patients with laboratory-confirmed Ebola virus infections was 52%. The probability of surviving decreased with increasing age and decreased with increasing Ebola viral load. Ebola virus–infected patients were 20% more likely to survive when Plasmodium species parasitemia was detected, even after controlling for Ebola viral load and age; those with the highest levels of parasitemia had a survival rate of 83%. This effect was independent of treatment with antimalarials, as this was provided to all patients. Moreover, treatment with antimalarials did not affect survival in the Ebola virus mouse model. Conclusions. Plasmodium species parasitemia is associated with an increase in the probability of surviving Ebola virus infection. More research is needed to understand the molecular mechanism underlying this remarkable phenomenon and translate it into treatment options for Ebola virus infection. PMID:27531847

Survival benefit of surgery in recurrent glioblastoma multiforme.

Science.gov (United States)

Choudry, Usama Khalid; Khan, Saad Akhtar; Shamim, Muhammad Shahzad

2017-12-01

There is an ongoing debate regarding role of surgery for recurrent glioblastoma multiforme (GBM). Older literature hinted at only modest survival benefits with surgery and a high rate of morbidity. However, more recent literature suggests better survival that may be attributed to better surgical techniques and better options in adjuvant treatment. Herein the authors review recent literature with regards to the possible role of surgery in recurrent GBM and also look into the key factors impacting second surgery. .

Chemotherapy increases long-term survival in patients with adult medulloblastoma

DEFF Research Database (Denmark)

Kocakaya, Selin; Beier, Christoph Patrick; Beier, Dagmar

2016-01-01

chemotherapy first-line survived significantly longer (mOS: 108 mo, 95% CI: 68.6-148.4) than patients treated with radiation alone (mOS: 57 mo, 95% CI: 39.6-74.4) or patients who received chemotherapy at tumor recurrence. This effect was not biased by tumor stage or decade of treatment. Importantly, (neo...... parts of treatment regimes; however, established prognostic factors and data clarifying the role of chemotherapy are missing. METHODS: We investigated 227 publications from 1969-2013, with 907 identifiable, individual patients being available for meta-analysis. Demographic data, risk stratification......)adjuvant chemotherapy also significantly increased the chance for long-term survival (>5 y) compared with radiotherapy alone or chemotherapy at tumor recurrence. CONCLUSIONS: This meta-analysis clarifies relevant prognostic factors and suggests that chemotherapy as part of first-line therapy improves overall survival...

Effect of Warfarin Treatment on Survival of Patients With Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL).

Science.gov (United States)

Preston, Ioana R; Roberts, Kari E; Miller, Dave P; Sen, Ginny P; Selej, Mona; Benton, Wade W; Hill, Nicholas S; Farber, Harrison W

2015-12-22

Long-term anticoagulation is recommended in idiopathic pulmonary arterial hypertension (IPAH). In contrast, limited data support anticoagulation in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc-PAH). We assessed the effect of warfarin anticoagulation on survival in IPAH and SSc-PAH patients enrolled in Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), a longitudinal registry of group I PAH. Patients who initiated warfarin on study (n=187) were matched 1:1 with patients never on warfarin, by enrollment site, etiology, and diagnosis status. Descriptive analyses were conducted to compare warfarin users and nonusers by etiology. Survival analyses with and without risk adjustment were performed from the time of warfarin initiation or a corresponding quarterly update in matched pairs to avoid immortal time bias. Time-varying covariate models were used as sensitivity analyses. Mean warfarin treatment was 1 year; mean international normalized ratios were 1.9 (IPAH) and 2.0 (SSc-PAH). Two-thirds of patients initiating warfarin discontinued treatment before the last study assessment. There was no survival difference with warfarin in IPAH patients (adjusted hazard ratio, 1.37; P=0.21) or in SSc-PAH patients (adjusted hazard ratio, 1.60; P=0.15) in comparison with matched controls. However, SSc-PAH patients receiving warfarin within the previous year (hazard ratio, 1.57; P=0.031) or any time postbaseline (hazard ratio, 1.49; P=0.046) had increased mortality in comparison with warfarin-naïve patients. No significant survival advantage was observed in IPAH patients who started warfarin. In SSc-PAH patients, long-term warfarin was associated with poorer survival than in patients not receiving warfarin, even after adjusting for confounders. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214. © 2015 The Authors.

Survival rate in nasopharyngeal carcinoma improved by high caseload volume: a nationwide population-based study in Taiwan

International Nuclear Information System (INIS)

Lee, Ching-Chih; Hung, Shih-Kai; Huang, Tze-Ta; Lee, Moon-Sing; Su, Yu-Chieh; Chou, Pesus; Hsiao, Shih-Hsuan; Chiou, Wen-Yen; Lin, Hon-Yi; Chien, Sou-Hsin

2011-01-01

Positive correlation between caseload and outcome has previously been validated for several procedures and cancer treatments. However, there is no information linking caseload and outcome of nasopharyngeal carcinoma (NPC) treatment. We used nationwide population-based data to examine the association between physician case volume and survival rates of patients with NPC. Between 1998 and 2000, a total of 1225 patients were identified from the Taiwan National Health Insurance Research Database. Survival analysis, the Cox proportional hazards model, and propensity score were used to assess the relationship between 10-year survival rates and physician caseloads. As the caseload of individual physicians increased, unadjusted 10-year survival rates increased (p < 0.001). Using a Cox proportional hazard model, patients with NPC treated by high-volume physicians (caseload ≥ 35) had better survival rates (p = 0.001) after adjusting for comorbidities, hospital, and treatment modality. When analyzed by propensity score, the adjusted 10-year survival rate differed significantly between patients treated by high-volume physicians and patients treated by low/medium-volume physicians (75% vs. 61%; p < 0.001). Our data confirm a positive volume-outcome relationship for NPC. After adjusting for differences in the case mix, our analysis found treatment of NPC by high-volume physicians improved 10-year survival rate

Causal inference in survival analysis using pseudo-observations.

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Andersen, Per K; Syriopoulou, Elisavet; Parner, Erik T

2017-07-30

Causal inference for non-censored response variables, such as binary or quantitative outcomes, is often based on either (1) direct standardization ('G-formula') or (2) inverse probability of treatment assignment weights ('propensity score'). To do causal inference in survival analysis, one needs to address right-censoring, and often, special techniques are required for that purpose. We will show how censoring can be dealt with 'once and for all' by means of so-called pseudo-observations when doing causal inference in survival analysis. The pseudo-observations can be used as a replacement of the outcomes without censoring when applying 'standard' causal inference methods, such as (1) or (2) earlier. We study this idea for estimating the average causal effect of a binary treatment on the survival probability, the restricted mean lifetime, and the cumulative incidence in a competing risks situation. The methods will be illustrated in a small simulation study and via a study of patients with acute myeloid leukemia who received either myeloablative or non-myeloablative conditioning before allogeneic hematopoetic cell transplantation. We will estimate the average causal effect of the conditioning regime on outcomes such as the 3-year overall survival probability and the 3-year risk of chronic graft-versus-host disease. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Reduction in non-protein respiratory quotient is related to overall survival after hepatocellular carcinoma treatment.

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Masaya Saito

Full Text Available BACKGROUND: Transcatheter arterial chemoembolization (TACE is an effective treatment for hepatocellular carcinoma (HCC that can occasionally lead to the shortening of life expectancy. We aimed to make a new and more accurate prognostic model taking into account the course of disease after TACE. METHODOLOGY/PRINCIPAL FINDINGS: We performed a prospective cohort study involving 100 HCC patients who underwent TACE at Kobe University Hospital. Indirect calorimetry and blood biochemical examinations were performed before and 7 days after TACE. Time-dependent and time-fixed factors associated with 1-year mortality after TACE were assessed by multivariate analyses. A predictive model of 1-year mortality was established by the combination of odds ratios of these factors. Multivariate analyses showed that the ratio of non-protein respiratory quotient (npRQ (7 days after/before TACE and Cancer of Liver Italian Program (CLIP score were independent factors of 1-year mortality after TACE (p = 0.014 and 0.013, respectively. Patient-specific 1-year mortality risk scores can be calculated by summarizing the individual risk scores and looking up the patient-specific risk on the graph. CONCLUSIONS: The short-term reduction of npRQ was a time-dependent prognostic factor associated with overall survival in HCC patients undergoing TACE. CLIP score was a time-fixed prognostic factor associated with overall survival. Using the prediction model, which consists of the combination of time-dependent (npRQ ratio and time-fixed (CLIP score prognostic factors, 1-year mortality risk after TACE would be better estimated by taking into account changes during the course of disease.

Chemoembolization With Doxorubicin-Eluting Beads for Unresectable Hepatocellular Carcinoma: Five-Year Survival Analysis

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Malagari, Katerina, E-mail: kmalag@otonet.gr [University of Athens, Second Department of Radiology (Greece); Pomoni, Mary [University of Athens, Imaging and Research Unit (Greece); Moschouris, Hippocrates, E-mail: hipmosch@gmail.com [Tzanion Hospital, Department of Radiology (Greece); Bouma, Evanthia [University of Athens, Imaging and Research Unit (Greece); Koskinas, John [Ippokration Hospital, University of Athens, Department of Internal Medicine and Hepatology (Greece); Stefaniotou, Aspasia [University of Athens, Imaging and Research Unit (Greece); Marinis, Athanasios [Tzanion Hospital, Department of Surgery (Greece); Kelekis, Alexios; Alexopoulou, Efthymia [University of Athens, Second Department of Radiology (Greece); Chatziioannou, Achilles [University of Athens, First Department of Radiology (Greece); Chatzimichael, Katerina [University of Athens, Second Department of Radiology (Greece); Dourakis, Spyridon [Ippokration Hospital, University of Athens, Department of Internal Medicine and Hepatology (Greece); Kelekis, Nikolaos [University of Athens, Second Department of Radiology (Greece); Rizos, Spyros [Tzanion Hospital, Department of Surgery (Greece); Kelekis, Dimitrios [University of Athens, Imaging and Research Unit (Greece)

2012-10-15

Purpose: The purpose of this study was to report on the 5-year survival of hepatocellular carcinoma (HCC) patients treated with DC Bead loaded with doxorubicin (DEB-DOX) in a scheduled scheme in up to three treatments and thereafter on demand. Materials and Methods: 173 HCC patients not suitable for curable treatments were prospectively enrolled (mean age 70.4 {+-} 7.4 years). Child-Pugh (Child) class was A/B (102/71 [59/41 %]), Okuda stage was 0/1/2 (91/61/19 [53.2/35.7/11.1 %]), and mean lesion diameter was 7.6 {+-} 2.1 cm. Lesion morphology was one dominant {<=}5 cm (22 %), one dominant >5 cm (41.6 %), multifocal {<=}5 (26 %), and multifocal >5 (10.4 %). Results: Overall survival at 1, 2, 3, 4, and 5 years was 93.6, 83.8, 62, 41.04, and 22.5 %, with higher rates achieved in Child class A compared with Child class B patients (95, 88.2, 61.7, 45, and 29.4 % vs. 91.5, 75, 50.7, 35.2, and 12.8 %). Mean overall survival was 43.8 months (range 1.2-64.8). Cumulative survival was better for Child class A compared with Child class B patients (p = 0.029). For patients with dominant lesions {<=}5 cm 1-, 2-, 3-, 4-, and 5-year survival rates were 100, 95.2, 71.4, 66.6, and 47.6 % for Child class A and 94.1, 88.2, 58.8, 41.2, 29.4, and 23.5 % for Child class B patients. Regarding DEB-DOX treatment, multivariate analysis identified number of lesions (p = 0.033), lesion vascularity (p < 0.0001), initially achieved complete response (p < 0.0001), and objective response (p = 0.046) as significant and independent determinants of 5-year survival. Conclusion: DEB-DOX results, with high rates of 5-year survival for patients, not amenable to curative treatments. Number of lesions, lesion vascularity, and local response were significant independent determinants of 5-year survival.

Chemoembolization With Doxorubicin-Eluting Beads for Unresectable Hepatocellular Carcinoma: Five-Year Survival Analysis

International Nuclear Information System (INIS)

Malagari, Katerina; Pomoni, Mary; Moschouris, Hippocrates; Bouma, Evanthia; Koskinas, John; Stefaniotou, Aspasia; Marinis, Athanasios; Kelekis, Alexios; Alexopoulou, Efthymia; Chatziioannou, Achilles; Chatzimichael, Katerina; Dourakis, Spyridon; Kelekis, Nikolaos; Rizos, Spyros; Kelekis, Dimitrios

2012-01-01

Purpose: The purpose of this study was to report on the 5-year survival of hepatocellular carcinoma (HCC) patients treated with DC Bead loaded with doxorubicin (DEB-DOX) in a scheduled scheme in up to three treatments and thereafter on demand. Materials and Methods: 173 HCC patients not suitable for curable treatments were prospectively enrolled (mean age 70.4 ± 7.4 years). Child-Pugh (Child) class was A/B (102/71 [59/41 %]), Okuda stage was 0/1/2 (91/61/19 [53.2/35.7/11.1 %]), and mean lesion diameter was 7.6 ± 2.1 cm. Lesion morphology was one dominant ≤5 cm (22 %), one dominant >5 cm (41.6 %), multifocal ≤5 (26 %), and multifocal >5 (10.4 %). Results: Overall survival at 1, 2, 3, 4, and 5 years was 93.6, 83.8, 62, 41.04, and 22.5 %, with higher rates achieved in Child class A compared with Child class B patients (95, 88.2, 61.7, 45, and 29.4 % vs. 91.5, 75, 50.7, 35.2, and 12.8 %). Mean overall survival was 43.8 months (range 1.2–64.8). Cumulative survival was better for Child class A compared with Child class B patients (p = 0.029). For patients with dominant lesions ≤5 cm 1-, 2-, 3-, 4-, and 5-year survival rates were 100, 95.2, 71.4, 66.6, and 47.6 % for Child class A and 94.1, 88.2, 58.8, 41.2, 29.4, and 23.5 % for Child class B patients. Regarding DEB-DOX treatment, multivariate analysis identified number of lesions (p = 0.033), lesion vascularity (p < 0.0001), initially achieved complete response (p < 0.0001), and objective response (p = 0.046) as significant and independent determinants of 5-year survival. Conclusion: DEB-DOX results, with high rates of 5-year survival for patients, not amenable to curative treatments. Number of lesions, lesion vascularity, and local response were significant independent determinants of 5-year survival.

Probiotics improve survival of septic rats by suppressing conditioned pathogens in ascites

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Liu, Da-Quan; Gao, Qiao-Ying; Liu, Hong-Bin; Li, Dong-Hua; Wu, Shang-Wei

2013-01-01

AIM: To investigate the benefits of probiotics treatment in septic rats. METHODS: The septic rats were induced by cecal ligation and puncture. The animals of control, septic model and probiotics treated groups were treated with vehicle and mixed probiotics, respectively. The mixture of probiotics included Bifidobacterium longum, Lactobacillus bulgaricus and Streptococcus thermophilus. We observed the survival of septic rats using different amounts of mixed probiotics. We also detected the bacterial population in ascites and blood of experimental sepsis using cultivation and real-time polymerase chain reaction. The severity of mucosal inflammation in colonic tissues was determined. RESULTS: Probiotics treatment improved survival of the rats significantly and this effect was dose dependent. The survival rate was 30% for vehicle-treated septic model group. However, 1 and 1/4 doses of probiotics treatment increased survival rate significantly compared with septic model group (80% and 55% vs 30%, P probiotics treated group compared with septic model group (5.20 ± 0.57 vs 9.81 ± 0.67, P probiotics treated group compared with septic model group (33.3% vs 100.0%, P probiotics treated group were decreased significantly compared with that of septic model group (3.93 ± 0.73 vs 8.80 ± 0.83, P probiotics treatment, there was a decrease in the scores of inflammatory cell infiltration into the intestinal mucosa in septic animals (1.50 ± 0.25 vs 2.88 ± 0.14, P Probiotics improve survival of septic rats by suppressing these conditioned pathogens. PMID:23840152

Epidemiological Data and Survival Rate of Removable Partial Dentures

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Moreno, Amália; Haddad, Marcela Filié; Rocha, Eduardo Passos; Assunção, Wirley Gonçalves; Filho, Humberto Gennari; Santos, Emerson Gomes Dos; Sonego, Mariana Vilela; Santos, Daniela Micheline Dos

2016-01-01

Introduction The use of removable partial denture (RPD) is considered as low-cost and common treatment option to rehabilitate edentulous areas. Aim This study aimed to investigate the epidemiological data of patients rehabilitated with removable partial denture (RPD) in order to assess treatment survival rate and failures. Materials and Methods Epidemiological data and medical records of patients treated with RPD between 2007 and 2012 at the RPD discipline of a Brazilian University (Aracatuba Dental School- UNESP) were evaluated as well as dental records of patients who underwent RPD treatments (fabrication or repairs) between 2000 and 2010. Factors such as gender, age, presence of systemic disease, main complaint, edentulous arch, period and cause of denture replacement and the prosthesis characteristics were recorded. The chi-square test was used to assess the differences between the variables and the Kaplan Meyer to assess the survival of the RPDs evaluated. Results A total of 324 maxillary RPD and 432 mandibular RPD were fabricated. Most of the patients were women aging 41 to 60-year-old. The number of mandibular RPD Kennedy class I (26%) was statistically higher for the maxillary arch (p<.05). There was no association between main complaint to gender or the presence of systemic disease. The lingual plate was the most common major connector used in the mandible (32%). The main reason for altering the design of replaced RPDs were changes during treatment plan. Conclusion The number of patients who require RPD is large; most of RPDs are Kennedy Class I. A good treatment plan is very important for achieving a positive treatment outcome, and it is strictly related to the survival rate. PMID:27437367

Survival rates and predictors of survival among colorectal cancer patients in a Malaysian tertiary hospital.

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Magaji, Bello Arkilla; Moy, Foong Ming; Roslani, April Camilla; Law, Chee Wei

2017-05-18

Colorectal cancer is the third most commonly diagnosed malignancy and the fourth leading cause of cancer-related death globally. It is the second most common cancer among both males and females in Malaysia. The economic burden of colorectal cancer is likely to increase over time owing to its current trend and aging population. Cancer survival analysis is an essential indicator for early detection and improvement in cancer treatment. However, there was a scarcity of studies concerning survival of colorectal cancer patients as well as its predictors. Therefore, we aimed to determine the 1-, 3- and 5-year survival rates, compare survival rates among ethnic groups and determine the predictors of survival among colorectal cancer patients. This was an ambidirectional cohort study conducted at the University Malaya Medical Centre (UMMC) in Kuala Lumpur, Malaysia. All Malaysian citizens or permanent residents with histologically confirmed diagnosis of colorectal cancer seen at UMMC from 1 January 2001 to 31 December 2010 were included in the study. Demographic and clinical characteristics were extracted from the medical records. Patients were followed-up until death or censored at the end of the study (31st December 2010). Censored patients' vital status (whether alive or dead) were cross checked with the National Registration Department. Survival analyses at 1-, 3- and 5-year intervals were performed using the Kaplan-Meier method. Log-rank test was used to compare the survival rates, while Cox proportional hazard regression analysis was carried out to determine the predictors of 5-year colorectal cancer survival. Among 1212 patients, the median survival for colorectal, colon and rectal cancers were 42.0, 42.0 and 41.0 months respectively; while the 1-, 3-, and 5-year relative survival rates ranged from 73.8 to 76.0%, 52.1 to 53.7% and 40.4 to 45.4% respectively. The Chinese patients had the lowest 5-year survival compared to Malay and Indian patients. Based on the 814

In vitro evidence for impaired neuroprotective capacities of adult mesenchymal stem cells derived from a rat model of familial amyotrophic lateral sclerosis (hSOD1(G93A)).

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Boucherie, Cédric; Caumont, Anne-Sophie; Maloteaux, Jean-Marie; Hermans, Emmanuel

2008-08-01

Protection of neurons by stem cells is an attractive challenge in the development of efficient therapies of neurodegenerative diseases. When giving preference to autologous grafts, the bone marrow constitutes a valuable source of adult stem cells. Therefore, we herein studied the acquisition of neuroprotective functions by cultured mesenchymal stem cells (MSCs) exposed to growth factors known to promote the differentiation of neural stem cells into astrocytes. In these conditions, MSCs showed increased transcription and expression of the high-affinity glutamate transporter GLT-1 and functional studies revealed increased aspartate uptake activity. In addition, differentiation was shown to endow the cells with the capacity to respond to riluzole which triggers a robust up-regulation of the GDNF production. In parallel, MSCs derived from the bone marrow of a transgenic rat model of familial ALS (hSOD1(G93A)) were also characterised. Unexpectedly, cells from this rat strain submitted to the differentiation protocol showed modest capacity to take up aspartate and did not respond to the riluzole treatments. These data highlight the neuroprotective potential attributable to MSCs, supporting their use as valuable tools for the treatment of neurodegenerative disorders. However, the cells from the transgenic animal model of ALS appeared deficient in their capacity to gain the neuroprotective properties, raising questions regarding the suitability of autologous stem cell grafts in future therapies against familial forms of this disease.

Survival rate in nasopharyngeal carcinoma improved by high caseload volume: a nationwide population-based study in Taiwan

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Chou Pesus

2011-08-01

Full Text Available Abstract Background Positive correlation between caseload and outcome has previously been validated for several procedures and cancer treatments. However, there is no information linking caseload and outcome of nasopharyngeal carcinoma (NPC treatment. We used nationwide population-based data to examine the association between physician case volume and survival rates of patients with NPC. Methods Between 1998 and 2000, a total of 1225 patients were identified from the Taiwan National Health Insurance Research Database. Survival analysis, the Cox proportional hazards model, and propensity score were used to assess the relationship between 10-year survival rates and physician caseloads. Results As the caseload of individual physicians increased, unadjusted 10-year survival rates increased (p p = 0.001 after adjusting for comorbidities, hospital, and treatment modality. When analyzed by propensity score, the adjusted 10-year survival rate differed significantly between patients treated by high-volume physicians and patients treated by low/medium-volume physicians (75% vs. 61%; p Conclusions Our data confirm a positive volume-outcome relationship for NPC. After adjusting for differences in the case mix, our analysis found treatment of NPC by high-volume physicians improved 10-year survival rate.

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

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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

Association Between Treatment at High-Volume Facilities and Improved Overall Survival in Soft Tissue Sarcomas.

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Venigalla, Sriram; Nead, Kevin T; Sebro, Ronnie; Guttmann, David M; Sharma, Sonam; Simone, Charles B; Levin, William P; Wilson, Robert J; Weber, Kristy L; Shabason, Jacob E

2018-03-15

Soft tissue sarcomas (STS) are rare malignancies that require complex multidisciplinary management. Therefore, facilities with high sarcoma case volume may demonstrate superior outcomes. We hypothesized that STS treatment at high-volume (HV) facilities would be associated with improved overall survival (OS). Patients aged ≥18 years with nonmetastatic STS treated with surgery and radiation therapy at a single facility from 2004 through 2013 were identified from the National Cancer Database. Facilities were dichotomized into HV and low-volume (LV) cohorts based on total case volume over the study period. OS was assessed using multivariable Cox regression with propensity score-matching. Patterns of care were assessed using multivariable logistic regression analysis. Of 9025 total patients, 1578 (17%) and 7447 (83%) were treated at HV and LV facilities, respectively. On multivariable analysis, high educational attainment, larger tumor size, higher grade, and negative surgical margins were statistically significantly associated with treatment at HV facilities; conversely, black race and non-metropolitan residence were negative predictors of treatment at HV facilities. On propensity score-matched multivariable analysis, treatment at HV facilities versus LV facilities was associated with improved OS (hazard ratio, 0.87, 95% confidence interval, 0.80-0.95; P = .001). Older age, lack of insurance, greater comorbidity, larger tumor size, higher tumor grade, and positive surgical margins were associated with statistically significantly worse OS. In this observational cohort study using the National Cancer Database, receipt of surgery and radiation therapy at HV facilities was associated with improved OS in patients with STS. Potential sociodemographic disparities limit access to care at HV facilities for certain populations. Our findings highlight the importance of receipt of care at HV facilities for patients with STS and warrant further study into improving access to

Cost per median overall survival month associated with abiraterone acetate and enzalutamide for treatment of patients with metastatic castration-resistant prostate cancer.

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Pilon, Dominic; Queener, Marykay; Lefebvre, Patrick; Ellis, Lorie A

2016-08-01

To calculate costs per median overall survival (OS) month in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate plus prednisone (AA + P) or enzalutamide. Median treatment duration and median OS data from published Phase 3 clinical trials and prescribing information were used to calculate costs per median OS month based on wholesale acquisition costs (WACs) for patients with mCRPC treated with AA + P or enzalutamide. Sensitivity analyses were performed to understand how variations in treatment duration and treatment-related monitoring recommendations influenced cost per median OS month. Cost-effectiveness estimates of other Phase 3 trial outcomes were also explored: cost per month of chemotherapy avoided and per median radiographic progression-free survival (rPFS) month. The results demonstrated that AA + P has a lower cost per median OS month than enzalutamide ($3231 vs 4512; 28% reduction), based on the following assumptions: median treatment duration of 14 months for AA + P and 18 months for enzalutamide, median OS of 34.7 months for AA + P and 35.3 months for enzalutamide, and WAC per 30-day supply of $8007.17 for AA + P vs $8847.98 for enzalutamide. Sensitivity analyses showed that accounting for recommended treatment-related monitoring costs or assuming identical treatment durations for AA + P and enzalutamide (18 months) resulted in costs per median OS month 8-27% lower for AA + P than for enzalutamide. Costs per month of chemotherapy avoided were $4448 for AA + P and $5688 for enzalutamide, while costs per month to achieve median rPFS were $6794 for AA + P and $7963 for enzalutamide. This cost-effectiveness analysis demonstrated that costs per median OS month, along with costs of other Phase 3 trial outcomes, were lower for AA + P than for enzalutamide. The findings were robust to sensitivity analyses. These results have important implications

Effect of postharvest UV-C treatment on the bacterial diversity of Ataulfo mangoes by PCR-DGGE, survival of E. coli and antimicrobial activity

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Fernández-Suárez, Rocío; Ramírez-Villatoro, Guadalupe; Díaz-Ruiz, Gloria; Eslava, Carlos; Calderón, Montserrat; Navarro-Ocaña, Arturo; Trejo-Márquez, Andrea; Wacher, Carmen

2013-01-01

Since Mexico is the second largest exporter of mangoes, its safety assurance is essential. Research in microbial ecology and knowledge of complex interactions among microbes must be better understood to achieve maximal control of pathogens. Therefore, we investigated the effect of UV-C treatments on bacterial diversity of the Ataulfo mangoes surface using PCR-DGGE analysis of variable region V3 of 16S rRNA genes, and the survival of E. coli, by plate counting. The UV-C irradiation reduced the microbial load on the surface of mangoes immediately after treatment and the structure of bacterial communities was modified during storage. We identified the key members of the bacterial communities on the surface of fruits, predominating Enterobacter genus. Genera as Lactococcus and Pantoea were only detected on the surface of non-treated (control) mangoes. This could indicate that these genera were affected by the UV-C treatment. On the other hand, the treatment did not have a significant effect on survival of E. coli. However, genera that have been recognized as antagonists against foodborne pathogens were identified in the bands patterns. Also, phenolic compounds were determined by HPLC and antimicrobial activity was assayed according to the agar diffusion method. The main phenolic compounds were chlorogenic, gallic, and caffeic acids. Mango peel methanol extracts (UV-C treated and control mangoes) showed antimicrobial activity against strains previously isolated from mango, detecting significant differences (P < 0.05) among treated and control mangoes after 4 and 12 days of storage. Ps. fluorescens and Ps. stutszeri were the most sensitive. PMID:23761788

A case of long term survival with skeletal only metastatic breast cancer.

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Kuechle, Joseph B; McGrath, Brian E; Khoury, Thaer; Mindell, Eugene R

2015-01-01

The prognosis of patients with metastatic breast cancer is very poor. Because of this, treatment of skeletal metastasis is often palliative with limited goals rather than cure. However, there are those patients, such as presented here, who survive for an extended time. This thirty-six year old female presented with lytic lesions to one ulna and rib five years after mastectomy for breast cancer. Despite radiation and chemotherapy, the ulnar lesion expanded and resulted in an elbow dislocation. The rib lesion was resected and the arm amputated above the elbow. She developed local recurrence in both her above elbow amputation stump and chest wall and a more proximal below shoulder amputation was performed with resection of chest wall lesion. Even though she had locally aggressive disease, she has survived for 31 years after diagnosis without any evidence of disease. Reports of metastatic breast cancer survival indicate the five year survival to be 15%. There have been few reports indicating that those patients with skeletal only or oligometastatic disease have improved prognosis. It is not clear what biological properties of these tumors results in the improved survival. This case highlights the challenges of giving patients the optimal treatment in the light of limited ability to predict prognosis. It also highlights the need to further investigate the phenotypes of breast cancer that can, despite metastatic disease and with modern treatment go on to long survival. In addition this case demonstrates the importance of long term followup. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Survival after Second and Subsequent Recurrences in Osteosarcoma: A Retrospective Multicenter Analysis.

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Tirtei, Elisa; Asaftei, Sebastian D; Manicone, Rosaria; Cesari, Marilena; Paioli, Anna; Rocca, Michele; Ferrari, Stefano; Fagioli, Franca

2017-05-01

Purpose Osteosarcoma (OS) is the most common primary bone tumor. Despite complete surgical removal and intensive chemotherapeutic treatment, 30%-35% of patients with OS have local or systemic recurrence. Some patients survive multiple recurrences, but overall survival after OS recurrence is poor. This analysis aims to describe and identify factors influencing post-relapse survival (PRS) after a second OS relapse. Methods This is a retrospective analysis of 60 patients with a second relapse of OS of the extremities in 2 Italian centers between 2003 and 2013. Results Treatment for first and subsequent relapses was planned according to institutional guidelines. After complete surgical remission (CSR) following the first recurrence, patients experienced a second OS relapse with a median disease-free interval (DFI) of 6 months. Lung disease was prevalent: 44 patients (76%) had pulmonary metastases. Survival after the second relapse was 22% at 5 years. Lung disease only correlated with better survival at 5 years (33.6%) compared with other sites of recurrence (5%; p = 0.008). Patients with a single pulmonary lesion had a better 5-year second PRS (42%; p = 0.02). Patients who achieved a second CSR had a 5-year second PRS of 33.4%. Chemotherapy (p<0.001) benefited patients without a third CSR. Conclusions This analysis confirms the importance of an aggressive, repeated surgical approach. Lung metastases only, the number of lesions, DFI and CSR influenced survival. It also confirms the importance of chemotherapy in patients in whom surgical treatment is not feasible.

Plasmodium Parasitemia Associated With Increased Survival in Ebola Virus-Infected Patients.

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Rosenke, Kyle; Adjemian, Jennifer; Munster, Vincent J; Marzi, Andrea; Falzarano, Darryl; Onyango, Clayton O; Ochieng, Melvin; Juma, Bonventure; Fischer, Robert J; Prescott, Joseph B; Safronetz, David; Omballa, Victor; Owuor, Collins; Hoenen, Thomas; Groseth, Allison; Martellaro, Cynthia; van Doremalen, Neeltje; Zemtsova, Galina; Self, Joshua; Bushmaker, Trenton; McNally, Kristin; Rowe, Thomas; Emery, Shannon L; Feldmann, Friederike; Williamson, Brandi N; Best, Sonja M; Nyenswah, Tolbert G; Grolla, Allen; Strong, James E; Kobinger, Gary; Bolay, Fatorma K; Zoon, Kathryn C; Stassijns, Jorgen; Giuliani, Ruggero; de Smet, Martin; Nichol, Stuart T; Fields, Barry; Sprecher, Armand; Massaquoi, Moses; Feldmann, Heinz; de Wit, Emmie

2016-10-15

The ongoing Ebola outbreak in West Africa has resulted in 28 646 suspected, probable, and confirmed Ebola virus infections. Nevertheless, malaria remains a large public health burden in the region affected by the outbreak. A joint Centers for Disease Control and Prevention/National Institutes of Health diagnostic laboratory was established in Monrovia, Liberia, in August 2014, to provide laboratory diagnostics for Ebola virus. All blood samples from suspected Ebola virus-infected patients admitted to the Médecins Sans Frontières ELWA3 Ebola treatment unit in Monrovia were tested by quantitative real-time polymerase chain reaction for the presence of Ebola virus and Plasmodium species RNA. Clinical outcome in laboratory-confirmed Ebola virus-infected patients was analyzed as a function of age, sex, Ebola viremia, and Plasmodium species parasitemia. The case fatality rate of 1182 patients with laboratory-confirmed Ebola virus infections was 52%. The probability of surviving decreased with increasing age and decreased with increasing Ebola viral load. Ebola virus-infected patients were 20% more likely to survive when Plasmodium species parasitemia was detected, even after controlling for Ebola viral load and age; those with the highest levels of parasitemia had a survival rate of 83%. This effect was independent of treatment with antimalarials, as this was provided to all patients. Moreover, treatment with antimalarials did not affect survival in the Ebola virus mouse model. Plasmodium species parasitemia is associated with an increase in the probability of surviving Ebola virus infection. More research is needed to understand the molecular mechanism underlying this remarkable phenomenon and translate it into treatment options for Ebola virus infection. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Socioeconomic disparity in survival after breast cancer in ireland: observational study.

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Paul M Walsh

Full Text Available We evaluated the relationship between breast cancer survival and deprivation using data from the Irish National Cancer Registry. Cause-specific survival was compared between five area-based socioeconomic deprivation strata using Cox regression. Patient and tumour characteristics and treatment were compared using modified Poisson regression with robust variance estimation. Based on 21356 patients diagnosed 1999-2008, age-standardized five-year survival averaged 80% in the least deprived and 75% in the most deprived stratum. Age-adjusted mortality risk was 33% higher in the most deprived group (hazard ratio 1.33, 95% CI 1.21-1.45, P<0.001. The most deprived groups were more likely to present with advanced stage, high grade or hormone receptor-negative cancer, symptomatically, or with significant comorbidity, and to be smokers or unmarried, and less likely to have breast-conserving surgery. Cox modelling suggested that the available data on patient, tumour and treatment factors could account for only about half of the survival disparity (adjusted hazard ratio 1.18, 95% CI 0.97-1.43, P = 0.093. Survival disparity did not diminish over time, compared with the period 1994-1998. Persistent survival disparities among Irish breast cancer patients suggest unequal use of or access to services and highlight the need for further research to understand and remove the behavioural or other barriers involved.

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

Guideline-Concordant Cancer Care and Survival Among American Indian/Alaskan Native Patients

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Javid, Sara H.; Varghese, Thomas K.; Morris, Arden M.; Porter, Michael P.; He, Hao; Buchwald, Dedra; Flum, David R.

2014-01-01

BACKGROUND American Indians/Alaskan Natives (AI/ANs) have the worst 5-year cancer survival of all racial/ethnic groups in the United States. Causes for this disparity are unknown. The authors of this report examined the receipt of cancer treatment among AI/AN patients compared with white patients. METHODS This was a retrospective cohort study of 338,204 patients who were diagnosed at age ≥65 years with breast, colon, lung, or prostate cancer between 1996 and 2005 in the Surveillance, Epidemiology, and End Results-Medicare database. Nationally accepted guidelines for surgical and adjuvant therapy and surveillance were selected as metrics of optimal, guideline-concordant care. Treatment analyses compared AI/ANs with matched whites. RESULTS Across cancer types, AI/ANs were less likely to receive optimal cancer treatment and were less likely to undergo surgery (P ≤ .025 for all cancers). Adjuvant therapy rates were significantly lower for AI/AN patients with breast cancer (P <.001) and colon cancer (P = .001). Rates of post-treatment surveillance also were lower among AI/ANs and were statistically significantly lower for AI/AN patients with breast cancer (P = .002) and prostate cancer (P <.001). Nonreceipt of optimal cancer treatment was associated with significantly worse survival across cancer types. Disease-specific survival for those who did not undergo surgery was significantly lower for patients with breast cancer (hazard ratio [HR], 0.62), colon cancer (HR, 0.74), prostate cancer (HR, 0.52), and lung cancer (HR, 0.36). Survival rates also were significantly lower for those patients who did not receive adjuvant therapy for breast cancer (HR, 0.56), colon cancer (HR, 0.59), or prostate cancer (HR, 0.81; all 95% confidence intervals were <1.0). CONCLUSIONS Fewer AI/AN patients than white patients received guideline-concordant cancer treatment across the 4 most common cancers. Efforts to explain these differences are critical to improving cancer care and

Androgen deprivation does predict bNED survival in unfavorable prostate cancer PTS treated with external beam radiation therapy

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Anderson, Penny R.; Hanlon, Alexandra L.; Hanks, Gerald E.

1996-01-01

Purpose: Cooperative groups have investigated the outcome of androgen deprivation therapy combined with radiation therapy in prostate cancer pts with variable prerx prognostic indicators. This report describes an objective means of selecting pts for adjuvant hormonal therapy by examining bNED survival for groups of pts with specific prognostic indicators treated with adjuvant hormones (RT+H) vs matched controls treated with radiation therapy alone (RT). In addition, this report shows the 5-yr bNED survival for pts selected by this method for RT+H vs RT alone. Further, bNED survival is assessed multivariately according to treatment (RT+H vs RT) and predetermined prognostic treatment and prerx covariates. Materials and Methods: From (10(88)) to (12(94)), 684 T1-T3 NXM0 pts with known prerx PSA level were treated at Fox Chase Cancer Center. 568 of those pts were treated with RT alone while 116 were treated with RT+H. Table 1 lists the patient distributions for each of the putative prognostic factors indicative of bNED survival. We compare actuarial bNED survival rates according to treatment group within each of the prognostic groups. bNED survival is also compared for the two treatment groups using 107 RT+H pts and 107 matched (by stage, grade, and prerx PSA) controls randomly selected from the RT alone group. bNED survival for the 214 pts is then analyzed multivariately using stepwise Cox regression to determine independent predictors of outcome. Covariates considered for entry into the model included stage, grade, prerx PSA, treatment (RT vs RT+H), and center of prostate dose. bNED failure is defined as PSA ≥1.5 ngm/ml and rising on two consective determinations. The median follow-up is 30 mos (2 to 90 mos). Results: Table 1 presents three-year bNED actuarial survival rates according to treatment group for prerx PSA, gleason score, and stage groups. It is apparent that the T2C/T3, gleason 7-10, and the prerx PSA > 15 ngm/ml groups of pts benefit from hormonal

Trends in colorectal cancer survival in northern Denmark: 1985-2004

DEFF Research Database (Denmark)

Iversen, Lene Hjerrild; Nørgaard, Mette; Jepsen, Peter

2007-01-01

OBJECTIVE: The prognosis for colorectal cancer (CRC) is less favourable in Denmark than in neighbouring countries. To improve cancer treatment in Denmark, a National Cancer Plan was proposed in 2000. We conducted this population-based study to monitor recent trends in CRC survival and mortality...... for age and gender. A total of 19,515 CRC patients were identified and linked with the Central Office of Civil Registration to ascertain survival through January 2005. Results: From 1985 to 2004, 1-year and 5-year survival improved both for patients with colon and rectal cancer. From 1995-1999 to 2000......-2004, overall 1-year survival of 65% for colon cancer did not improve, and some age groups experienced a decreasing 1-year survival probability. For rectal cancer, overall 1-year survival increased from 71% in 1995-1999 to 74% in 2000-2004. Using 1985-1989 as reference period, 30-day mortality did not decrease...

Survival and predictors of mortality among human immunodeficiency virus patients on anti-retroviral treatment at Jinka Hospital, South Omo, Ethiopia: a six years retrospective cohort study

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Ameni, Gobena

2016-01-01

OBJECTIVES The survival rate of human immunodeficiency virus (HIV)-infected patients receiving treatment in Ethiopia is poorly understood. This study aimed to determine the survival rate and predictors of mortality among HIV-infected adults on antiretroviral therapy (ART) at Jinka Hospital, South Omo, Ethiopia. METHODS A 6-year retrospective cohort study was conducted using 350 patient records drawn from 1,899 patients on ART at Jinka Hospital from September 2010 to August 2015. The data were analyzed using Kaplan-Meier statistics and Cox regression models. RESULTS Of the 350 study participants, 315 (90.0%) were censored and 35 (10.0%) died. Twenty-two (62.9%) of the deaths occurred during the first year of treatment. The total follow-up encompassed 1,995 person-years, with an incidence rate of 1.75 deaths per 100 person-years. The mean survival time of patients on highly active antiretroviral therapy (HAART) was 30.84±19.57 months. The overall survival of patients on HAART was 64.00% (95% confidence interval [CI], 61.85 to 66.21%) at 72 months of follow-up. The significant predictors of mortality included non-disclosure of HIV status (adjusted hazard ratio [aHR], 5.82; 95% CI, 1.91 to 17.72), a history of tuberculosis (aHR, 1.82; 95% CI, 1.41 to 3.51), and ambulatory (aHR, 2.97; 95% CI, 1.20 to 8.86) or bedridden (aHR, 4.67; 95% CI, 1.30 to 17.27) functional status, World Health Organization (WHO) clinical stage IV illness (aHR, 24.97; 95% CI, 2.75 to 26.45), and substance abusers (aHR, 3.72; 95% CI, 1.39 to 9.97). CONCLUSIONS Patients with a history of tuberculosis treatment, ambulatory or bedridden functional status, or advanced WHO clinical stage disease, as well substance abusers, should be carefully monitored, particularly in the first few months after initiating antiretroviral therapy. Patients should also be encouraged to disclose their status to their relatives. PMID:27820957

Survival and predictors of mortality among human immunodeficiency virus patients on anti-retroviral treatment at Jinka Hospital, South Omo, Ethiopia: a six years retrospective cohort study

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Erdaw Tachbele

2016-11-01

Full Text Available OBJECTIVES The survival rate of human immunodeficiency virus (HIV-infected patients receiving treatment in Ethiopia is poorly understood. This study aimed to determine the survival rate and predictors of mortality among HIV-infected adults on antiretroviral therapy (ART at Jinka Hospital, South Omo, Ethiopia. METHODS A 6-year retrospective cohort study was conducted using 350 patient records drawn from 1,899 patients on ART at Jinka Hospital from September 2010 to August 2015. The data were analyzed using Kaplan-Meier statistics and Cox regression models. RESULTS Of the 350 study participants, 315 (90.0% were censored and 35 (10.0% died. Twenty-two (62.9% of the deaths occurred during the first year of treatment. The total follow-up encompassed 1,995 person-years, with an incidence rate of 1.75 deaths per 100 person-years. The mean survival time of patients on highly active antiretroviral therapy (HAART was 30.84±19.57 months. The overall survival of patients on HAART was 64.00% (95% confidence interval [CI], 61.85 to 66.21% at 72 months of follow-up. The significant predictors of mortality included non-disclosure of HIV status (adjusted hazard ratio [aHR], 5.82; 95% CI, 1.91 to 17.72, a history of tuberculosis (aHR, 1.82; 95% CI, 1.41 to 3.51, and ambulatory (aHR, 2.97; 95% CI, 1.20 to 8.86 or bedridden (aHR, 4.67; 95% CI, 1.30 to 17.27 functional status, World Health Organization (WHO clinical stage IV illness (aHR, 24.97; 95% CI, 2.75 to 26.45, and substance abusers (aHR, 3.72; 95% CI, 1.39 to 9.97. CONCLUSIONS Patients with a history of tuberculosis treatment, ambulatory or bedridden functional status, or advanced WHO clinical stage disease, as well substance abusers, should be carefully monitored, particularly in the first few months after initiating antiretroviral therapy. Patients should also be encouraged to disclose their status to their relatives.

Whole-brain radiotherapy with or without efaproxiral for the treatment of brain metastases: Determinants of response and its prognostic value for subsequent survival

International Nuclear Information System (INIS)

Stea, Baldassarre; Suh, John H.; Boyd, Adam P. M.S.; Cagnoni, Pablo J.; Shaw, Edward

2006-01-01

Purpose: To determine the prognostic factors for radiographic response and its prognostic value for subsequent survival in patients undergoing whole-brain radiotherapy (WBRT) for brain metastases. Methods and Materials: Five hundred fifteen eligible patients were randomized in a phase III trial evaluating WBRT and supplemental oxygen with or without efaproxiral, an allosteric modifier of hemoglobin that reduces hemoglobin oxygen-binding affinity and enhances tumor oxygenation, potentially increasing tumor radiosensitivity. Brain images were obtained at baseline and at scheduled follow-up visits after WBRT. Landmark analysis was used to assess the ability of response at selected time points to predict subsequent survival. Logistic regression was used to assess determinants of response at 3 months. Results: Treatment arm, Karnofsky Performance Status, presence or absence of liver metastases, and primary site were all determinants of response at the 3-month follow-up visit, with patients in the efaproxiral arm experiencing a 67% greater odds of response at this visit (p = 0.02). Response at 3 and 6 months was a significant prognostic factor for longer subsequent survival. Conclusions: The 3-month scan is a valuable prognostic factor for subsequent survival in patients with brain metastases treated with WBRT. Patients in the efaproxiral arm had a higher response rate at 3 and 6 months than those in the control arm

Survival analysis of colorectal cancer patients with tumor recurrence using global score test methodology

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Zain, Zakiyah, E-mail: zac@uum.edu.my; Ahmad, Yuhaniz, E-mail: yuhaniz@uum.edu.my [School of Quantitative Sciences, Universiti Utara Malaysia, UUM Sintok 06010, Kedah (Malaysia); Azwan, Zairul, E-mail: zairulazwan@gmail.com, E-mail: farhanaraduan@gmail.com, E-mail: drisagap@yahoo.com; Raduan, Farhana, E-mail: zairulazwan@gmail.com, E-mail: farhanaraduan@gmail.com, E-mail: drisagap@yahoo.com; Sagap, Ismail, E-mail: zairulazwan@gmail.com, E-mail: farhanaraduan@gmail.com, E-mail: drisagap@yahoo.com [Surgery Department, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Bandar Tun Razak, Kuala Lumpur (Malaysia); Aziz, Nazrina, E-mail: nazrina@uum.edu.my

2014-12-04

Colorectal cancer is the third and the second most common cancer worldwide in men and women respectively, and the second in Malaysia for both genders. Surgery, chemotherapy and radiotherapy are among the options available for treatment of patients with colorectal cancer. In clinical trials, the main purpose is often to compare efficacy between experimental and control treatments. Treatment comparisons often involve several responses or endpoints, and this situation complicates the analysis. In the case of colorectal cancer, sets of responses concerned with survival times include: times from tumor removal until the first, the second and the third tumor recurrences, and time to death. For a patient, the time to recurrence is correlated to the overall survival. In this study, global score test methodology is used in combining the univariate score statistics for comparing treatments with respect to each survival endpoint into a single statistic. The data of tumor recurrence and overall survival of colorectal cancer patients are taken from a Malaysian hospital. The results are found to be similar to those computed using the established Wei, Lin and Weissfeld method. Key factors such as ethnic, gender, age and stage at diagnose are also reported.

Strategies for clinical approach to neurodegeneration in Amyotrophic lateral sclerosis.

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Carlesi, Cecilia; Pasquali, Livia; Piazza, Selina; Lo Gerfo, Annalisa; Caldarazzo Ienco, Elena; Alessi, Rosaria; Fornai, Francesco; Siciliano, Gabriele

2011-03-01

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disorder of unknown aetiology that involves the loss of upper and lower motor neurons in the cerebral cortex, brainstem and spinal cord. Significant progress in understanding the cellular mechanisms of motor neuron degeneration in ALS has not been matched with the development of therapeutic strategies to prevent disease progression, and riluzole remains the only available therapy, with only marginal effects on disease survival. More recently alterations of mRNA processing in genetically defined forms of ALS, as those related to TDP-43 and FUS-TLS gene mutations have provided important insights into the molecular networks implicated in the disease pathogenesis. Here we review some of the recent progress in promoting therapeutic strategies for neurodegeneration.

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.

Joint Serum Tumor Markers Serve as survival predictive model of Erlotinib in the treatment of recurrent Non-small Cell Lung Cancer

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Lan SHAO

2014-05-01

Full Text Available Background and objective Molecular targeting therapy is the direction of individualized treatment of lung cancer, scholars has been established targeted therapy prediction models which provide more guidance for clinical individual therapy. This study investigated the relationship among pulmonary surfactant-associated protein D (SP-D, transforming growth factor α (TGF-α, matrix metalloproteinase 9 (MMP-9, tissue polypeptide specific antigen (TPS, and Krebs von den Lungen-6 (KL-6 and response as well as survival in the patients with recurrent non-small cell lung cancer, which Erlotinib was as second line treatment after failure to chemotherapy. This study also established a predictive prognostic model. Methods Serum levels of SP-D, TGF-α, MMP-9, TPS, and KL-6 in 114 patients before erlotinib treatment were detected by ELISA method. Combined with clinical factors, these levels were used to investigate the relationship with efficacy in erlotinib treatment and construct a predicted prognostic model by Kaplan-Meier curve and Cox proportional hazard model multivariate analysis. Results The objective response rate (ORR and disease control rate (DCR in the 114 patients, were 22.8% (26/114 and 72.8% (83/114, to Erlotinib treatment respectively. The median progression-free survival (PFS and one year survival rate with Erlotinib treatment were 5.13 months and 69.3%, respectively. Patients in the SP-D>110 ng/mL group exhibited more ORR (33.3% vs 13.3%, P=0.011 and DCR (83.3% vs 63.3%, P=0.017 than those in the ≤110 ng/mL group. Patients in the MMP-9≤535 ng/mL group showed more DCR (83.9% than those in the >535 ng/mL group (62.1% (P=0.009. Patients in the TPS110 ng/mL (5.95 months vs 3.25 months, P=0.009, MMP-9≤535 ng/mL (5.83 months vs 3.47 months, P=0.046, KL-6<500 U/mL (6.03 months vs 3.40 months, P=0.040, and TPS<80 U/L (6.15 months vs 2.42 months, P=0.014 groups showed better PFS. Multivariate analysis showed that current or ever-smoker, wild

Determinants of occurrence and survival after sudden cardiac arrest-A European perspective

DEFF Research Database (Denmark)

Empana, Jean-Philippe; Blom, Marieke T; Bӧttiger, Bernd W

2018-01-01

AIMS: The ESCAPE-NET project ("European Sudden Cardiac Arrest network- towards Prevention, Education and New Effective Treatments") aims to study: (1) risk factors and mechanisms for the occurrence of sudden cardiac arrest (SCA) in the population, and (2) risk factors and treatment strategies...... for survival after SCA on a European scale. METHODS: This is an Horizon2020 funded program of the European Union, performed by a European public-private consortium of 16 partners across 10 EU countries. There are 11 deep-phenotyped SCA cohorts for the study of risk factors and treatment strategies for survival...... ongoing efforts on SCA outside Europe and within Europe including the EuReCa project....

Modelling survival after treatment of intraocular melanoma using artificial neural networks and Bayes theorem

International Nuclear Information System (INIS)

Taktak, Azzam F G; Fisher, Anthony C; Damato, Bertil E

2004-01-01

This paper describes the development of an artificial intelligence (AI) system for survival prediction from intraocular melanoma. The system used artificial neural networks (ANNs) with five input parameters: coronal and sagittal tumour location, anterior tumour margin, largest basal tumour diameter and the cell type. After excluding records with missing data, 2331 patients were included in the study. These were split randomly into training and test sets. Date censorship was applied to the records to deal with patients who were lost to follow-up and patients who died from general causes. Bayes theorem was then applied to the ANN output to construct survival probability curves. A validation set with 34 patients unseen to both training and test sets was used to compare the AI system with Cox's regression (CR) and Kaplan-Meier (KM) analyses. Results showed large differences in the mean 5 year survival probability figures when the number of records with matching characteristics was small. However, as the number of matches increased to >100 the system tended to agree with CR and KM. The validation set was also used to compare the system with a clinical expert in predicting time to metastatic death. The rms error was 3.7 years for the system and 4.3 years for the clinical expert for 15 years survival. For <10 years survival, these figures were 2.7 and 4.2, respectively. We concluded that the AI system can match if not better the clinical expert's prediction. There were significant differences with CR and KM analyses when the number of records was small, but it was not known which model is more accurate

Modelling survival after treatment of intraocular melanoma using artificial neural networks and Bayes theorem

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Taktak, Azzam F G [Department of Clinical Engineering, Duncan Building, Royal Liverpool University Hospital, Liverpool L7 8XP (United Kingdom); Fisher, Anthony C [Department of Clinical Engineering, Duncan Building, Royal Liverpool University Hospital, Liverpool L7 8XP (United Kingdom); Damato, Bertil E [Department of Ophthalmology, Royal Liverpool University Hospital, Liverpool L7 8XP (United Kingdom)

2004-01-07

This paper describes the development of an artificial intelligence (AI) system for survival prediction from intraocular melanoma. The system used artificial neural networks (ANNs) with five input parameters: coronal and sagittal tumour location, anterior tumour margin, largest basal tumour diameter and the cell type. After excluding records with missing data, 2331 patients were included in the study. These were split randomly into training and test sets. Date censorship was applied to the records to deal with patients who were lost to follow-up and patients who died from general causes. Bayes theorem was then applied to the ANN output to construct survival probability curves. A validation set with 34 patients unseen to both training and test sets was used to compare the AI system with Cox's regression (CR) and Kaplan-Meier (KM) analyses. Results showed large differences in the mean 5 year survival probability figures when the number of records with matching characteristics was small. However, as the number of matches increased to >100 the system tended to agree with CR and KM. The validation set was also used to compare the system with a clinical expert in predicting time to metastatic death. The rms error was 3.7 years for the system and 4.3 years for the clinical expert for 15 years survival. For <10 years survival, these figures were 2.7 and 4.2, respectively. We concluded that the AI system can match if not better the clinical expert's prediction. There were significant differences with CR and KM analyses when the number of records was small, but it was not known which model is more accurate.

Depressive symptoms predict head and neck cancer survival: Examining plausible behavioral and biological pathways.

Science.gov (United States)

Zimmaro, Lauren A; Sephton, Sandra E; Siwik, Chelsea J; Phillips, Kala M; Rebholz, Whitney N; Kraemer, Helena C; Giese-Davis, Janine; Wilson, Liz; Bumpous, Jeffrey M; Cash, Elizabeth D

2018-03-01

Head and neck cancers are associated with high rates of depression, which may increase the risk for poorer immediate and long-term outcomes. Here it was hypothesized that greater depressive symptoms would predict earlier mortality, and behavioral (treatment interruption) and biological (treatment response) mediators were examined. Patients (n = 134) reported depressive symptomatology at treatment planning. Clinical data were reviewed at the 2-year follow-up. Greater depressive symptoms were associated with significantly shorter survival (hazard ratio, 0.868; 95% confidence interval [CI], 0.819-0.921; P ratio, 0.865; 95% CI, 0.774-0.966; P = .010), and poorer treatment response (odds ratio, 0.879; 95% CI, 0.803-0.963; P = .005). The poorer treatment response partially explained the depression-survival relation. Other known prognostic indicators did not challenge these results. Depressive symptoms at the time of treatment planning predict overall 2-year mortality. Effects are partly influenced by the treatment response. Depression screening and intervention may be beneficial. Future studies should examine parallel biological pathways linking depression to cancer survival, including endocrine disruption and inflammation. Cancer 2018;124:1053-60. © 2018 American Cancer Society. © 2018 American Cancer Society.

Precision oncology in advanced cancer patients improves overall survival with lower weekly healthcare costs

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Haslem, Derrick S.; Chakravarty, Ingo; Fulde, Gail; Gilbert, Heather; Tudor, Brian P.; Lin, Karen; Ford, James M.; Nadauld, Lincoln D.

2018-01-01

The impact of precision oncology on guiding treatment decisions of late-stage cancer patients was previously studied in a retrospective analysis. However, the overall survival and costs were not previously evaluated. We report the overall survival and healthcare costs associated with precision oncology in these patients with advanced cancer. Building on a matched cohort study of 44 patients with metastatic cancer who received all of their care within a single institution, we evaluated the overall survival and healthcare costs for each patient. We analyzed the outcomes of 22 patients who received genomic testing and targeted therapy (precision oncology) between July 1, 2013 and January 31, 2015, and compared to 22 historically controlled patients (control) who received standard chemotherapy (N = 17) or best supportive care (N = 5). The median overall survival was 51.7 weeks for the targeted treatment group and 25.8 weeks for the control group (P = 0.008) when matching on age, gender, histological diagnosis and previous treatment lines. Average costs over the entire period were $2,720 per week for the targeted treatment group and $3,453 per week for the control group, (P = 0.036). A separate analysis of 1,814 patients with late-stage cancer diagnoses found that those who received a targeted cancer treatment (N = 93) had 6.9% lower costs in the last 3 months of life compared with those who did not. These findings suggest that precision oncology may improve overall survival for refractory cancer patients while lowering average per-week healthcare costs, resource utilization and end-of-life costs. PMID:29552312

Effects of oral hygiene, residual caries and cervical Marginal-gaps on the survival of proximal atraumatic restorative treatment approach restorations

Directory of Open Access Journals (Sweden)

Arthur M Kemoli

2011-01-01

Full Text Available Background: Although Atraumatic restorative treatment (ART approach has been in existence for a while, the reasons for the poor performance of multisurface ART restorations are not very clear. Aim: The aim of this study is to investigate the effects of oral hygiene, residual caries and cervical marginal-gaps on survival of proximal ART restorations. Settings: Two rural divisions in Kenya were selected for the study. Design: A randomized clinical trial. Material and Methods: The 804 children in the study had their baseline- and 2-year dental plaque levels documented. Each child received one proximal restoration in a primary molar using ART approach, together with trained and pre-tested operators/assistants, three glass ionomer cements (GIC-brands and two tooth-isolation methods. The restorations were clinically evaluated soon after placement and after 2 years. Post-restorative bite-wing radiographs taken soon after restoration were also evaluated. Statistical analysis: Statistical Package for Social Sciences (SPSS version 14 computer programme was used and results tested using Pearson′s correlation, Cox Proportional Hazards regression analysis and Multiple Logistic regression models tests. Results: At baseline and after 2 years, the mean cumulative survival and plaque index changed from 94.4% to 30.8% and 2.34 (Standard Deviation, or SD of 0.46 to 1.92 (SD 2.1 respectively, with higher plaque indices associated with higher restoration failures. Of the 507 radiographs evaluated, 48 (9.5%, 63 (12.4% and 9 (1.8% restorations had residual caries (RC, cervical marginal-gaps (CMG and both RC/CMG respectively. Survival of the restorations with RC/CMG was significantly lower (p = 0.003 compared to those with RC or without RC. Conclusion: Low survival of proximal restorations in the study was associated with the presence of cervical marginal-gaps.

Progression-free survival as a potential surrogate for overall survival in metastatic breast cancer

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Beauchemin C

2014-06-01

Full Text Available Catherine Beauchemin,1 Dan Cooper,2 Marie-Ève Lapierre,1 Louise Yelle,3 Jean Lachaine11Université de Montréal, Faculté de pharmacie, Montreal, 2Institut national d'excellence en santé et en services sociaux (INESSS, 3Centre Hospitalier de l'Université de Montréal – Hôpital Notre-Dame, Département de médecine, Université de Montréal, Montreal, QC, CanadaBackground: Progression-free survival (PFS and time to progression (TTP are frequently used to establish the clinical efficacy of anti-cancer drugs. However, the surrogacy of PFS/TTP for overall survival (OS remains a matter of uncertainty in metastatic breast cancer (mBC. This study assessed the relationship between PFS/TTP and OS in mBC using a trial-based approach.Methods: We conducted a systematic literature review according to the PICO method: 'Population' consisted of women with mBC; 'Interventions' and 'Comparators' were standard treatments for mBC or best supportive care; 'Outcomes' of interest were median PFS/TTP and OS. We first performed a correlation analysis between median PFS/TTP and OS, and then conducted subgroup analyses to explore possible reasons for heterogeneity. Then, we assessed the relationship between the treatment effect on PFS/TTP and OS. The treatment effect on PFS/TTP and OS was quantified by the absolute difference of median values. We also conducted linear regression analysis to predict the effects of a new anti-cancer drug on OS on the basis of its effects on PFS/TTP.Results: A total of 5,041 studies were identified, and 144 fulfilled the eligibility criteria. There was a statistically significant relationship between median PFS/TTP and OS across included trials (r=0.428; P<0.01. Correlation coefficient for the treatment effect on PFS/TTP and OS was estimated at 0.427 (P<0.01. The obtained linear regression equation was ΔOS =−0.088 (95% confidence interval [CI] −1.347–1.172 + 1.753 (95% CI 1.307–2.198 × ΔPFS (R2=0.86.Conclusion: Results of

Advanced gastric adenocarcinoma. Influence of preoperative radiation therapy on toxicity and long-term survival rates

International Nuclear Information System (INIS)

Malzoni, Carlos Eduardo

1996-01-01

The surgical treatment of gastric cancer has better long-term survival rates when performed in patients with early gastric cancer. Worse results are obtained in treatment of advanced gastric cancer. Most patients in west centers are treated in advanced stages. A great number of them go through a surgical treatment unable by itself to cure them. the frequent local recurrence caused by failure of the surgical treatment has been keeping poor survival rates in patients with advanced gastric cancer for decades. The desire of improving survival is the reason of the use of adjuvant therapies. This paper achieved the retrospective study of the influence of preoperative radiation therapy (2000 cGy) in long-term survival rates (120 months) of patients with advanced gastric cancer on stages IIIa, IIIb and IV. The possible injuries caused in the liver and kidney were observed also as well as first group was treated by surgical and radiation therapies and the second received surgical treatment only. There was no statistical difference between the two groups when sex, age, race, occurrence of other diseases, nutritional assessment, TNM stage, occurrence of obstruction or bleeding caused by tumor, surgical procedure and hepatic and renal function were considered. Survival rates and changes on hepatic and renal function were statistically compared. The results showed a statistic improvement on the long-term survival rates of stage IIIa patients treated by preoperative radiation therapy. No statistic difference was observed on hepatic or renal function between the groups. No adverse influence of radiation therapy method was detected by the used parameters. There was no statistical difference between the two groups when immediate surgical complications were considered. (author)

Effects of malnutrition on treatment-related morbidity and survival of children with cancer in Nicaragua.

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Pribnow, Allison K; Ortiz, Roberta; Báez, Luis Fulgencio; Mendieta, Luvy; Luna-Fineman, Sandra

2017-11-01

Most children with cancer live in resource-limited countries where malnutrition is often prevalent. We identified the relationship between malnutrition and treatment-related morbidity (TRM), abandonment of therapy, and survival of children with cancer in Nicaragua to better inform targeted nutritional interventions. We conducted a retrospective review of patients aged 6 months to 18 years with newly diagnosed acute lymphoblastic leukemia, acute myeloid leukemia (AML), Wilms tumor, Hodgkin lymphoma, or Burkitt lymphoma (BL) who were treated between January 1, 2004, and December 31, 2007 at Children's Hospital Manuel de Jesus Rivera in Managua, Nicaragua. Statistical analysis examined the relations among nutritional status and cancer type, risk category, TRM, and event-free survival (EFS). Sixty-seven percent of patients (189/282) were malnourished at diagnosis. Malnutrition was highest among patients with Wilms tumor (85.7%), BL (75%), and AML (74.3%). A total of 92.2% of patients (225/244) experienced morbidity during the first 90 days. Malnutrition was associated with severe infection (P = 0.033). Severely malnourished patients had ≥grade 3 TRM on more days (P = 0.023) and were more likely to experience severe TRM on >50% of days (P = 0.032; OR, 3.27 [95% CI, 1.05-10.16]). Malnourished patients had inferior median EFS (2.25 vs. 5.58 years; P = 0.049), and abandoned therapy more frequently (P = 0.015). In Nicaragua, pediatric oncology patients with malnutrition at diagnosis experienced increased TRM, abandoned therapy more frequently, and had inferior EFS. Standardized nutritional evaluation of patients with newly diagnosed cancer and targeted provision of nutritional support are essential to decrease TRM and improve outcomes. © 2017 Wiley Periodicals, Inc.

The impact of chemotherapy and its timing on survival in malignant peritoneal mesothelioma treated with complete debulking.

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Naffouje, Samer A; Tulla, Kiara A; Salti, George I

2018-04-12

The current standard of treatment for malignant peritoneal mesothelioma (MPM) is cytoreductive surgery when the disease distribution is favorable. The role of chemotherapy, as an adjunct to surgery, remains unclear. The national database of mesothelioma was used to identify MPM patients who were treated with curative intent. Patients were divided into treatment groups: (1) chemotherapy only, (2) surgery only, (3) neoadjuvant chemotherapy + surgery, and (4) surgery + adjuvant chemotherapy. A negative control group of patients who did not receive any treatment was added (group 0). Totally, 1740 patients were included. Mean age was 63.04 ± 14.58 and 60.7% were males. The patients' distribution into the treatment groups was 604, 684, 169, 55, and 228 patients in groups 0-4, respectively, with a median survival of 3.61 ± 0.37, 11.10 ± 0.73, 57.41 ± 11.91, 52.30 ± 7.20, and 55.00 ± 9.19 months. The addition of chemotherapy, in any setting, to surgery provided an improved survival at 1 year (p = 0.006). This survival benefit ceased at the 2-, 3-, and 5-year checkpoints. The multivariate analysis identified age, sarcomatoid/biphasic histologies, nodal and distant metastasis, and offering no treatment or chemotherapy only as poor prognostic factors for overall survival. No difference in overall survival was noted with the addition of chemotherapy to complete debulking regardless of the timing. Complete debulking remains the standard treatment for MPM. The addition of systemic chemotherapy provides a short-term survival improvement at 1 year only and was similar whether given in the neoadjuvant or adjuvant setting. Nevertheless, it did not add a survival benefit beyond the 1-year time point.

Oral squamous cell carcinoma: survival, recurrence and death

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Antônio Camilo Souza Cruz

2014-10-01

Full Text Available This paper was based in data survey from macro and microscopic oral lesions characteristics, personal data and medical history of patients diagnosed with oral squamous cell carcinoma in the Lab of Pathological Anatomy from the Federal University of Alfenas from January 2000 to December 2010, establishing comparative parameters among clinical data, type of treatment, recurrence, survival and anatomic pathological characteristics of the lesions. Were analyzed the histopathological reports, dental and hospital records. The highest incidence was in white men, age between 50 and 60 years, married, with low education and socioeconomic levels. The beginning of treatment occurred in average 67 days after the histopathological diagnosis. The estimated survival of patients at five years was 42%. The consumption of alcohol and tobacco and the occurrence of metastasis were statistically significant for the increase of recurrence and lethality.

Influence of specific comorbidities on survival after early-stage breast cancer

DEFF Research Database (Denmark)

Ewertz, Marianne; Land, Lotte Holm; Dalton, Susanne Oksbjerg

2018-01-01

elevated for patients with prior myocardial infarction, congestive heart failure, cerebrovascular disease, connective tissue disease, ulcer disease, and diabetes. The similar effect of adjuvant treatment in patients with and without comorbidity underlines the importance of adhering to guideline therapy.......BACKGROUND: While comorbidity indices are useful for describing trends in survival, information on specific comorbidities is needed for the clinician advising the individual breast cancer patient on her treatment. Here we present an analysis of overall survival, breast cancer-specific mortality......, and effect of medical adjuvant treatment among breast cancer patients suffering from 12 major comorbidities compared with breast cancer patients without comorbidities. MATERIAL AND METHODS: The study population was identified from the Danish Breast Cancer Cooperative Group and included 59,673 women without...

Survival analysis

International Nuclear Information System (INIS)

Badwe, R.A.

1999-01-01

The primary endpoint in the majority of the studies has been either disease recurrence or death. This kind of analysis requires a special method since all patients in the study experience the endpoint. The standard method for estimating such survival distribution is Kaplan Meier method. The survival function is defined as the proportion of individuals who survive beyond certain time. Multi-variate comparison for survival has been carried out with Cox's proportional hazard model

Survival of patients with Ewing's sarcoma in Yazd-Iran.

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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.

Survival of flexible, braided, bonded stainless steel lingual retainers : a historic cohort study

NARCIS (Netherlands)

Foek, D. J. Lie Sam; Ozcan, M.; Verkerke, G. J.; Sandham, John; Dijkstra, P. U.

The objectives of this study were to retrospectively evaluate the clinical survival rate of flexible, braided, rectangular bonded stainless steel lingual retainers, and to investigate the influence of gender, age of the patient, and operator experience on survival after orthodontic treatment at the

Survival outcome of intermediate risk neuroblastoma at Children Cancer Hospital Egypt

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Hossam Elzomor

2018-03-01

Conclusion: A very high rate of survival is currently achievable in patients with intermediate risk neuroblastoma by chemotherapy or chemotherapy and surgery. In addition to response, our plan is to adopt biologically-based treatment to reduce treatment-induced complications among survivors.

Errantum: Treatment of human astrocytoma U87 cells with silicon dioxide nanoparticles lowers their survival and alters their expression of mitochondrial and cell signaling proteins

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Lai JCK

2010-12-01

Full Text Available Lai JCK, Ananthakrishnan G, Jandhyam S, et al. Treatment of human astrocytoma U87 cells with silicon dioxide nanoparticles lowers their survival and alters their expression of mitochondrial and cell signaling proteins. Int J Nanomedicine. 2010;5:715–723.The wrong image was used in Figure 5 on page 719.

Survival of irradiated mice treated with WR-151327, synthetic trehalose dicorynomycolate, or ofloxacin

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Ledney, G. D.; Elliott, T. B.; Landauer, M. R.; Vigneulle, R. M.; Henderson, P. L.; Harding, R. A.; Tom, S. P.

1994-10-01

Spaceflight personnel need treatment options that would enhance survival from radiation and would not disrupt task performance. Doses of prophylactic or therapeutic agents known to induce significant short-term (30-day) survival with minimal behavioral (locomotor) changes were used for 180-day survival studies. In protection studies, groups of mice were treated with the phosphorothioate WR-151327 (200 mg/kg, 25% of the LD10) or the immunomodulator, synthetic trehalose dicorynomycolate (S-TDCM; 8 mg/kg), before lethal irradiation with reactor-generated fission neutrons and γ-rays (n/γ = 1) or 60Co γ-rays. In therapy studies, groups of mice received either S-TDCM, the antimicrobial ofloxacin, or S-TDCM plus ofloxacin after irradiation. For WR-151327 treated-mice, survival at 180 days for n/γ = 1 and γ-irradiated mice was 90% and 92%, respectively; for S-TDCM (protection), 57% and 78%, respectively; for S-TDCM (therapy), 20% and 25%, respectively; for ofloxacin, 38% and 5%, respectively; for S-TDCM combined with ofloxacin, 30% and 30%, respectively; and for saline, 8% and 5%, respectively. Ofloxacin or combined ofloxacin and S-TDCM increased survival from the gram-negative bacterial sepsis that predominated in n/γ = 1) irradiated mice. The efficacies of the treatments depended on radiation quality, treatment agent and its mode of use, and microflora of the host.

Systemic administration of bevacizumab prolongs survival in an in vivo model of platinum pre-treated ovarian cancer

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REIN, DANIEL T.; VOLKMER, ANNE KATHRIN; VOLKMER, JENS; BEYER, INES M.; JANNI, WOLFGANG; FLEISCH, MARKUS C.; WELTER, ANNE KATHRIN; BAUERSCHLAG, DIRK; SCHÖNDORF, THOMAS; BREIDENBACH, MARTINA

2012-01-01

Ovarian cancer patients often suffer from malignant ascites and pleural effusion. Apart from worsening the outcome, this condition frequently impairs the quality of life in patients who are already distressed by ovarian cancer. This study investigated whether single intraperitoneal administration of the anti-VEGF antibody bevacizumab is capable of reducing the ascites-related body surface and prolonging survival. The study was performed in an orthotopic murine model of peritoneal disseminated platin-resistant ovarian cancer. Mice were treated with bevacizumab and/or paclitaxel or buffer (control). Reduction of body surface and increased survival rates were assessed as therapeutic success. Survival of mice in all treatment groups was significantly enhanced when compared to the non-treatment control group. The combination of paclitaxel plus bevacizumab significantly improved body surface as well as overall survival in comparison to a treatment with only one of the drugs. Treatment of malignant effusion with a single dose of bevacizumab as an intraperitoneal application, with or without cytostatic co-medication, may be a powerful alternative to systemic treatment. PMID:22740945

EGFR overexpressing cells and tumors are dependent on autophagy for growth and survival

International Nuclear Information System (INIS)

Jutten, Barry; Keulers, Tom G.; Schaaf, Marco B.E.; Savelkouls, Kim; Theys, Jan; Span, Paul N.; Vooijs, Marc A.; Bussink, Johan; Rouschop, Kasper M.A.

2013-01-01

Background and purpose: The epidermal growth factor receptor (EGFR) is overexpressed, amplified or mutated in various human epithelial tumors, and is associated with tumor aggressiveness and therapy resistance. Autophagy activation provides a survival advantage for cells in the tumor microenvironment. In the current study, we assessed the potential of autophagy inhibition (using chloroquine (CQ)) in treatment of EGFR expressing tumors. Material and methods: Quantitative PCR, immunohistochemistry, clonogenic survival, proliferation assays and in vivo tumor growth were used to assess this potential. Results: We show that EGFR overexpressing xenografts are sensitive to CQ treatment and are sensitized to irradiation by autophagy inhibition. In HNSSC xenografts, a correlation between EGFR and expression of the autophagy marker LC3b is observed, suggesting a role for autophagy in EGFR expressing tumors. This observation was substantiated in cell lines, showing high EGFR expressing cells to be more sensitive to CQ addition as reflected by decreased proliferation and survival. Surprisingly high EGFR expressing cells display a lower autophagic flux. Conclusions: The EGFR high expressing cells and tumors investigated in this study are highly dependent on autophagy for growth and survival. Inhibition of autophagy may therefore provide a novel treatment opportunity for EGFR overexpressing tumors

Effect of Thoracic Surgeons on Lung Cancer Patients’ Survival

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Ning LI

2018-02-01

Full Text Available Background and objective Surgeons are the direct decision-makers and performers in the surgical treatment of patients with lung cancer. Whether the differences among doctors affect the survival of patients is unclear. This study analyzed the five-year survival rates of different thoracic surgeries in patients undergoing surgery to assess the physician's impact and impact. Methods A retrospective analysis of five years between 2002-2007 in the Department of Thoracic Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, for surgical treatment of lung cancer patients. According to different surgeons grouping doctors to compare the basic information of patients, surgical methods, short-term results and long-term survival differences. Results A total of 712 patients treated by 11 experienced thoracic surgeons were included in this study. The patients have nosignificant difference with gender, age, smoking, pathological type between groups. There were significant differences in clinical staging, surgery type, operation time, blood transfusion rate, number of lymph node dissection, palliative resection rate, postoperative complications and perioperative mortality. There was a significant difference in five-year survival rates among patients treated by different doctors. This difference can be seen in all clinical stage analyzes with consistency. In the multivariate analysis, it was suggested that surgeon was an independent factor influencing the prognosis of patients. Conclusion Thoracic surgeon has a significant effect on the therapeutic effect of lung cancer patients.

Treatment outcome of immediate, early and conventional single-tooth implants in the aesthetic zone : a systematic review to survival, bone level, soft-tissue, aesthetics and patient satisfaction

NARCIS (Netherlands)

den Hartog, Laurens; Huddleston Slater, James J. R.; Vissink, Arjan; Meijer, Henny J. A.; Raghoebar, Gerry M.

2008-01-01

den Hartog L, Huddleston Slater JJR, Vissink A, Meijer HJA, Raghoebar GM. Treatment outcome of immediate, early and conventional single-tooth implants in the aesthetic zone: a systematic review to survival, bone level, soft-tissue, aesthetics and patient satisfaction. J Clin Periodontol 2008; 35:

The validity of EORTC GBM prognostic calculator on survival of GBM patients in the West of Scotland.

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Teo, Mario; Clark, Brian; MacKinnon, Mairi; Stewart, Willie; Paul, James; St George, Jerome

2014-06-01

It is now accepted that the addition of temozolomide to radiotherapy in the treatment of patients with newly diagnosed glioblastoma multiforme (GBM) significantly improves survival. In 2008, a subanalysis of the original study data was performed, and an online "GBM Calculator" was made available on the European Organisation for Research and Treatment of Cancer (EORTC) website allowing users to estimate patients' survival outcomes. We tested this calculator against actual local survival data to validate its use in our patients. Prospectively collected clinical data were analysed on 105 consecutive patients receiving concurrent chemoradiotherapy following surgical treatment of GBM between December 2004 and February 2009. Using the EORTC online calculator, survival outcomes were generated for these patients and compared with their actual survival. The median overall survival for the entire cohort was 15.3 months (range 2.8-50.5 months), with 1-year and 2-year overall survival of 65.7% and 19%, respectively. This is in comparison to the median overall predictive survival of 21.3 months, with 1-year and 2-year survival of 95% and 39.5%, respectively. Case by case analysis also showed that the survival was overestimated in nearly 80% of patients. Subgroup analyses showed similar overestimation of patients' survival, except calculator Model 3 which utilised MGMT status. Use of the EORTC GBM prognostic calculator would have overestimated the survival of the majority of our patients with GBM. Uncertainty exists as to the cause of overestimation in the cohort although local socioeconomic factors might play a role. The different calculator models yielded different outcomes and the "best" predictor of survival for the cohort under study utilised the tumour MGMT status. We would strongly encourage similar local studies of validity testing prior to employing the online prognostic calculator for other population groups.

Human and Autologous Adipose-derived Stromal Cells Increase Flap Survival in Rats Independently of Host Immune Response

DEFF Research Database (Denmark)

Toyserkani, Navid Mohamadpour; Jensen, Charlotte Harken; Andersen, Ditte Caroline

2018-01-01

evaluated after 7 days. RESULTS: The mean survival rates for SVF treatment regardless of human or autologous origin were significantly increased as compared with the control group. Adipose stem/stromal cell and SVF lysate injection did not increase flap survival. Vessel density was increased for human...... injections lead to increased vessel density, but it did not necessarily lead to increased flap survival. Further research should elaborate which molecular events make SVF treatment more efficacious than ASC....

Alexandrium fundyense cyst viability and germling survival in light vs. dark at a constant low temperature

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Vahtera, Emil; Crespo, Bibiana G.; McGillicuddy, Dennis J.; Olli, Kalle; Anderson, Donald M.

2014-05-01

Both observations and models suggest that large-scale coastal blooms of Alexandrium fundyense in the Gulf of Maine are seeded by deep-bottom cyst accumulation zones (“seed beds”) where cysts germinate from the sediment surface or the overlying near-bottom nepheloid layers at water depths exceeding 100 m. The germling cells and their vegetative progeny are assumed to be subject to mortality while in complete darkness, as they swim to illuminated surface waters. To test the validity of this assumption we conducted laboratory investigations of cyst viability and the survival of the germling cells and their vegetative progeny during prolonged exposure to darkness at a temperature of 6 °C, simulating the conditions in deep Gulf of Maine waters. We isolated cysts from bottom sediments collected in the Gulf of Maine under low red light and incubated them in 96-well tissue culture-plates in culture medium under a 10:14 h light:dark cycle and under complete darkness. Cyst viability was high, with excystment frequency reaching 90% in the illuminated treatment after 30 days and in the dark treatment after 50 days. Average germination rates were 0.062 and 0.038 d-1 for light and dark treatments, respectively. The dark treatment showed an approximately 2-week time lag in maximum germination rates compared to the light treatment. Survival of germlings was considerably lower in the dark treatment. In the light treatments, 47% of germinated cysts produced germlings that were able to survive for 7 days and produce vegetative progeny, i.e., there were live cells in the well along with an empty cyst at least once during the experiment. In the dark treatments 12% of the cysts produced germlings that were able to survive for the same length of time. When dark treatments are scaled to take into account non-darkness related mortality, approximately 28% of the cysts produced germlings that were able to survive for at least 7 days. Even though cysts are able to germinate in darkness

Additive homeopathy in cancer patients: Retrospective survival data from a homeopathic outpatient unit at the Medical University of Vienna.

Science.gov (United States)

Gaertner, Katharina; Müllner, Michael; Friehs, Helmut; Schuster, Ernst; Marosi, Christine; Muchitsch, Ilse; Frass, Michael; Kaye, Alan David

2014-04-01

Current literature suggests a positive influence of additive classical homeopathy on global health and well-being in cancer patients. Besides encouraging case reports, there is little if any research on long-term survival of patients who obtain homeopathic care during cancer treatment. Data from cancer patients who had undergone homeopathic treatment complementary to conventional anti-cancer treatment at the Outpatient Unit for Homeopathy in Malignant Diseases, Medical University Vienna, Department of Medicine I, Vienna, Austria, were collected, described and a retrospective subgroup-analysis with regard to survival time was performed. Patient inclusion criteria were at least three homeopathic consultations, fatal prognosis of disease, quantitative and qualitative description of patient characteristics, and survival time. In four years, a total of 538 patients were recorded to have visited the Outpatient Unit Homeopathy in Malignant Diseases, Medical University Vienna, Department of Medicine I, Vienna, Austria. 62.8% of them were women, and nearly 20% had breast cancer. From the 53.7% (n=287) who had undergone at least three homeopathic consultations within four years, 18.7% (n=54) fulfilled inclusion criteria for survival analysis. The surveyed neoplasms were glioblastoma, lung, cholangiocellular and pancreatic carcinomas, metastasized sarcoma, and renal cell carcinoma. Median overall survival was compared to expert expectations of survival outcomes by specific cancer type and was prolonged across observed cancer entities (p<0.001). Extended survival time in this sample of cancer patients with fatal prognosis but additive homeopathic treatment is interesting. However, findings are based on a small sample, and with only limited data available about patient and treatment characteristics. The relationship between homeopathic treatment and survival time requires prospective investigation in larger samples possibly using matched-pair control analysis or randomized

Chemotherapy increases long-term survival in patients with adult medulloblastoma--a literature-based meta-analysis.

Science.gov (United States)

Kocakaya, Selin; Beier, Christoph Patrick; Beier, Dagmar

2016-03-01

Adult medulloblastoma is a potentially curable malignant entity with an incidence of 0.5-1 per million. Valid data on prognosis, treatment, and demographics are lacking, as most current knowledge stems from retrospective studies. Surgical resection followed by radiotherapy are accepted parts of treatment regimes; however, established prognostic factors and data clarifying the role of chemotherapy are missing. We investigated 227 publications from 1969-2013, with 907 identifiable, individual patients being available for meta-analysis. Demographic data, risk stratification, and treatment of these patients were similar to previous cohorts. The median overall survival (mOS) was 65 months (95% CI: 54.6-75.3) , the 5-year overall survival was 50.9% with 16% of the patients dying more than 5 years after diagnosis. Incomplete resection, clinical and radiological signs for brainstem infiltration, and abstinence from radiotherapy were predictive of worse outcome. Metastatic disease at tumor recurrence was identified as a new prognostic factor, while neither metastasis at initial diagnosis nor desmoplastic/classic histology was correlated with survival. Patients receiving chemotherapy first-line survived significantly longer (mOS: 108 mo, 95% CI: 68.6-148.4) than patients treated with radiation alone (mOS: 57 mo, 95% CI: 39.6-74.4) or patients who received chemotherapy at tumor recurrence. This effect was not biased by tumor stage or decade of treatment. Importantly, (neo)adjuvant chemotherapy also significantly increased the chance for long-term survival (>5 y) compared with radiotherapy alone or chemotherapy at tumor recurrence. This meta-analysis clarifies relevant prognostic factors and suggests that chemotherapy as part of first-line therapy improves overall survival and increases the proportion of patients with long-term survival. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions

Comparison of long-term survival and toxicity of simultaneous integrated boost vs conventional fractionation with intensity-modulated radiotherapy for the treatment of nasopharyngeal carcinoma

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Tao HM

2016-03-01

Full Text Available Hengmin Tao,1,2 Yumei Wei,1 Wei Huang,1 Xiujuan Gai,1,2 Baosheng Li11Department of 6th Radiation Oncology, Shandong Cancer Hospital and Institute, 2School of Medicine and Life Sciences, Jinan University-Shandong Academy of Medical Sciences, Jinan, People’s Republic of ChinaAim: In recent years, the intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB and intensity-modulated radiotherapy with conventional fractionation (IMRT-CF have been involved in the treatment of nasopharyngeal carcinoma (NPC. However, the potential clinical effects and toxicities are still controversial.Methods: Here, 107 patients with biopsy-proven locally advanced NPC between March 2004 and January 2011 were enrolled in the retrospective study. Among them, 54 patients received IMRT-SIB, and 53 patients received IMRT-CF. Subsequently, overall survival (OS, 5-year progression-free survival (PFS, 5-year locoregional recurrence-free survival (LRFS, and relevant toxicities were analyzed.Results: In the present study, all patients completed the treatment, and the overall median follow-up time was 80 months (range: 8–126 months. The 5-year OS analysis revealed no significant difference between the IMRT-SIB and IMRT-CF groups (80.9% vs 80.5%, P=0.568. In addition, there were also no significant between-group differences in 5-year PFS (73.3% vs 74.4%, P=0.773 and 5-year LRFS (88.1% vs 90.8%, P=0.903. Notably, the dose to critical organs (spinal cord, brainstem, and parotid gland in patients treated by IMRT-CF was significantly lower than that in patients treated by IMRT-SIB (all P<0.05.Conclusion: Both IMRT-SIB and IMRT-CF techniques are effective in treating locally advanced NPC, with similar OS, PFS, and LRFS. However, IMRT-CF has more advantages than IMRT-SIB in protecting spinal cord, brainstem, and parotid gland from acute and late toxicities, such as xerostomia. Further prospective study is warranted to confirm our findings.Keywords: intensity

Post-treatment surveillance testing of patients with colorectal cancer and the association with survival: protocol for a retrospective cohort study of the Surveillance, Epidemiology, and End Results (SEER)-Medicare database.

Science.gov (United States)

Hines, Robert B; Jiban, Md Jibanul Haque; Choudhury, Kanak; Loerzel, Victoria; Specogna, Adrian V; Troy, Steven P; Zhang, Shunpu

2018-04-28

Although the colorectal cancer (CRC) mortality rate has significantly improved over the past several decades, many patients will have a recurrence following curative treatment. Despite this high risk of recurrence, adherence to CRC surveillance testing guidelines is poor which increases cancer-related morbidity and potentially, mortality. Several randomised controlled trials (RCTs) with varying surveillance strategies have yielded conflicting evidence regarding the survival benefit associated with surveillance testing. However, due to differences in study protocols and limitations of sample size and length of follow-up, the RCT may not be the best study design to evaluate this relationship. An observational comparative effectiveness research study can overcome the sample size/follow-up limitations of RCT designs while assessing real-world variability in receipt of surveillance testing to provide much needed evidence on this important clinical issue. The gap in knowledge that this study will address concerns whether adherence to National Comprehensive Cancer Network CRC surveillance guidelines improves survival. Patients with colon and rectal cancer aged 66-84 years, who have been diagnosed between 2002 and 2008 and have been included in the Surveillance, Epidemiology, and End Results-Medicare database, are eligible for this retrospective cohort study. To minimise bias, patients had to survive at least 12 months following the completion of treatment. Adherence to surveillance testing up to 5 years post-treatment will be assessed in each year of follow-up and overall. Binomial regression will be used to assess the association between patients' characteristics and adherence. Survival analysis will be conducted to assess the association between adherence and 5-year survival. This study was approved by the National Cancer Institute and the Institutional Review Board of the University of Central Florida. The results of this study will be disseminated by publishing in

The effects of 137Cs irradiation and MAP on the survival and growth of salmonella Spp in pork

International Nuclear Information System (INIS)

Gao Meixu

2000-01-01

The effects of 137 Cs irradiation (0 to 2 kGy) and MAP combination treatment on the survival and growth of Salmonella Spp are studied in sterile pork in the absence of competing microflora. A central composite response-surface design is used to test the response of the pathogen to the treatments in a single experiment. Predictive equations are developed from the analyses of variances of the resulting data. The results show that the survival of Salmonella is significant decrease with the increasing of irradiation dose, but there are no evident effects on the survival of salmonella due to the MAP. Five kinds of MAP do not show the difference on the growth of Salmonella. 50% CO 2 treatment shows the irradiation protection of Salmonella compared with air. The results indicate that the treatment combined irradiation with MAP is not more effective for controlling the survival and growth of Salmonella Spp

Causal inference in survival analysis using pseudo-observations

DEFF Research Database (Denmark)

Andersen, Per K; Syriopoulou, Elisavet; Parner, Erik T

2017-01-01

Causal inference for non-censored response variables, such as binary or quantitative outcomes, is often based on either (1) direct standardization ('G-formula') or (2) inverse probability of treatment assignment weights ('propensity score'). To do causal inference in survival analysis, one needs ...

Network survivability performance

Science.gov (United States)

1993-11-01

This technical report has been developed to address the survivability of telecommunications networks including services. It responds to the need for a common understanding of, and assessment techniques for network survivability, availability, integrity, and reliability. It provides a basis for designing and operating telecommunications networks to user expectations for network survivability and a foundation for continuing industry activities in the subject area. This report focuses on the survivability of both public and private networks and covers a wide range of users. Two frameworks are established for quantifying and categorizing service outages, and for classifying network survivability techniques and measures. The performance of the network survivability techniques is considered; however, recommended objectives are not established for network survivability performance.

Treatment of metastatic brain lesion

Directory of Open Access Journals (Sweden)

A. M. Zaytsev

2015-01-01

Full Text Available Objective. Increasing survival in patients with secondary brain damage, and identifying the factors of favorable and adverse prognosis.Material and method. In P. A. Hertsen Moscow Oncology Research Institute from 2007 to 2013 there were treated 268 patients with brain metastases. The mean age was 55.8 years (from 24 to 81 years. Metastases of colorectal cancer identified in 7.8%, cases of lung cancer in 34%, melanoma 9.3 %, breast cancer in 26%, kidney cancer in 11%, with non-identified primary tumor in 4.5%, other tumors accounted for 6.7%. Solitary metastasis was diagnosed in 164 (61,19% patients, oligometastasis (2-3 - 72 (26,87% patients with polymetastasis (more than 3 – 32 (11,94% patients. In 106 (39,55% of patients with brain metastases it was the only manifestation of the generalization process. To control the radical removal of the tumor in 93 (34,7% patients we used the method of fluorescence navigation (FN with the drug Alasens. In 66 (24,6% patients intraoperatively was held a session of photodynamic therapy (PDT. In 212 (79,1% cases, the removal of metastasis performed totally, 55 (20,9% patients stated Subtotal removal.Results. The observation period for the patients ranged from 3 to 79 months. Survival median among the entire group of patients with metastatic brain lesion was 12 months. Overall survival was significantly dependent on RPA class, the volume of postoperative treatment, histological type of primary tumor, number of intracerebral metastases and the timing of the relapse-free period.Conclusions. Factors that affects the overall survival are the features of the histology of the primary lesion, multiplicity of metastatic lesions, RPA class and the synchronous nature of the metastasis. The median of overall survival of patients who did not receive after surgical treatment of a particular type of therapy was only 4 months. If to use the combined treatment (surgical treatment with the irradiation of the whole brain median

Effect of Herbal Drugs on Survivability of Piglets

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S. Kumar

Full Text Available The present study was conducted on 75 pigs (gilts and sows of Tamworth and Desi (T&D breed distributed in six groups. Different herbal treatment viz. Clemenstol syrup, Femelin, Lecorin plus and Asoka cordial in various stages of reproduction namely pubertal stage, periparturient stage, post farrowing stage and around weaning stage were given, Group I (C for gilts and Group 2 (C1 for sows were kept as control, lower was observed during earlier ages i.e. during first seven days. Almost 100% survivability was recorded after 29th day of age. Piglet survivability was higher during latter ages i.e. 29th to 56th day of age in comparison to earlier ages i.e. from birth to 28th day of age. However, there was no definite trend observed in different treatment groups and were statistically non significant. [Veterinary World 2008; 1(7.000: 205-206

[Medulloblastoma: improved survival in recent decades. Unicentric experience].

Science.gov (United States)

Igual Estellés, Lucía; Berlanga Charriel, Pablo; Cañete Nieto, Adela

2017-01-01

The aim of the study is to analyse variations in the treatment of medulloblastoma, the most common childhood brain tumour, and its impact on survival over the past two decades, as well as its clinical and pathological features. Survival analysis of all patients under 14 years old diagnosed with medulloblastoma between January 1990 and December 2013 in a Paediatric Oncology Unit. Sixty-three patients were diagnosed and treated for medulloblastoma, with a median follow-up of 5.1 years (range 0.65-21.7 years). The overall survival (OS) at 3 and 5 years was 66±13% and 55±14%, respectively. The OS at 5 years was 44%±25% in patients diagnosed in the 1990's, showing an increase to 70%±23% (p=0.032) since 2000. Clinical prognosis factors were included in the logistic regression model: age (p=0.008), presence of metastases and/or residual tumour (p=0.007), and receiving chemotherapy with radiotherapy after surgery (p=0.008). Statistically significant differences were observed for all of them. In our institution there has been a significant increase in medulloblastoma survival in the last decades. Multivariate analysis showed that this improvement was not related to the date of diagnosis, but with the introduction of chemotherapy in adjuvant treatment. This study confirmed that clinical factors significantly associated with worse outcome were age and presence of metastases at diagnosis. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Intravoxel Incoherent Motion Metrics as Potential Biomarkers for Survival in Glioblastoma.

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Josep Puig

Full Text Available Intravoxel incoherent motion (IVIM is an MRI technique with potential applications in measuring brain tumor perfusion, but its clinical impact remains to be determined. We assessed the usefulness of IVIM-metrics in predicting survival in newly diagnosed glioblastoma.Fifteen patients with glioblastoma underwent MRI including spin-echo echo-planar DWI using 13 b-values ranging from 0 to 1000 s/mm2. Parametric maps for diffusion coefficient (D, pseudodiffusion coefficient (D*, and perfusion fraction (f were generated for contrast-enhancing regions (CER and non-enhancing regions (NCER. Regions of interest were manually drawn in regions of maximum f and on the corresponding dynamic susceptibility contrast images. Prognostic factors were evaluated by Kaplan-Meier survival and Cox proportional hazards analyses.We found that fCER and D*CER correlated with rCBFCER. The best cutoffs for 6-month survival were fCER>9.86% and D*CER>21.712 x10-3mm2/s (100% sensitivity, 71.4% specificity, 100% and 80% positive predictive values, and 80% and 100% negative predictive values; AUC:0.893 and 0.857, respectively. Treatment yielded the highest hazard ratio (5.484; 95% CI: 1.162-25.88; AUC: 0.723; P = 0.031; fCER combined with treatment predicted survival with 100% accuracy.The IVIM-metrics fCER and D*CER are promising biomarkers of 6-month survival in newly diagnosed glioblastoma.

VEGF improves survival of mesenchymal stem cells in infarcted hearts

International Nuclear Information System (INIS)

Pons, Jennifer; Huang Yu; Arakawa-Hoyt, Janice; Washko, Daniel; Takagawa, Junya; Ye, Jianqin; Grossman, William; Su Hua

2008-01-01

Bone marrow-derived mesenchymal stem cells (MSC) are a promising source for cell-based treatment of myocardial infarction (MI), but existing strategies are restricted by low cell survival and engraftment. We examined whether vascular endothelial growth factor (VEGF) improve MSC viability in infracted hearts. We found long-term culture increased MSC-cellular stress: expressing more cell cycle inhibitors, p16 INK , p21 and p19 ARF . VEGF treatment reduced cellular stress, increased pro-survival factors, phosphorylated-Akt and Bcl-xL expression and cell proliferation. Co-injection of MSCs with VEGF to MI hearts increased cell engraftment and resulted in better improvement of cardiac function than that injected with MSCs or VEGF alone. In conclusion, VEGF protects MSCs from culture-induce cellular stress and improves their viability in ischemic myocardium, which results in improvements of their therapeutic effect for the treatment of MI

GENOMIC PREDICTOR OF RESPONSE AND SURVIVAL FOLLOWING TAXANE-ANTHRACYCLINE CHEMOTHERAPY FOR INVASIVE BREAST CANCER

Science.gov (United States)

Hatzis, Christos; Pusztai, Lajos; Valero, Vicente; Booser, Daniel J.; Esserman, Laura; Lluch, Ana; Vidaurre, Tatiana; Holmes, Frankie; Souchon, Eduardo; Martin, Miguel; Cotrina, José; Gomez, Henry; Hubbard, Rebekah; Chacón, J. Ignacio; Ferrer-Lozano, Jaime; Dyer, Richard; Buxton, Meredith; Gong, Yun; Wu, Yun; Ibrahim, Nuhad; Andreopoulou, Eleni; Ueno, Naoto T.; Hunt, Kelly; Yang, Wei; Nazario, Arlene; DeMichele, Angela; O’Shaughnessy, Joyce; Hortobagyi, Gabriel N.; Symmans, W. Fraser

2017-01-01

CONTEXT Accurate prediction of who will (or won’t) have high probability of survival benefit from standard treatments is fundamental for individualized cancer treatment strategies. OBJECTIVE To develop a predictor of response and survival from chemotherapy for newly diagnosed invasive breast cancer. DESIGN Development of different predictive signatures for resistance and response to neoadjuvant chemotherapy (stratified according to estrogen receptor (ER) status) from gene expression microarrays of newly diagnosed breast cancer (310 patients). Then prediction of breast cancer treatment-sensitivity using the combination of signatures for: 1) sensitivity to endocrine therapy, 2) chemo-resistance, and 3) chemo-sensitivity. Independent validation (198 patients) and comparison with other reported genomic predictors of chemotherapy response. SETTING Prospective multicenter study to develop and test genomic predictors for neoadjuvant chemotherapy. PATIENTS Newly diagnosed HER2-negative breast cancer treated with chemotherapy containing sequential taxane and anthracycline-based regimens then endocrine therapy (if hormone receptor-positive). MAIN OUTCOME MEASURES Distant relapse-free survival (DRFS) if predicted treatment-sensitive and absolute risk reduction (ARR, difference in DRFS of the two predicted groups) at median follow-up (3 years), and their 95% confidence intervals (CI). RESULTS Patients in the independent validation cohort (99% clinical Stage II–III) who were predicted to be treatment-sensitive (28% of total) had DRFS of 92% (CI 85–100) and survival benefit compared to others (absolute risk reduction (ARR) 18%; CI 6–28). Predictions were accurate if breast cancer was ER-positive (30% predicted sensitive, DRFS 97%, CI 91–100; ARR 11%, CI 0.1–21) or ER-negative (26% predicted sensitive, DRFS 83%, CI 68–100; ARR 26%, CI 4–28), and were significant in multivariate analysis after adjusting for relevant clinical-pathologic characteristics. Other

Time-dose considerations in the treatment of anal cancer

International Nuclear Information System (INIS)

Constantinou, Eugene C.; Daly, William; Fung, Claire Y.; Willett, Christopher G.; Kaufman, Donald S.; DeLaney, Thomas F.

1997-01-01

Purpose: To analyze the impact of patient and treatment parameters in concurrent chemoradiation treatment for anal carcinoma. Methods and Materials: Retrospective review of 50 MO anal cancer patients treated from 1984-1994. Most patients received concurrent 5-FU, mitomycin, and radiation. Local control and disease-free/overall survival were determined and analyzed according to patient and treatment parameters. Results: With 43 month median follow-up, projected overall survival is 66% at 5 and 8 years. Disease-free survival is 67% at 5 years and 59% at 8 years. Local control is 70% at 5 and 8 years. Doses of ≥54 Gy are associated with improved 5-year survival (84 vs. 47%, p = 0.02), disease-free survival (74 v. 56%, p = 0.09), and local control (77 vs. 61%, p = 0.04). Although local control, disease-free survival, and overall survival were improved in patients whose overall treatment time was <40 days, this was not statistically significant. Outcome in the four patients with pretreatment hemoglobin (Hgb) <10 appeared worse with 3-year overall survival 50 vs. 68% (p = 0.07), disease-free survival 0 vs. 67% (p = 0.11), and local control 0 vs. 74% (p = 0.05). Projected 5-year overall survival, relapse-free survival, and local control in 4 HIV (+) patients is 0, 75, and 75%. Multivariate analysis reveals that dose (p 0.02) and Hgb (p = 0.05) independently affect local control, dose (p = 0.02) affects disease-free survival, and dose (p = 0.01), Hgb (p = 0.03), T-stage (p = 0.03), and HIV-status (0.07) independently influence overall survival. Conclusion: Radiation doses of ≥54 Gy are associated with significantly improved survival and local control in anal cancer patients treated with chemoradiation. Overall treatment times of less than 40 days are associated with a trend towards improved outcome, but this is not significant. Pretreatment hemoglobin <10 is associated with worse treatment outcome. Survival of HIV (+) patient is poor, but the majority of such patients

Marital Status and Survival in Patients with Carcinoid Tumors.

Science.gov (United States)

Greenleaf, Erin K; Cooper, Amanda B; Hollenbeak, Christopher S

2016-01-01

Marital status is a known prognostic factor in overall and disease-specific survival in several types of cancer. The impact of marital status on survival in patients with carcinoid tumors remains unknown. We hypothesized that married patients have higher rates of survival than similar unmarried patients with carcinoid tumors. Using the Surveillance, Epidemiology, and End Results database, we identified 23,126 people diagnosed with a carcinoid tumor between 2000 and 2011 and stratified them according to marital status. Univariate and multivariable analyses were performed to compare the characteristics and outcomes between patient cohorts. Overall and cancer-related survival were analyzed using the Kaplan-Meier method. Multivariable survival analyses were performed using Cox proportional hazards models (hazards ratio [HR]), controlling for demographics and tumor-related and treatment-related variables. Propensity score analysis was performed to determine surgical intervention distributions among married and unmarried (ie, single, separated, divorced, widowed) patients. Marital status was significantly related to both overall and cancer-related survival in patients with carcinoid tumors. Divorced and widowed patients had worse overall survival (HR, 1.33 [95% confidence interval {CI}, 1.08-1.33] and 1.34 [95% CI, 1.22-1.46], respectively) and cancer-related survival (HR, 1.15 [95% CI, 1.00-1.31] and 1.15 [95% CI, 1.03-1.29], respectively) than married patients over five years. Single and separated patients had worse overall survival (HR, 1.20 [95% CI, 1.08-1.33] and 1.62 [95% CI, 1.25-2.11], respectively) than married patients over five years, but not worse cancer-related survival. Unmarried patients were more likely than matched married patients to undergo definitive surgical intervention (62.67% vs 53.11%, respectively, P married patients have a survival advantage after diagnosis of any carcinoid tumor, potentially reflecting better social support and financial means

Chemoradiotherapy of Anal Carcinoma: Survival and Recurrence in an Unselected National Cohort

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Bentzen, Anne Gry, E-mail: anne.gry.bentzen@unn.no [Department of Oncology, University Hospital of Northern Norway, Tromso (Norway); Institute of Clinical Medicine, University of Tromso, Tromso (Norway); Guren, Marianne G.; Wanderas, Eva H. [Department of Oncology, Oslo University Hospital, Oslo (Norway); Frykholm, Gunilla [Department of Oncology, St. Olav' s University Hospital, Trondheim, Norway and The Norwegian Radiation Protection Authority (NRPA), Osteras (Norway); Tveit, Kjell M. [Department of Oncology, Oslo University Hospital, Oslo (Norway); Faculty of Medicine, University of Oslo, Oslo (Norway); Wilsgaard, Tom [Department of Community Medicine, University of Tromso, Tromso (Norway); Dahl, Olav [Section of Oncology, Institute of Medicine, University of Bergen and Department of Oncology, Haukeland University Hospital, Bergen (Norway); Balteskard, Lise [Department of Oncology, University Hospital of Northern Norway, Tromso (Norway); Centre for Clinical Documentation and Evaluation, Northern Norway Regional Health Authority, Tromso (Norway)

2012-06-01

Purpose: To evaluate treatment results, elucidate whether national guidelines were followed, and identify areas demanding further treatment optimization. Methods and Material: Between July 2000 and June 2007, 328 patients were treated with curatively intended chemoradiotherapy (CRT) for nonmetastatic squamous cell carcinoma of the anal region, according to national treatment guidelines based on tumor stage. Results: Complete response after CRT was obtained in 87% of patients, rising to 93% after salvage surgery. Chemotherapy, elective irradiation of the groin and salvage surgery were performed to a lesser extent in elderly patients, mainly because of frailty and comorbidity. Recurrence occurred in 24% of the patients, resulting in a 3- and 5-year recurrence-free survival (RFS) of 79% and 74%, respectively. Locoregional recurrences dominated, most commonly in the primary tumor site. Recurrence was treated with curative intent in 45% of the cases. The 3- and 5-year overall survival were 79% and 66%, and cancer-specific survival (CSS) were 84% and 75%, respectively. The risk of adverse outcome increased significantly with more locally advanced tumors and for male gender in multivariable analyses for RFS and CSS. Conclusions: The treatment results are in accordance with similar cohorts. The primary treatment control rate was high, but there was a significant risk of locoregional recurrence in advanced tumors. The loyalty to national guidelines was broad, although individual adjustments occurred. However, caution to avoid toxicity must not lead to inadequate treatment. Male gender seems to have inferior outcome.

Chemoradiotherapy of Anal Carcinoma: Survival and Recurrence in an Unselected National Cohort

International Nuclear Information System (INIS)

Bentzen, Anne Gry; Guren, Marianne G.; Wanderås, Eva H.; Frykholm, Gunilla; Tveit, Kjell M.; Wilsgaard, Tom; Dahl, Olav; Balteskard, Lise

2012-01-01

Purpose: To evaluate treatment results, elucidate whether national guidelines were followed, and identify areas demanding further treatment optimization. Methods and Material: Between July 2000 and June 2007, 328 patients were treated with curatively intended chemoradiotherapy (CRT) for nonmetastatic squamous cell carcinoma of the anal region, according to national treatment guidelines based on tumor stage. Results: Complete response after CRT was obtained in 87% of patients, rising to 93% after salvage surgery. Chemotherapy, elective irradiation of the groin and salvage surgery were performed to a lesser extent in elderly patients, mainly because of frailty and comorbidity. Recurrence occurred in 24% of the patients, resulting in a 3- and 5-year recurrence-free survival (RFS) of 79% and 74%, respectively. Locoregional recurrences dominated, most commonly in the primary tumor site. Recurrence was treated with curative intent in 45% of the cases. The 3- and 5-year overall survival were 79% and 66%, and cancer-specific survival (CSS) were 84% and 75%, respectively. The risk of adverse outcome increased significantly with more locally advanced tumors and for male gender in multivariable analyses for RFS and CSS. Conclusions: The treatment results are in accordance with similar cohorts. The primary treatment control rate was high, but there was a significant risk of locoregional recurrence in advanced tumors. The loyalty to national guidelines was broad, although individual adjustments occurred. However, caution to avoid toxicity must not lead to inadequate treatment. Male gender seems to have inferior outcome.

Treatment planning with ion beams

International Nuclear Information System (INIS)

Foss, M.H.

1985-01-01

Ions have higher linear energy transfer (LET) near the end of their range and lower LET away from the end of their range. Mixing radiations of different LET complicates treatment planning because radiation kills cells in two statistically independent ways. In some cases, cells are killed by a single-particle, which causes a linear decrease in log survival at low dosage. When the linear decrease is subtracted from the log survival curve, the remaining curve has zero slope at zero dosage. This curve is the log survival curve for cells that are killed only by two or more particles. These two mechanisms are statistically independent. To calculate survival, these two kinds of doses must be accumulated separately. The effect of each accumulated dosage must be read from its survival curve, and the logarithms of the two effects added to get the log survival. Treatment plans for doses of protons, He 3 ions, and He 4 ions suggest that these ions will be useful therapeutic modalities

The Impact of Radiation Treatment Time on Survival in Patients With Head and Neck Cancer

International Nuclear Information System (INIS)

Shaikh, Talha; Handorf, Elizabeth A.; Murphy, Colin T.; Mehra, Ranee; Ridge, John A.; Galloway, Thomas J.

2016-01-01

Purpose: To assess the impact of radiation treatment time (RTT) in head and neck cancers on overall survival (OS) in the era of chemoradiation. Methods and Materials: Patients with diagnoses of tongue, hypopharynx, larynx, oropharynx, or tonsil cancer were identified by use of the National Cancer Database. RTT was defined as date of first radiation treatment to date of last radiation treatment. In the definitive setting, prolonged RTT was defined as >56 days, accelerated RTT was defined as 49 days, accelerated RTT was defined as <40 days, and standard RTT was defined as 40 to 49 days. We used χ"2 tests to identify predictors of RTT. The Kaplan-Meier method was used to compare OS among groups. Cox proportional hazards model was used for OS analysis in patients with known comorbidity status. Results: 19,531 patients were included; 12,987 (67%) had a standard RTT, 4,369 (34%) had an accelerated RTT, and 2,165 (11%) had a prolonged RTT. On multivariable analysis, accelerated RTT (hazard ratio [HR] 0.84; 95% confidence interval [CI] 0.73-0.97) was associated with an improved OS, and prolonged RTT (HR 1.25; 95% CI 1.14-1.37) was associated with a worse OS relative to standard RTT. When the 9,200 (47%) patients receiving definitive concurrent chemoradiation were examined, prolonged RTT (HR 1.29; 95% CI 1.11-1.50) was associated with a worse OS relative to standard RTT, whereas there was no significant association between accelerated RTT and OS (HR 0.76; 95% CI 0.57-1.01). Conclusion: Prolonged RTT is associated with worse OS in patients receiving radiation therapy for head and neck cancer, even in the setting of chemoradiation. Expeditious completion of radiation should continue to be a quality metric for the management of head and neck malignancies.

Chronic consequences of acute injuries: worse survival after discharge.

Science.gov (United States)

Shafi, Shahid; Renfro, Lindsay A; Barnes, Sunni; Rayan, Nadine; Gentilello, Larry M; Fleming, Neil; Ballard, David

2012-09-01

The Trauma Quality Improvement Program uses inhospital mortality to measure quality of care, which assumes patients who survive injury are not likely to suffer higher mortality after discharge. We hypothesized that survival rates in trauma patients who survive to discharge remain stable afterward. Patients treated at an urban Level I trauma center (2006-2008) were linked with the Social Security Administration Death Master File. Survival rates were measured at 30, 90, and 180 days and 1 and 2 years from injury among two groups of trauma patients who survived to discharge: major trauma (Abbreviated Injury Scale score ≥ 3 injuries, n = 2,238) and minor trauma (Abbreviated Injury Scale score ≤ 2 injuries, n = 1,171). Control groups matched to each trauma group by age and sex were simulated from the US general population using annual survival probabilities from census data. Kaplan-Meier and log-rank analyses conditional upon survival to each time point were used to determine changes in risk of mortality after discharge. Cox proportional hazards models with left truncation at the time of discharge were used to determine independent predictors of mortality after discharge. The survival rate in trauma patients with major injuries was 92% at 30 days posttrauma and declined to 84% by 3 years (p > 0.05 compared with general population). Minor trauma patients experienced a survival rate similar to the general population. Age and injury severity were the only independent predictors of long-term mortality given survival to discharge. Log-rank tests conditional on survival to each time point showed that mortality risk in patients with major injuries remained significantly higher than the general population for up to 6 months after injury. The survival rate of trauma patients with major injuries remains significantly lower than survival for minor trauma patients and the general population for several months postdischarge. Surveillance for early identification and treatment of