Sample records for actuarial progression-free survival

  1. Diminished Disease-Free Survival After Lobectomy: Screening Implications.

    PubMed

    Reich, Jerome M; Kim, Jong S; Asaph, James W

    2015-09-01

    The aim of this study was to estimate the effect of lobectomy on life expectancy in healthy smokers and consider the implications for lung cancer screening. In a retrospective cohort study that provided a minimum of 15 years of follow-up, we analyzed lung cancer survival, all-cause survival, and fatality (1-survival) of 261 persons with stage I non-small-cell lung cancer who underwent lobectomy at Portland Providence Medical Center between 1978 and 1994. We: (1) compared 5-year disease-free fatality (non-lung-cancer fatality) with lung cancer fatality; and (2) based on actuarial data that demonstrated life expectancy equivalence of the healthiest smokers (whom we assumed would be comparable with subjects judged eligible for lobectomy) in the US population, we compared their long-term, disease-free survival (our primary end point) with actuarial expectations by computing the Kaplan-Meier survival function of the differences between lifetimes since surgery in disease-free persons versus matched, expected remaining lifetimes in the US population. (1) Five-year disease-free fatality (16.1%) was 58% as high as 5-year lung cancer fatality (27.6%); (2) disease-free survival was reduced by 6.9-years (95% confidence interval, 5.5-8.3), 41% of actuarial life expectancy (17 years). The divergence from expected survival took place largely after 6 years of follow-up. Lobectomy materially diminishes long-term disease-free survival in the healthiest smokers--persons judged healthy enough to tolerate major surgery and to have sufficient pulmonary reserve to sustain loss of one-fifth of their lung tissue. In screened populations, diminished survival in overdiagnosed persons will offset, to an undetermined extent, the mortality benefit imparted by preemption of advanced lung cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Sorafenib improved progression-free survival in desmoid tumor study

    Cancer.gov

    In an NCI-funded trial for patients with desmoid tumors or aggressive fibromatosis (DT/DF), rare sarcomas with limited treatment options, the drug sorafenib tosylate (Nexavar) extended progression-free survival compared with a placebo.

  3. Therapeutic effect of apatinib on overall survival is mediated by prolonged progression-free survival in advanced gastric cancer patients

    PubMed Central

    Shen, Sipeng; Shi, Qianwen; Bai, Jianling; Li, Jin; Qin, Shukui; Yu, Hao; Chen, Feng

    2017-01-01

    Apatinib is reported to significantly improve the overall survival (OS) of patients with advanced gastric cancer who have previously failed second-line chemotherapy. However, it is not well understood whether apatinib acts by improving progression or by prolonging post-progression survival. Here, based on phase III clinical trial data, the mediating effect of apatinib on patient overall survival was systematically quantified, through progression-free survival (PFS), post-progression survival (PPS), and the disease control rate (DCR). PFS was the primary mediator of the association between apatinib treatment and OS, with an indirect-effect mean survival time ratio of 1.63 (95%CI 1.35-1.97), which mediated 93.5% of the treatment effect. The DCR was also a significant mediator among secondary efficacy endpoints, and had an indirect-effect mean survival time ratio of 1.47 (95%CI 1.20-1.79, 50.9% mediated). Both primary and other targets of the DCR had similar results. The results indicated that apatinib treatment prolongs progression-free survival rather than post-progression survival, and in turn, leads to improved overall survival. Additionally, our study highlights the value of mediation analysis in clinical trials in providing additional information to build upon traditional primary analysis. PMID:27793017

  4. Therapeutic effect of apatinib on overall survival is mediated by prolonged progression-free survival in advanced gastric cancer patients.

    PubMed

    Huang, Lihong; Wei, Yongyue; Shen, Sipeng; Shi, Qianwen; Bai, Jianling; Li, Jin; Qin, Shukui; Yu, Hao; Chen, Feng

    2017-04-25

    Apatinib is reported to significantly improve the overall survival (OS) of patients with advanced gastric cancer who have previously failed second-line chemotherapy. However, it is not well understood whether apatinib acts by improving progression or by prolonging post-progression survival. Here, based on phase III clinical trial data, the mediating effect of apatinib on patient overall survival was systematically quantified, through progression-free survival (PFS), post-progression survival (PPS), and the disease control rate (DCR). PFS was the primary mediator of the association between apatinib treatment and OS, with an indirect-effect mean survival time ratio of 1.63 (95%CI 1.35-1.97), which mediated 93.5% of the treatment effect. The DCR was also a significant mediator among secondary efficacy endpoints, and had an indirect-effect mean survival time ratio of 1.47 (95%CI 1.20-1.79, 50.9% mediated). Both primary and other targets of the DCR had similar results. The results indicated that apatinib treatment prolongs progression-free survival rather than post-progression survival, and in turn, leads to improved overall survival. Additionally, our study highlights the value of mediation analysis in clinical trials in providing additional information to build upon traditional primary analysis.

  5. Association between progression-free survival and health-related quality of life in oncology: a systematic review protocol.

    PubMed

    Kovic, Bruno; Guyatt, Gordon; Brundage, Michael; Thabane, Lehana; Bhatnagar, Neera; Xie, Feng

    2016-09-02

    There is an increasing number of new oncology drugs being studied, approved and put into clinical practice based on improvement in progression-free survival, when no overall survival benefits exist. In oncology, the association between progression-free survival and health-related quality of life is currently unknown, despite its importance for patients with cancer, and the unverified assumption that longer progression-free survival indicates improved health-related quality of life. Thus far, only 1 study has investigated this association, providing insufficient evidence and inconclusive results. The objective of this study protocol is to provide increased transparency in supporting a systematic summary of the evidence bearing on this association in oncology. Using the OVID platform in MEDLINE, Embase and Cochrane databases, we will conduct a systematic review of randomised controlled human trials addressing oncology issues published starting in 2000. A team of reviewers will, in pairs, independently screen and abstract data using standardised, pilot-tested forms. We will employ numerical integration to calculate mean incremental area under the curve between treatment groups in studies for health-related quality of life, along with total related error estimates, and a 95% CI around incremental area. To describe the progression-free survival to health-related quality of life association, we will construct a scatterplot for incremental health-related quality of life versus incremental progression-free survival. To estimate the association, we will use a weighted simple regression approach, comparing mean incremental health-related quality of life with either median incremental progression-free survival time or the progression-free survival HR, in the absence of overall survival benefit. Identifying direction and magnitude of association between progression-free survival and health-related quality of life is critically important in interpreting results of oncology

  6. Association between progression-free survival and health-related quality of life in oncology: a systematic review protocol

    PubMed Central

    Kovic, Bruno; Guyatt, Gordon; Brundage, Michael; Thabane, Lehana; Bhatnagar, Neera; Xie, Feng

    2016-01-01

    Introduction There is an increasing number of new oncology drugs being studied, approved and put into clinical practice based on improvement in progression-free survival, when no overall survival benefits exist. In oncology, the association between progression-free survival and health-related quality of life is currently unknown, despite its importance for patients with cancer, and the unverified assumption that longer progression-free survival indicates improved health-related quality of life. Thus far, only 1 study has investigated this association, providing insufficient evidence and inconclusive results. The objective of this study protocol is to provide increased transparency in supporting a systematic summary of the evidence bearing on this association in oncology. Methods and analysis Using the OVID platform in MEDLINE, Embase and Cochrane databases, we will conduct a systematic review of randomised controlled human trials addressing oncology issues published starting in 2000. A team of reviewers will, in pairs, independently screen and abstract data using standardised, pilot-tested forms. We will employ numerical integration to calculate mean incremental area under the curve between treatment groups in studies for health-related quality of life, along with total related error estimates, and a 95% CI around incremental area. To describe the progression-free survival to health-related quality of life association, we will construct a scatterplot for incremental health-related quality of life versus incremental progression-free survival. To estimate the association, we will use a weighted simple regression approach, comparing mean incremental health-related quality of life with either median incremental progression-free survival time or the progression-free survival HR, in the absence of overall survival benefit. Discussion Identifying direction and magnitude of association between progression-free survival and health-related quality of life is critically

  7. Zoledronic acid in metastatic osteosarcoma: encouraging progression free survival in four consecutive patients.

    PubMed

    Conry, Robert M; Rodriguez, Michael G; Pressey, Joseph G

    2016-01-01

    Zoledronic acid (ZA) is a third-generation bisphosphonate in widespread clinical use to reduce pain and skeletal events in patients from a variety of malignancies with bone metastases. Pre-clinical studies indicate that ZA inhibits osteosarcoma through direct anti-proliferative effects, immune activation and anti-angiogenic activity. The purpose of this study was to evaluate the antitumor efficacy of ZA at standard dose until progression in patients with stage IV osteosarcoma lacking a standard of care treatment option proven to influence survival. Researchers retrospectively reviewed medical records of all patients at our institution with high-grade osteosarcoma presumed to be incurable due to metastases progressive after primary combination chemotherapy who received single agent ZA in an effort to delay progression. In our four-patient cohort following initiation of ZA, the median progression-free survival was 19 months, and median overall survival was 56+ months. Two of four patients have remained progression-free since starting ZA. The other two initially progressed after 18-20 months on ZA followed by metastasectomy of lung or dural metastases and further stability for over a year following resumption of ZA. After a 20-month progression-free interval on ZA alone, one patient had partial response following addition of pazopanib to ZA that likely contributed to long term disease control. The four patients experienced no significant toxicities despite protracted dosing of ZA for up to 5 years, and none have required chemotherapy since beginning ZA. Single agent ZA was associated with encouraging progression-free survival in four consecutive patients with metastatic osteosarcoma. Prospective trials of single agent ZA are warranted as protracted maintenance therapy in surgically incurable osteosarcoma relapsed or refractory to first line combination chemotherapy with radiographically measurable metastases.

  8. Progression-free survival as a primary endpoint in clinical trials of metastatic colorectal cancer

    PubMed Central

    Gill, S.; Berry, S.; Biagi, J.; Butts, C.; Buyse, M.; Chen, E.; Jonker, D.; Mărginean, C.; Samson, B.; Stewart, J.; Thirlwell, M.; Wong, R.; Maroun, J.A.

    2011-01-01

    In recent years, significant advances have been made in the management of metastatic colorectal cancer. Traditionally, an improvement in overall survival has been considered the “gold standard”—the most convincing measure of efficacy. However, overall survival requires larger patient numbers and longer follow-up and may often be confounded by other factors, including subsequent therapies and crossover. Given the number of active therapies for potential investigation, demand for rapid evaluation and early availability of new therapies is growing. Progression-free survival is regarded as an important measure of treatment benefit and, compared with overall survival, can be evaluated earlier, with fewer patients and no confounding by subsequent lines of therapy. The present paper reviews the advantages, limitations, and relevance of progression-free survival as a primary endpoint in randomized trials of metastatic colorectal cancer. PMID:21969810

  9. Sunitinib-induced hypothyroidism predicts progression-free survival in metastatic renal cell carcinoma patients.

    PubMed

    Buda-Nowak, Anna; Kucharz, Jakub; Dumnicka, Paulina; Kuzniewski, Marek; Herman, Roman Maria; Zygulska, Aneta L; Kusnierz-Cabala, Beata

    2017-04-01

    Sunitinib is a tyrosine kinase inhibitor (TKI) used in treatment of metastatic renal cell carcinoma (mRCC), gastrointestinal stromal tumors and pancreatic neuroendocrine tumors. One of the most common side effects related to sunitinib is hypothyroidism. Recent trials suggest correlation between the incidence of hypothyroidism and treatment outcome in patients treated with TKI. This study evaluates whether development of hypothyroidism is a predictive marker of progression-free survival (PFS) in patients with mRCC treated with sunitinib. Twenty-seven patients diagnosed with clear cell mRCC, after nephrectomy and in 'good' or 'intermediate' MSKCC risk prognostic group, were included in the study. All patients received sunitinib as a first-line treatment on a standard schedule (initial dose 50 mg/day, 4 weeks on, 2 weeks off). The thyroid-stimulating hormone serum levels were obtained at the baseline and every 12 weeks of treatment. In statistic analyses, we used Kaplan-Meier method for assessment of progression-free survival; for comparison of survival, we used log-rank test. In our study, the incidence of hypothyroidism was 44%. The patients who had developed hypothyroidism had better median PFS to patients with normal thyroid function 28,3 months [95% (CI) 20.4-36.2 months] versus 9.8 months (6.4-13.1 months). In survival analysis, we perceive that thyroid dysfunction is a predictive factor of a progression-free survival (PFS). In the unified group of patients, the development of hypothyroidism during treatment with sunitinib is a positive marker for PFS. During that treatment, thyroid function should be evaluated regularly.

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

    PubMed

    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.

  11. Plasma Cytokines Correlated With Disease Characteristics, Progression-Free Survival, and Overall Survival in Testicular Germ-Cell Tumor Patients.

    PubMed

    Svetlovska, Daniela; Miskovska, Viera; Cholujova, Dana; Gronesova, Paulina; Cingelova, Silvia; Chovanec, Michal; Sycova-Mila, Zuzana; Obertova, Jana; Palacka, Patrik; Rajec, Jan; Kalavska, Katarina; Usakova, Vanda; Luha, Jan; Ondrus, Dalibor; Spanik, Stanislav; Mardiak, Jozef; Mego, Michal

    2017-06-01

    Cytokines are the communicators of immune system and are involved in all immune responses. The aim of this study was to assess the correlation among plasma cytokines, patient and tumor characteristics, and clinical outcome in chemonaive testicular germ-cell tumor (TGCT) patients. This study included 92 metastatic chemotherapy-naive TGCT patients treated with platinum-based chemotherapy from July 2010 to March 2014. Plasma was isolated before first administration of chemotherapy, and the concentration of 51 plasma cytokines were analyzed using multiplex bead arrays. At a median follow-up of 33.2 months (range, 0.1-54.8 months), 10.9% of patients experienced disease progression, and 7.6% died. Several cytokines were associated with different baseline clinicopathologic features. Elevated plasma levels of interferon (IFN)-α2, interleukin (IL)-2Rα, IL-16, hepatocyte growth factor (HGF), and monocyte chemotactic protein (MCP)-3 were significantly associated with worse progression-free survival and overall survival (OS). Moreover, elevated levels of stem-cell growth factor (SCGF)-β were also associated with worse OS. Patients with elevated levels of all 6 cytokines experienced significantly worse outcomes compared to patients who had fewer than 6 cytokines elevated (hazard ratio = 12.06; 95% confidence interval, 7.39-19.49; P = .002 for progression-free survival, and hazard ratio = 39.65; 95% confidence interval, 25.03-62.18; P < .00001 for OS, respectively). Results were independent of International Germ Cell Cancer Collaborative Group criteria. We found a correlation among progression free-survival, OS, and circulating cytokines in TGCT. This suggests the existence an association between plasma cytokines and baseline clinicopathologic features in TGCT. Plasma cytokines could be used for identification of high-risk patients who are candidates for new therapeutic approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. [Survival functions and life tables at the origins of actuarial mathematics].

    PubMed

    Spelta, D

    1997-01-01

    "In the determination of death probabilities of an insured subject one can use either statistical data or a mathematical function. In this paper a survey of the relationship between mortality tables and survival functions from the origins until the first half of the nineteenth century is presented. The author has tried to find the methodological grounds which have induced the actuaries to prefer either of these tools." (EXCERPT)

  13. Association of surgical approach with complication rate, progression-free survival time, and disease-specific survival time in cats with mammary adenocarcinoma: 107 cases (1991-2014).

    PubMed

    Gemignani, Francesco; Mayhew, Philipp D; Giuffrida, Michelle A; Palaigos, Jason; Runge, Jeffrey J; Holt, David E; Robertson, Nicholas A; Seguin, Bernard; Walker, Meaghan; Singh, Ameet; Liptak, Julius M; Romanelli, Giorgio; Martano, Marina; Boston, Sarah E; Lux, Cassie; Busetto, Roberto; Culp, William T N; Skorupski, Katherine A; Burton, Jenna H

    2018-06-01

    OBJECTIVE To evaluate potential associations between surgical approach and complication rate, progression-free survival time, and disease-specific survival time in cats with mammary adenocarcinoma. DESIGN Retrospective case series. ANIMALS 107 client-owned cats. PROCEDURES Medical records of cats that underwent surgical excision of mammary adenocarcinoma by means of a unilateral or bilateral (staged or single-session) mastectomy at 9 hospitals between 1991 and 2014 were reviewed. Relevant clinicopathologic data and details of surgical and adjuvant treatments were recorded. Outcome data were obtained, including postoperative complications, progression-free survival time, and disease-specific survival time. RESULTS Complications occurred in 12 of 61 (19.7%) cats treated with unilateral mastectomy, 5 of 14 (35.7%) cats treated with staged bilateral mastectomy, and 13 of 32 (40.6%) cats treated with single-session bilateral mastectomy. Complications were significantly more likely to occur in cats undergoing bilateral versus unilateral mastectomy. Median progression-free survival time was longer for cats treated with bilateral mastectomy (542 days) than for cats treated with unilateral mastectomy (289 days). Significant risk factors for disease progression included unilateral mastectomy, tumor ulceration, lymph node metastasis, and tumors arising in the fourth mammary gland. Significant risk factors for disease-specific death included lymph node metastasis and development of regional or distant metastasis. Among cats that did not develop metastasis, unilateral mastectomy was a significant risk factor for disease-specific death. Treatment with chemotherapy was associated with a significantly decreased risk of disease-specific death. CONCLUSIONS AND CLINICAL RELEVANCE Results supported bilateral mastectomy for the treatment of mammary adenocarcinoma in cats to improve progression-free and disease-specific survival time. Performing bilateral mastectomy in a staged fashion

  14. Underlying theory of actuarial analyses.

    PubMed

    Benjamin, B

    1985-05-01

    The developments in theory governing the calculation of mortality rates for use in survival measurements working through the initial basic concept of exposure to risk to the later introduction of stochastic elements are reviewed. I have indicated the way in which actuaries and statisticians who work closely with those in the fields of medicine and biology have, by the exchange of methodologic ideas, come to an identity of approach. Recent new actuarial work and likely future developments in actuarial interests are reviewed.

  15. An audit strategy for progression-free survival

    PubMed Central

    Dodd, Lori E.; Korn, Edward L.; Freidlin, Boris; Gray, Robert; Bhattacharya, Suman

    2010-01-01

    Summary In randomized clinical trials, the use of potentially subjective endpoints has led to frequent use of blinded independent central review (BICR) and event adjudication committees to reduce possible bias in treatment effect estimators based on local evaluations (LE). In oncology trials, progression-free survival (PFS) is one such endpoint. PFS requires image interpretation to determine whether a patient’s cancer has progressed, and BICR has been advocated to reduce the potential for endpoints to be biased by knowledge of treatment assignment. There is current debate, however, about the value of such reviews with time-to-event outcomes like PFS. We propose a BICR audit strategy as an alternative to a complete-case BICR to provide assurance of the presence of a treatment effect. We develop an auxiliary-variable estimator of the log-hazard ratio that is more efficient than simply using the audited (i.e., sampled) BICR data for estimation. Our estimator incorporates information from the LE on all the cases and the audited BICR cases, and is an asymptotically unbiased estimator of the log-hazard ratio from BICR. The estimator offers considerable efficiency gains that improve as the correlation between LE and BICR increases. A two-stage auditing strategy is also proposed and evaluated through simulation studies. The method is applied retrospectively to a large oncology trial that had a complete-case BICR, showing the potential for efficiency improvements. PMID:21210772

  16. Autologous stem cell transplantation in first complete remission may not extend progression-free survival in patients with peripheral T cell lymphomas.

    PubMed

    Yam, Clinton; Landsburg, Daniel J; Nead, Kevin T; Lin, Xinyi; Mato, Anthony R; Svoboda, Jakub; Loren, Alison W; Frey, Noelle V; Stadtmauer, Edward A; Porter, David L; Schuster, Stephen J; Nasta, Sunita D

    2016-07-01

    Patients with peripheral T cell lymphomas (PTCL) generally have a poor prognosis when treated with conventional chemotherapy. Consolidation with autologous stem cell transplantation (ASCT) has been reported to improve progression-free survival. However, these studies have not compared consolidative ASCT with active observation in patients with PTCL achieving first complete remission (CR1) following induction chemotherapy. We conducted a retrospective analysis of PTCL patients treated at the University of Pennsylvania between 1/1/2007 and 12/31/2014. Patients with cutaneous T cell lymphoma, concurrent B cell lymphomas, and anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK-positive ALCL) were excluded from the study. We compared progression-free survival for patients who underwent ASCT in CR1 following CHOP-like induction regimens and patients who underwent active observation during CR1. 48 patients met all inclusion and exclusion criteria and underwent either active observation (28 patients) or consolidative ASCT (20 patients) in CR1. The 1-year cumulative incidence of relapse in the observation and ASCT groups was 50% (95% confidence interval [CI]: 30-67%) and 46% (95% CI: 23-67%), respectively (P = 0.55). Median progression-free survival in the observation and ASCT groups was 15.8 and 12.8 months, respectively (log rank, P = 0.79). Estimated 3-year progression-free survival in the observation and ASCT groups was 37 and 41%, respectively. In conclusion, for PTCL patients achieving CR1 following CHOP-like induction chemotherapy, ASCT does not appear to improve progression-free survival compared to active observation. This finding should be confirmed in a larger, prospective study. Am. J. Hematol. 91:672-676, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Hepatic Progression-free and Overall Survival After Regional Therapy to the Liver for Metastatic Melanoma.

    PubMed

    Abbott, Andrea M; Doepker, Matthew P; Kim, Youngchul; Perez, Matthew C; Gandle, Cassandra; Thomas, Kerry L; Choi, Junsung; Shridhar, Ravi; Zager, Jonathan S

    2017-01-04

    Regional therapy for metastatic melanoma to the liver represents an alternative to systemic therapy. Hepatic progression-free survival (HPFS), progression-free survival (PFS), and overall survival (OS) were evaluated. A retrospective review of patients with liver metastases from cutaneous or uveal melanoma treated with yttrium-90 (Y90), chemoembolization (CE), or percutaneous hepatic perfusion (PHP) was conducted. Thirty patients (6 Y90, 10 PHP, 12 CE, 1 PHP then Y90, 1 CE then PHP) were included. Multivariate analysis showed improved HPFS for PHP versus Y90 (P=0.004), PHP versus CE (P=0.02) but not for CE versus Y90. PFS was also significantly different: Y90 (54 d), CE (52 d), PHP (245 d), P=0.03. PHP treatment and lower tumor burden were significant predictors of prolonged PFS on multivariate analysis. Median OS from time of treatment was longest, but not significant, for PHP at 608 days versus Y90 (295 d) and CE (265 d), P=0.24. Only PHP treatment versus Y90 and lower tumor burden had improved OS on multivariate analysis (P=0.03, 0.03, respectively). HPFS and PFS were significantly prolonged in patients treated with PHP versus CE or Y90. Median OS in PHP patients was over double that seen in Y90 or CE patients but was significant only between PHP and Y90.

  18. PSA nadir as a predictive factor for biochemical disease-free survival and overall survival following whole-gland salvage HIFU following radiotherapy failure.

    PubMed

    Shah, T T; Peters, M; Kanthabalan, A; McCartan, N; Fatola, Y; van der Voort van Zyp, J; van Vulpen, M; Freeman, A; Moore, C M; Arya, M; Emberton, M; Ahmed, H U

    2016-09-01

    Treatment options for radio-recurrent prostate cancer are either androgen-deprivation therapy or salvage prostatectomy. Whole-gland high-intensity focussed ultrasound (HIFU) might have a role in this setting. An independent HIFU registry collated consecutive cases of HIFU. Between 2005 and 2012, we identified 50 men who underwent whole-gland HIFU following histological confirmation of localised disease following prior external beam radiotherapy (2005-2012). No upper threshold was applied for risk category, PSA or Gleason grade either at presentation or at the time of failure. Progression was defined as a composite with biochemical failure (Phoenix criteria (PSA>nadir+2 ng ml(-1))), start of systemic therapies or metastases. Median age (interquartile range (IQR)), pretreatment PSA (IQR) and Gleason score (range) were 68 years (64-72), 5.9 ng ml(-1) (2.2-11.3) and 7 (6-9), respectively. Median follow-up was 64 months (49-84). In all, 24/50 (48%) avoided androgen-deprivation therapies. Also, a total of 28/50 (56%) achieved a PSA nadir <0.5 ng ml(-1), 15/50 (30%) had a nadir ⩾0.5 ng ml(-1) and 7/50 (14%) did not nadir (PSA non-responders). Actuarial 1, 3 and 5-year progression-free survival (PFS) was 72, 40 and 31%, respectively. Actuarial 1, 3 and 5-year overall survival (OS) was 100, 94 and 87%, respectively. When comparing patients with PSA nadir <0.5 ng ml(-1), nadir ⩾0.5 and non-responders, a statistically significant difference in PFS was seen (P<0.0001). Three-year PFS in each group was 57, 20 and 0%, respectively. Five-year OS was 96, 100 and 38%, respectively. Early in the learning curve, between 2005 and 2007, 3/50 (6%) developed a fistula. Intervention for bladder outlet obstruction was needed in 27/50 (54%). Patient-reported outcome measure questionnaires showed incontinence (any pad-use) as 8/26 (31%). In our series of high-risk patients, in whom 30-50% may have micro-metastases, disease control rates were promising in PSA

  19. PSA response to cabazitaxel is associated with improved progression-free survival in metastatic castration-resistant prostate cancer: the non-interventional QoLiTime study.

    PubMed

    Hammerer, Peter; Al-Batran, Salah-Eddin; Windemuth-Kieselbach, Christine; Keller, Martin; Hofheinz, Ralf-Dieter

    2018-03-01

    To evaluate the association between prostate-specific antigen (PSA) response and progression-free and overall survival in men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel. Men with mCRPC receiving cabazitaxel (25 mg/m 2 , every 3 weeks) plus oral prednis(ol)one (10 mg/day) were enrolled in the non-interventional, prospective QoLiTime study. Main outcome measures were progression-free survival and overall survival, in all patients and in those who showed a ≥ 50 or a ≥ 30% decrease in PSA relative to baseline after four cycles of cabazitaxel, as well as quality-of-life parameters. Of the 527 men (median age 72 years), 266 received ≥ 4 cycles of cabazitaxel and had PSA response data. After four cycles, 34.6% of men achieved a PSA decrease ≥ 50% and 49.6% a decrease ≥ 30%. Median progression-free survival was 7.7 (95% CI 6.2, 9.5) months, and overall survival was 19.5 (95% CI 16.0, 30.9) months, corresponding to 1-year event rates of 39.4 and 78.8%, respectively. Median progression-free survival was longer in PSA responders versus non-responders (15.7 vs 5.5 months at 50% cut-off; 15.7 vs 5.3 months for 30% cut-off; both P < 0.0001). Overall survival (50% cut-off) was 23.3 months in responders and 16.0 months in non-responders (P = 0.068); corresponding data at the 30% cut-off are 21.7 and 16.0 months (P = 0.057). Overall, 55.4% of men experienced ≥ 1 adverse event, 59.6% of whom had a serious adverse event. PSA response after four cycles of cabazitaxel is associated with improved progression-free survival in men with mCRPC treated with cabazitaxel plus prednis(ol)one.

  20. Combined high-field intraoperative magnetic resonance imaging and endoscopy increase extent of resection and progression-free survival for pituitary adenomas

    PubMed Central

    Sylvester, Peter T.; Evans, John A.; Zipfel, Gregory J.; Chole, Richard A.; Uppaluri, Ravindra; Haughey, Bruce H.; Getz, Anne E.; Silverstein, Julie; Rich, Keith M.; Kim, Albert H.; Dacey, Ralph G.

    2014-01-01

    Purpose The clinical benefit of combined intraoperative magnetic resonance imaging (iMRI) and endoscopy for transsphenoidal pituitary adenoma resection has not been completely characterized. This study assessed the impact of microscopy, endoscopy, and/or iMRI on progression-free survival, extent of resection status (gross-, near-, and subtotal resection), and operative complications. Methods Retrospective analyses were performed on 446 transsphenoidal pituitary adenoma surgeries at a single institution between 1998 and 2012. Multivariate analyses were used to control for baseline characteristics, differences during extent of resection status, and progression-free survival analysis. Results Additional surgery was performed after iMRI in 56/156 cases (35.9 %), which led to increased extent of resection status in 15/156 cases (9.6 %). Multivariate ordinal logistic regression revealed no increase in extent of resection status following iMRI or endoscopy alone; however, combining these modalities increased extent of resection status (odds ratio 2.05, 95 % CI 1.21–3.46) compared to conventional transsphenoidal microsurgery. Multivariate Cox regression revealed that reduced extent of resection status shortened progression-free survival for near- versus gross-total resection [hazard ratio (HR) 2.87, 95 % CI 1.24–6.65] and sub- versus near-total resection (HR 2.10; 95 % CI 1.00–4.40). Complication comparisons between microscopy, endoscopy, and iMRI revealed increased perioperative deaths for endoscopy versus microscopy (4/209 and 0/237, respectively), but this difference was non-significant considering multiple post hoc comparisons (Fisher exact, p = 0.24). Conclusions Combined use of endoscopy and iMRI increased pituitary adenoma extent of resection status compared to conventional transsphenoidal microsurgery, and increased extent of resection status was associated with longer progression-free survival. Treatment modality combination did not significantly impact

  1. A review of statistical issues with progression-free survival as an interval-censored time-to-event endpoint.

    PubMed

    Sun, Xing; Li, Xiaoyun; Chen, Cong; Song, Yang

    2013-01-01

    Frequent rise of interval-censored time-to-event data in randomized clinical trials (e.g., progression-free survival [PFS] in oncology) challenges statistical researchers in the pharmaceutical industry in various ways. These challenges exist in both trial design and data analysis. Conventional statistical methods treating intervals as fixed points, which are generally practiced by pharmaceutical industry, sometimes yield inferior or even flawed analysis results in extreme cases for interval-censored data. In this article, we examine the limitation of these standard methods under typical clinical trial settings and further review and compare several existing nonparametric likelihood-based methods for interval-censored data, methods that are more sophisticated but robust. Trial design issues involved with interval-censored data comprise another topic to be explored in this article. Unlike right-censored survival data, expected sample size or power for a trial with interval-censored data relies heavily on the parametric distribution of the baseline survival function as well as the frequency of assessments. There can be substantial power loss in trials with interval-censored data if the assessments are very infrequent. Such an additional dependency controverts many fundamental assumptions and principles in conventional survival trial designs, especially the group sequential design (e.g., the concept of information fraction). In this article, we discuss these fundamental changes and available tools to work around their impacts. Although progression-free survival is often used as a discussion point in the article, the general conclusions are equally applicable to other interval-censored time-to-event endpoints.

  2. Prognosis of patients after open mitral commissurotomy. Actuarial analysis of late results in 100 patients.

    PubMed

    Housman, L B; Bonchek, L; Lambert, L; Grunkemeier, G; Starr, A

    1977-05-01

    The continuing controversy between proponents of open and closed commissurotomy might be clarified by analysis of late follow-up with modern actuarial techniques that provide a true perspective of patient risk. We have used open mitral commissurotomy exclusively for 15 years in 100 patients. There was one operative death from pancreatitis and one late death from cancer; the actuarially projected survival rate (+/- the standard error) at 10 years is 97 per cent (+/- 2). Thirteen patients had preoperative emboli, 6 of whom were in sinus rhythm and 7 in atrial fibrillation. Two patients had postoperative emboli, both in sinus rhythm. The actuarial chance of remaining free of embolism at 10 years is 97 per cent (+/- 2). Sixteen patients required reoperation on the mitral valve for functional deterioration. The remaining survivors were in Class I or II when last seen. The actuarial chance of not requiring a reoperation after 5 years is 91 per cent (+/- 4) and at 10 years, 38 per cent(+/- 16). Results in different centers are difficult to compare for many reasons, but imprecise statistical methods further obscure such comparisons. The use of actuarial techniques may help to define the role of open mitral commissurotomy.

  3. Progression-free survival/time to progression as a potential surrogate for overall survival in HR+, HER2- metastatic breast cancer.

    PubMed

    Forsythe, Anna; Chandiwana, David; Barth, Janina; Thabane, Marroon; Baeck, Johan; Tremblay, Gabriel

    2018-01-01

    Several recent randomized controlled trials (RCTs) in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) have demonstrated significant improvements in progression-free survival (PFS); however, few have reported improvement in overall survival (OS). The surrogacy of PFS or time to progression (TTP) for OS has not been formally investigated in HR+, HER2- MBC. A systematic literature review of RCTs in HR+, HER2- MBC was conducted to identify studies that reported both median PFS/TTP and OS. The correlation between PFS/TTP and OS was evaluated using Pearson's product-moment correlation and Spearman's rank correlation. Subgroup analyses were performed to explore possible reasons for heterogeneity. Errors-in-variables weighted least squares regression (LSR) was used to model incremental OS months as a function of incremental PFS/TTP months. An exploratory analysis investigated the impact of three covariates (chemotherapy vs hormonal/targeted therapy, PFS vs TTP, and first-line therapy vs second-line therapy or greater) on OS prediction. The lower 95% prediction band was used to determine the minimum incremental PFS/TTP months required to predict OS benefit (surrogate threshold effect [STE]). Forty studies were identified. There was a statistically significant correlation between median PFS/TTP and OS (Pearson =0.741, P =0.000; Spearman =0.650, P =0.000). These results proved consistent for chemotherapy and hormonal/targeted therapy. Univariate LSR analysis yielded an R 2 of 0.354 with 1 incremental PFS/TTP month corresponding to 1.13 incremental OS months. Controlling the type of treatment (chemotherapy vs hormonal/targeted therapy), line of therapy (first vs subsequent), and progression measure (PFS vs TTP) led to an improved R 2 of 0.569 with 1 PFS/TTP month corresponding to 0.78 OS months. The STE for OS benefit was 5-6 months of incremental PFS/TTP. We demonstrated a significant association

  4. Split-course, high-dose palliative pelvic radiotherapy for locally progressive hormone-refractory prostate cancer.

    PubMed

    Gogna, Nirdosh Kumar; Baxi, Siddhartha; Hickey, Brigid; Baumann, Kathryn; Burmeister, Elizabeth; Holt, Tanya

    2012-06-01

    Local progression, in patients with hormone-refractory prostate cancer, often causes significant morbidity. Pelvic radiotherapy (RT) provides effective palliation in this setting, with most published studies supporting the use of high-dose regimens. The aim of the present study was to examine the role of split-course hypofractionated RT used at our institution in treating this group of patients. A total of 34 men with locoregionally progressive hormone-refractory prostate cancer, treated with a split course of pelvic RT (45-60 Gy in 18-24 fractions) between 2000 and 2008 were analyzed. The primary endpoints were the response rate and actuarial locoregional progression-free survival. Secondary endpoints included overall survival, compliance, and acute and late toxicity. The median age was 71 years (range, 53-88). Treatment resulted in an overall initial response rate of 91%, a median locoregional progression-free survival of 43 months, and median overall survival of 28 months. Compliance was excellent and no significant late toxicity was reported. The split course pelvic RT described has an acceptable toxicity profile, is effective, and compares well with other high-dose palliative regimens that have been previously reported. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. The Casualty Actuarial Society: Helping Universities Train Future Actuaries

    ERIC Educational Resources Information Center

    Boa, J. Michael; Gorvett, Rick

    2014-01-01

    The Casualty Actuarial Society (CAS) believes that the most effective way to advance the actuarial profession is to work in partnership with universities. The CAS stands ready to assist universities in creating or enhancing courses and curricula associated with property/casualty actuarial science. CAS resources for university actuarial science…

  6. Evaluation of Overall Response Rate and Progression-Free Survival as Potential Surrogate Endpoints for Overall Survival in Immunotherapy Trials.

    PubMed

    Mushti, Sirisha L; Mulkey, Flora; Sridhara, Rajeshwari

    2018-05-15

    Purpose: With the approval of immunotherapies for a variety of indications, methods to assess treatment benefit addressing the response patterns observed are important. We evaluated RECIST criteria-based overall response rate (ORR) and progression-free survival (PFS) as potential surrogate endpoints of overall survival (OS), and explored a modified definition of PFS by altering the threshold percentage determining disease progression to assess the association with survival benefit in immunotherapy trials. Experimental Design: Thirteen randomized, multicenter, active-control trials containing immunotherapeutic agents submitted to the FDA were analyzed. Associations between treatment effects of ORR, PFS, modified PFS, and OS were evaluated at individual and trial levels. Patient-level responder analysis was performed for PFS and OS. Results: The coefficient of determination ( R ²) measured the strength of associations, where values near 1 imply surrogacy and values close to 0 suggest no association. At the trial level, the association between hazard ratios (HR) of PFS and OS was R 2 = 0.1303, and between the odds ratio (OR) of ORR and HR of OS was R 2 = 0.1277. At the individual level, the Spearman rank correlation coefficient between PFS and OS was 0.61. Trial-level associations between modified PFS and OS ranged between 0.07 and 0.1, and individual-level correlations were approximately 0.6. HRs of PFS and OS for responders versus nonresponders were 0.129 [95% confidence interval (CI), 0.11-0.15] and 0.118 (95% CI, 0.11-0.13), respectively. Conclusions: Although responders exhibited longer survival and PFS than nonresponders, the trial-level and individual-level associations were weak between PFS/ORR and OS. Modifications to PFS did not improve associations. Clin Cancer Res; 24(10); 2268-75. ©2018 AACR See related commentary by Korn and Freidlin, p. 2239 . ©2018 American Association for Cancer Research.

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

    PubMed

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

    2013-01-01

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

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

    PubMed

    Forsythe, Anna; Chandiwana, David; Barth, Janina; Thabane, Marroon; Baeck, Johan; Shor, Anastasiya; Tremblay, Gabriel

    2018-01-01

    Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), metastatic breast cancer (MBC) accounts for 73% of all MBCs. Endocrine therapy (ET) is the basis of first-line (1L) therapy for patients with HR+/HER2- MBC. Novel therapies have demonstrated improvements in progression-free survival (PFS) compared to ET. The clinical relevance of PFS is being debated, as there is no proven direct correlation with overall survival (OS) benefit to date. We reviewed studies of HR+/HER2- MBC to assess PFS and other factors that influence OS and treatment response, and health-related quality of life (HRQoL). The Embase ® , Medline ® , and Cochrane databases were systematically searched to identify studies in adult women with HR+/HER2- MBC, published between January 2006 and January 2017, and written in English. Phase II and III randomized controlled trials (RCTs), observational, and retrospective studies were included. Seventy-nine RCTs were identified: 58 (73%) in the 1L+ setting and 21 (27%) in second-line or greater settings. PFS hazard ratios (HRs) were reported in 61 (77%) studies; 31 (39%) reported significant PFS improvements. OS was reported in 44 (41%) studies; 12 (15%) reported significant OS improvements. Significant improvements in both PFS and OS were reported in only 6 (8%) studies (1 Phase II; 5 Phase III). Patients with HER2- MBC received, on average, ≥5 lines of therapy, with no consistent treatment pathway. Baseline characteristics, prior therapies, and the type and number of post-progression therapies significantly impacted OS. PFS, response rates, and HRQoL decreased with each line of therapy (EuroQol 5 Dimensions: 0.78 1L vs. 0.70 post-progression). Few RCTs in HR+/HER2- MBC have demonstrated significant improvements in OS. Factors other than choice of 1L therapy impact OS, including post-progression therapies, which cannot be controlled in RCTs. This study emphasizes the importance of PFS improvement in 1L treatment of

  9. Embolotherapy for Neuroendocrine Tumor Liver Metastases: Prognostic Factors for Hepatic Progression-Free Survival and Overall Survival

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, James X.; Rose, Steven; White, Sarah B.

    PurposeThe purpose of the study was to evaluate prognostic factors for survival outcomes following embolotherapy for neuroendocrine tumor (NET) liver metastases.Materials and MethodsThis was a multicenter retrospective study of 155 patients (60 years mean age, 57 % male) with NET liver metastases from pancreas (n = 71), gut (n = 68), lung (n = 8), or other/unknown (n = 8) primary sites treated with conventional transarterial chemoembolization (TACE, n = 50), transarterial radioembolization (TARE, n = 64), or transarterial embolization (TAE, n = 41) between 2004 and 2015. Patient-, tumor-, and treatment-related factors were evaluated for prognostic effect on hepatic progression-free survival (HPFS) and overall survival (OS) using unadjusted and propensity score-weighted univariate and multivariate Coxmore » proportional hazards models.ResultsMedian HPFS and OS were 18.5 and 125.1 months for G1 (n = 75), 12.2 and 33.9 months for G2 (n = 60), and 4.9 and 9.3 months for G3 tumors (n = 20), respectively (p < 0.05). Tumor burden >50 % hepatic volume demonstrated 5.5- and 26.8-month shorter median HPFS and OS, respectively, versus burden ≤50 % (p < 0.05). There were no significant differences in HPFS or OS between gut or pancreas primaries. In multivariate HPFS analysis, there were no significant differences among embolotherapy modalities. In multivariate OS analysis, TARE had a higher hazard ratio than TACE (unadjusted Cox model: HR 2.1, p = 0.02; propensity score adjusted model: HR 1.8, p = 0.11), while TAE did not differ significantly from TACE.ConclusionHigher tumor grade and tumor burden prognosticated shorter HPFS and OS. TARE had a higher hazard ratio for OS than TACE. There were no significant differences in HPFS among embolotherapy modalities.« less

  10. Actuarial Valuation.

    ERIC Educational Resources Information Center

    Teachers Retirement System of Louisiana, Baton Rouge.

    This report presents the results of the actuarial valuation of assets and liabilities as well as funding requirements for the Teachers Retirement System of Louisiana as of June 30, 1996. Data reported include current funding, actuarial assets and valuation assets. These include the Louisiana State University Agriculture and Extension Service Fund,…

  11. Recruiting and Advising Challenges in Actuarial Science

    ERIC Educational Resources Information Center

    Case, Bettye Anne; Guan, Yuanying Michelle; Paris, Stephen

    2014-01-01

    Some challenges to increasing actuarial science program size through recruiting broadly among potential students are identified. Possible solutions depend on the structures and culture of the school. Up to three student cohorts may result from partition of potential students by the levels of academic progress before program entry: students…

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

    PubMed

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

    2016-12-01

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

  13. Clinical versus actuarial judgment.

    PubMed

    Dawes, R M; Faust, D; Meehl, P E

    1989-03-31

    Professionals are frequently consulted to diagnose and predict human behavior; optimal treatment and planning often hinge on the consultant's judgmental accuracy. The consultant may rely on one of two contrasting approaches to decision-making--the clinical and actuarial methods. Research comparing these two approaches shows the actuarial method to be superior. Factors underlying the greater accuracy of actuarial methods, sources of resistance to the scientific findings, and the benefits of increased reliance on actuarial approaches are discussed.

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

    PubMed

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

    2013-10-01

    Effective treatments for hormone-receptor-positive (HR(+)) breast cancer (BC) following relapse/progression on nonsteroidal aromatase inhibitor (NSAI) therapy are needed. Initial Breast Cancer Trials of OraL EveROlimus-2 (BOLERO-2) trial data demonstrated that everolimus and exemestane significantly prolonged progression-free survival (PFS) versus placebo plus exemestane alone in this patient population. BOLERO-2 is a phase 3, double-blind, randomized, international trial comparing everolimus (10 mg/day) plus exemestane (25 mg/day) versus placebo plus exemestane in postmenopausal women with HR(+) advanced BC with recurrence/progression during or after NSAIs. The primary endpoint was PFS by local investigator review, and was confirmed by independent central radiology review. Overall survival, response rate, and clinical benefit rate were secondary endpoints. Final study results with median 18-month follow-up show that median PFS remained significantly longer with everolimus plus exemestane versus placebo plus exemestane [investigator review: 7.8 versus 3.2 months, respectively; hazard ratio = 0.45 (95% confidence interval 0.38-0.54); log-rank P < 0.0001; central review: 11.0 versus 4.1 months, respectively; hazard ratio = 0.38 (95% confidence interval 0.31-0.48); log-rank P < 0.0001] in the overall population and in all prospectively defined subgroups, including patients with visceral metastases, [corrected] and irrespective of age. The incidence and severity of adverse events were consistent with those reported at the interim analysis and in other everolimus trials. The addition of everolimus to exemestane markedly prolonged PFS in patients with HR(+) advanced BC with disease recurrence/progression following prior NSAIs. These results further support the use of everolimus plus exemestane in this patient population. ClinicalTrials.gov #NCT00863655.

  15. Levels of uninvolved immunoglobulins predict clinical status and progression-free survival for multiple myeloma patients.

    PubMed

    Harutyunyan, Nika M; Vardanyan, Suzie; Ghermezi, Michael; Gottlieb, Jillian; Berenson, Ariana; Andreu-Vieyra, Claudia; Berenson, James R

    2016-07-01

    Multiple myeloma (MM) is characterized by the enhanced production of the same monoclonal immunoglobulin (M-Ig or M protein). Techniques such as serum protein electrophoresis and nephelometry are routinely used to quantify levels of this protein in the serum of MM patients. However, these methods are not without their shortcomings and problems accurately quantifying M proteins remain. Precise quantification of the types and levels of M-Ig present is critical to monitoring patient response to therapy. In this study, we investigated the ability of the HevyLite (HLC) immunoassay to correlate with clinical status based on levels of involved and uninvolved antibodies. In our cohort of MM patients, we observed that significantly higher ratios and greater differences of involved HLC levels compared to uninvolved HLC levels correlated with a worse clinical status. Similarly, higher absolute levels of involved HLC antibodies and lower levels of uninvolved HLC antibodies also correlated with a worse clinical status and a shorter progression-free survival. These findings suggest that the HLC assay is a useful and a promising tool for determining the clinical status and survival time for patients with multiple myeloma. © 2016 John Wiley & Sons Ltd.

  16. Development of a clinical prediction model to calculate patient life expectancy: the measure of actuarial life expectancy (MALE).

    PubMed

    Clarke, M G; Kennedy, K P; MacDonagh, R P

    2009-01-01

    To develop a clinical prediction model enabling the calculation of an individual patient's life expectancy (LE) and survival probability based on age, sex, and comorbidity for use in the joint decision-making process regarding medical treatment. A computer software program was developed with a team of 3 clinicians, 2 professional actuaries, and 2 professional computer programmers. This incorporated statistical spreadsheet and database access design methods. Data sources included life insurance industry actuarial rating factor tables (public and private domain), Government Actuary Department UK life tables, professional actuarial sources, and evidence-based medical literature. The main outcome measures were numerical and graphical display of comorbidity-adjusted LE; 5-, 10-, and 15-year survival probability; in addition to generic UK population LE. Nineteen medical conditions, which impacted significantly on LE in actuarial terms and were commonly encountered in clinical practice, were incorporated in the final model. Numerical and graphical representations of statistical predictions of LE and survival probability were successfully generated for patients with either no comorbidity or a combination of the 19 medical conditions included. Validation and testing, including actuarial peer review, confirmed consistency with the data sources utilized. The evidence-based actuarial data utilized in this computer program design represent a valuable resource for use in the clinical decision-making process, where an accurate objective assessment of patient LE can so often make the difference between patients being offered or denied medical and surgical treatment. Ongoing development to incorporate additional comorbidities and enable Web-based access will enhance its use further.

  17. Long-Term Post-CABG Survival: Performance of Clinical Risk Models Versus Actuarial Predictions.

    PubMed

    Carr, Brendan M; Romeiser, Jamie; Ruan, Joyce; Gupta, Sandeep; Seifert, Frank C; Zhu, Wei; Shroyer, A Laurie

    2016-01-01

    Clinical risk models are commonly used to predict short-term coronary artery bypass grafting (CABG) mortality but are less commonly used to predict long-term mortality. The added value of long-term mortality clinical risk models over traditional actuarial models has not been evaluated. To address this, the predictive performance of a long-term clinical risk model was compared with that of an actuarial model to identify the clinical variable(s) most responsible for any differences observed. Long-term mortality for 1028 CABG patients was estimated using the Hannan New York State clinical risk model and an actuarial model (based on age, gender, and race/ethnicity). Vital status was assessed using the Social Security Death Index. Observed/expected (O/E) ratios were calculated, and the models' predictive performances were compared using a nested c-index approach. Linear regression analyses identified the subgroup of risk factors driving the differences observed. Mortality rates were 3%, 9%, and 17% at one-, three-, and five years, respectively (median follow-up: five years). The clinical risk model provided more accurate predictions. Greater divergence between model estimates occurred with increasing long-term mortality risk, with baseline renal dysfunction identified as a particularly important driver of these differences. Long-term mortality clinical risk models provide enhanced predictive power compared to actuarial models. Using the Hannan risk model, a patient's long-term mortality risk can be accurately assessed and subgroups of higher-risk patients can be identified for enhanced follow-up care. More research appears warranted to refine long-term CABG clinical risk models. © 2015 The Authors. Journal of Cardiac Surgery Published by Wiley Periodicals, Inc.

  18. Long‐Term Post‐CABG Survival: Performance of Clinical Risk Models Versus Actuarial Predictions

    PubMed Central

    Carr, Brendan M.; Romeiser, Jamie; Ruan, Joyce; Gupta, Sandeep; Seifert, Frank C.; Zhu, Wei

    2015-01-01

    Abstract Background/aim Clinical risk models are commonly used to predict short‐term coronary artery bypass grafting (CABG) mortality but are less commonly used to predict long‐term mortality. The added value of long‐term mortality clinical risk models over traditional actuarial models has not been evaluated. To address this, the predictive performance of a long‐term clinical risk model was compared with that of an actuarial model to identify the clinical variable(s) most responsible for any differences observed. Methods Long‐term mortality for 1028 CABG patients was estimated using the Hannan New York State clinical risk model and an actuarial model (based on age, gender, and race/ethnicity). Vital status was assessed using the Social Security Death Index. Observed/expected (O/E) ratios were calculated, and the models' predictive performances were compared using a nested c‐index approach. Linear regression analyses identified the subgroup of risk factors driving the differences observed. Results Mortality rates were 3%, 9%, and 17% at one‐, three‐, and five years, respectively (median follow‐up: five years). The clinical risk model provided more accurate predictions. Greater divergence between model estimates occurred with increasing long‐term mortality risk, with baseline renal dysfunction identified as a particularly important driver of these differences. Conclusions Long‐term mortality clinical risk models provide enhanced predictive power compared to actuarial models. Using the Hannan risk model, a patient's long‐term mortality risk can be accurately assessed and subgroups of higher‐risk patients can be identified for enhanced follow‐up care. More research appears warranted to refine long‐term CABG clinical risk models. doi: 10.1111/jocs.12665 (J Card Surg 2016;31:23–30) PMID:26543019

  19. The case for an actuary.

    PubMed

    Renaud, Patrick N

    2002-12-01

    The author describes the role of the actuary, the need for qualified actuaries and how to find them. Qualified actuarial help, in the form of a Fellow of the Society of Actuaries (FSA), is necessary to ensure the best outcome when setting annual premium rates and realistic budgets for self-funded group benefit plans.

  20. Actuarial senescence in a long-lived orchid challenges our current understanding of ageing.

    PubMed

    Dahlgren, Johan Petter; Colchero, Fernando; Jones, Owen R; Øien, Dag-Inge; Moen, Asbjørn; Sletvold, Nina

    2016-11-16

    The dominant evolutionary theory of actuarial senescence-an increase in death rate with advancing age-is based on the concept of a germ cell line that is separated from the somatic cells early in life. However, such a separation is not clear in all organisms. This has been suggested to explain the paucity of evidence for actuarial senescence in plants. We used a 32 year study of Dactylorhiza lapponica that replaces its organs each growing season, to test whether individuals of this tuberous orchid senesce. We performed a Bayesian survival trajectory analysis accounting for reproductive investment, for individuals under two types of land use, in two climatic regions. The mortality trajectory was best approximated by a Weibull model, showing clear actuarial senescence. Rates of senescence in this model declined with advancing age, but were slightly higher in mown plots and in the more benign climatic region. At older ages, senescence was evident only when accounting for a positive effect of reproductive investment on mortality. Our results demonstrate actuarial senescence as well as a survival-reproduction trade-off in plants, and indicate that environmental context may influence senescence rates. This knowledge is crucial for understanding the evolution of demographic senescence and for models of plant population dynamics. © 2016 The Author(s).

  1. Progression-free survival as surrogate and as true end point: insights from the breast and colorectal cancer literature.

    PubMed

    Saad, E D; Katz, A; Hoff, P M; Buyse, M

    2010-01-01

    Significant achievements in the systemic treatment of both advanced breast cancer and advanced colorectal cancer over the past 10 years have led to a growing number of drugs, combinations, and sequences to be tested. The choice of surrogate and true end points has become a critical issue and one that is currently the subject of much debate. Many recent randomized trials in solid tumor oncology have used progression-free survival (PFS) as the primary end point. PFS is an attractive end point because it is available earlier than overall survival (OS) and is not influenced by second-line treatments. PFS is now undergoing validation as a surrogate end point in various disease settings. The question of whether PFS can be considered an acceptable surrogate end point depends not only on formal validation studies but also on a standardized definition and unbiased ascertainment of disease progression in clinical trials. In advanced breast cancer, formal validation of PFS as a surrogate for OS has so far been unsuccessful. In advanced colorectal cancer, in contrast, current evidence indicates that PFS is a valid surrogate for OS after first-line treatment with chemotherapy. The other question is whether PFS sufficiently reflects clinical benefit to be considered a true end point in and of itself.

  2. Nomograms Predicting Platinum Sensitivity, Progression-Free Survival, and Overall Survival Using Pretreatment Complete Blood Cell Counts in Epithelial Ovarian Cancer.

    PubMed

    Paik, E Sun; Sohn, Insuk; Baek, Sun-Young; Shim, Minhee; Choi, Hyun Jin; Kim, Tae-Joong; Choi, Chel Hun; Lee, Jeong-Won; Kim, Byoung-Gie; Lee, Yoo-Young; Bae, Duk-Soo

    2017-07-01

    This study was conducted to evaluate the prognostic significance of pre-treatment complete blood cell count (CBC), including white blood cell (WBC) differential, in epithelial ovarian cancer (EOC) patients with primary debulking surgery (PDS) and to develop nomograms for platinum sensitivity, progression-free survival (PFS), and overall survival (OS). We retrospectively reviewed the records of 757 patients with EOC whose primary treatment consisted of surgical debulking and chemotherapy at Samsung Medical Center from 2002 to 2012. We subsequently created nomograms for platinum sensitivity, 3-year PFS, and 5-year OS as prediction models for prognostic variables including age, stage, grade, cancer antigen 125 level, residual disease after PDS, and pre-treatment WBC differential counts. The models were then validated by 10-fold cross-validation (CV). In addition to stage and residual disease after PDS, which are known predictors, lymphocyte and monocyte count were found to be significant prognostic factors for platinum-sensitivity, platelet count for PFS, and neutrophil count for OS on multivariate analysis. The area under the curves of platinum sensitivity, 3-year PFS, and 5-year OS calculated by the 10-fold CV procedure were 0.7405, 0.8159, and 0.815, respectively. Prognostic factors including pre-treatment CBC were used to develop nomograms for platinum sensitivity, 3-year PFS, and 5-year OS of patients with EOC. These nomograms can be used to better estimate individual outcomes.

  3. Progression-free survival in advanced ovarian cancer: a Canadian review and expert panel perspective

    PubMed Central

    Oza, A.M.; Castonguay, V.; Tsoref, D.; Diaz–Padilla, I.; Karakasis, K.; Mackay, H.; Welch, S.; Weberpals, J.; Hoskins, P.; Plante, M.; Provencher, D.; Tonkin, K.; Covens, A.; Ghatage, P.; Gregoire, J.; Hirte, H.; Miller, D.; Rosen, B.; Maroun, J.; Buyse, M.; Coens, C.; Brady, M.F.; Stuart, G.C.E.

    2011-01-01

    Ovarian cancer is leading cause of gynecologic cancer mortality in Canada. To date, overall survival (os) has been the most-used endpoint in oncology trials because of its relevance and objectivity. However, as a result of various factors, including the pattern of sequential salvage therapies, measurement of os and collection of os data are becoming particularly challenging. Phase ii and iii trials have therefore adopted progression-free survival (pfs) as a more convenient surrogate endpoint; however, the clinical significance of pfs remains unclear. This position paper presents discussion topics and findings from a pan-Canadian meeting of experts that set out to evaluate the relevance of pfs as a valid endpoint in ovarian cancer;reach a Canadian consensus on the relevance of pfs in ovarian cancer; andtry to address how pfs translates into clinical benefit in ovarian cancer. Overall, the findings and the group consensus posit that future studies should ensure that trials are designed to evaluate pfs, os, and other clinically relevant endpoints such as disease-related symptoms or quality of life;incorporate interim futility analyses intended to stop accrual early when the experimental regimen is not active;stop trials early to declare superiority only when compelling evidence suggests that a new treatment provides benefit for a pre-specified, clinically relevant endpoint such as os or symptom relief; anddiscourage early release of secondary endpoint results when such a release might increase the frequency of crossover to the experimental intervention. PMID:21969808

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

    PubMed

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

    2017-10-01

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

  5. Improved progression-free and event-free survival in myeloma patients undergoing PBSCH receiving a cyclophosphamide + G-CSF regimen than G-CSF alone.

    PubMed

    Tanimura, Akira; Hirai, Risen; Nakamura, Miki; Takeshita, Masataka; Hagiwara, Shotaro; Miwa, Akiyoshi

    2018-05-01

    Two regimens are commonly used for peripheral blood hematopoietic stem cell harvesting (PBSCH) in multiple myeloma: high-dose cyclophosphamide (HD-CY) + granulocyte-colony stimulating factor (G-CSF), and G-CSF alone. The objective of the present study was to evaluate the anti-myeloma effect of the PBSCH regimen including HD-CY. We retrospectively assessed harvesting efficiency, complications, and anti-myeloma effects in 115 patients receiving HD-CY + G-CSF (HD-CY group) and 32 patients receiving G-CSF alone (G-alone group). We collected > 2 × 10 6 CD34-positive cells/kg from 93 and 75% of patients in the HD-CY and G-alone groups, respectively (P = 0.0079). The mean HSC count was also higher in the HD-CY group. No severe complications were observed in the G-alone group, whereas 66% of patients in the HD-CY group were treated with intravenous antibiotics. The median progression-free and event-free survival (PFS and EFS) were longer in the HD-CY group than in the G-alone group (28 vs. 18 months and 25 vs. 13 months, respectively; P = 0.0127 and 0.0139), with no difference in median overall survival. HD-CY showed anti-myeloma effect, as verified by prolonged EFS and PFS, when a vincristine, doxorubicin, and dexamethasone regimen was administered as induction before PBSCH.

  6. Nomograms Predicting Platinum Sensitivity, Progression-Free Survival, and Overall Survival Using Pretreatment Complete Blood Cell Counts in Epithelial Ovarian Cancer

    PubMed Central

    Paik, E Sun; Sohn, Insuk; Baek, Sun-Young; Shim, Minhee; Choi, Hyun Jin; Kim, Tae-Joong; Choi, Chel Hun; Lee, Jeong-Won; Kim, Byoung-Gie; Lee, Yoo-Young; Bae, Duk-Soo

    2017-01-01

    Purpose This study was conducted to evaluate the prognostic significance of pre-treatment complete blood cell count (CBC), including white blood cell (WBC) differential, in epithelial ovarian cancer (EOC) patients with primary debulking surgery (PDS) and to develop nomograms for platinum sensitivity, progression-free survival (PFS), and overall survival (OS). Materials and Methods We retrospectively reviewed the records of 757 patients with EOC whose primary treatment consisted of surgical debulking and chemotherapy at Samsung Medical Center from 2002 to 2012. We subsequently created nomograms for platinum sensitivity, 3-year PFS, and 5-year OS as prediction models for prognostic variables including age, stage, grade, cancer antigen 125 level, residual disease after PDS, and pre-treatment WBC differential counts. The models were then validated by 10-fold cross-validation (CV). Results In addition to stage and residual disease after PDS, which are known predictors, lymphocyte and monocyte count were found to be significant prognostic factors for platinum-sensitivity, platelet count for PFS, and neutrophil count for OS on multivariate analysis. The area under the curves of platinum sensitivity, 3-year PFS, and 5-year OS calculated by the 10-fold CV procedure were 0.7405, 0.8159, and 0.815, respectively. Conclusion Prognostic factors including pre-treatment CBC were used to develop nomograms for platinum sensitivity, 3-year PFS, and 5-year OS of patients with EOC. These nomograms can be used to better estimate individual outcomes. PMID:27669704

  7. VEGF-A polymorphisms predict progression-free survival among advanced castration-resistant prostate cancer patients treated with metronomic cyclophosphamide

    PubMed Central

    Orlandi, P; Fontana, A; Fioravanti, A; Di Desidero, T; Galli, L; Derosa, L; Canu, B; Marconcini, R; Biasco, E; Solini, A; Francia, G; Danesi, R; Falcone, A; Bocci, G

    2013-01-01

    Background: No data are available on the pharmacogenetics of metronomic chemotherapy in prostate cancer. The aim of this study was to evaluate the association between VEGF-A sequence variants and prostate-specific antigen (PSA) progression, progression-free survival (PFS) and overall survival (OS), in advanced castration-resistant prostate cancer patients treated with metronomic cyclophosphamide (CTX), celecoxib and dexamethasone. Methods: Forty-three patients were enrolled, and genomic DNA was extracted. VEGF-A gene SNPs (−2578A/C, −634C/G, +936C/T) were analysed using TaqMan PCR assays. Hardy–Weinberg equilibrium was tested for each SNP, and genetic effects were evaluated by Fisher's exact test. PFS and OS were analysed with GraphPad Prism software, using the product limit method of Kaplan and Meier, and comparing survival curves using both the log-rank test and the Gehan–Wilcoxon test. We used Bonferroni correction to account for multiple testing, and a two-tailed P-value of <0.017 was considered statistically significant. Results: Overall, 20 patients (46%) experienced a reduction in PSA levels from baseline and, among them, 14 (32%) showed a confirmed PSA ≥50% decrease. In non-responders, the −2578CC genotype was more frequent (18.60% vs 2.33% in responders; P=0.0212) whereas the −634CC genotype frequency was 22.73% vs 0% in responders (P=0.0485). With regard to PFS, patients harbouring the −634CC genotype had a median PFS of 2.2 months whereas patients with the genotype −634CG/GG had a median PFS of 6.25 months (P=0.0042). Conclusion: The −634CC genotype is significantly associated with a shorter PFS in patients treated with a metronomic CTX schedule. PMID:23860526

  8. High expression of insulin receptor on tumour-associated blood vessels in invasive bladder cancer predicts poor overall and progression-free survival.

    PubMed

    Roudnicky, Filip; Dieterich, Lothar C; Poyet, Cedric; Buser, Lorenz; Wild, Peter; Tang, Dave; Camenzind, Peter; Ho, Chien Hsien; Otto, Vivianne I; Detmar, Michael

    2017-06-01

    Bladder cancer is a frequently recurring disease with a very poor prognosis once progressed to invasive stages, and tumour-associated blood vessels play a crucial role in this process. In order to identify novel biomarkers associated with progression, we isolated blood vascular endothelial cells (BECs) from human invasive bladder cancers and matched normal bladder tissue, and found that tumour-associated BECs greatly up-regulated the expression of insulin receptor (INSR). High expression of INSR on BECs of invasive bladder cancers was significantly associated with shorter progression-free and overall survival. Furthermore, increased expression of the INSR ligand IGF-2 in invasive bladder cancers was associated with reduced overall survival. INSR may therefore represent a novel biomarker to predict cancer progression. Mechanistically, we observed pronounced hypoxia in human bladder cancer tissue, and found a positive correlation between the expression of the hypoxia marker gene GLUT1 and vascular INSR expression, indicating that hypoxia drives INSR expression in tumour-associated blood vessels. In line with this, exposure of cultured BECs and human bladder cancer cell lines to hypoxia led to increased expression of INSR and IGF-2, respectively, and IGF-2 increased BEC migration through the activation of INSR in vitro. Taken together, we identified vascular INSR expression as a potential biomarker for progression in bladder cancer. Furthermore, our data suggest that IGF-2/INSR mediated paracrine crosstalk between bladder cancer cells and endothelial cells is functionally involved in tumour angiogenesis and may thus represent a new therapeutic target. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  9. Radiographic Progression-Free Survival as a Clinically Meaningful End Point in Metastatic Castration-Resistant Prostate Cancer

    PubMed Central

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

    2018-01-01

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

  10. Coffee consumption protects against progression in liver cirrhosis and increases long-term survival after liver transplantation.

    PubMed

    Friedrich, Kilian; Smit, Mark; Wannhoff, Andreas; Rupp, Christian; Scholl, Sabine G; Antoni, Christoph; Dollinger, Matthias; Neumann-Haefelin, Christoph; Stremmel, Wolfgang; Weiss, Karl Heinz; Schemmer, Peter; Gotthardt, Daniel Nils

    2016-08-01

    Therapeutic options to treat progression of end-stage liver disease (ESLD) or improve long-term survival after liver transplantation remain scarce. We investigated the impact of coffee consumption under these conditions. We recorded coffee consumption habits of 379 patients with ESLD awaiting liver transplantation and 260 patients after liver transplantation. Survival was analyzed based on coffee intake. One hundred ninety-five patients with ESLD consumed coffee on a daily basis, while 184 patients did not. Actuarial survival was impaired (P = 0.041) in non-coffee drinkers (40.4 ± 4.3 months, 95% confidence interval [CI]: 32.0-48.9) compared with coffee drinkers (54.9 ± 5.5 months, 95% CI: 44.0-65.7). In subgroup analysis, the survival of patients with alcoholic liver disease (ALD; P = 0.020) and primary sclerosing cholangitis (PSC; P = 0.017) was increased with coffee intake while unaffected in patients with chronic viral hepatitis (P = 0.517) or other liver disease entities (P = 0.652). Multivariate analysis showed that coffee consumption of PSC and ALD patients retained as an independent risk factor (odds ratio [OR]: 1.94; 95% CI: 1.15-3.28; P = 0.013) along with MELD score (OR: 1.13; 95% CI: 1.09-1.17; P = 0.000). Following liver transplantation, long-term survival was longer in coffee drinkers (coffee: 61.8 ± 2.0 months, 95% CI: 57.9-65.8) than non-drinkers (52.3 ± 3.5 months, 95% CI: 45.4-59.3; P = 0.001). Coffee consumption delayed disease progression in ALD and PSC patients with ESLD and increased long-term survival after liver transplantation. We conclude that regular coffee intake might be recommended for these patients. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  11. Body weight changes in patients undergoing chemotherapy for ovarian cancer influence progression-free and overall survival.

    PubMed

    Mardas, Marcin; Stelmach-Mardas, Marta; Madry, Radosław

    2017-03-01

    The aim of this study was to evaluate whether body weight changes in patients undergoing chemotherapy for epithelial ovarian cancer (EOC) influence progression-free survival (PFS) and overall survival (OS). An analysis of 190 patients diagnosed with ovarian cancer after first-line chemotherapy was conducted. Changes in body weight were assessed by comparing measurements at baseline to those of the third and sixth cycles of chemotherapy. PFS and OS were calculated with the Kaplan-Meier method and multivariate Cox model. Significant reduction in body weight in advanced EOC was observed with no changes in early EOC. Significant differences in PFS were observed in advanced EOC patients that lost more than 5 % of their body weight (6 months), maintained weight (13 months), or gained more than 5 % of their body weight (15 months). Similarly, significant differences in OS were noted in advanced EOC at the following time points: 24.3, 42.4, and 66.2 months. No effect was reported for early EOC patients. The multivariate Cox analysis showed significant body weight changes from the first to the sixth chemotherapy cycle for PFS (HR = 0.97; 95 % CI 0.95-0.99) and OS (HR = 0.94; 95 % CI 0.91-0.97) as well as from the first to the third chemotherapy cycle for OS (HR = 0.93; 95 % CI 0.88-0.98). Body weight changes can be recognized as a prognostic factor for PFS and OS in advanced EOC patients undergoing chemotherapy. Weight loss is associated with poorer survival while weight gain improved outcomes.

  12. Larger number of invariant natural killer T cells in PBSC allografts correlates with improved GVHD-free and progression-free survival.

    PubMed

    Malard, Florent; Labopin, Myriam; Chevallier, Patrice; Guillaume, Thierry; Duquesne, Alix; Rialland, Fanny; Derenne, Sophie; Peterlin, Pierre; Leauté, Anne-Gaelle; Brissot, Eolia; Gregoire, Marc; Moreau, Philippe; Saas, Philippe; Gaugler, Béatrice; Mohty, Mohamad

    2016-04-07

    We studied the impact of a set of immune cells contained within granulocyte colony-stimulating factor-mobilized peripheral blood stem cell grafts (naïve and memory T-cell subsets, B cells, regulatory T cells, invariant natural killer T cells [iNKTs], NK cells, and dendritic cell subsets) in patients (n = 80) undergoing allogeneic stem cell transplantation (SCT), using the composite end point of graft-versus-host disease (GVHD)-free and progression-free survival (GPFS) as the primary end point. We observed that GPFS incidences in patients receiving iNKT doses above and below the median were 49% vs 22%, respectively (P= .007). In multivariate analysis, the iNKT dose was the only parameter with a significant impact on GPFS (hazard ratio = 0.48; 95% confidence interval, 0.27-0.85;P= .01). The incidences of severe grade III to IV acute GVHD and National Institutes of Health grade 2 to 3 chronic GVHD (12% and 16%, respectively) were low and associated with the use of antithymocyte globulin in 91% of patients. No difference in GVHD incidence was reported according to the iNKT dose. In conclusion, a higher dose of iNKTs within the graft is associated with an improved GPFS. These data may pave the way for prospective and active interventions aiming to manipulate the graft content to improve allo-SCT outcome. © 2016 by The American Society of Hematology.

  13. Progression-free survival as primary endpoint in randomized clinical trials of targeted agents for advanced renal cell carcinoma. Correlation with overall survival, benchmarking and power analysis.

    PubMed

    Bria, Emilio; Massari, Francesco; Maines, Francesca; Pilotto, Sara; Bonomi, Maria; Porta, Camillo; Bracarda, Sergio; Heng, Daniel; Santini, Daniele; Sperduti, Isabella; Giannarelli, Diana; Cognetti, Francesco; Tortora, Giampaolo; Milella, Michele

    2015-01-01

    A correlation, power and benchmarking analysis between progression-free and overall survival (PFS, OS) of randomized trials with targeted agents or immunotherapy for advanced renal cell carcinoma (RCC) was performed to provide a practical tool for clinical trial design. For 1st-line of treatment, a significant correlation was observed between 6-month PFS and 12-month OS, between 3-month PFS and 9-month OS and between the distributions of the cumulative PFS and OS estimates. According to the regression equation derived for 1st-line targeted agents, 7859, 2873, 712, and 190 patients would be required to determine a 3%, 5%, 10% and 20% PFS advantage at 6 months, corresponding to an absolute increase in 12-month OS rates of 2%, 3%, 6% and 11%, respectively. These data support PFS as a reliable endpoint for advanced RCC receiving up-front therapies. Benchmarking and power analyses, on the basis of the updated survival expectations, may represent practical tools for future trial' design. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Actually, What Is an Actuary?

    ERIC Educational Resources Information Center

    Oudshoorn, Susan; Finkelstein, Gary

    1991-01-01

    The actuarial profession is described to provide secondary school mathematics teachers insights into how actuaries use mathematics in solving real life problems. Examples are provided involving compound interest, the probability of dying, and inflation with computer modeling. (MDH)

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

    PubMed

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

    2015-01-01

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

  16. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer.

    PubMed

    Smith, Matthew R; Saad, Fred; Chowdhury, Simon; Oudard, Stéphane; Hadaschik, Boris A; Graff, Julie N; Olmos, David; Mainwaring, Paul N; Lee, Ji Youl; Uemura, Hiroji; Lopez-Gitlitz, Angela; Trudel, Géralyn C; Espina, Byron M; Shu, Youyi; Park, Youn C; Rackoff, Wayne R; Yu, Margaret K; Small, Eric J

    2018-04-12

    Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis. We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death. A total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35; P<0.001). Time to symptomatic progression was significantly longer with apalutamide than with placebo (hazard ratio, 0.45; 95% CI, 0.32 to 0.63; P<0.001). The rate of adverse events leading to discontinuation of the trial regimen was 10.6% in the apalutamide group and 7.0% in the placebo group. The following adverse events occurred at a higher rate with apalutamide than with placebo: rash (23.8% vs. 5.5%), hypothyroidism (8.1% vs. 2.0%), and fracture (11.7% vs. 6.5%). Among men with nonmetastatic castration-resistant prostate cancer, metastasis-free survival and time to symptomatic progression were significantly longer with apalutamide than with placebo. (Funded by Janssen Research and Development; SPARTAN ClinicalTrials.gov number, NCT01946204 .).

  17. Oligoclonal and monoclonal bands after single autologous stem cell transplant in patients with multiple myeloma: impact on overall survival and progression-free survival.

    PubMed

    Jimenez-Zepeda, Victor H; Reece, Donna E; Trudel, Suzanne; Franke, Norman; Winter, Andrew; Chen, Christine; Tiedemann, Rodger; Kukreti, Vishal

    2014-10-01

    Abstract Recently, the occurrence of oligoclonal and monoclonal bands (OB/MB) unrelated to the original clone has been reported in patients with multiple myeloma who undergo autologous stem cell transplant (ASCT) and/or receive treatment with novel agents. The aim of our study was to assess the impact of OB/MB occurrence on overall (OS) and progression-free survival (PFS) for patients with MM undergoing single ASCT at our institution. All consecutive patients with documented MM undergoing single ASCT from January 2000 to December 2012 were evaluated. Ninety-nine patients (11.8%) developed OB/MB at day 100 post-ASCT (32.3%, OB and 67.7%, MB). Multivariate analysis identified the development of OBs/MBs as an independent favorable prognostic factor for OS and PFS (p = 0.008 and 0.012, respectively). In conclusion, the occurrence of OB/MB is an important prognostic factor in patients with MM who undergo ASCT. Its impact on clinical outcomes should be prospectively validated and its biological significance further elucidated.

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

    PubMed

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

    2016-09-01

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

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

    PubMed Central

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

    2016-01-01

    The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n = 48; Rd, n = 52) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standard-risk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01080391. PMID:27439911

  20. A look inside the actuarial black box.

    PubMed

    Math, S E; Youngerman, H

    1992-12-01

    Hospital executives often rely on actuaries (and their "black boxes") to determine self-insurance program liabilities and funding contributions. Typically, the hospital supplies the actuary with a myriad of statistics, and eventually the hospital receives a liability estimate and recommended funding level. The mysterious actuarial calculations that occur in between data reporting and receipt of the actuary's report are akin to a black box--a complicated device whose internal mechanism is hidden from or mysterious to the user.

  1. 42 CFR 403.258 - Statement of actuarial opinion.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... actuarial opinion means a signed declaration in which a qualified actuary states that the assumptions used... policy experience, if any, and reasonable expectations. (b) Qualified actuary means— (1) A member in good standing of the American Academy of Actuaries; or (2) A person who has otherwise demonstrated his or her...

  2. 42 CFR 403.258 - Statement of actuarial opinion.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... actuarial opinion means a signed declaration in which a qualified actuary states that the assumptions used... policy experience, if any, and reasonable expectations. (b) Qualified actuary means— (1) A member in good standing of the American Academy of Actuaries; or (2) A person who has otherwise demonstrated his or her...

  3. 42 CFR 403.258 - Statement of actuarial opinion.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... actuarial opinion means a signed declaration in which a qualified actuary states that the assumptions used... policy experience, if any, and reasonable expectations. (b) Qualified actuary means— (1) A member in good standing of the American Academy of Actuaries; or (2) A person who has otherwise demonstrated his or her...

  4. 42 CFR 403.258 - Statement of actuarial opinion.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... actuarial opinion means a signed declaration in which a qualified actuary states that the assumptions used... policy experience, if any, and reasonable expectations. (b) Qualified actuary means— (1) A member in good standing of the American Academy of Actuaries; or (2) A person who has otherwise demonstrated his or her...

  5. 42 CFR 403.258 - Statement of actuarial opinion.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... actuarial opinion means a signed declaration in which a qualified actuary states that the assumptions used... policy experience, if any, and reasonable expectations. (b) Qualified actuary means— (1) A member in good standing of the American Academy of Actuaries; or (2) A person who has otherwise demonstrated his or her...

  6. Sexual Reconviction Rates in the United Kingdom and Actuarial Risk Estimates

    ERIC Educational Resources Information Center

    Craig, Leam A.; Browne, Kevin D.; Stringer, Ian; Hogue, Todd E.

    2008-01-01

    Objective: Assessing the risk of further offending behavior by adult sexual perpetrators of children is highly relevant and important to professionals involved in child protection. Recent progress in assessing risk in sexual offenders has established the validity of actuarial measures, although there continues to be some debate about the…

  7. Progression-free survival as a surrogate endpoint for overall survival in glioblastoma: a literature-based meta-analysis from 91 trials

    PubMed Central

    Han, Kelong; Ren, Melanie; Wick, Wolfgang; Abrey, Lauren; Das, Asha; Jin, Jin; Reardon, David A.

    2014-01-01

    Background The aim of this study was to determine correlations between progression-free survival (PFS) and the objective response rate (ORR) with overall survival (OS) in glioblastoma and to evaluate their potential use as surrogates for OS. Method Published glioblastoma trials reporting OS and ORR and/or PFS with sufficient detail were included in correlative analyses using weighted linear regression. Results Of 274 published unique glioblastoma trials, 91 were included. PFS and OS hazard ratios were strongly correlated; R2 = 0.92 (95% confidence interval [CI], 0.71–0.99). Linear regression determined that a 10% PFS risk reduction would yield an 8.1% ± 0.8% OS risk reduction. R2 between median PFS and median OS was 0.70 (95% CI, 0.59–0.79), with a higher value in trials using Response Assessment in Neuro-Oncology (RANO; R2 = 0.96, n = 8) versus Macdonald criteria (R2 = 0.70; n = 83). No significant differences were demonstrated between temozolomide- and bevacizumab-containing regimens (P = .10) or between trials using RANO and Macdonald criteria (P = .49). The regression line slope between median PFS and OS was significantly higher in newly diagnosed versus recurrent disease (0.58 vs 0.35, P = .04). R2 for 6-month PFS with 1-year OS and median OS were 0.60 (95% CI, 0.37–0.77) and 0.64 (95% CI, 0.42–0.77), respectively. Objective response rate and OS were poorly correlated (R2 = 0.22). Conclusion In glioblastoma, PFS and OS are strongly correlated, indicating that PFS may be an appropriate surrogate for OS. Compared with OS, PFS offers earlier assessment and higher statistical power at the time of analysis. PMID:24335699

  8. Actuarial senescence in a long-lived orchid challenges our current understanding of ageing

    PubMed Central

    Colchero, Fernando; Jones, Owen R.; Øien, Dag-Inge; Moen, Asbjørn; Sletvold, Nina

    2016-01-01

    The dominant evolutionary theory of actuarial senescence—an increase in death rate with advancing age—is based on the concept of a germ cell line that is separated from the somatic cells early in life. However, such a separation is not clear in all organisms. This has been suggested to explain the paucity of evidence for actuarial senescence in plants. We used a 32 year study of Dactylorhiza lapponica that replaces its organs each growing season, to test whether individuals of this tuberous orchid senesce. We performed a Bayesian survival trajectory analysis accounting for reproductive investment, for individuals under two types of land use, in two climatic regions. The mortality trajectory was best approximated by a Weibull model, showing clear actuarial senescence. Rates of senescence in this model declined with advancing age, but were slightly higher in mown plots and in the more benign climatic region. At older ages, senescence was evident only when accounting for a positive effect of reproductive investment on mortality. Our results demonstrate actuarial senescence as well as a survival–reproduction trade-off in plants, and indicate that environmental context may influence senescence rates. This knowledge is crucial for understanding the evolution of demographic senescence and for models of plant population dynamics. PMID:27852801

  9. {sup 18}Fluorodeoxyglucose PET Is Prognostic of Progression-Free and Overall Survival in Locally Advanced Pancreas Cancer Treated With Stereotactic Radiotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schellenberg, Devin; Quon, Andy; Minn, A. Yuriko

    2010-08-01

    Purpose: This study analyzed the prognostic value of positron emission tomography (PET) for locally advanced pancreas cancer patients undergoing stereotactic body radiotherapy (SBRT). Patients and Methods: Fifty-five previously untreated, unresectable pancreas cancer patients received a single fraction of 25-Gy SBRT sequentially with gemcitabine-based chemotherapy. On the preradiation PET-CT, the tumor was contoured and the maximum standardized uptake value (SUVmax) and metabolic tumor burden (MTB) were calculated using an in-house software application. High-SUVmax and low-SUVmax subgroups were created by categorizing patients above or below the median SUVmax. The analysis was repeated to form high-MTB and low-MTB subgroups as well as clinicallymore » relevant subgroups with SUVmax values of <5, 5-10, or >10. Multivariate analysis analyzing SUVmax, MTB, age, chemotherapy cycles, and pretreatment carbohydrate antigen (CA)19-9 was performed. Results: For the entire population, median survival was 12.7 months. Median survival was 9.8 vs.15.3 months for the high- and low- SUVmax subgroups (p <0.01). Similarly, median survival was 10.1 vs. 18.0 months for the high MTB and low MTB subgroups (p <0.01). When clinical SUVmax cutoffs were used, median survival was 6.4 months in those with SUVmax >10, 9.5 months with SUVmax 5.0-10.0, and 17.7 months in those with SUVmax <5 (p <0.01). On multivariate analysis, clinical SUVmax was an independent predictor for overall survival (p = 0.03) and progression-free survival (p = 0.03). Conclusion: PET scan parameters can predict for length of survival in locally advanced pancreas cancer patients.« less

  10. Tumour-derived alkaline phosphatase regulates tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer

    PubMed Central

    Rao, S R; Snaith, A E; Marino, D; Cheng, X; Lwin, S T; Orriss, I R; Hamdy, F C; Edwards, C M

    2017-01-01

    Background: Recent evidence suggests that bone-related parameters are the main prognostic factors for overall survival in advanced prostate cancer (PCa), with elevated circulating levels of alkaline phosphatase (ALP) thought to reflect the dysregulated bone formation accompanying distant metastases. We have identified that PCa cells express ALPL, the gene that encodes for tissue nonspecific ALP, and hypothesised that tumour-derived ALPL may contribute to disease progression. Methods: Functional effects of ALPL inhibition were investigated in metastatic PCa cell lines. ALPL gene expression was analysed from published PCa data sets, and correlated with disease-free survival and metastasis. Results: ALPL expression was increased in PCa cells from metastatic sites. A reduction in tumour-derived ALPL expression or ALP activity increased cell death, mesenchymal-to-epithelial transition and reduced migration. Alkaline phosphatase activity was decreased by the EMT repressor Snail. In men with PCa, tumour-derived ALPL correlated with EMT markers, and high ALPL expression was associated with a significant reduction in disease-free survival. Conclusions: Our studies reveal the function of tumour-derived ALPL in regulating cell death and epithelial plasticity, and demonstrate a strong association between ALPL expression in PCa cells and metastasis or disease-free survival, thus identifying tumour-derived ALPL as a major contributor to the pathogenesis of PCa progression. PMID:28006818

  11. Controlling Tumor Progression with Cyclophosphamide, Vincristine, and Dacarbazine Treatment Improves Survival in Patients with Metastatic and Unresectable Malignant Pheochromocytomas/Paragangliomas.

    PubMed

    Asai, Shiko; Katabami, Takuyuki; Tsuiki, Mika; Tanaka, Yasushi; Naruse, Mitsuhide

    2017-04-01

    Evidence has not been established to support that combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine (CVD) improves survival in patients with malignant pheochromocytoma and paraganglioma (M-PPGL). To investigate the efficacy of CVD for this disease, we retrospectively analyzed data of 23 patients with metastatic and unresectable M-PPGL (mean age, 41.7 ± 15.4 years) who received at least 2 cycles of this regimen. The follow-up period after initiation of CVD ranged from 0.3 to 13.7 years, with a median of 3.3 years. CVD therapy achieved a complete tumor response (CR) in 1 patient (4%), a partial response (PR) in 5 (22%), stable disease (SD) in 5 (22%), and progressive disease (PD) in 13 (52%), respectively. All of the responders (CR and PR) but 6% of the non-responders (SD and PD) showed substantial biochemical improvement. The progression-free survival period in the responders was significantly longer than in the non-responders (p < 0.01). Although the overall survival and survival after the diagnosis of M-PPGL were longer in the responders than the non-responders, the difference was not statistically significant (p = 0.08). The progression-free and overall survival period were significantly longer in the non-progression group (CR, PR, and SD) than in the progression group (PD) (1.7 ± 3.3 vs. 0.3 ± 0.3 years, p < 0.01, and 4.6 ± 3.6 vs. 2.0 ± 3.7 years, p = 0.01, respectively). It is therefore suggested that CVD chemotherapy could be useful in controlling tumor progression and improving survival in patients with metastatic and progressive M-PPGL.

  12. 20 CFR 200.9 - Selection of members of Actuarial Advisory Committee.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... actuaries to serve on an Actuarial Advisory Committee. This section describes how the two actuaries are selected. (b) Carrier actuary. One member of the Actuarial Advisory Committee shall be selected by... railroad mileage within the United States. (c) Railway labor actuary. The other member of the Actuarial...

  13. 20 CFR 200.9 - Selection of members of Actuarial Advisory Committee.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... actuaries to serve on an Actuarial Advisory Committee. This section describes how the two actuaries are selected. (b) Carrier actuary. One member of the Actuarial Advisory Committee shall be selected by... railroad mileage within the United States. (c) Railway labor actuary. The other member of the Actuarial...

  14. 20 CFR 200.9 - Selection of members of Actuarial Advisory Committee.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... actuaries to serve on an Actuarial Advisory Committee. This section describes how the two actuaries are selected. (b) Carrier actuary. One member of the Actuarial Advisory Committee shall be selected by... railroad mileage within the United States. (c) Railway labor actuary. The other member of the Actuarial...

  15. 20 CFR 200.9 - Selection of members of Actuarial Advisory Committee.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... actuaries to serve on an Actuarial Advisory Committee. This section describes how the two actuaries are selected. (b) Carrier actuary. One member of the Actuarial Advisory Committee shall be selected by... railroad mileage within the United States. (c) Railway labor actuary. The other member of the Actuarial...

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gielda, Benjamin T., E-mail: Benjamin_gielda@rush.edu; Mehta, Par; Khan, Atif

    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 correlationmore » 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.« less

  17. Progression-Free and Overall Survival of Patients With ALK Rearrangement-Positive Non-Small Cell Lung Cancer Treated Sequentially With Crizotinib and Alectinib.

    PubMed

    Watanabe, Satomi; Hayashi, Hidetoshi; Okamoto, Kunio; Fujiwara, Kimiko; Hasegawa, Yoshikazu; Kaneda, Hiroyasu; Tanaka, Kaoru; Takeda, Masayuki; Nakagawa, Kazuhiko

    2016-11-01

    Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) show marked therapeutic efficacy in patients with non-small cell lung cancer (NSCLC) harboring the echinoderm microtubule-associated protein-like 4-ALK fusion gene. The effect on overall survival (OS) of sequential treatment with the first- and second-generation ALK-TKIs crizotinib and alectinib, respectively, has remained unknown. We have examined the clinical outcome of such sequential treatment in a retrospective analysis of patients with ALK-rearranged NSCLC. Eleven patients with ALK-rearranged NSCLC treated with crizotinib followed by alectinib were identified. The progression-free survival (PFS) and OS for these patients were determined from a retrospective review of their medical records. The median PFS on crizotinib or alectinib was 6.1 months (range, 1.0-15.4 months) and 15.2 months (range, 1.0-28.3 months), respectively. The median combined PFS for both crizotinib and alectinib was 18.2 months (range, 10.4-43.7 months). Crizotinib was continued beyond radiographic evidence of progressive disease in 6 of the 11 patients, with a median duration of postprogression crizotinib treatment of 9.4 months (range, 0-20.5 months). The OS period from the diagnosis of metastatic disease or the initiation of crizotinib treatment was 51.1 months (range, 20.9-69.5 months) and 48.6 months (range, 19.8-50.1 months), respectively. Our retrospective study has revealed durable survival for alectinib treatment after crizotinib failure in patients with ALK-rearranged NSCLC. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Actuarial Science.

    ERIC Educational Resources Information Center

    Warren, Bette

    1982-01-01

    Details are provided of a program on actuarial training developed at the State University of New York (SUNY) at Binghamton through the Department of Mathematical Sciences. An outline of its operation, including a few statistics on students in the program, is included. (MP)

  19. 20 CFR 901.2 - Eligibility to perform actuarial services.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .... 901.2 Section 901.2 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS.... (a) Enrolled actuary. Subject to the standards of performance set forth in subpart C of this part, any individual who is an enrolled actuary as defined in § 901.1(g) may perform actuarial services...

  20. 20 CFR 901.2 - Eligibility to perform actuarial services.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    .... 901.2 Section 901.2 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS.... (a) Enrolled actuary. Subject to the standards of performance set forth in subpart C of this part, any individual who is an enrolled actuary as defined in § 901.1(g) may perform actuarial services...

  1. 20 CFR 901.2 - Eligibility to perform actuarial services.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    .... 901.2 Section 901.2 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS.... (a) Enrolled actuary. Subject to the standards of performance set forth in subpart C of this part, any individual who is an enrolled actuary as defined in § 901.1(g) may perform actuarial services...

  2. 20 CFR 901.2 - Eligibility to perform actuarial services.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    .... 901.2 Section 901.2 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS.... (a) Enrolled actuary. Subject to the standards of performance set forth in subpart C of this part, any individual who is an enrolled actuary as defined in § 901.1(g) may perform actuarial services...

  3. 20 CFR 901.2 - Eligibility to perform actuarial services.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... 901.2 Section 901.2 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS.... (a) Enrolled actuary. Subject to the standards of performance set forth in subpart C of this part, any individual who is an enrolled actuary as defined in § 901.1(g) may perform actuarial services...

  4. Intercalated Treatment Following Rebiopsy Is Associated with a Shorter Progression-Free Survival of Osimertinib Treatment.

    PubMed

    Tseng, Jeng-Sen; Yang, Tsung-Ying; Chen, Kun-Chieh; Hsu, Kuo-Hsuan; Huang, Yen-Hsiang; Su, Kang-Yi; Yu, Sung-Liang; Chang, Gee-Chen

    2017-12-11

    Epidermal growth factor receptor (EGFR) T790M mutation serves as an important predictor of osimertinib efficacy. However, little is known about how it works among patients with various timings of T790M emergence and treatment. Advanced EGFR-mutant lung adenocarcinoma patients with positive T790M mutation in tumor were retrospectively enrolled and observed to determine the outcomes of osimertinib treatment. We evaluated the association between patients' characteristics and the efficacy of osimertinib treatment, particularly with respect to the timing of T790M emergence and osimertinib prescription. A total of 91 patients were enrolled, including 14 (15.4%) with primary and 77 (84.6%) with acquired T790M mutation. The objective response rate and disease control rate were 60.9% and 85.1%, respectively. The median progression-free survival (PFS) and overall survival were 11.5 months (95% confidence interval [CI], 9.0 to 14.0) and 30.4 months (95% CI, 11.3 to 49.5), respectively. There was no significant difference in response rate and PFS between primary and acquired T790M populations. In the acquired T790M subgroup, patients who received osimertinib after T790M had been confirmed by rebiopsy had a longer PFS than those with intercalated treatments between rebiopsy and osimertinib prescription (14.0 months [95% CI, 9.0 to 18.9] vs. 7.2 months [95% CI, 3.7 to 10.8]; adjusted hazard ratio 0.48 [95% CI, 0.24 to 0.98; p=0.043]. Rebiopsy timing did not influence the outcome. Osimertinib prescription with intercalated treatment following rebiopsy but not the timing of T790M emergence influenced the treatment outcome. We suggest that it is better to start osimertinib treatment once T790M mutation has been confirmed by biopsy.

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

    PubMed

    Combescure, Christophe; Foucher, Yohann; Jackson, Daniel

    2014-07-10

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

  6. Expression of FAS-L Differs from Primary to Relapsed Low-grade Gliomas and Predicts Progression-free Survival.

    PubMed

    Werner, Jan-Michael; Kuhl, Saskia; Stavrinou, Pantelis; Röhn, Gabriele; Krischek, Boris; Blau, Tobias; Goldbrunner, Roland; Timmer, Marco

    2017-12-01

    The tumor necrosis factor FAS is overexpressed in high-grade gliomas (HGG). Only little is known about FAS or FAS ligand (FAS-L) in low-grade gliomas (LGG). We explored FAS/FAS-L expression in LGG, focusing on differences in primary and relapsed LGG and on its prognostic value. A total of 133 glioma samples (73 LGG, 60 HGG) were collected. The LGG samples included 15 matched pairs of primary and relapsed tumors. RT-PCR was performed to measure FAS/FAS-L expression, using subunit A, flavoprotein variant (SDHA) as housekeeper. Clinical data included progression free- (PFS) and overall survival (OS). LGG showed significantly lower FAS but higher FAS-L expression than HGG. The FAS-L expression was higher in primary compared to relapsed LGG and had a positive prognostic value concerning PFS (median 45.20 vs. 31.37 months). FAS-L could act as a prognostic marker and potential target in primary LGG. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  7. 26 CFR 301.6059-1 - Periodic report of actuary.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 18 2014-04-01 2014-04-01 false Periodic report of actuary. 301.6059-1 Section...-1 Periodic report of actuary. (a) In general. The actuarial report described in this section must be... funding deficiency (as defined in section 412(a)) to zero, (4) A statement by the enrolled actuary signing...

  8. 26 CFR 301.6059-1 - Periodic report of actuary.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 18 2012-04-01 2012-04-01 false Periodic report of actuary. 301.6059-1 Section...-1 Periodic report of actuary. (a) In general. The actuarial report described in this section must be... funding deficiency (as defined in section 412(a)) to zero, (4) A statement by the enrolled actuary signing...

  9. 26 CFR 301.6059-1 - Periodic report of actuary.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 18 2013-04-01 2013-04-01 false Periodic report of actuary. 301.6059-1 Section...-1 Periodic report of actuary. (a) In general. The actuarial report described in this section must be... funding deficiency (as defined in section 412(a)) to zero, (4) A statement by the enrolled actuary signing...

  10. 26 CFR 301.6059-1 - Periodic report of actuary.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 18 2011-04-01 2011-04-01 false Periodic report of actuary. 301.6059-1 Section...-1 Periodic report of actuary. (a) In general. The actuarial report described in this section must be... funding deficiency (as defined in section 412(a)) to zero, (4) A statement by the enrolled actuary signing...

  11. 26 CFR 301.6059-1 - Periodic report of actuary.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Periodic report of actuary. 301.6059-1 Section...-1 Periodic report of actuary. (a) In general. The actuarial report described in this section must be... funding deficiency (as defined in section 412(a)) to zero, (4) A statement by the enrolled actuary signing...

  12. RISK FACTORS FOR NONREMISSION AND PROGRESSION-FREE SURVIVAL AFTER I-131 THERAPY IN PATIENTS WITH LUNG METASTASIS FROM DIFFERENTIATED THYROID CANCER: A SINGLE-INSTITUTE, RETROSPECTIVE ANALYSIS IN SOUTHERN CHINA.

    PubMed

    Chen, Pan; Feng, Hui-Juan; Ouyang, Wei; Wu, Ju-Qing; Wang, Jing; Sun, Yun-Gang; Xian, Jia-Lang; Huang, Liu-Hua

    2016-09-01

    Prognostic factors related to progression-free survival (PFS) have not received much attention in the literature regarding iodine-131 ((131)I) therapy for patients with differentiated thyroid cancer and lung metastases. We sought to explore the factors associated with PFS and nonremission in a group of patients with differentiated thyroid cancer and pulmonary metastases at initial diagnosis and to investigate the impact of (131)I therapy on pulmonary function and peripheral blood counts in the same cohort of patients. The medical records of 1,050 patients with differentiated thyroid cancer treated at the Zhujiang Hospital of Southern Medical University from January 2006 to January 2015 were retrospectively reviewed. Among them, 107 patients fulfilled the inclusion criteria. Multivariate Cox regression analysis indicated that age ≥45 years and (131)I nonavidity were independent risk factors for disease progression. Multivariate logistic regression analysis revealed that pulmonary nodule size ≥1 cm and (131)I nonavidity were the strongest risk factors predicting nonremission. Varying cumulative (131)I dosage had no association with posttreatment pulmonary function or peripheral blood cell counts. Similar to earlier studies, our results confirm that (131)I nonavidity was associated with an increased risk of disease progression and greater odds of nonremission. In addition, patients with differentiated thyroid cancer and lung metastases with pulmonary nodules ≥1 cm had a reduced likelihood of achieving remission. Furthermore, special attention is needed when monitoring patients over 45 years at a higher risk of disease progression. CI = confidence interval DTC = differentiated thyroid cancer (18)F-FDG = fluoro-18 fluorodeoxyglucose FEF = forced expiratory flow FTC = follicular thyroid cancer FVC = forced vital capacity GR = granulocytes Hb = hemoglobin HR = hazard ratio (131)I = iodine-131 LN = lymph node OR = odds ratio OS = overall survival PET/CT = positive

  13. Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score.

    PubMed

    Hasford, Joerg; Baccarani, Michele; Hoffmann, Verena; Guilhot, Joelle; Saussele, Susanne; Rosti, Gianantonio; Guilhot, François; Porkka, Kimmo; Ossenkoppele, Gert; Lindoerfer, Doris; Simonsson, Bengt; Pfirrmann, Markus; Hehlmann, Rudiger

    2011-07-21

    The outcome of chronic myeloid leukemia (CML) has been profoundly changed by the introduction of tyrosine kinase inhibitors into therapy, but the prognosis of patients with CML is still evaluated using prognostic scores developed in the chemotherapy and interferon era. The present work describes a new prognostic score that is superior to the Sokal and Euro scores both in its prognostic ability and in its simplicity. The predictive power of the score was developed and tested on a group of patients selected from a registry of 2060 patients enrolled in studies of first-line treatment with imatinib-based regimes. The EUTOS score using the percentage of basophils and spleen size best discriminated between high-risk and low-risk groups of patients, with a positive predictive value of not reaching a CCgR of 34%. Five-year progression-free survival was significantly better in the low- than in the high-risk group (90% vs 82%, P = .006). These results were confirmed in the validation sample. The score can be used to identify CML patients with significantly lower probabilities of responding to therapy and survival, thus alerting physicians to those patients who require closer observation and early intervention.

  14. Association of Dasatinib With Progression-Free Survival Among Patients With Advanced Gastrointestinal Stromal Tumors Resistant to Imatinib.

    PubMed

    Schuetze, Scott M; Bolejack, Vanessa; Thomas, Dafydd G; von Mehren, Margaret; Patel, Shreyaskumar; Samuels, Brian; Choy, Edwin; D'Amato, Gina; Staddon, Arthur P; Ganjoo, Kristen N; Chow, Warren A; Rushing, Daniel A; Forscher, Charles A; Priebat, Dennis A; Loeb, David M; Chugh, Rashmi; Okuno, Scott; Reinke, Denise K; Baker, Laurence H

    2018-04-26

    Gastrointestinal stromal tumors (GISTs) are life-threatening when metastatic or not amenable to surgical removal. In a few patients with advanced GISTs refractory to imatinib mesylate, treatment with sunitinib malate followed by regorafenib provides tumor control; however, additional active treatments are needed for most patients. To evaluate the 6-month progression-free survival (PFS), tumor objective response, and overall survival rates in patients with GISTs treated with dasatinib. This single-arm clinical trial used a Bayesian design to enroll patients 13 years or older with measurable imatinib-refractory metastatic GISTs treated at 14 sarcoma referral centers from June 1, 2008, through December 31, 2009. A control group was not included. Patients were followed up for survival for a minimum of 5 years from date of enrollment. Tumor imaging using computed tomography or magnetic resonance imaging was performed every 8 weeks for the first 24 weeks and every 12 weeks thereafter. Tumor response was assessed by local site using the Choi criteria. Treatment was continued until tumor progression, unacceptable toxic effects after reduction in drug dose, or patient or physician decision. Archival tumor tissue was evaluated for expression of the proto-oncogene tyrosine-protein kinase Src (SRC), phosphorylated SRC (pSRC), and succinate dehydrogenase complex iron sulfur subunit B (SDHB) proteins and for mutation in the V-Kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) and platelet-derived growth factor receptor α (PDGFRA) genes. Data analysis was performed from May 19, 2017, through December 20, 2017. Dasatinib, 70 mg orally twice daily. The primary end point was the 6-month PFS estimate using greater than 30% as evidence of an active drug and less than 10% as evidence of inactive treatment. In this study, 50 patients were enrolled (median age, 60 years; age range, 19-78 years; 31 [62%] male and 19 [38%] female; 41 [82%] white), and 48 were evaluable for

  15. Do age-specific survival patterns of wild boar fit current evolutionary theories of senescence?

    PubMed

    Gamelon, Marlène; Focardi, Stefano; Gaillard, Jean-Michel; Gimenez, Olivier; Bonenfant, Christophe; Franzetti, Barbara; Choquet, Rémi; Ronchi, Francesca; Baubet, Eric; Lemaître, Jean-François

    2014-12-01

    Actuarial senescence is widespread in age-structured populations. In growing populations, the progressive decline of Hamiltonian forces of selection with age leads to decreasing survival. As actuarial senescence is overcompensated by a high fertility, actuarial senescence should be more intense in species with high reproductive effort, a theoretical prediction that has not been yet explicitly tested across species. Wild boar (Sus scrofa) females have an unusual life-history strategy among large mammals by associating both early and high reproductive effort with potentially long lifespan. Therefore, wild boar females should show stronger actuarial senescence than similar-sized related mammals. Moreover, being polygynous and much larger than females, males should display higher senescence rates than females. Using a long-term monitoring (18 years) of a wild boar population, we tested these predictions. We provided clear evidence of actuarial senescence in both sexes. Wild boar females had earlier but not stronger actuarial senescence than similar-sized ungulates. Both sexes displayed similar senescence rates. Our study indicates that the timing of senescence, not the rate, is associated with the magnitude of fertility in ungulates. This demonstrates the importance of including the timing of senescence in addition to its rate to understand variation in senescence patterns in wild populations. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

  16. 75 FR 63505 - Renewal of Advisory Committee on Actuarial Examinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-15

    ... actuarial mathematics and methodology. The Joint Board administers such examinations in discharging its... JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES Renewal of Advisory Committee on Actuarial... Committee on Actuarial Examinations. FOR FURTHER INFORMATION CONTACT: Patrick W. McDonough, 202-622-8225...

  17. Partial T-cell depletion improves the composite endpoint graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Simonetta, Federico; Masouridi-Levrat, Stavroula; Beauverd, Yan; Tsopra, Olga; Tirefort, Yordanka; Koutsi, Aikaterini; Stephan, Caroline; Polchlopek-Blasiak, Karolina; Pradier, Amandine; Dantin, Carole; Ansari, Marc; Roosnek, Eddy; Chalandon, Yves

    2018-03-01

    Graft-versus-host disease (GvHD)-free, relapse-free survival (GRFS) is a recently reported composite endpoint that allows to simultaneously estimate risk of death, relapse and GvHD after allogeneic hematopoietic stem cell transplantation (HSCT). In this retrospective study comprising 333 patients transplanted for hematologic malignancies, we compared GRFS in patients receiving partial T-cell-depleted (pTCD) grafts with patients receiving T-cell-replete grafts (No-TCD). pTCD was associated with a significantly improved GRFS. The beneficial effect of pTCD on GRFS remained highly significant in multivariable analysis taking into account clinical factors differing between patient groups. We observed no effect of pTCD on overall survival, progression-free survival, and relapse cumulative incidence, while non-relapse mortality cumulative incidence was significantly lower in patients receiving pTCD. The results of our retrospective analysis suggest that pTCD could improve GRFS in allogeneic HSCT recipients without significantly affecting OS and PFS, thus improving patients' quality of life without impairing the curative potential of allogeneic HSCT.

  18. Recovery of polyclonal immunoglobulins one year after autologous stem cell transplantation as a long-term predictor marker of progression and survival in multiple myeloma.

    PubMed

    González-Calle, Verónica; Cerdá, Seila; Labrador, Jorge; Sobejano, Eduardo; González-Mena, Beatriz; Aguilera, Carmen; Ocio, Enrique María; Vidriales, María Belén; Puig, Noemí; Gutiérrez, Norma Carmen; García-Sanz, Ramón; Alonso, José María; López, Rosa; Aguilar, Carlos; de Coca, Alfonso García; Hernández, Roberto; Hernández, José Mariano; Escalante, Fernando; Mateos, María-Victoria

    2017-05-01

    Immunoparesis or suppression of polyclonal immunoglobulins is a very common condition in newly diagnosed myeloma patients. However, the recovery of polyclonal immunoglobulins in the setting of immune reconstitution after autologous stem cell transplantation and its effect on outcome has not yet been explored. We conducted this study in a cohort of 295 patients who had undergone autologous transplantation. In order to explore the potential role of immunoglubulin recovery as a dynamic predictor of progression or survival after transplantation, conditional probabilities of progression-free survival and overall survival were estimated according to immunoglobulin recovery at different time points using a landmark approach. One year after transplant, when B-cell reconstitution is expected to be completed, among 169 patients alive and progression free, 88 patients (52%) showed immunoglobulin recovery and 81 (48%) did not. Interestingly, the group with immunoglobulin recovery had a significantly longer median progression-free survival than the group with persistent immunoparesis (median 60.4 vs. 27.9 months, respectively; Hazard Ratio: 0.45, 95%Confidence Interval: 0.31-0.66; P <0.001), and improved overall survival (11.3 vs. 7.3 years; Hazard Ratio: 0.45, 95%Confidence Interval: 0.27-0.74; P =0.002). Furthermore, the percentage of normal plasma cells detected by flow cytometry in the bone marrow assessed at day 100 after transplantation was associated with the immunoglobulin recovery at that time and may predict immunoglobulin recovery in the subsequent months: nine months and one year. In conclusion, the recovery of polyclonal immunoglobulins one year after autologous transplantation in myeloma patients is an independent long-term predictor marker for progression and survival. Copyright© Ferrata Storti Foundation.

  19. Impact of educational differences as measure of socioeconomic status on survival for breast cancer patients.

    PubMed

    Nowara, Elżbieta; Suwiński, Rafał

    2012-01-01

    Breast cancer is the most frequent malignancy affecting women. Some reports suggest the influence of socioeconomic status, including education, on survival rates for cancer patients. This report analyzes the effect of patients' education level on their survival. A retrospective analysis of the group of 810 breast cancer patients treated in single center in Poland was performed. The analyzed group included women with elementary education (24%), vocational training (19%), secondary (38%) or higher education (16%). Overall, recurrence-free and metastasis free survival times were analyzed. The actuarial 5-year overall survival was 72% (median 4.7 years), 5-year local recurrence-free survival was 84%, whereas metastasis-free survival 76%. Multivariate Cox model has shown that lower education had independent significantly negative influence on local recurrence-free survival time (p = 0.024). The highest risk of recurrence was found for patients with elementary education (p = 0.009). The same was confirmed for distant metastasis-free survival (p = 0.001), with the highest risk of metastases in patients with vocational education and stage IIIB breast cancer (p < 0.001). Education level had significant impact on overall survival. The patients with higher-level education lived longer (p = 0.042). Shorter recurrence-free survival time among women attaining lowest education level and longer overall survival time for women with higher education level suggest the necessity for intensified cancer awareness educational effort and screening among less-educated healthy Polish women.

  20. Donor KIR B Genotype Improves Progression-Free Survival of Non-Hodgkin Lymphoma Patients Receiving Unrelated Donor Transplantation.

    PubMed

    Bachanova, Veronika; Weisdorf, Daniel J; Wang, Tao; Marsh, Steven G E; Trachtenberg, Elizabeth; Haagenson, Michael D; Spellman, Stephen R; Ladner, Martha; Guethlein, Lisbeth A; Parham, Peter; Miller, Jeffrey S; Cooley, Sarah A

    2016-09-01

    Donor killer immunoglobulin-like receptor (KIR) genotypes are associated with relapse protection and survival after allotransplantation for acute myelogenous leukemia. We examined the possibility of a similar effect in a cohort of 614 non-Hodgkin lymphoma (NHL) patients receiving unrelated donor (URD) T cell-replete marrow or peripheral blood grafts. Sixty-four percent (n = 396) of donor-recipient pairs were 10/10 allele HLA matched and 26% were 9/10 allele matched. Seventy percent of donors had KIR B/x genotype; the others had KIR A/A genotype. NHL patients receiving 10/10 HLA-matched URD grafts with KIR B/x donors experienced significantly lower relapse at 5 years (26%; 95% confidence interval [CI], 21% to 32% versus 37%; 95% CI, 27% to 46%; P = .05) compared with KIR A/A donors, resulting in improved 5-year progression-free survival (PFS) (35%; 95% CI, 26% to 44% versus 22%; 95% CI, 11% to 35%; P = .007). In multivariate analysis, use of KIR B/x donors was associated with significantly reduced relapse risk (relative risk [RR], .63, P = .02) and improved PFS (RR, .71, P = .008). The relapse protection afforded by KIR B/x donors was not observed in HLA-mismatched transplantations and was not specific to any particular KIR-B gene. Selecting 10/10 HLA-matched and KIR B/x donors should benefit patients with NHL receiving URD allogeneic transplantation. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  1. 42 CFR 457.431 - Actuarial report for benchmark-equivalent coverage.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...— (1) By an individual who is a member of the American Academy of Actuaries; (2) Using generally accepted actuarial principles and methodologies of the American Academy of Actuaries; (3) Using a... coverage. (c) The actuary who prepares the opinion must select and specify the standardized set and...

  2. 20 CFR 901.32 - Receipt of information concerning enrolled actuaries.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... actuaries. 901.32 Section 901.32 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS... Suspension or Termination of Enrollment § 901.32 Receipt of information concerning enrolled actuaries. If an... Guaranty Corporation, or a member of the Joint Board has reason to believe that an enrolled actuary has...

  3. 20 CFR 901.20 - Standards of performance of actuarial services.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... services. 901.20 Section 901.20 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS... Standards of Performance for Enrolled Actuaries § 901.20 Standards of performance of actuarial services. In the discharge of duties required by ERISA of enrolled actuaries with respect to any plan to which the...

  4. 20 CFR 901.20 - Standards of performance of actuarial services.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... services. 901.20 Section 901.20 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS... Standards of Performance for Enrolled Actuaries § 901.20 Standards of performance of actuarial services. In the discharge of duties required by ERISA of enrolled actuaries with respect to any plan to which the...

  5. 20 CFR 901.32 - Receipt of information concerning enrolled actuaries.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... actuaries. 901.32 Section 901.32 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS... Suspension or Termination of Enrollment § 901.32 Receipt of information concerning enrolled actuaries. If an... Guaranty Corporation, or a member of the Joint Board has reason to believe that an enrolled actuary has...

  6. 20 CFR 901.32 - Receipt of information concerning enrolled actuaries.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... actuaries. 901.32 Section 901.32 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS... Suspension or Termination of Enrollment § 901.32 Receipt of information concerning enrolled actuaries. If an... Guaranty Corporation, or a member of the Joint Board has reason to believe that an enrolled actuary has...

  7. 20 CFR 901.32 - Receipt of information concerning enrolled actuaries.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... actuaries. 901.32 Section 901.32 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS... Suspension or Termination of Enrollment § 901.32 Receipt of information concerning enrolled actuaries. If an... Guaranty Corporation, or a member of the Joint Board has reason to believe that an enrolled actuary has...

  8. 20 CFR 901.20 - Standards of performance of actuarial services.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... services. 901.20 Section 901.20 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS... Standards of Performance for Enrolled Actuaries § 901.20 Standards of performance of actuarial services. In the discharge of duties required by ERISA of enrolled actuaries with respect to any plan to which the...

  9. 20 CFR 901.20 - Standards of performance of actuarial services.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... services. 901.20 Section 901.20 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS... Standards of Performance for Enrolled Actuaries § 901.20 Standards of performance of actuarial services. In the discharge of duties required by ERISA of enrolled actuaries with respect to any plan to which the...

  10. 20 CFR 901.32 - Receipt of information concerning enrolled actuaries.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... actuaries. 901.32 Section 901.32 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS... Suspension or Termination of Enrollment § 901.32 Receipt of information concerning enrolled actuaries. If an... Guaranty Corporation, or a member of the Joint Board has reason to believe that an enrolled actuary has...

  11. Carboplatin–paclitaxel-induced leukopenia and neuropathy predict progression-free survival in recurrent ovarian cancer

    PubMed Central

    Lee, C K; Gurney, H; Brown, C; Sorio, R; Donadello, N; Tulunay, G; Meier, W; Bacon, M; Maenpaa, J; Petru, E; Reed, N; Gebski, V; Pujade-Lauraine, E; Lord, S; Simes, R J; Friedlander, M

    2011-01-01

    Background: We assess the prognostic value of chemotherapy-induced leukopenia and sensory neuropathy in the CALYPSO trial patients treated with carboplatin–paclitaxel (CP) or carboplatin–liposomal doxorubicin (CPLD). Methods: We performed a landmark analysis at first month after randomisation to correlate leukopenia (nadir white blood cell <4.0 × 109 per litre or severe infection) during cycle 1 of chemotherapy with progression-free survival (PFS). Using time-dependent proportional-hazards models, we also investigated the association between neuropathy and PFS. Results: Of 608 patients with nadir blood and did not receive growth factors, 72% (CP=70%, CPLD=73%) had leukopenia. Leukopenia was prognostic for PFS in those receiving CP (adjusted hazard ratio (aHR) 0.66, P=0.01). Carboplatin–liposomal doxorubicin was more effective than CP in patients without leukopenia (aHR 0.51, P=0.001), but not those experiencing leukopenia (aHR 0.93, P=0.54; interaction P=0.008). Of 949 patients, 32% (CP=62%, CPLD=28%) reported neuropathy during landmark. Neuropathy was prognostic for PFS in the CP group only (aHR 0.77, P=0.02). Carboplatin–liposomal doxorubicin appeared to be more effective than CP among patients without neuropathy (aHR 0.70, P<0.0001), but not those with neuropathy (aHR 0.96, P=0.81; interaction P=0.15). Conclusion: First-cycle leukopenia and neuropathy were prognostic for patients treated with CP. Efficacy of CP treatment was similar to CPLD in patients who developed leukopenia. These findings support further research to understand the mechanisms of treatment-related toxicity. PMID:21750553

  12. Progression-Free and Overall Survival in ALK-Positive NSCLC Patients Treated with Sequential Crizotinib and Ceritinib.

    PubMed

    Gainor, Justin F; Tan, Daniel S W; De Pas, Tomasso; Solomon, Benjamin J; Ahmad, Aziah; Lazzari, Chiara; de Marinis, Filippo; Spitaleri, Gianluca; Schultz, Katherine; Friboulet, Luc; Yeap, Beow Y; Engelman, Jeffrey A; Shaw, Alice T

    2015-06-15

    Anaplastic lymphoma kinase (ALK) rearrangements are important therapeutic targets in non-small cell lung cancer (NSCLC) that confer sensitivity to the ALK inhibitors crizotinib and ceritinib. To determine the outcome of sequential treatment with crizotinb and ceritinib, we retrospectively evaluated a cohort of ALK-positive patients treated with both agents. We identified 73 ALK-positive NSCLC patients treated with crizotinib followed by ceritinib at four institutions. Medical records were reviewed to determine overall survival (OS) and progression-free survival (PFS) on crizotinib and ceritinib. Among 73 ALK-positive patients, the median PFS (mPFS) on crizotinib was 8.2 months [95% confidence interval (CI), 7.4-10.6]. The median interval from crizotinib discontinuation to initiation of ceritinib was 25 days (range, 1-694). The mPFS on ceritinib was 7.8 months (6.5-9.1). Among 53 patients with no interval therapies between crizotinib and ceritinib, the mPFS on ceritinib was similar at 7.8 months (5.4-9.8). The median combined PFS for sequential treatment with crizotinib and ceritinib was 17.4 months (15.5-19.4). Among 23 patients who underwent post-crizotinib/pre-ceritinib biopsies, there was no difference in PFS on ceritinib between patients with or without ALK resistance mutations (mPFS 5.8 vs. 6.5 months, respectively; P = 0.510). In the overall study population, median OS was 49.4 months (35.5-63.1). Ceritinib has significant antitumor activity in ALK-positive NSCLC-even when crizotinib immediately precedes treatment with ceritinib (median combined PFS 17.0 months). Additional studies are necessary to further define the impact of specific ALK resistance mutations on duration of response to ceritinib. ©2015 American Association for Cancer Research.

  13. Association of progression-free survival, overall survival, and patient-reported outcomes by skin toxicity and KRAS status in patients receiving panitumumab monotherapy.

    PubMed

    Peeters, Marc; Siena, Salvatore; Van Cutsem, Eric; Sobrero, Alberto; Hendlisz, Alain; Cascinu, Stefano; Kalofonos, Haralabos; Devercelli, Giovanna; Wolf, Michael; Amado, Rafael G

    2009-04-01

    The authors explored the association of skin toxicity (ST) severity as measured by patient-reported ST and Common Terminology Criteria for Adverse Events (CTCAE) grading with efficacy of panitumumab, a fully human antiepidermal growth factor receptor antibody, from a phase 3 metastatic colorectal cancer (CRC) trial. Patients were randomized to panitumumab plus best supportive care (BSC) vs BSC alone. ST by modified National Cancer Institute CTCAE v3.0 and modified Dermatology Life Quality Index (mDLQI), health-related quality of life (HRQOL), and CRC symptoms were measured. ST was analyzed using a landmark approach. Associations by KRAS mutational status were also assessed. Of 463 patients, 208 of 231 (90%) panitumumab patients and 184 of 232 (79%) BSC patients had > or = 1 postbaseline patient-reported outcome (PRO) assessment. Panitumumab patients with more severe ST had significantly longer overall survival (OS) (grade 2-4:grade 1; hazard ratio, 0.60; P = .0033). Lower mDLQI scores (< 67; more bothersome ST) were associated with longer OS (Cox model, P < .0001). Similar results were observed with progression-free survival (PFS). An inverse relation between mDLQI and HRQOL scores was observed, suggesting that ST bother correlated with better HRQOL. KRAS and PRO data were available in 363 patients (188 panitumumab; 175 BSC). Longer OS was associated with lower mDLQI scores, regardless of KRAS status. Longer PFS was associated with more severe ST (lower mDLQI scores and higher CTCAE grade ST) in patients with wild-type (WT) KRAS tumors, but not in patients with mutant KRAS tumors. More severe ST, by both clinical grading and PRO, is associated with better CRC symptoms and HRQOL and with longer OS and PFS among panitumumab-treated patients. The associations for PFS were more pronounced in patients with WT KRAS tumors. (c) 2009 American Cancer Society

  14. Predictors of response, progression-free survival, and overall survival using NANT Response Criteria (v1.0) in relapsed and refractory high-risk neuroblastoma.

    PubMed

    Villablanca, Judith G; Ji, Lingyun; Shapira-Lewinson, Adi; Marachelian, Araz; Shimada, Hiroyuki; Hawkins, Randall A; Pampaloni, Miguel; Lai, Hollie; Goodarzian, Fariba; Sposto, Richard; Park, Julie R; Matthay, Katherine K

    2018-05-01

    The New Approaches to Neuroblastoma Therapy Response Criteria (NANTRC) were developed to optimize response assessment in patients with recurrent/refractory neuroblastoma. Response predictors and associations of the NANTRC version 1.0 (NANTRCv1.0) and prognostic factors with outcome were analyzed. A retrospective analysis was performed of patients with recurrent/refractory neuroblastoma enrolled from 2000 to 2009 on 13 NANT Phase 1/2 trials. NANTRC overall response integrated CT/MRI (Response Evaluation Criteria in Solid Tumors [RECIST]), metaiodobenzylguanidine (MIBG; Curie scoring), and percent bone marrow (BM) tumor (morphology). Fourteen (6.9%) complete response (CR) and 14 (6.9%) partial response (PR) occurred among 203 patients evaluable for response. Five-year progression-free survival (PFS) was 16 ± 3%; overall survival (OS) was 27 ± 3%. Disease sites at enrollment included MIBG-avid lesions (100% MIBG trials; 84% non-MIBG trials), measurable CT/MRI lesions (48%), and BM (49%). By multivariable analysis, Curie score of 0 (P < 0.001), lower Curie score (P = 0.003), no measurable CT/MRI lesions (P = 0.044), and treatment on peripheral blood stem cell (PBSC) supported trials (P = 0.005) were associated with achieving CR/PR. Overall response of stable disease (SD) or better was associated with better OS (P < 0.001). In multivariable analysis, MYCN amplification (P = 0.037) was associated with worse PFS; measurable CT/MRI lesions (P = 0.041) were associated with worse OS; prior progressive disease (PD; P < 0.001/P < 0.001), Curie score ≥ 1 (P < 0.001; P = 0.001), higher Curie score (P = 0.048/0.037), and treatment on non-PBSC trials (P = < 0.001/0.003) were associated with worse PFS and OS. NANTRCv1.0 response of at least SD is associated with better OS in patients with recurrent/refractory neuroblastoma. Patient and tumor characteristics may predict response and outcome. Identifying these variables can optimize Phase 1/2 trial

  15. Post-Progression Survival Associated with Overall Survival in Patients with Advanced Non-Small-Cell Lung Cancer Receiving Docetaxel Monotherapy as Second-Line Chemotherapy.

    PubMed

    Kotake, Mie; Miura, Yosuke; Imai, Hisao; Mori, Keita; Sakurai, Reiko; Kaira, Kyoichi; Tomizawa, Yoshio; Minato, Koichi; Saito, Ryusei; Hisada, Takeshi

    2017-01-01

    In patients with non-small-cell lung cancer (NSCLC), the effects of second-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies. Therefore, using individual-level data, we aimed to determine the relationships between progression-free survival (PFS) and post-progression survival (PPS) with OS in patients with advanced NSCLC treated with docetaxel monotherapy as second-line chemotherapy. Between April 2002 and December 2014, data from 86 patients with advanced NSCLC who underwent second-line docetaxel monotherapy following first-line treatment with platinum combination chemotherapy were analyzed. The relationships of PFS and PPS with OS were analyzed at the individual level. Spearman rank correlation and linear regression analyses showed that PPS was strongly associated with OS (r = 0.86, p < 0.05, R2 = 0.93), whereas PFS was moderately correlated with OS (r = 0.50, p < 0.05, R2 = 0.21). Performance status at the end of second-line treatment and the number of regimens after progression beyond second-line chemotherapy were significantly associated with PPS (p < 0.05). In patients with advanced NSCLC with unknown oncogenic driver mutations undergoing docetaxel monotherapy as second-line chemotherapy, when compared with PFS, PPS had a stronger association with OS. This finding suggests that subsequent treatment after disease progression following second-line docetaxel monotherapy has a significant influence on OS. © 2017 S. Karger AG, Basel.

  16. 26 CFR 300.7 - Enrollment of enrolled actuary fee.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 18 2014-04-01 2014-04-01 false Enrollment of enrolled actuary fee. 300.7... AND ADMINISTRATION USER FEES § 300.7 Enrollment of enrolled actuary fee. (a) Applicability. This section applies to the initial enrollment of enrolled actuaries with the Joint Board for the Enrollment of...

  17. 26 CFR 300.7 - Enrollment of enrolled actuary fee.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 18 2013-04-01 2013-04-01 false Enrollment of enrolled actuary fee. 300.7... AND ADMINISTRATION USER FEES § 300.7 Enrollment of enrolled actuary fee. (a) Applicability. This section applies to the initial enrollment of enrolled actuaries with the Joint Board for the Enrollment of...

  18. 26 CFR 300.7 - Enrollment of enrolled actuary fee.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 18 2011-04-01 2011-04-01 false Enrollment of enrolled actuary fee. 300.7... AND ADMINISTRATION USER FEES § 300.7 Enrollment of enrolled actuary fee. (a) Applicability. This section applies to the initial enrollment of enrolled actuaries with the Joint Board for the Enrollment of...

  19. 26 CFR 300.7 - Enrollment of enrolled actuary fee.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 18 2012-04-01 2012-04-01 false Enrollment of enrolled actuary fee. 300.7... AND ADMINISTRATION USER FEES § 300.7 Enrollment of enrolled actuary fee. (a) Applicability. This section applies to the initial enrollment of enrolled actuaries with the Joint Board for the Enrollment of...

  20. 26 CFR 300.7 - Enrollment of enrolled actuary fee.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Enrollment of enrolled actuary fee. 300.7... AND ADMINISTRATION USER FEES § 300.7 Enrollment of enrolled actuary fee. (a) Applicability. This section applies to the initial enrollment of enrolled actuaries with the Joint Board for the Enrollment of...

  1. Progression-Free Survival Among Patients With Well-Differentiated or Dedifferentiated Liposarcoma Treated With CDK4 Inhibitor Palbociclib: A Phase 2 Clinical Trial.

    PubMed

    Dickson, Mark A; Schwartz, Gary K; Keohan, Mary Louise; D'Angelo, Sandra P; Gounder, Mrinal M; Chi, Ping; Antonescu, Cristina R; Landa, Jonathan; Qin, Li-Xuan; Crago, Aimee M; Singer, Samuel; Koff, Andrew; Tap, William D

    2016-07-01

    More than 90% of well-differentiated or dedifferentiated liposarcomas (WD/DDLS) have CDK4 amplification. The selective CDK4 and CDK6 inhibitor palbociclib inhibits growth and induces senescence in liposarcoma cell lines and xenografts. Our prior phase 2 study demonstrated that treatment with palbociclib (200 mg daily for 14 days every 21 days) resulted in clinical benefit in WD/DDLS but moderate hematologic toxic effects. It is important to understand whether palbociclib at a new dose and schedule-125 mg daily for 21 days every 28 days-results in clinical benefit and manageable toxic effects. To determine the progression-free survival (PFS) at 12 weeks of patients with WD/DDLS treated with palbociclib (PD0332991). In this phase 2, nonrandomized, open-label clinical trial conducted at the Memorial Sloan Kettering Cancer Center, 60 patients 18 years and older with advanced WD/DDLS and measurable disease by RECIST 1.1 were enrolled from December 2011 to January 2014 and followed to March 2015. Patients received oral palbociclib at 125 mg daily for 21 days in 28-day cycles. Primary end point was PFS. Secondary end points included response rate and toxic effects. Overall, 30 patients were enrolled in the initial cohort and 30 more in an expansion cohort. Median (range) age was 61.5 (35-87) years; 31 patients (52%) were male; median (range) Eastern Cooperative Oncology Group score was 0 (0-1). Progression-free survival at 12 weeks was 57.2% (2-sided 95% CI, 42.4%-68.8%), and the median PFS was 17.9 weeks (2-sided 95% CI, 11.9-24.0 weeks). There was 1 complete response. Toxic effects were primarily hematologic and included neutropenia (grade 3, n = 20 [33%]; grade 4, n = 2 [3%]) but no neutropenic fever. In patients with advanced WD/DDLS, treatment with palbociclib was associated with a favorable PFS and occasional tumor response. This dose and schedule appears active and may have less toxic effects than 200 mg for 14 days. clinicaltrials.gov Identifier: NCT

  2. Actuarial considerations of medical malpractice evaluations in M&As.

    PubMed

    Frese, Richard C

    2014-11-01

    To best project an actuarial estimate for medical malpractice exposure for a merger and acquisition, a organization's leaders should consider the following factors, among others: How to support an unbiased actuarial estimation. Experience of the actuary. The full picture of the organization's malpractice coverage. The potential for future loss development. Frequency and severity trends.

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

    PubMed Central

    2012-01-01

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

  4. 29 CFR 4231.10 - Actuarial calculations and assumptions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... MULTIEMPLOYER PLANS § 4231.10 Actuarial calculations and assumptions. (a) Most recent valuation. All calculations required by this part must be based on the most recent actuarial valuation as of the date of...

  5. 29 CFR 4231.10 - Actuarial calculations and assumptions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... MULTIEMPLOYER PLANS § 4231.10 Actuarial calculations and assumptions. (a) Most recent valuation. All calculations required by this part must be based on the most recent actuarial valuation as of the date of...

  6. 29 CFR 4231.10 - Actuarial calculations and assumptions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... MULTIEMPLOYER PLANS § 4231.10 Actuarial calculations and assumptions. (a) Most recent valuation. All calculations required by this part must be based on the most recent actuarial valuation as of the date of...

  7. 29 CFR 4231.10 - Actuarial calculations and assumptions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... MULTIEMPLOYER PLANS § 4231.10 Actuarial calculations and assumptions. (a) Most recent valuation. All calculations required by this part must be based on the most recent actuarial valuation as of the date of...

  8. 29 CFR 4231.10 - Actuarial calculations and assumptions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... MULTIEMPLOYER PLANS § 4231.10 Actuarial calculations and assumptions. (a) Most recent valuation. All calculations required by this part must be based on the most recent actuarial valuation as of the date of...

  9. Developing an Actuarial Track Utilizing Existing Resources

    ERIC Educational Resources Information Center

    Rodgers, Kathy V.; Sarol, Yalçin

    2014-01-01

    Students earning a degree in mathematics often seek information on how to apply their mathematical knowledge. One option is to follow a curriculum with an actuarial emphasis designed to prepare students as an applied mathematician in the actuarial field. By developing only two new courses and utilizing existing courses for Validation by…

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

    PubMed

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

    2014-01-01

    Obesity, smoking, hypertension, and diabetes are risk factors for renal cell carcinoma development. Their presence has been associated with a worse outcome in various cancers. We sought to determine their association with outcome of sunitinib treatment in metastatic renal cell carcinoma (mRCC). An international multicenter retrospective study of sunitinib-treated mRCC patients was performed. Multivariate analyses were performed to determine the association between outcome and the pretreatment status of smoking, body mass index, hypertension, diabetes, and other known prognostic factors. Between 2004 and 2013, 278 mRCC patients were treated with sunitinib: 59 were active smokers, 67 were obese, 73 were diabetic, and 165 had pretreatment hypertension. Median progression-free survival (PFS) was 9 months, and overall survival (OS) was 22 months. Factors associated with PFS were smoking status (past and active smokers: hazard ratio [HR]: 1.17, p = .39; never smokers: HR: 2.94, p < .0001), non-clear cell histology (HR: 1.62, p = .011), pretreatment neutrophil-to-lymphocyte ratio >3 (HR: 3.51, p < .0001), use of angiotensin system inhibitors (HR: 0.63, p = .01), sunitinib dose reduction or treatment interruption (HR: 0.72, p = .045), and Heng risk (good and intermediate risk: HR: 1.07, p = .77; poor risk: HR: 1.87, p = .046). Factors associated with OS were smoking status (past and active smokers: HR: 1.25, p = .29; never smokers: HR: 2.7, p < .0001), pretreatment neutrophil-to-lymphocyte ratio >3 (HR: 2.95, p < .0001), and sunitinib-induced hypertension (HR: 0.57, p = .002). Active smoking may negatively affect the PFS and OS of sunitinib-treated mRCC. Clinicians should consider advising patients to quit smoking at initiation of sunitinib treatment for mRCC.

  11. Historical time to disease progression and progression-free survival in patients with recurrent/refractory neuroblastoma treated in the modern era on Children's Oncology Group early-phase trials.

    PubMed

    London, Wendy B; Bagatell, Rochelle; Weigel, Brenda J; Fox, Elizabeth; Guo, Dongjing; Van Ryn, Collin; Naranjo, Arlene; Park, Julie R

    2017-12-15

    Early-phase trials in patients with recurrent neuroblastoma historically used an objective "response" of measureable disease (Response Evaluation Criteria In Solid Tumors [RECIST], without bone/bone marrow assessment) to select agents for further study. Historical cohorts may be small and potentially biased; to the authors' knowledge, disease recurrence studies from international registries are outdated. Using a large recent cohort of patients with recurrent/refractory neuroblastoma from Children's Oncology Group (COG) modern-era early-phase trials, the authors determined outcome and quantified parameters for designing future studies. The first early-phase COG trial enrollment (sequential) of 383 distinct patients with recurrent/refractory neuroblastoma on 23 phase 1, 3 phase 1/2, and 9 phase 2 trials (August 2002 to January 2014) was analyzed for progression-free survival (PFS), overall survival (OS), and time to disease progression (TTP). Planned frontline therapy for patients with high-risk neuroblastoma included hematopoietic stem cell transplantation (approximately two-thirds of patients underwent ≥1 hematopoietic stem cell transplantation); 13.2% of patients received dinutuximab. From the time of the patient's first early-phase trial enrollment (383 patients), the 1-year and 4-year PFS rates ( ± standard error) were 21% ± 2% and 6% ± 1%, respectively, whereas the 1-year and 4-year OS rates were 57% ± 3% and 20% ± 2%, respectively. The median TTP was 58 days (interquartile range, 31-183 days [350 patients]); the median follow-up was 25.3 months (33 patients were found to be without disease recurrence/progression). The median time from diagnosis to first disease recurrence/progression was 18.7 months (range, 1.4-64.8 months) (176 patients). MYCN amplification and 11q loss of heterozygosity were prognostic of worse PFS and OS (P = .003 and P<.0001, respectively, and P = .02 and P = .03, respectively) after early-phase trial

  12. 20 CFR 901.20 - Standards of performance of actuarial services.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... explanation relative to any report signed or certified by such enrolled actuary. (d) Conflicts of interest. In any situation in which the enrolled actuary has a conflict of interest with respect to the performance... not of a distinctive nature. (h) Notification. An enrolled actuary shall provide written notification...

  13. The Undergraduate Statistics Major--A Prelude to Actuarial Science Training.

    ERIC Educational Resources Information Center

    Ratliff, Michael I.; Williams, Raymond E.

    Recently there has been increased interest related to the Actuarial Science field. An actuary is a business professional who uses mathematical skills to define, analyze, and solve financial and social problems. This paper examines: (1) the interface between Statistical and Actuarial Science training; (2) statistical courses corresponding to…

  14. 77 FR 63337 - Renewal of Charter of Advisory Committee on Actuarial Examinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-16

    ... examinations in actuarial mathematics and methodology. The Joint Board administers such examinations in... JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES Renewal of Charter of Advisory Committee on Actuarial... the Advisory Committee on Actuarial Examinations. FOR FURTHER INFORMATION CONTACT: Patrick McDonough...

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

    PubMed

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

    2017-10-01

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

  16. Bone Scan Index and Progression-free Survival Data for Progressive Metastatic Castration-resistant Prostate Cancer Patients Who Received ODM-201 in the ARADES Multicentre Study.

    PubMed

    Reza, Mariana; Jones, Robert; Aspegren, John; Massard, Christophe; Mattila, Leena; Mustonen, Mika; Wollmer, Per; Trägårdh, Elin; Bondesson, Eva; Edenbrandt, Lars; Fizazi, Karim; Bjartell, Anders

    2016-12-01

    ODM-201, a new-generation androgen receptor inhibitor, has shown clinical efficacy in prostate cancer (PCa). Quantitative methods are needed to accurately assess changes in bone as a measurement of treatment response. The Bone Scan Index (BSI) reflects the percentage of skeletal mass a given tumour affects. To evaluate the predictive value of the BSI in metastatic castration-resistant PCa (mCRPC) patients undergoing treatment with ODM-201. From a total of 134 mCRPC patients who participated in the Activity and Safety of ODM-201 in Patients with Progressive Metastatic Castration-resistant Prostate Cancer clinical trial and received ODM-201, we retrospectively selected all those patients who had bone scan image data of sufficient quality to allow for both baseline and 12-wk follow-up BSI-assessments (n=47). We used the automated EXINI bone BSI software (EXINI Diagnostics AB, Lund, Sweden) to obtain BSI data. We used the Cox proportional hazards model and Kaplan-Meier estimates to investigate the association among BSI, traditional clinical parameters, disease progression, and radiographic progression-free survival (rPFS). In the BSI assessments, at follow-up, patients who had a decrease or at most a 20% increase from BSI baseline had a significantly longer time to progression in bone (median not reached vs 23 wk, hazard ratio [HR]: 0.20; 95% confidence interval [CI], 0.07-0.58; p=0.003) and rPFS (median: 50 wk vs 14 wk; HR: 0.35; 95% CI, 0.17-0.74; p=0.006) than those who had a BSI increase >20% during treatment. The on-treatment change in BSI was significantly associated with rPFS in mCRPC patients, and an increase >20% in BSI predicted reduced rPFS. BSI for quantification of bone metastases may be a valuable complementary method for evaluation of treatment response in mCRPC patients. An increase in Bone Scan Index (BSI) was associated with shorter time to disease progression in patients treated with ODM-201. BSI may be a valuable method of complementing treatment

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

    Purpose Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Methods Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti–epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R2 statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models. Results Forty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R2, 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy. Conclusion In modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents. PMID:25385741

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

    PubMed

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

    2017-01-01

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

  20. Inferior progression-free survival for Thai patients with diffuse large B-cell lymphoma treated under Universal Coverage Scheme: the impact of rituximab inaccessability.

    PubMed

    Intragumtornchai, Tanin; Bunworasate, Udomsak; Siritanaratkul, Noppadol; Khuhapinant, Archrob; Nawarawong, Weerasak; Norasetthada, Lalita; Lekhakula, Arnuparp; Rujirojindakul, Pairaya; Sirijerachai, Chittima; Chansung, Kanjana; Suwanban, Tawatchai; Chuncharunee, Suporn; Niparuck, Pimjai; Wongkhantee, Somchai; Mongkonsritragoon, Wichean; Numbenjapon, Tontanai

    2013-01-01

    The impact of health insurance with inequitable rituximab coverage on the survival of patients with diffuse large B-cell lymphoma (DLBCL) has never been reported. We conducted a nationwide multicenter analysis on the outcome of 553 adult patients consecutively diagnosed with DLBCL between July 2003 and June 2006, in whom treatment cost was reimbursed under the Civil Servant Medical Benefit Scheme (CSMBS) (n =201) or the Universal Coverage Scheme (UCS) (n =352). The international prognostic index was comparable between the two payment groups. Rituximab-based therapy was administered in 45.3% and 3.1% of CSMBS and UCS patients, respectively (p <0.001). With a median follow-up of 24.6 months, the 6-year progression-free survival (PFS) was superior for CSMBS patients (34.2 vs. 23.2%, p =0.005). "Not treated with rituximab-based therapy" was the strongest adverse prognostic feature indicating a short PFS (hazard ratio 2.1, p <0.001). It is concluded that lack of access to rituximab is the principal factor accounting for the inferior PFS observed in Thai patients with DLBCL who are treated under the UCS.

  1. Development and validation of a radiomics nomogram for progression-free survival prediction in stage IV EGFR-mutant non-small cell lung cancer

    NASA Astrophysics Data System (ADS)

    Song, Jiangdian; Zang, Yali; Li, Weimin; Zhong, Wenzhao; Shi, Jingyun; Dong, Di; Fang, Mengjie; Liu, Zaiyi; Tian, Jie

    2017-03-01

    Accurately predict the risk of disease progression and benefit of tyrosine kinase inhibitors (TKIs) therapy for stage IV non-small cell lung cancer (NSCLC) patients with activing epidermal growth factor receptor (EGFR) mutations by current staging methods are challenge. We postulated that integrating a classifier consisted of multiple computed tomography (CT) phenotypic features, and other clinicopathological risk factors into a single model could improve risk stratification and prediction of progression-free survival (PFS) of EGFR TKIs for these patients. Patients confirmed as stage IV EGFR-mutant NSCLC received EGFR TKIs with no resection; pretreatment contrast enhanced CT performed at approximately 2 weeks before the treatment was enrolled. A six-CT-phenotypic-feature-based classifier constructed by the LASSO Cox regression model, and three clinicopathological factors: pathologic N category, performance status (PS) score, and intrapulmonary metastasis status were used to construct a nomogram in a training set of 115 patients. The prognostic and predictive accuracy of this nomogram was then subjected to an external independent validation of 107 patients. PFS between the training and independent validation set is no statistical difference by Mann-Whitney U test (P = 0.2670). PFS of the patients could be predicted with good consistency compared with the actual survival. C-index of the proposed individualized nomogram in the training set (0·707, 95%CI: 0·643, 0·771) and the independent validation set (0·715, 95%CI: 0·650, 0·780) showed the potential of clinical prognosis to predict PFS of stage IV EGFR-mutant NSCLC from EGFR TKIs. The individualized nomogram might facilitate patient counselling and individualise management of patients with this disease.

  2. Cardiovascular risk factors predictive for survival and morbidity-free survival in the oldest-old Framingham Heart Study participants.

    PubMed

    Terry, Dellara F; Pencina, Michael J; Vasan, Ramachandran S; Murabito, Joanne M; Wolf, Philip A; Hayes, Margaret Kelly; Levy, Daniel; D'Agostino, Ralph B; Benjamin, Emelia J

    2005-11-01

    To examine whether midlife cardiovascular risk factors predict survival and survival free of major comorbidities to the age of 85. Prospective community-based cohort study. Framingham Heart Study, Massachusetts. Two thousand five hundred thirty-one individuals (1,422 women) who attended at least two examinations between the ages of 40 and 50. Risk factors were classified at routine examinations performed between the ages of 40 and 50. Stepwise sex-adjusted logistic regression models predicting the outcomes of survival and survival free of morbidity to age 85 were selected from the following risk factors: systolic and diastolic blood pressure, total serum cholesterol, glucose intolerance, cigarette smoking, education, body mass index, physical activity index, pulse pressure, antihypertensive medication, and electrocardiographic left ventricular hypertrophy. More than one-third of the study sample survived to age 85, and 22% of the original study sample survived free of morbidity. Lower midlife blood pressure and total cholesterol levels, absence of glucose intolerance, nonsmoking status, higher educational attainment, and female sex predicted overall and morbidity-free survival. The predicted probability of survival to age 85 fell in the presence of accumulating risk factors: 37% for men with no risk factors to 2% with all five risk factors and 65% for women with no risk factors to 14% with all five risk factors. Lower levels of key cardiovascular risk factors in middle age predicted overall survival and major morbidity-free survival to age 85. Recognizing and modifying these factors may delay, if not prevent, age-related morbidity and mortality.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wiegel, Thomas, E-mail: thomas.wiegel@uniklinik-ulm.de; Bartkowiak, Detlef; Bottke, Dirk

    2015-02-01

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

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

    PubMed

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

    2018-05-01

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

  5. Resection of synchronous liver metastases between radiotherapy and definitive surgery for locally advanced rectal cancer: short-term surgical outcomes, overall survival and recurrence-free survival.

    PubMed

    Labori, K J; Guren, M G; Brudvik, K W; Røsok, B I; Waage, A; Nesbakken, A; Larsen, S; Dueland, S; Edwin, B; Bjørnbeth, B A

    2017-08-01

    There is debate as to the correct treatment algorithm sequence for patients with locally advanced rectal cancer with liver metastases. The aim of the study was to assess safety, resectability and survival after a modified 'liver-first' approach. This was a retrospective study of patients undergoing preoperative radiotherapy for the primary rectal tumour, followed by liver resection and, finally, resection of the primary tumour. Short-term surgical outcome, overall survival and recurrence-free survival are reported. Between 2009 and 2013, 45 patients underwent liver resection after preoperative radiotherapy. Thirty-four patients (76%) received neoadjuvant chemotherapy, 24 (53%) concomitant chemotherapy during radiotherapy and 17 (43%) adjuvant chemotherapy. The median time interval from the last fraction of radiotherapy to liver resection and rectal surgery was 21 (range 7-116) and 60 (range 31-156) days, respectively. Rectal resection was performed in 42 patients but was not performed in one patient with complete response and two with progressive metastatic disease. After rectal surgery three patients did not proceed to a planned second stage liver (n = 2) or lung (n = 1) resection due to progressive disease. Clavien-Dindo ≥Grade III complications developed in 6.7% after liver resection and 19% after rectal resection. The median overall survival and recurrence-free survival in the patients who completed the treatment sequence (n = 40) were 49.7 and 13.0 months, respectively. Twenty of the 30 patients who developed recurrence underwent further treatment with curative intent. The modified liver-first approach is safe and efficient in patients with locally advanced rectal cancer and allows initial control of both the primary tumour and the liver metastases. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

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

    PubMed

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

    2009-02-01

    Prognosis in women with ovarian cancer mainly depends on International Federation of Gynecology and Obstetrics stage and the ability to perform optimal cytoreductive surgery. Since ovarian cancer has a heterogeneous presentation and clinical course, predicting progression-free survival (PFS) and overall survival (OS) in the individual patient is difficult. The objective of this study was to determine predictors of PFS and OS in women with advanced stage epithelial ovarian cancer (EOC) after primary cytoreductive surgery and first-line platinum-based chemotherapy. Retrospective observational study. Two teaching hospitals and one university hospital in the south-western part of the Netherlands. Women with advanced stage EOC. All women who underwent primary cytoreductive surgery for advanced stage EOC followed by first-line platinum-based chemotherapy between January 1998 and October 2004 were identified. To investigate independent predictors of PFS and OS, a Cox' proportional hazard model was used. Nomograms were generated with the identified predictive parameters. The primary outcome measure was OS and the secondary outcome measures were response and PFS. A total of 118 women entered the study protocol. Median PFS and OS were 15 and 44 months, respectively. Preoperative platelet count (P = 0.007), and residual disease <1 cm (P = 0.004) predicted PFS with a optimism corrected c-statistic of 0.63. Predictive parameters for OS were preoperative haemoglobin serum concentration (P = 0.012), preoperative platelet counts (P = 0.031) and residual disease <1 cm (P = 0.028) with a optimism corrected c-statistic of 0.67. PFS could be predicted by postoperative residual disease and preoperative platelet counts, whereas residual disease, preoperative platelet counts and preoperative haemoglobin serum concentration were predictive for OS. The proposed nomograms need to be externally validated.

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

    PubMed

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

    2013-05-01

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

  8. Different actuarial risk measures produce different risk rankings for sexual offenders.

    PubMed

    Barbaree, Howard E; Langton, Calvin M; Peacock, Edward J

    2006-10-01

    Percentile ranks were computed for N=262 sex offenders using each of 5 actuarial risk instruments commonly used with adult sex offenders (RRASOR, Static-99, VRAG, SORAG, and MnSOST-R). Mean differences between percentile ranks obtained by different actuarial measures were found to vary inversely with the correlation between the actuarial scores. Following studies of factor analyses of actuarial items, we argue that the discrepancies among actuarial instruments can be substantially accounted for by the way in which the factor Antisocial Behavior and various factors reflecting sexual deviance are represented among the items contained in each instrument. In the discussion, we provide guidance to clinicians in resolving discrepancies between instruments and we discuss implications for future developments in sex offender risk assessment.

  9. Outpatient biopsy of breast cancer. Influence on survival.

    PubMed Central

    Bertario, L; Reduzzi, D; Piromalli, D; Piva, L; Di Pietro, S

    1985-01-01

    From 1948 to 1975, at the Istituto Nazionale Tumori of Milan, 209 patients underwent extended radical mastectomy (ERM) for breast cancer classified as T1 NO-1 MO. In 57 patients (27.3%), the ERM was preceded by an excisional biopsy performed in the outpatient clinic (Group A), of which 75% were performed within 30 days of admission and 25% after 30 days (average, 25 days; range 5-99). The remaining 152 patients (Group B) underwent an extemporaneous frozen biopsy. There was no difference in the distribution of the histologic types in the two groups. The axillary lymph nodes (N) and the internal mammary chain (MI) were free of neoplastic invasion (N-, MI-) in 156 patients (74.6%), 44 in Group A (77.2%) and 112 in Group B (73.7%). Actuarial 10-year survival of the patients was 79.9% in Group A and 77.7% in Group B (p = NS). It was 90% in N- MI- patients of Group A and 81.9% in those of Group B (p = NS). Instead, for N+ patients, actuarial survival at 10 years was 50% in Group A and 67% in Group B (p = NS), and for MI+ patients it was 50% and 49.8%, respectively. These present data do not support the hypothesis that a delay between biopsy and radical surgery of breast cancer is an important prognostic factor. PMID:3966829

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

    PubMed

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

    2017-02-01

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

  11. 26 CFR 300.8 - Renewal of enrollment of enrolled actuary fee.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 18 2014-04-01 2014-04-01 false Renewal of enrollment of enrolled actuary fee...) PROCEDURE AND ADMINISTRATION USER FEES § 300.8 Renewal of enrollment of enrolled actuary fee. (a) Applicability. This section applies to the renewal of enrollment of enrolled actuaries with the Joint Board for...

  12. 26 CFR 300.8 - Renewal of enrollment of enrolled actuary fee.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 18 2013-04-01 2013-04-01 false Renewal of enrollment of enrolled actuary fee...) PROCEDURE AND ADMINISTRATION USER FEES § 300.8 Renewal of enrollment of enrolled actuary fee. (a) Applicability. This section applies to the renewal of enrollment of enrolled actuaries with the Joint Board for...

  13. 26 CFR 300.8 - Renewal of enrollment of enrolled actuary fee.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 18 2012-04-01 2012-04-01 false Renewal of enrollment of enrolled actuary fee...) PROCEDURE AND ADMINISTRATION USER FEES § 300.8 Renewal of enrollment of enrolled actuary fee. (a) Applicability. This section applies to the renewal of enrollment of enrolled actuaries with the Joint Board for...

  14. 26 CFR 300.8 - Renewal of enrollment of enrolled actuary fee.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 18 2011-04-01 2011-04-01 false Renewal of enrollment of enrolled actuary fee...) PROCEDURE AND ADMINISTRATION USER FEES § 300.8 Renewal of enrollment of enrolled actuary fee. (a) Applicability. This section applies to the renewal of enrollment of enrolled actuaries with the Joint Board for...

  15. 26 CFR 300.8 - Renewal of enrollment of enrolled actuary fee.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Renewal of enrollment of enrolled actuary fee...) PROCEDURE AND ADMINISTRATION USER FEES § 300.8 Renewal of enrollment of enrolled actuary fee. (a) Applicability. This section applies to the renewal of enrollment of enrolled actuaries with the Joint Board for...

  16. Strategic Curricular Decisions in Butler University's Actuarial Science Major

    ERIC Educational Resources Information Center

    Wilson, Christopher James

    2014-01-01

    We describe specific curricular decisions employed at Butler University that have resulted in student achievement in the actuarial science major. The paper includes a discussion of how these decisions might be applied in the context of a new actuarial program.

  17. Post-operative radiation therapy for advanced-stage oropharyngeal cancer.

    PubMed

    Hansen, Eric; Panwala, Kathryn; Holland, John

    2002-11-01

    Between 1985 and 1999, 43 patients with locally-advanced, resectable oropharyngeal cancer were treated with combined surgery and post-operative radiation therapy (RT) at Oregon Health and Science University. Five patients (12 per cent) had Stage III disease and 38 patients (88 per cent) had Stage IV disease. All patients had gross total resections of the primary tumour. Thirty-seven patients had neck dissections for regional disease. RT consisted of a mean tumour-bed dose of 63.0 Gy delivered in 1.8-2.0 Gy fractions over a mean of 49 days. At three- and five-years, the actuarial local control was 96 per cent and the actuarial local/regional control was 80 per cent. The three- and five-year actuarial rates of distant metastases were 41 per cent and 46 per cent, respectively. The actuarial overall survival at three- and five-years was 41 per cent and 34 per cent, respectively. The actuarial rates of progression-free survival were 49 per cent at three-years and 45 per cent at five years. Combined surgery and post-operative RT for advanced-stage oropharyngeal cancer results in excellent local/regional control. This particular group of patients experienced a high-rate of developing distant metastases.

  18. 42 CFR 440.340 - Actuarial report for benchmark-equivalent coverage.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... individual who is a member of the American Academy of Actuaries (AAA). (2) Using generally accepted actuarial principles and methodologies of the AAA. (3) Using a standardized set of utilization and price factors. (4...

  19. Detection of minimal residual disease following induction immunochemotherapy predicts progression free survival in mantle cell lymphoma: final results of CALGB 59909

    PubMed Central

    Liu, Hongtao; Johnson, Jeffrey L.; Koval, Greg; Malnassy, Greg; Sher, Dorie; Damon, Lloyd E.; Hsi, Eric D.; Bucci, Donna Marie; Linker, Charles A.; Cheson, Bruce D.; Stock, Wendy

    2012-01-01

    Background In the present study, the prognostic impact of minimal residual disease during treatment on time to progression and overall survival was analyzed prospectively in patients with mantle cell lymphoma treated on the Cancer and Leukemia Group B 59909 clinical trial. Design and Methods Peripheral blood and bone marrow samples were collected during different phases of the Cancer and Leukemia Group B 59909 study for minimal residual disease analysis. Minimal residual disease status was determined by quantitative polymerase chain reaction of IgH and/or BCL-1/JH gene rearrangement. Correlation of minimal residual disease status with time to progression and overall survival was determined. In multivariable analysis, minimal residual disease, and other risk factors were correlated with time to progression. Results Thirty-nine patients had evaluable, sequential peripheral blood and bone marrow samples for minimal residual disease analysis. Using peripheral blood monitoring, 18 of 39 (46%) achieved molecular remission following induction therapy. The molecular remission rate increased from 46 to 74% after one course of intensification therapy. Twelve of 21 minimal residual disease positive patients (57%) progressed within three years of follow up compared to 4 of 18 (22%) molecular remission patients (P=0.049). Detection of minimal residual disease following induction therapy predicted disease progression with a hazard ratio of 3.7 (P=0.016). The 3-year probability of time to progression among those who were in molecular remission after induction chemotherapy was 82% compared to 48% in patients with detectable minimal residual disease. The prediction of time to progression by post-induction minimal residual disease was independent of other prognostic factors in multivariable analysis. Conclusions Detection of minimal residual disease following induction immunochemotherapy was an independent predictor of time to progression following immunochemotherapy and autologous

  20. Actuarial risk assessment: commentary on Berlin et al.

    PubMed

    Hart, Stephen D

    2003-10-01

    F. S. Berlin, N. W. Galbreath, B. Geary, and G. McGlone (this issue) have raised some important questions regarding the use of acturial risk assessment instruments in sex offender civil commitment proceedings, also known as sexually violent predator or SVP proceedings. Their primary point is that interpreting the findings of existing actuarial risk assessment instruments is a tricky business because it is not certain whether the extent to which probability estimates derived from group data can be applied to individual cases. I agree completely with Berlin et al. on this point, but disagree with them concerning the extent to which probability estimates--and, therefore, actuarial instruments--are legally relevant in SVP proceedings. I outline some potential problems with respect to the legal admissibility of actuarial instruments, including their legal relevance.

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

    PubMed Central

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

    2017-01-01

    Purpose: The advent of genomic diagnostic technologies such as next-generation sequencing has recently enabled the use of genomic information to guide targeted treatment in patients with cancer, an approach known as precision medicine. However, clinical outcomes, including survival and the cost of health care associated with precision cancer medicine, have been challenging to measure and remain largely unreported. Patients and Methods: We conducted a matched cohort study of 72 patients with metastatic cancer of diverse subtypes in the setting of a large, integrated health care delivery system. We analyzed the outcomes of 36 patients who received genomic testing and targeted therapy (precision cancer medicine) between July 1, 2013, and January 31, 2015, compared with 36 historical control patients who received standard chemotherapy (n = 29) or best supportive care (n = 7). Results: The average progression-free survival was 22.9 weeks for the precision medicine group and 12.0 weeks for the control group (P = .002) with a hazard ratio of 0.47 (95% CI, 0.29 to 0.75) when matching on age, sex, histologic diagnosis, and previous lines of treatment. In a subset analysis of patients who received all care within the Intermountain Healthcare system (n = 44), per patient charges per week were $4,665 in the precision treatment group and $5,000 in the control group (P = .126). Conclusion: These findings suggest that precision cancer medicine may improve survival for patients with refractory cancer without increasing health care costs. Although the results of this study warrant further validation, this precision medicine approach may be a viable option for patients with advanced cancer. PMID:27601506

  2. Neuroblastoma cells depend on HDAC11 for mitotic cell cycle progression and survival

    PubMed Central

    Thole, Theresa M; Lodrini, Marco; Fabian, Johannes; Wuenschel, Jasmin; Pfeil, Sebastian; Hielscher, Thomas; Kopp-Schneider, Annette; Heinicke, Ulrike; Fulda, Simone; Witt, Olaf; Eggert, Angelika; Fischer, Matthias; Deubzer, Hedwig E

    2017-01-01

    The number of long-term survivors of high-risk neuroblastoma remains discouraging, with 10-year survival as low as 20%, despite decades of considerable international efforts to improve outcome. Major obstacles remain and include managing resistance to induction therapy, which causes tumor progression and early death in high-risk patients, and managing chemotherapy-resistant relapses, which can occur years after the initial diagnosis. Identifying and validating novel therapeutic targets is essential to improve treatment. Delineating and deciphering specific functions of single histone deacetylases in neuroblastoma may support development of targeted acetylome-modifying therapeutics for patients with molecularly defined high-risk neuroblastoma profiles. We show here that HDAC11 depletion in MYCN-driven neuroblastoma cell lines strongly induces cell death, mostly mediated by apoptotic programs. Genes necessary for mitotic cell cycle progression and cell division were most prominently enriched in at least two of three time points in whole-genome expression data combined from two cell systems, and all nine genes in these functional categories were strongly repressed, including CENPA, KIF14, KIF23 and RACGAP1. Enforced expression of one selected candidate, RACGAP1, partially rescued the induction of apoptosis caused by HDAC11 depletion. High-level expression of all nine genes in primary neuroblastomas significantly correlated with unfavorable overall and event-free survival in patients, suggesting a role in mediating the more aggressive biological and clinical phenotype of these tumors. Our study identified a group of cell cycle-promoting genes regulated by HDAC11, being both predictors of unfavorable patient outcome and essential for tumor cell viability. The data indicate a significant role of HDAC11 for mitotic cell cycle progression and survival of MYCN-amplified neuroblastoma cells, and suggests that HDAC11 could be a valuable drug target. PMID:28252645

  3. 75 FR 22754 - Federal Advisory Committee; Department of Defense Board of Actuaries; Charter Renewal

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-30

    ... Board of Actuaries; Charter Renewal AGENCY: Department of Defense (DoD). ACTION: Renewal of Federal... Department of Defense Board of Actuaries (hereafter referred to as the Board). FOR FURTHER INFORMATION... qualified professional actuaries who are members of the Society of Actuaries. Board members shall be...

  4. 26 CFR 301.6692-1 - Failure to file actuarial report.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... enrolled actuary (see § 301.6059-1(d)) is considered a material item of information. Further, for any report filed for a plan year ending after January 25, 1982, if the actuary seeks to materially qualify a...

  5. 26 CFR 301.6692-1 - Failure to file actuarial report.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... enrolled actuary (see § 301.6059-1(d)) is considered a material item of information. Further, for any report filed for a plan year ending after January 25, 1982, if the actuary seeks to materially qualify a...

  6. 26 CFR 301.6692-1 - Failure to file actuarial report.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... enrolled actuary (see § 301.6059-1(d)) is considered a material item of information. Further, for any report filed for a plan year ending after January 25, 1982, if the actuary seeks to materially qualify a...

  7. 26 CFR 301.6692-1 - Failure to file actuarial report.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... enrolled actuary (see § 301.6059-1(d)) is considered a material item of information. Further, for any report filed for a plan year ending after January 25, 1982, if the actuary seeks to materially qualify a...

  8. 26 CFR 301.6692-1 - Failure to file actuarial report.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... enrolled actuary (see § 301.6059-1(d)) is considered a material item of information. Further, for any report filed for a plan year ending after January 25, 1982, if the actuary seeks to materially qualify a...

  9. Very Early Salvage Radiotherapy Improves Distant Metastasis-Free Survival.

    PubMed

    Abugharib, Ahmed; Jackson, William C; Tumati, Vasu; Dess, Robert T; Lee, Jae Y; Zhao, Shuang G; Soliman, Moaaz; Zumsteg, Zachary S; Mehra, Rohit; Feng, Felix Y; Morgan, Todd M; Desai, Neil; Spratt, Daniel E

    2017-03-01

    Early salvage radiotherapy following radical prostatectomy for prostate cancer is commonly advocated in place of adjuvant radiotherapy. We aimed to determine the optimal definition of early salvage radiotherapy. We performed a multi-institutional retrospective study of 657 men who underwent salvage radiotherapy between 1986 and 2013. Two comparisons were made to determine the optimal definition of early salvage radiotherapy, including 1) the time from radical prostatectomy to salvage radiotherapy (less than 9, 9 to 21, 22 to 47 or greater than 48 months) and 2) the level of detectable pre-salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 or greater than 0.5 ng/ml). Outcomes included freedom from salvage androgen deprivation therapy, and biochemical relapse-free, distant metastases-free and prostate cancer specific survival. Median followup was 9.8 years. Time from radical prostatectomy to salvage radiotherapy did not correlate with 10-year biochemical relapse-free survival rates (R 2 = 0.18). Increasing pre-salvage radiotherapy prostate specific antigen strongly correlated with biochemical relapse-free survival (R 2 = 0.91). Increasing detectable pre-salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 and greater than 0.5 ng/ml) predicted worse 10-year biochemical relapse-free survival (62%, 44% and 27%), freedom from salvage androgen deprivation therapy (77%, 66% and 49%), distant metastases-free survival (86%, 79% and 66%, each p <0.001) and prostate cancer specific survival (93%, 89% and 80%, respectively, p = 0.001). On multivariable analysis early salvage radiotherapy (prostate specific antigen greater than 0.2 to 0.5 ng/ml) was associated with a twofold increase in biochemical failure, use of salvage androgen deprivation therapy and distant metastases compared to very early salvage radiotherapy (prostate specific antigen 0.01 to 0.2 ng/ml). The duration from radical prostatectomy to salvage

  10. What does postradiotherapy PSA nadir tell us about freedom from PSA failure and progression-free survival in patients with low and intermediate-risk localized prostate cancer?

    PubMed

    DeWitt, K D; Sandler, H M; Weinberg, V; McLaughlin, P W; Roach, M

    2003-09-01

    To determine whether the post-external beam radiotherapy (RT) prostate-specific antigen nadir (nPSA) improves our ability to predict freedom from PSA failure, progression-free survival (PFS), and overall survival. Controversy regarding the importance of nPSA after external beam RT as a prognostic indicator for patients with localized prostate cancer has continued. This analysis was based on the data from 748 patients with low and intermediate-risk localized prostate cancer treated with external beam RT alone. Patients were categorized by nPSA quartile groups with cutpoints of less than 0.3, 0.3 to less than 0.6, 0.6 to less than 1.2, and 1.2 ng/mL or greater. Both univariate and multivariate analyses were used to determine the significance of nPSA on PSA failure (American Society for Therapeutic Radiology Oncology consensus definition), PFS (death after PSA failure), and overall survival (death from any cause). Freedom from PSA failure was strongly associated with nadir quartile groups (P <0.0001). PFS was also significantly different statistically among nadir quartile groups (P = 0.02). No statistically significant difference was found in overall survival associated with nPSA at this point. nPSA is a strong independent predictor of freedom from PSA failure and PFS in patients with low and intermediate-risk localized prostate cancer treated with RT alone. Longer follow-up and larger patient numbers are required to confirm these observations.

  11. Prediction of survival benefits from progression-free survival benefits in advanced non-small-cell lung cancer: evidence from a meta-analysis of 2334 patients from 5 randomised trials

    PubMed Central

    Laporte, Silvy; Squifflet, Pierre; Baroux, Noémie; Fossella, Frank; Georgoulias, Vassilis; Pujol, Jean-Louis; Douillard, Jean-Yves; Kudoh, Shinzohy; Pignon, Jean-Pierre; Quinaux, Emmanuel; Buyse, Marc

    2013-01-01

    Objectives To investigate whether progression-free survival (PFS) can be considered a surrogate endpoint for overall survival (OS) in advanced non-small-cell lung cancer (NSCLC). Design Meta-analysis of individual patient data from randomised trials. Setting Five randomised controlled trials comparing docetaxel-based chemotherapy with vinorelbine-based chemotherapy for the first-line treatment of NSCLC. Participants 2331 patients with advanced NSCLC. Primary and secondary outcome measures Surrogacy of PFS for OS was assessed through the association between these endpoints and between the treatment effects on these endpoints. The surrogate threshold effect was the minimum treatment effect on PFS required to predict a non-zero treatment effect on OS. Results The median follow-up of patients still alive was 23.4 months. Median OS was 10 months and median PFS was 5.5 months. The treatment effects on PFS and OS were correlated, whether using centres (R²=0.62, 95% CI 0.52 to 0.72) or prognostic strata (R²=0.72, 95% CI 0.60 to 0.84) as units of analysis. The surrogate threshold effect was a PFS hazard ratio (HR) of 0.49 using centres or 0.53 using prognostic strata. Conclusions These analyses provide only modest support for considering PFS as an acceptable surrogate for OS in patients with advanced NSCLC. Only treatments that have a major impact on PFS (risk reduction of at least 50%) would be expected to also have a significant effect on OS. Whether these results also apply to targeted therapies is an open question that requires independent evaluation. PMID:23485717

  12. High free fall with survival.

    PubMed

    Layton, T R; Villella, E R; Kelly, E G

    1981-11-01

    A free fall, the unimpeded drop of a body from a known point to a known impaction point, is common in modern society. Death usually results when distance is more than six stories. The following case report describes the circumstances which allowed a young man attempting suicide to survive a 17-storey free fall. Although his impact velocity was estimated to be 72 m.p.h. (uncorrected for air drag), he impacted in a supine position on an automobile trunk lid so that some of the force was dissipated by tires and shock absorbers. Multiple fractures and soft-tissue injuries and a subsequent stress ulcer were successfully treated and the patient has a satisfactory level of physical activity while remaining under psychiatric care 1 year postinjury.

  13. 75 FR 6359 - Federal Advisory Committee; DoD Board of Actuaries; Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-09

    ... DEPARTMENT OF DEFENSE Office of the Secretary Federal Advisory Committee; DoD Board of Actuaries... the DoD Board of Actuaries will meet on July 22 and 23, 2010. Subject to the availability of space...D Office of the Actuary, 4040 N. Fairfax Drive, Suite 308, Arlington, VA 22203; phone 703-696-7413...

  14. Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis.

    PubMed

    Howlett, Christina; Snedecor, Sonya J; Landsburg, Daniel J; Svoboda, Jakub; Chong, Elise A; Schuster, Stephen J; Nasta, Sunita Dwivedy; Feldman, Tatyana; Rago, Allison; Walsh, Kristy M; Weber, Scott; Goy, Andre; Mato, Anthony

    2015-08-01

    'Double-hit lymphomas' (DHL), defined by concurrent MYC and BCL2 (or, alternatively, BCL6) rearrangements, have a very poor outcome compared to standard-risk, diffuse large B-cell lymphomas (DLBCL). Consequently, dose-intensive (DI) therapies and/or consolidation with high-dose therapy and transplant have been explored in DHL, although benefit has been debated. This meta-analysis compared survival outcomes in DHL patients receiving dose-escalated regimens [DI: R-Hyper-CVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone) or R-CODOX-M/IVAC (rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high dose cytarabine); or intermediate-dose: R-EPOCH (rituximab, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone)] versus standard-dose regimens (R-CHOP; rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) in the first-line setting. Data were synthesized to estimate hazard ratios of dose-escalated treatments versus R-CHOP using a Weibull proportional hazards model within a Bayesian meta-analysis framework. Eleven studies examining 394 patients were included. Patients were treated with either front-line R-CHOP (n = 180), R-EPOCH (n = 91), or R-Hyper-CVAD/rituximab, methotrexate, cytarabine (R-M/C), R-CODOX-M/R-IVAC (DI) (n = 123). Our meta-analysis revealed that median progression-free survival (n = 350) for the R-CHOP, R-EPOCH and DI groups was 12·1, 22·2, and 18·9 months, respectively. First-line treatment with R-EPOCH significantly reduced the risk of a progression compared with R-CHOP (relative risk reduction of 34%; P = 0·032); however, overall survival (n = 374) was not significantly different across treatment approaches. A subset of patients might benefit from intensive induction with/without transplant. Further investigation into the role of transplant and novel therapy combinations is necessary. © 2015 John Wiley & Sons Ltd.

  15. Development of an Actuarial Science Program at Salisbury University

    ERIC Educational Resources Information Center

    Wainwright, Barbara A.

    2014-01-01

    This paper focuses on the development of an actuarial science track for the mathematics major at Salisbury University (SU). A timeline from the initial investigation into such a program through the proposal and approval processes is shared for those who might be interested in developing a new actuarial program. It is wise to start small and take…

  16. 5 CFR 839.1115 - What is an actuarial reduction?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...? An actuarial reduction allows you to receive benefits without having to pay an amount due in a lump sum. OPM reduces your annuity in a way that, on average, allows the Fund to recover the amount of the... have to pay at that time. To compute an actuarial reduction, OPM divides the lump sum amount by the...

  17. 5 CFR 839.1115 - What is an actuarial reduction?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...? An actuarial reduction allows you to receive benefits without having to pay an amount due in a lump sum. OPM reduces your annuity in a way that, on average, allows the Fund to recover the amount of the... have to pay at that time. To compute an actuarial reduction, OPM divides the lump sum amount by the...

  18. When do changes in cancer survival mean progress? The insight from population incidence and mortality.

    PubMed

    Cho, Hyunsoon; Mariotto, Angela B; Schwartz, Lisa M; Luo, Jun; Woloshin, Steven

    2014-11-01

    It is often assumed that increases in cancer survival reflect true progress against cancer. This is true when these increases are accompanied by decreased burden of disease: Fewer people being diagnosed or dying from cancer (ie, decreased incidence and mortality). But increased survival can also occur even when incidence is increasing and mortality is unchanged. To use trends in cancer burden-incidence and mortality-to illustrate when changes in survival reflect true progress. Using data from 1975 to 2010 collected by the Surveillance, Epidemiology, and End Results Program (incidence, survival) and the National Center for Health Statistics (mortality), we analyzed US trends in five-year relative survival, age-adjusted incidence, and mortality for selected cancers to identify patterns that do and do not reflect progress. Among the nine common cancers examined, survival increased in seven, and changed little or not at all for two. In some cases, increased survival was accompanied by decreased burden of disease, reflecting true progress. For example, from 1975 to 2010, five-year survival for colon cancer patients improved (from 48% to 68%) while cancer burden fell: Fewer cases (incidence decreased from 60 to 41 per 100,000) and fewer deaths (mortality decreased from 28 to 16 per 100,000), a pattern explained by both increased early detection (with removal of cancer precursors) and more effective treatment. In other cases, however, increased survival did not reflect true progress. In melanoma, kidney, and thyroid cancer, five-year survival increased but incidence increased with no change in mortality. This pattern suggests overdiagnosis from increased early detection, an increase in cancer burden. Changes in survival must be interpreted in the context of incidence and mortality. Increased survival only represents progress when accompanied by a reduction in incidence, mortality, or ideally both. Published by Oxford University Press 2014.

  19. When Do Changes in Cancer Survival Mean Progress? The Insight From Population Incidence and Mortality

    PubMed Central

    Mariotto, Angela B.; Schwartz, Lisa M.; Luo, Jun; Woloshin, Steven

    2014-01-01

    Background It is often assumed that increases in cancer survival reflect true progress against cancer. This is true when these increases are accompanied by decreased burden of disease: Fewer people being diagnosed or dying from cancer (ie, decreased incidence and mortality). But increased survival can also occur even when incidence is increasing and mortality is unchanged. Objective To use trends in cancer burden—incidence and mortality—to illustrate when changes in survival reflect true progress. Methods Using data from 1975 to 2010 collected by the Surveillance, Epidemiology, and End Results Program (incidence, survival) and the National Center for Health Statistics (mortality), we analyzed US trends in five-year relative survival, age-adjusted incidence, and mortality for selected cancers to identify patterns that do and do not reflect progress. Results Among the nine common cancers examined, survival increased in seven, and changed little or not at all for two. In some cases, increased survival was accompanied by decreased burden of disease, reflecting true progress. For example, from 1975 to 2010, five-year survival for colon cancer patients improved (from 48% to 68%) while cancer burden fell: Fewer cases (incidence decreased from 60 to 41 per 100000) and fewer deaths (mortality decreased from 28 to 16 per 100000), a pattern explained by both increased early detection (with removal of cancer precursors) and more effective treatment. In other cases, however, increased survival did not reflect true progress. In melanoma, kidney, and thyroid cancer, five-year survival increased but incidence increased with no change in mortality. This pattern suggests overdiagnosis from increased early detection, an increase in cancer burden. Conclusions Changes in survival must be interpreted in the context of incidence and mortality. Increased survival only represents progress when accompanied by a reduction in incidence, mortality, or ideally both. PMID:25417232

  20. Human actuarial aging increases faster when back ground death rates are lower: a consequence of differential heterogeneity?

    PubMed Central

    Hawkes, Kristen; Smith, Ken R.; Blevins, James K.

    2014-01-01

    Many analyses of human populations have found that age-specific mortality rates increase faster across most of adulthood when overall mortality levels decline. This contradicts the relationship often expected from Williams′ classic hypothesis about the effects of natural selection on the evolution of senescence. More likely, much of the within-species difference in actuarial aging is not due to variation in senescence, but to the strength of filters on the heterogeneity of frailty in older survivors. A challenge to this differential frailty hypothesis was recently posed by an analysis of life tables from historical European populations and traditional societies that reported variation in actuarial aging consistent with Williams′ hypothesis after all. To investigate the challenge, we reconsidered those cases and aging measures. Here we show that the discrepancy depends on Ricklefs′ aging rate measure,ω, which decreases as mortality levels drop because it is an index of mortality level itself, not the rate of increase in mortality with age. We also show unappreciated correspondence among the parameters of Gompertz–Makeham and Weibull survival models. Finally, we compare the relationships among mortality parameters of the traditional societies and the historical series, providing further suggestive evidence that differential heterogeneity has strong effects on actuarial aging. PMID:22220868

  1. Germline polymorphisms in an enhancer of PSIP1 are associated with progression-free survival in epithelial ovarian cancer.

    PubMed

    French, Juliet D; Johnatty, Sharon E; Lu, Yi; Beesley, Jonathan; Gao, Bo; Kalimutho, Murugan; Henderson, Michelle J; Russell, Amanda J; Kar, Siddhartha; Chen, Xiaoqing; Hillman, Kristine M; Kaufmann, Susanne; Sivakumaran, Haran; O'Reilly, Martin; Wang, Chen; Korbie, Darren J; Lambrechts, Diether; Despierre, Evelyn; Van Nieuwenhuysen, Els; Lambrechts, Sandrina; Vergote, Ignace; Karlan, Beth; Lester, Jenny; Orsulic, Sandra; Walsh, Christine; Fasching, Peter A; Beckmann, Matthias W; Ekici, Arif B; Hein, Alexander; Matsuo, Keitaro; Hosono, Satoyo; Pisterer, Jacobus; Hillemanns, Peter; Nakanishi, Toru; Yatabe, Yasushi; Goodman, Marc T; Lurie, Galina; Matsuno, Rayna K; Thompson, Pamela J; Pejovic, Tanja; Bean, Yukie; Heitz, Florian; Harter, Philipp; du Bois, Andreas; Schwaab, Ira; Hogdall, Estrid; Kjaer, Susanne K; Jensen, Allan; Hogdall, Claus; Lundvall, Lene; Engelholm, Svend Aage; Brown, Bob; Flanagan, James M; Metcalf, Michelle D; Siddiqui, Nadeem; Sellers, Thomas; Fridley, Brooke; Cunningham, Julie; Schildkraut, Joellen M; Iversen, Ed; Weber, Rachel Palmieri; Brennan, Donal; Berchuck, Andrew; Pharoah, Paul; Harnett, Paul; Norris, Murray D; Haber, Michelle; Goode, Ellen L; Lee, Jason S; Khanna, Kum Kum; Meyer, Kerstin B; Chenevix-Trench, Georgia; deFazio, Anna; Edwards, Stacey L; MacGregor, Stuart

    2016-02-09

    Women with epithelial ovarian cancer (EOC) are usually treated with platinum/taxane therapy after cytoreductive surgery but there is considerable inter-individual variation in response. To identify germline single-nucleotide polymorphisms (SNPs) that contribute to variations in individual responses to chemotherapy, we carried out a multi-phase genome-wide association study (GWAS) in 1,244 women diagnosed with serous EOC who were treated with the same first-line chemotherapy, carboplatin and paclitaxel. We identified two SNPs (rs7874043 and rs72700653) in TTC39B (best P=7x10-5, HR=1.90, for rs7874043) associated with progression-free survival (PFS). Functional analyses show that both SNPs lie in a putative regulatory element (PRE) that physically interacts with the promoters of PSIP1, CCDC171 and an alternative promoter of TTC39B. The C allele of rs7874043 is associated with poor PFS and showed increased binding of the Sp1 transcription factor, which is critical for chromatin interactions with PSIP1. Silencing of PSIP1 significantly impaired DNA damage-induced Rad51 nuclear foci and reduced cell viability in ovarian cancer lines. PSIP1 (PC4 and SFRS1 Interacting Protein 1) is known to protect cells from stress-induced apoptosis, and high expression is associated with poor PFS in EOC patients. We therefore suggest that the minor allele of rs7874043 confers poor PFS by increasing PSIP1 expression.

  2. Germline polymorphisms in an enhancer of PSIP1 are associated with progression-free survival in epithelial ovarian cancer

    PubMed Central

    French, Juliet D.; Johnatty, Sharon E.; Lu, Yi; Beesley, Jonathan; Gao, Bo; Kalimutho, Murugan; Henderson, Michelle J.; Russell, Amanda J.; Kar, Siddhartha; Chen, Xiaoqing; Hillman, Kristine M.; Kaufmann, Susanne; Sivakumaran, Haran; O'Reilly, Martin; Wang, Chen; Korbie, Darren J.; Lambrechts, Diether; Despierre, Evelyn; Van Nieuwenhuysen, Els; Lambrechts, Sandrina; Vergote, Ignace; Karlan, Beth; Lester, Jenny; Orsulic, Sandra; Walsh, Christine; Fasching, Peter A.; Beckmann, Matthias W.; Ekici, Arif B.; Hein, Alexander; Matsuo, Keitaro; Hosono, Satoyo; Pisterer, Jacobus; Hillemanns, Peter; Nakanishi, Toru; Yatabe, Yasushi; Goodman, Marc T.; Lurie, Galina; Matsuno, Rayna K.; Thompson, Pamela J.; Pejovic, Tanja; Bean, Yukie; Heitz, Florian; Harter, Philipp; du Bois, Andreas; Schwaab, Ira; Hogdall, Estrid; Kjaer, Susanne K.; Jensen, Allan; Hogdall, Claus; Lundvall, Lene; Engelholm, Svend Aage; Brown, Bob; Flanagan, James M.; Metcalf, Michelle D.; Siddiqui, Nadeem; Sellers, Thomas; Fridley, Brooke; Cunningham, Julie; Schildkraut, Joellen M.; Iversen, Ed; Weber, Rachel Palmieri; Brennan, Donal; Berchuck, Andrew; Pharoah, Paul; Harnett, Paul; Norris, Murray D.; Haber, Michelle; Goode, Ellen L.; Lee, Jason S.; Khanna, Kum Kum; Meyer, Kerstin B.; Chenevix-Trench, Georgia; deFazio, Anna; Edwards, Stacey L.; MacGregor, Stuart

    2016-01-01

    Women with epithelial ovarian cancer (EOC) are usually treated with platinum/taxane therapy after cytoreductive surgery but there is considerable inter-individual variation in response. To identify germline single-nucleotide polymorphisms (SNPs) that contribute to variations in individual responses to chemotherapy, we carried out a multi-phase genome-wide association study (GWAS) in 1,244 women diagnosed with serous EOC who were treated with the same first-line chemotherapy, carboplatin and paclitaxel. We identified two SNPs (rs7874043 and rs72700653) in TTC39B (best P=7×10−5, HR=1.90, for rs7874043) associated with progression-free survival (PFS). Functional analyses show that both SNPs lie in a putative regulatory element (PRE) that physically interacts with the promoters of PSIP1, CCDC171 and an alternative promoter of TTC39B. The C allele of rs7874043 is associated with poor PFS and showed increased binding of the Sp1 transcription factor, which is critical for chromatin interactions with PSIP1. Silencing of PSIP1 significantly impaired DNA damage-induced Rad51 nuclear foci and reduced cell viability in ovarian cancer lines. PSIP1 (PC4 and SFRS1 Interacting Protein 1) is known to protect cells from stress-induced apoptosis, and high expression is associated with poor PFS in EOC patients. We therefore suggest that the minor allele of rs7874043 confers poor PFS by increasing PSIP1 expression. PMID:26840454

  3. The Role of an Actuarial Director in the Development of an Introductory Program

    ERIC Educational Resources Information Center

    Staples, Susan G.

    2014-01-01

    We describe the roles and duties of a director in developing an introductory actuarial program. Degree plan design, specialized exam courses, internship classes, coordination of efforts with Economics and Finance Departments, opportunities for creating a minor in actuarial mathematics, actuarial clubs, career advice, and interaction with actuarial…

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

    PubMed

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

    2016-06-19

    We evaluated the impact of Option A on HIV-free infant survival and mother-to-child transmission (MTCT) in Zimbabwe. Serial cross-sectional community-based serosurveys. We analyzed serosurvey data collected in 2012 and 2014 among mother-infant pairs from catchment areas of 132 health facilities from five of 10 provinces in Zimbabwe. Eligible infants (alive or deceased) were born 9-18 months before each survey to mothers at least 16 years old. We randomly selected mother-infant pairs and conducted questionnaires, verbal autopsies, and collected blood samples. We estimated the HIV-free infant survival and MTCT rate within each catchment area and compared the 2012 and 2014 estimates using a paired t test and number of HIV infections averted because of the intervention. We analyzed 7249 mother-infant pairs with viable maternal specimens collected in 2012 and 8551 in 2014. The mean difference in the catchment area level MTCT between 2014 and 2012 was -5.2 percentage points (95% confidence interval = -8.1, -2.3, P < 0.001). The mean difference in the catchment area level HIV-free survival was 5.5 percentage points (95% confidence interval = 2.6, 8.5, P < 0.001). Between 2012 and 2014, 1779 infant infections were averted compared with the pre-Option A regimen. The association between HIV-free infant survival and duration of Option A implementation was NS at the multivariate level (P = 0.093). We found a substantial and statistically significant increase in HIV-free survival and decrease in MTCT among infants aged 9-18 months following Option A rollout in Zimbabwe. This is the only evaluation of Option A and shows the effectiveness of Option A and Zimbabwe's remarkable progress toward eMTCT.

  5. An Overview of the Society of Actuaries and Its Education Programs

    ERIC Educational Resources Information Center

    Klugman, Stuart; Long, Gena

    2014-01-01

    The Society of Actuaries (SOA) is the world's largest actuarial organization. This article describes the SOA with particular attention paid to its education and qualification processes and resources available for university and college programs.

  6. Ten-Year Progression-Free and Overall Survival in Patients With Unresectable or Metastatic GI Stromal Tumors: Long-Term Analysis of the European Organisation for Research and Treatment of Cancer, Italian Sarcoma Group, and Australasian Gastrointestinal Trials Group Intergroup Phase III Randomized Trial on Imatinib at Two Dose Levels.

    PubMed

    Casali, Paolo G; Zalcberg, John; Le Cesne, Axel; Reichardt, Peter; Blay, Jean-Yves; Lindner, Lars H; Judson, Ian R; Schöffski, Patrick; Leyvraz, Serge; Italiano, Antoine; Grünwald, Viktor; Pousa, Antonio Lopez; Kotasek, Dusan; Sleijfer, Stefan; Kerst, Jan M; Rutkowski, Piotr; Fumagalli, Elena; Hogendoorn, Pancras; Litière, Saskia; Marreaud, Sandrine; van der Graaf, Winette; Gronchi, Alessandro; Verweij, Jaap

    2017-05-20

    Purpose To report on the long-term results of a randomized trial comparing a standard dose (400 mg/d) versus a higher dose (800 mg/d) of imatinib in patients with metastatic or locally advanced GI stromal tumors (GISTs). Patients and Methods Eligible patients with advanced CD117-positive GIST from 56 institutions in 13 countries were randomly assigned to receive either imatinib 400 mg or 800 mg daily. Patients on the 400-mg arm were allowed to cross over to 800 mg upon progression. Results Between February 2001 and February 2002, 946 patients were accrued. Median age was 60 years (range, 18 to 91 years). Median follow-up time was 10.9 years. Median progression-free survival times were 1.7 and 2.0 years in the 400- and 800-mg arms, respectively (hazard ratio, 0.91; P = .18), and median overall survival time was 3.9 years in both treatment arms. The estimated 10-year progression-free survival rates were 9.5% and 9.2% for the 400- and 800-mg arms, respectively, and the estimated 10-year overall survival rates were 19.4% and 21.5%, respectively. At multivariable analysis, age (< 60 years), performance status (0 v ≥ 1), size of the largest lesion (smaller), and KIT mutation (exon 11) were significant prognostic factors for the probability of surviving beyond 10 years. Conclusion This trial was carried out on a worldwide intergroup basis, at the beginning of the learning curve of the use of imatinib, in a large population of patients with advanced GIST. With a long follow-up, 6% of patients are long-term progression free and 13% are survivors. Among clinical prognostic factors, only performance status, KIT mutation, and size of largest lesion predicted long-term outcome, likely pointing to a lower burden of disease. Genomic and/or immune profiling could help understand long-term survivorship. Addressing secondary resistance remains a therapeutic challenge.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gorovets, Daniel; Department of Radiation Oncology, Perlmutter Cancer Center, NYU School of Medicine, New York, New York; Ayala-Peacock, Diandra

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

  8. Progression-free survival of early interim PET-positive patients with advanced stage Hodgkin's lymphoma treated with BEACOPPescalated alone or in combination with rituximab (HD18): an open-label, international, randomised phase 3 study by the German Hodgkin Study Group.

    PubMed

    Borchmann, Peter; Haverkamp, Heinz; Lohri, Andreas; Mey, Ulrich; Kreissl, Stefanie; Greil, Richard; Markova, Jana; Feuring-Buske, Michaela; Meissner, Julia; Dührsen, Ulrich; Ostermann, Helmut; Keller, Ulrich; Maschmeyer, Georg; Kuhnert, Georg; Dietlein, Markus; Kobe, Carsten; Eich, Hans; Baues, Christian; Stein, Harald; Fuchs, Michael; Diehl, Volker; Engert, Andreas

    2017-04-01

    Advanced stage Hodgkin's lymphoma represents a heterogeneous group of patients with different risk profiles. Data suggests that interim PET assessment during chemotherapy is superior to baseline international prognostic scoring in terms of predicting long-term treatment outcome in patients with Hodgkin's lymphoma. We therefore hypothesised that early interim PET-imaging after two courses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) might be suitable for guiding treatment in patients with advanced stage Hodgkin's lymphoma. We aimed to assess whether intensifying standard chemotherapy (BEACOPP escalated ) by adding rituximab would improve progression-free survival in patients with positive PET after two courses of chemotherapy. In this open-label, international, randomised, phase 3 study, we recruited patients aged 18-60 years with newly diagnosed, advanced stage Hodgkin's lymphoma from 160 hospitals and 77 private practices in Germany, Switzerland, Austria, the Netherlands, and the Czech Republic. Interim PET-imaging was done after two cycles of BEACOPP escalated and centrally assessed by an expert panel. Patients with a positive PET after 2 cycles of BEACOPP escalated chemotherapy (PET-2) were randomly assigned (1:1) to receive six additional courses of either BEACOPP escalated (BEACOPP escalated group) or BEACOPP escalated plus rituximab (R-BEACOPP escalated group). PET-2 was assessed using a 5-point scale with 18 FDG uptake higher than the mediastinal blood pool (corresponding to Deauville scale 3) defined as positive. BEACOPP escalated was given as previously described; rituximab was given intravenously at a dose of 375 mg/m 2 (maximum total dose 700 mg), the first administration starting 24 h before starting the fourth cycle of BEACOPP escalated (day 0 and day 3 in cycle 4, day 1 in cycles 5-8). Randomisation was done centrally and used the minimisation method including a random component

  9. Survival Analysis and Actuarial Parameters of Sternechus subsignatus (Coleoptera: Curculionidae) Adults.

    PubMed

    Guillermina Socías, María; Van Nieuwenhove, Guido; Murúa, María Gabriela; Willink, Eduardo; Liljesthröm, Gerardo Gustavo

    2016-04-01

    The soybean stalk weevil, Sternechus subsignatus Boheman 1836 (Coleoptera: Curculionidae), is a very serious soybean pest in the Neotropical region. Both adults and larvae feed on soybean, causing significant yield losses. Adult survival was evaluated during three soybean growing seasons under controlled environmental conditions. A survival analysis was performed using a parametric survival fit approach in order to generate survival curves and obtain information that could help optimize integrated management strategies for this weevil pest. Sex of the weevils, crop season, fortnight in which weevils emerged, and their interaction were studied regarding their effect on adult survival. The results showed that females lived longer than males, but both genders were actually long-lived, reaching 224 and 176 d, respectively. Mean lifetime (l50) was 121.88±4.56 d for females and 89.58±2.72 d for males. Although variations were observed in adult longevities among emergence fortnights and soybean seasons, only in December and January fortnights of the 2007–2008 season and December fortnights of 2009–2010 did the statistically longest and shortest longevities occur, respectively. Survivorship data (lx) of adult females and males were fitted to the Weibull frequency distribution model. The survival curve was type I for both sexes, which indicated that mortality corresponded mostly to old individuals.

  10. Tumor response and progression-free survival as potential surrogate endpoints for overall survival in extensive stage small-cell lung cancer: findings on the basis of North Central Cancer Treatment Group trials.

    PubMed

    Foster, Nathan R; Qi, Yingwei; Shi, Qian; Krook, James E; Kugler, John W; Jett, James R; Molina, Julian R; Schild, Steven E; Adjei, Alex A; Mandrekar, Sumithra J

    2011-03-15

    The authors investigated the putative surrogate endpoints of best response, complete response (CR), confirmed response, and progression-free survival (PFS) for associations with overall survival (OS), and as possible surrogate endpoints for OS. Individual patient data from 870 untreated extensive stage small-cell lung cancer patients participating in 6 single-arm (274 patients) and 3 randomized trials (596 patients) were pooled. Patient-level associations between putative surrogate endpoints and OS were assessed by Cox models using landmark analyses. Trial-level surrogacy of putative surrogate endpoints were assessed by the association of treatment effects on OS and individual putative surrogate endpoints. Trial-level surrogacy measures included: R(2) from weighted least squares regression model, Spearman correlation coefficient, and R(2) from bivariate survival model (Copula R(2) ). Median OS and PFS were 9.6 (95% confidence interval [CI], 9.1-10.0) and 5.5 (95% CI, 5.2-5.9) months, respectively; best response, CR, and confirmed response rates were 44%, 22%, and 34%, respectively. Patient-level associations showed that PFS status at 4 months was a strong predictor of subsequent survival (hazard ratio [HR], 0.42; 95% CI, 0.35-0.51; concordance index 0.63; P < .01), with 6-month PFS being the strongest (HR, 0.41; 95% CI, 0.35-0.49; concordance index, 0.66, P < .01). At the trial level, PFS showed the highest level of surrogacy for OS (weighted least squares R(2) = 0.79; Copula R(2) = 0.80), explaining 79% of the variance in OS. Tumor response endpoints showed lower surrogacy levels (weighted least squares R(2) ≤0.48). PFS was strongly associated with OS at both the patient and trial levels. PFS also shows promise as a potential surrogate for OS, but further validation is needed using data from a larger number of randomized phase 3 trials. Copyright © 2010 American Cancer Society.

  11. Human survivability of extreme impacts in free-fall.

    DOT National Transportation Integrated Search

    1963-08-01

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

  12. Including an Exam P/1 Prep Course in a Growing Actuarial Science Program

    ERIC Educational Resources Information Center

    Wakefield, Thomas P.

    2014-01-01

    The purpose of this article is to describe the actuarial science program at our university and the development of a course to enhance students' problem solving skills while preparing them for Exam P/1 of the Society of Actuaries (SOA) and the Casualty Actuary Society (CAS). The Exam P/1 prep course, formally titled Mathematical Foundations of…

  13. Connecting clinical and actuarial prediction with rule-based methods.

    PubMed

    Fokkema, Marjolein; Smits, Niels; Kelderman, Henk; Penninx, Brenda W J H

    2015-06-01

    Meta-analyses comparing the accuracy of clinical versus actuarial prediction have shown actuarial methods to outperform clinical methods, on average. However, actuarial methods are still not widely used in clinical practice, and there has been a call for the development of actuarial prediction methods for clinical practice. We argue that rule-based methods may be more useful than the linear main effect models usually employed in prediction studies, from a data and decision analytic as well as a practical perspective. In addition, decision rules derived with rule-based methods can be represented as fast and frugal trees, which, unlike main effects models, can be used in a sequential fashion, reducing the number of cues that have to be evaluated before making a prediction. We illustrate the usability of rule-based methods by applying RuleFit, an algorithm for deriving decision rules for classification and regression problems, to a dataset on prediction of the course of depressive and anxiety disorders from Penninx et al. (2011). The RuleFit algorithm provided a model consisting of 2 simple decision rules, requiring evaluation of only 2 to 4 cues. Predictive accuracy of the 2-rule model was very similar to that of a logistic regression model incorporating 20 predictor variables, originally applied to the dataset. In addition, the 2-rule model required, on average, evaluation of only 3 cues. Therefore, the RuleFit algorithm appears to be a promising method for creating decision tools that are less time consuming and easier to apply in psychological practice, and with accuracy comparable to traditional actuarial methods. (c) 2015 APA, all rights reserved).

  14. The Actuarial Society of South Africa AIDS model.

    PubMed

    1997-01-01

    The AIDS Committee of the Actuarial Society of South Africa has developed a demographic model to allow researchers to project the impact of HIV and AIDS in South Africa. The model is available for use as a projection tool rather than to endorse a given projected scenario as being representative. It is very flexible and can be adapted to suit different purposes by anyone with a working knowledge of Microsoft Excel. The need for a model, calibration of the model, the lack of allowance in the model for racial and cultural heterogeneity in the underlying population, and default scenario projections are discussed. The model is available free of charge via E-mail and on the worldwide web at the following respective addresses: awhitelo@oldmutual.com and http://www.und.ac.za/und/eco/eru/eru.htm.

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

    PubMed Central

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

    2016-01-01

    Objective We evaluated the impact of Option A on HIV-free infant survival and mother-to-child transmission (MTCT) in Zimbabwe. Design Serial cross-sectional community-based serosurveys. Methods We analyzed serosurvey data collected in 2012 and 2014 among mother-infant pairs from catchment areas (CAs) of 132 health facilities from 5 of 10 provinces in Zimbabwe. Eligible infants (alive or deceased) were born 9–18 months before each survey to mothers ≥16 years old. We randomly selected mother-infant pairs and conducted questionnaires, verbal autopsies and collected blood samples. We estimated: 1) the HIV-free infant survival and MTCT rate within each CA and compared the 2012 and 2014 estimates using a paired t-test, 2) number of HIV infections averted due to the intervention. Results We analyzed 7,249 mother-infant pairs with viable maternal specimens collected in 2012 and 8,551 in 2014. The mean difference in the CA-level MTCT between 2014 and 2012 was −5.2 percentage points (95% confidence interval (CI)=−8.1, −2.3, p<0.001). The mean difference in the CA-level HIV-free survival was 5.5 percentage points (95%CI=2.6,8.5, p<0.001). Between 2012 and 2014, 1,779 infant infections were averted compared to the pre-Option A regimen. The association between HIV-free infant survival and duration of Option A implementation was not significant at the multivariate level (p=0.093). Conclusions We found a substantial and statistically significant increase in HIV-free survival and decrease in MTCT among infants aged 9–18 months following Option A rollout in Zimbabwe. This is the only impact evaluation of Option A and shows the effectiveness of Option A and Zimbabwe’s remarkable progress towards eMTCT. PMID:27058354

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

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

    2017-01-01

    Purpose Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL. Methods Patients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled. Immunohistochemistry for MYC, BCL2, and BCL6 and fluorescence in situ hybridization (FISH) for MYC were performed. In cases with MYC rearrangement or copy gain, FISH for BCL2 and BCL6 was also performed. Results A total of 117 patients were included; 44% had DEL and 10% had DHL. DEL and DHL were associated with inferior progression-free survival (PFS), and DHL was associated with poorer overall survival (OS). The 4-year PFS in patients with DEL compared with those with non-DEL was 48% versus 59% (P = .049), and the 4-year OS was 56% versus 67% (P = .10); 4-year PFS in patients with DHL compared with those with non-DHL was 28% versus 57% (P = .013), and 4-year OS was 25% versus 61% (P = .002). The few patients with concurrent DEL and DHL had a poor outcome (4-year PFS, 0%). In multivariable models, DEL and DHL were independently associated with inferior PFS, whereas DHL and partial response (v complete response) at transplant were associated with inferior OS. Conclusion DEL and DHL are both associated with inferior outcomes after ASCT in patients with rel/ref DLBCL. Although ASCT remains a potentially curative approach, these patients, particularly those with DHL, are a high-risk subset who should be targeted for investigational strategies other than standard ASCT. PMID:28034071

  18. Effects of supervised exercise on progression-free survival in lymphoma patients: an exploratory follow-up of the HELP Trial.

    PubMed

    Courneya, Kerry S; Friedenreich, Christine M; Franco-Villalobos, Conrado; Crawford, Jennifer J; Chua, Neil; Basi, Sanraj; Norris, Mary K; Reiman, Tony

    2015-02-01

    Few randomized controlled trials in exercise oncology have examined survival outcomes. Here, we report an exploratory follow-up of progression-free survival (PFS) from the Healthy Exercise for Lymphoma Patients (HELP) Trial. The HELP Trial randomized 122 lymphoma patients between 2005 and 2008 to either control (n = 62) or 12 weeks of supervised aerobic exercise (n = 60). PFS events were abstracted from medical records in 2013. In addition to the randomized comparison, we explored the effects of exercise adherence (<80 % vs. ≥80 %) and control group crossover (no vs. yes). After a median follow-up of 61 months (interquartile range 36-67), the adjusted 5-year PFS was 64.8 % for the exercise group compared with 65.0 % for the control group (Hazard ratio [HR] 1.01, 95 % CI 0.51-2.01, p = 0.98). In the secondary analysis, the adjusted 5-year PFS was 59.0 % in the control group without crossover compared with 69.2 % for the control group with crossover (HR 0.68, 95 % CI 0.22-2.06, p = 0.49), 67.7 % for the exercise group with <80 % adherence (HR 0.72, 95 % CI 0.28-1.85, p = 0.50), and 68.4 % for the exercise group with ≥80 % adherence (HR 0.70, 95 % CI 0.32-1.56, p = 0.39). In a post hoc analysis combining the three groups that received supervised exercise, the adjusted 5-year PFS for the supervised exercise groups was 68.5 % compared with 59.0 % for the group that received no supervised exercise (HR 0.70, 95 % CI 0.35-1.39, p = 0.31). This exploratory follow-up of the HELP Trial suggests that supervised aerobic exercise may be associated with improved PFS in lymphoma patients. Larger trials designed to answer this question are needed.

  19. Are we selecting the right patients for treatment of localized prostate cancer? Results of an actuarial analysis.

    PubMed

    Koch, M O; Miller, D A; Butler, R; Lebos, L; Collings, D; Smith, J A

    1998-02-01

    To determine our accuracy in selecting patients with at least a 10-year life expectancy for aggressive treatment of localized prostate cancer. The medical records of 261 consecutive patients who underwent radical retropubic prostatectomy were submitted to the actuarial division of American General Life and Accident Insurance Company (AGLA) for estimation of life expectancy, excluding the diagnosis of prostate cancer. Survival curves were generated from predicted individual survivals. In patients with less than a 10-year life expectancy, AGLA provided us with the basis for assigning suboptimal survival rates. The mean life expectancy for the group was 15.2 years. Two hundred ten men (80%) were projected to have a life expectancy of more than 10 years, including 27 of 55 (49%) and 4 of 8 (50%) men who were older than or equal to 70 and 75 years of age, respectively. Coronary artery disease and diabetes mellitus were the most common coexisting medical conditions that adversely affected risk as single disease entities. Although clinicians do not estimate life expectancy with the scientific exactitude of an actuary, the ability to assess the patient in person and assimilate pertinent medical information in a less rigid format yields similar results. Selection of men for definitive treatment of localized prostate cancer should be based on the inherent aggressiveness of the disease and the health of the individual and should not be limited by specific age cutoffs. Populations of men undergoing radical prostatectomy are younger and healthier than those in reported series of watchful waiting for prostate cancer.

  20. Enteral autonomy, cirrhosis, and long term transplant-free survival in pediatric intestinal failure patients.

    PubMed

    Fullerton, Brenna S; Sparks, Eric A; Hall, Amber M; Duggan, Christopher; Jaksic, Tom; Modi, Biren P

    2016-01-01

    Patient selection for transplant evaluation in pediatric intestinal failure is predicated on the ability to assess long-term transplant-free survival. In light of trends toward improved survival of intestinal failure patients in recent decades, we sought to determine if the presence of biopsy-proven hepatic cirrhosis or the eventual achievement of enteral autonomy were associated with transplant-free survival. After IRB approval, records of all pediatric intestinal failure patients (parenteral nutrition (PN) >90 days) treated at a single intestinal failure center from February 2002 to September 2014 were reviewed. Chi-squared, Mann-Whitney, and log-rank testing were performed as appropriate. Of 313 patients, 174 eventually weaned off PN. Liver biopsies were available in 126 patients (most common indication was intestinal failure associated liver disease, IFALD), and 23 met histologic criteria for cirrhosis. Transplant-free survival for the whole cohort of 313 patients was 94.7% at 1 year and 89.2% at 5 years. Among patients with liver biopsies, transplant-free survival in cirrhotics vs. noncirrhotics was 95.5% vs. 94.1% at one year and 95.5% vs. 86.7% at 5 years (P=0.29). Transplant-free survival in patients who achieved enteral autonomy compared with patients who remained PN dependent was 98.2% vs. 90.3% at one year and 98.2% vs. 76.9% at 5 years (P<0.001). There was no association between cirrhosis and eventual enteral autonomy (P=0.88). Achieving enteral autonomy was associated with improved transplant-free survival in pediatric intestinal failure patients. There was no association between histopathological diagnosis of cirrhosis and transplant-free survival in the cohort. These data suggest that automatic transplant referral may not be required for histopathological diagnosis of cirrhosis alone, and that ongoing efforts aimed at achievement of enteral autonomy remain paramount in pediatric intestinal failure. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Differences in Treatment Effect Size Between Overall Survival and Progression-Free Survival in Immunotherapy Trials: A Meta-Epidemiologic Study of Trials With Results Posted at ClinicalTrials.gov.

    PubMed

    Tan, Aidan; Porcher, Raphael; Crequit, Perrine; Ravaud, Philippe; Dechartres, Agnes

    2017-05-20

    Purpose We aimed to compare treatment effect sizes between overall survival (OS) and progression-free survival (PFS) in trials of US Food and Drug Administration-approved oncology immunotherapy drugs with results posted at ClinicalTrials.gov . Methods We searched ClinicalTrials.gov for phase II to IV cancer trials of Food and Drug Administration-approved immunotherapy drugs and selected those reporting results for both OS and PFS. For each trial, we extracted the hazard ratios (HRs) with 95% CIs for both outcomes and evaluated the differences by a ratio of HRs (rHRs): the HR for PFS to that for OS. We performed a random effects meta-analysis across trials to obtain a summary rHR. We also evaluated surrogacy of PFS for OS by the coefficient of determination and the surrogacy threshold effect, the minimal value of HR for PFS to predict a non-null effect on OS. Results We identified 51 trials assessing 14 drugs across 15 conditions. Treatment effect sizes were 17% greater, on average, with PFS than with OS (rHR, 0.83; 95% CI, 0.79 to 0.88; I 2 = 34.4%; P = .01; τ 2 = 0.0129). Nearly one half of the trials (n = 23, 45%) showed statistically significant benefits for PFS but not for OS. Differences were great for trials of obinutuzumab (rHR, 0.21; 95% CI, 0.08 to 0.54), bevacizumab (rHR, 0.75; 95% CI, 0.67 to 0.84), and rituximab (rHR, 0.79; 95% CI, 0.64 to 0.98). The coefficient of determination was 38% and the surrogacy threshold effect was 0.50. Conclusion Treatment effect sizes in trials of immunotherapy drugs were greater for PFS than for OS, with important differences for some drugs, which is consistent with surrogacy metrics. Caution must be taken when interpreting PFS in the absence of OS data.

  2. Survival of high-velocity free-falls in water.

    DOT National Transportation Integrated Search

    1965-04-01

    Forty-four cases of free-falls survived by individuals impacting water environments under conditions of high velocity (50 to 116 ft/sec, corrected for aerodynamic drag) have been intensively investigated and analyzed. Ages varied from 7 to 80 years a...

  3. Expression of FGFR3 and FGFR4 and clinical risk factors associated with progression-free survival in synovial sarcoma.

    PubMed

    Charbonneau, Bridget; Vogel, Rachel Isaksson; Manivel, J Carlos; Rizzardi, Anthony; Schmechel, Stephen C; Ognjanovic, Simona; Subramanian, Subbaya; Largaespada, David; Weigel, Brenda

    2013-09-01

    Although rare, synovial sarcoma (SS) is one of the most common soft tissue sarcomas affecting young adults. To investigate potential tumor markers related to synovial sarcoma prognosis, we carried out a single-institution retrospective analysis of 103 patients diagnosed with SS between 1980 and 2009. Clinical outcome data were obtained from medical records, and archived tissue samples were used to evaluate the relationship between progression-free survival (PFS) and several prognostic factors, including tumor expression of FGFR3 and FGFR4. No associations were found between PFS and gender, body mass index, tumor site, SS18-SSX translocation, or FGFR4 expression. As seen in previous studies, age at diagnosis (<35, 63% versus ≥35 years, 31% 10-year PFS; P = .033), histologic subtype (biphasic, 75% versus monophasic 34% 10-year PFS; P = .034), and tumor size (≤5 cm, 70% versus >5 cm, 22% 10-year PFS; P < .0001) were associated with PFS in SS patients. In addition, in a subset of patients with available archived tumor samples taken prior to chemotherapy or radiation (n = 34), higher FGFR3 expression was associated with improved PFS (P = .030). To the best of our knowledge, this is the largest study of SS to date to suggest a potential clinical role for FGFR3. While small numbers make this investigation somewhat exploratory, the findings merit future investigation on a larger scale. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Nomograms Predicting Progression-Free Survival, Overall Survival, and Pelvic Recurrence in Locally Advanced Cervical Cancer Developed From an Analysis of Identifiable Prognostic Factors in Patients From NRG Oncology/Gynecologic Oncology Group Randomized Trials of Chemoradiotherapy

    PubMed Central

    Rose, Peter G.; Java, James; Whitney, Charles W.; Stehman, Frederick B.; Lanciano, Rachelle; Thomas, Gillian M.; DiSilvestro, Paul A.

    2015-01-01

    Purpose To evaluate the prognostic factors in locally advanced cervical cancer limited to the pelvis and develop nomograms for 2-year progression-free survival (PFS), 5-year overall survival (OS), and pelvic recurrence. Patients and Methods We retrospectively reviewed 2,042 patients with locally advanced cervical carcinoma enrolled onto Gynecologic Oncology Group clinical trials of concurrent cisplatin-based chemotherapy and radiotherapy. Nomograms for 2-year PFS, five-year OS, and pelvic recurrence were created as visualizations of Cox proportional hazards regression models. The models were validated by bootstrap-corrected, relatively unbiased estimates of discrimination and calibration. Results Multivariable analysis identified prognostic factors including histology, race/ethnicity, performance status, tumor size, International Federation of Gynecology and Obstetrics stage, tumor grade, pelvic node status, and treatment with concurrent cisplatin-based chemotherapy. PFS, OS, and pelvic recurrence nomograms had bootstrap-corrected concordance indices of 0.62, 0.64, and 0.73, respectively, and were well calibrated. Conclusion Prognostic factors were used to develop nomograms for 2-year PFS, 5-year OS, and pelvic recurrence for locally advanced cervical cancer clinically limited to the pelvis treated with concurrent cisplatin-based chemotherapy and radiotherapy. These nomograms can be used to better estimate individual and collective outcomes. PMID:25732170

  5. 75 FR 47650 - Actuarial Advisory Committee With Respect to the Railroad Retirement Account; Notice of Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-06

    ... Chief Actuary of the U.S. Railroad Retirement Board, 844 North Rush Street, Chicago, Illinois, on the... sent by the Chief Actuary to the Committee before the meeting. The meeting will be open to the public... communications or notices to the RRB Actuarial Advisory Committee, c/o Chief Actuary, U.S. Railroad Retirement...

  6. Estimation of Survival Probabilities for Use in Cost-effectiveness Analyses: A Comparison of a Multi-state Modeling Survival Analysis Approach with Partitioned Survival and Markov Decision-Analytic Modeling

    PubMed Central

    Williams, Claire; Lewsey, James D.; Mackay, Daniel F.; Briggs, Andrew H.

    2016-01-01

    Modeling of clinical-effectiveness in a cost-effectiveness analysis typically involves some form of partitioned survival or Markov decision-analytic modeling. The health states progression-free, progression and death and the transitions between them are frequently of interest. With partitioned survival, progression is not modeled directly as a state; instead, time in that state is derived from the difference in area between the overall survival and the progression-free survival curves. With Markov decision-analytic modeling, a priori assumptions are often made with regard to the transitions rather than using the individual patient data directly to model them. This article compares a multi-state modeling survival regression approach to these two common methods. As a case study, we use a trial comparing rituximab in combination with fludarabine and cyclophosphamide v. fludarabine and cyclophosphamide alone for the first-line treatment of chronic lymphocytic leukemia. We calculated mean Life Years and QALYs that involved extrapolation of survival outcomes in the trial. We adapted an existing multi-state modeling approach to incorporate parametric distributions for transition hazards, to allow extrapolation. The comparison showed that, due to the different assumptions used in the different approaches, a discrepancy in results was evident. The partitioned survival and Markov decision-analytic modeling deemed the treatment cost-effective with ICERs of just over £16,000 and £13,000, respectively. However, the results with the multi-state modeling were less conclusive, with an ICER of just over £29,000. This work has illustrated that it is imperative to check whether assumptions are realistic, as different model choices can influence clinical and cost-effectiveness results. PMID:27698003

  7. Estimation of Survival Probabilities for Use in Cost-effectiveness Analyses: A Comparison of a Multi-state Modeling Survival Analysis Approach with Partitioned Survival and Markov Decision-Analytic Modeling.

    PubMed

    Williams, Claire; Lewsey, James D; Mackay, Daniel F; Briggs, Andrew H

    2017-05-01

    Modeling of clinical-effectiveness in a cost-effectiveness analysis typically involves some form of partitioned survival or Markov decision-analytic modeling. The health states progression-free, progression and death and the transitions between them are frequently of interest. With partitioned survival, progression is not modeled directly as a state; instead, time in that state is derived from the difference in area between the overall survival and the progression-free survival curves. With Markov decision-analytic modeling, a priori assumptions are often made with regard to the transitions rather than using the individual patient data directly to model them. This article compares a multi-state modeling survival regression approach to these two common methods. As a case study, we use a trial comparing rituximab in combination with fludarabine and cyclophosphamide v. fludarabine and cyclophosphamide alone for the first-line treatment of chronic lymphocytic leukemia. We calculated mean Life Years and QALYs that involved extrapolation of survival outcomes in the trial. We adapted an existing multi-state modeling approach to incorporate parametric distributions for transition hazards, to allow extrapolation. The comparison showed that, due to the different assumptions used in the different approaches, a discrepancy in results was evident. The partitioned survival and Markov decision-analytic modeling deemed the treatment cost-effective with ICERs of just over £16,000 and £13,000, respectively. However, the results with the multi-state modeling were less conclusive, with an ICER of just over £29,000. This work has illustrated that it is imperative to check whether assumptions are realistic, as different model choices can influence clinical and cost-effectiveness results.

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

    PubMed

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

    2017-07-01

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

  9. Tumor Control Outcomes After Hypofractionated and Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases From Renal Cell Carcinoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zelefsky, Michael J., E-mail: zelefskm@mskcc.org; Greco, Carlo; Motzer, Robert

    2012-04-01

    Purpose: To report tumor local progression-free outcomes after treatment with single-dose, image-guided, intensity-modulated radiotherapy and hypofractionated regimens for extracranial metastases from renal cell primary tumors. Patients and Methods: Between 2004 and 2010, 105 lesions from renal cell carcinoma were treated with either single-dose, image-guided, intensity-modulated radiotherapy to a prescription dose of 18-24 Gy (median, 24) or hypofractionation (three or five fractions) with a prescription dose of 20-30 Gy. The median follow-up was 12 months (range, 1-48). Results: The overall 3-year actuarial local progression-free survival for all lesions was 44%. The 3-year local progression-free survival for those who received a highmore » single-dose (24 Gy; n = 45), a low single-dose (<24 Gy; n = 14), or hypofractionation regimens (n = 46) was 88%, 21%, and 17%, respectively (high single dose vs. low single dose, p = .001; high single dose vs. hypofractionation, p < .001). Multivariate analysis revealed the following variables were significant predictors of improved local progression-free survival: 24 Gy dose compared with a lower dose (p = .009) and a single dose vs. hypofractionation (p = .008). Conclusion: High single-dose, image-guided, intensity-modulated radiotherapy is a noninvasive procedure resulting in high probability of local tumor control for metastatic renal cell cancer generally considered radioresistant according to the classic radiobiologic ranking.« less

  10. 78 FR 9890 - DoD Board of Actuaries; Notice of Federal Advisory Committee Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ... DEPARTMENT OF DEFENSE Office of the Secretary DoD Board of Actuaries; Notice of Federal Advisory... Advisory Committee meeting of the DoD Board of Actuaries will take place. DATES: July 18, 2013, from 1:00 p... Defense Human Resource Activity, DoD Office of the Actuary, 4800 Mark Center Drive, STE 06J25-01...

  11. Intratumoral heterogeneity characterized by pretreatment PET in non-small cell lung cancer patients predicts progression-free survival on EGFR tyrosine kinase inhibitor

    PubMed Central

    Paeng, Jin Chul; Keam, Bhumsuk; Kim, Tae Min; Kim, Dong-Wan; Heo, Dae Seog

    2018-01-01

    Intratumoral heterogeneity has been suggested to be an important resistance mechanism leading to treatment failure. We hypothesized that radiologic images could be an alternative method for identification of tumor heterogeneity. We tested heterogeneity textural parameters on pretreatment FDG-PET/CT in order to assess the predictive value of target therapy. Recurred or metastatic non-small cell lung cancer (NSCLC) subjects with an activating EGFR mutation treated with either gefitinib or erlotinib were reviewed. An exploratory data set (n = 161) and a validation data set (n = 21) were evaluated, and eight parameters were selected for survival analysis. The optimal cutoff value was determined by the recursive partitioning method, and the predictive value was calculated using Harrell’s C-index. Univariate analysis revealed that all eight parameters showed an increased hazard ratio (HR) for progression-free survival (PFS). The highest HR was 6.41 (P<0.01) with co-occurrence (Co) entropy. Increased risk remained present after adjusting for initial stage, performance status (PS), and metabolic volume (MV) (aHR: 4.86, P<0.01). Textural parameters were found to have an incremental predictive value of early EGFR tyrosine kinase inhibitor (TKI) failure compared to that of the base model of the stage and PS (C-index 0.596 vs. 0.662, P = 0.02, by Co entropy). Heterogeneity textural parameters acquired from pretreatment FDG-PET/CT are highly predictive factors for PFS of EGFR TKI in EGFR-mutated NSCLC patients. These parameters are easily applicable to the identification of a subpopulation at increased risk of early EGFR TKI failure. Correlation to genomic alteration should be determined in future studies. PMID:29385152

  12. The effect of lymphadenectomy on survival and recurrence in patients with ovarian cancer: a systematic review and meta-analysis.

    PubMed

    Zhou, Jinhong; Shan, Guoping; Chen, Yiwen

    2016-08-01

    Our objective was to perform a meta-analysis examining the effectiveness of lymphadenectomy in patients with ovarian cancer. PubMed and CENTRAL databases were searched on 15 November 2015 using the terms 'lymphadenectomy', 'ovarian cancer', 'dissection', 'para-aortic', 'pelvic' and survival. Prospective and retrospective studies comparing the outcomes of surgery with or without lymphadenectomy were included. Outcomes were 5-year overall survival, progression-free survival and recurrence rate. Of the 556 studies identified, 3 randomized controlled trials and 11 retrospective studies were included. Lymphadenectomy was associated with greater 5-year overall survival than no lymphadenectomy (pooled odds ratio = 1.58, 95% confidence interval: 1.41-1.77, p < 0.001). There was no difference in progression-free survival between the groups (pooled overall survival = 1.62, 95% confidence interval: 0.82-3.21, p = 0.168). Lymphadenectomy was associated with greater progression-free survival in randomized clinical trials (pooled overall survival = 1.57, 95% confidence interval: 1.11-2.21, p = 0.010), but not in retrospective studies. Lymphadenectomy was associated with a significantly lower recurrence rate (pooled overall survival = 0.51, 95% confidence interval: 0.30-0.85, p = 0.011). Lymphadenectomy was associated with greater 5-year overall survival in patients with both early and advanced stage cancer, but was associated with greater progression-free survival and lower recurrence rate only in patients with advanced stage cancer. Lymphadenectomy is associated with greater 5-year overall survival in patients with early and advanced stage ovarian cancer, but an effect on progression-free survival and recurrence rate was only found in patients with advanced stage ovarian cancer. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Postoperative Treatment of Primary Glioblastoma Multiforme With Radiation and Concomitant Temozolomide in Elderly Patients

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Combs, Stephanie E.; Wagner, Johanna; Bischof, Marc

    2008-03-15

    Purpose: To evaluate efficacy and toxicity in elderly patients with glioblastoma multiforme (GBM) treated with postoperative radiochemotherapy with temozolomide (TMZ). Patients and Methods: Forty-three patients aged 65 years or older were treated with postoperative with radiochemotherapy using TMZ for primary GBM. Median age at primary diagnosis was 67 years; 14 patients were female, 29 were male. A complete surgical resection was performed in 12 patients, subtotal resection in 17 patients, and biopsy only in 14 patients. Radiotherapy was applied with a median dose of 60 Gy, in a median fractionation of 5 x 2 Gy/wk. Thirty-five patients received concomitant TMZmore » at 50 mg/m{sup 2}, and in 8 patients 75 mg/m{sup 2} of TMZ was applied. Adjuvant cycles of TMZ were prescribed in 5 patients only. Results: Median overall survival was 11 months in all patients; the actuarial overall survival rate was 48% at 1 year and 8% at 2 years. Median overall survival was 18 months after complete resection, 16 months after subtotal resection, and 6 months after biopsy only. Median progression-free survival was 4 months; the actuarial progression-free survival rate was 41% at 6 months and 18% at 12 months. Radiochemotherapy was well tolerated in most patients and could be completed without interruption in 38 of 43 patients. Four patients developed hematologic side effects greater than Common Terminology Criteria Grade 2, which led to early discontinuation of TMZ in 1 patient. Conclusions: Radiochemotherapy is safe and effective in a subgroup of elderly patients with GBM and should be considered in patients without major comorbidities.« less

  14. Cytokine Profiling of Ascites at Primary Surgery Identifies an Interaction of Tumor Necrosis Factor-α and Interleukin-6 in Predicting Reduced Progression-Free Survival in Epithelial Ovarian Cancer

    PubMed Central

    Kolomeyevskaya, Nonna; Eng, Kevin H.; Khan, Anm Nazmul H.; Grzankowski, Kassondra S.; Singel, Kelly L.; Moysich, Kirsten; Segal, Brahm H.

    2015-01-01

    Objectives Epithelial ovarian cancer (EOC) typically presents with advanced disease. Even with optimal debulking and response to adjuvant chemotherapy, the majority of patients will have disease relapse. We evaluated cytokine and chemokine profiles in ascites at primary surgery as biomarkers for progression-free survival (PFS) and overall survival (OS) in patients with advanced EOC. Methods Retrospective analysis of patients (n =70) who underwent surgery at Roswell Park Cancer Institute between 2002-12, followed by platinum-based chemotherapy. Results The mean age at diagnosis was 61.8 years, 85.3% had serous EOC, and 95.7% had stage IIIB, IIIC, or IV disease. Univariate analysis showed that ascites levels of tumor necrosis factor (TNF)-α were associated with reduced PFS after primary surgery. Although the ascites concentration of interleukin (IL)-6 was not by itself predictive of PFS, we found that stratifying patients by high TNF-α and high IL-6 levels identified a sub-group of patients at high risk for rapid disease relapse. This effect was largely independent of clinical prognostic variables. Conclusions The combination of high TNF-α and high IL-6 ascites levels at primary surgery predicts worse PFS in patients with advanced EOC. These results suggest an interaction between ascites TNF-α and IL-6 in driving tumor progression and resistance to chemotherapy in advanced EOC, and raise the potential for pre-treatment ascites levels of these cytokines as prognostic biomarkers. This study involved a small sample of patients and was an exploratory analysis; therefore, findings require validation in a larger independent cohort. PMID:26001328

  15. Cytokine profiling of ascites at primary surgery identifies an interaction of tumor necrosis factor-α and interleukin-6 in predicting reduced progression-free survival in epithelial ovarian cancer.

    PubMed

    Kolomeyevskaya, Nonna; Eng, Kevin H; Khan, Anm Nazmul H; Grzankowski, Kassondra S; Singel, Kelly L; Moysich, Kirsten; Segal, Brahm H

    2015-08-01

    Epithelial ovarian cancer (EOC) typically presents with advanced disease. Even with optimal debulking and response to adjuvant chemotherapy, the majority of patients will have disease relapse. We evaluated cytokine and chemokine profiles in ascites at primary surgery as biomarkers for progression-free survival (PFS) and overall survival (OS) in patients with advanced EOC. Retrospective analysis of patients (n =70) who underwent surgery at Roswell Park Cancer Institute between 2002 and 2012, followed by platinum-based chemotherapy. The mean age at diagnosis was 61.8 years, 85.3% had serous EOC, and 95.7% had stage IIIB, IIIC, or IV disease. Univariate analysis showed that ascites levels of tumor necrosis factor (TNF)-α were associated with reduced PFS after primary surgery. Although the ascites concentration of interleukin (IL)-6 was not by itself predictive of PFS, we found that stratifying patients by high TNF-α and high IL-6 levels identified a sub-group of patients at high risk for rapid disease relapse. This effect was largely independent of clinical prognostic variables. The combination of high TNF-α and high IL-6 ascites levels at primary surgery predicts worse PFS in patients with advanced EOC. These results suggest an interaction between ascites TNF-α and IL-6 in driving tumor progression and resistance to chemotherapy in advanced EOC, and raise the potential for pre-treatment ascites levels of these cytokines as prognostic biomarkers. This study involved a small sample of patients and was an exploratory analysis; therefore, findings require validation in a larger independent cohort. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Impact of actuarial assumptions on pension costs: A simulation analysis

    NASA Astrophysics Data System (ADS)

    Yusof, Shaira; Ibrahim, Rose Irnawaty

    2013-04-01

    This study investigates the sensitivity of pension costs to changes in the underlying assumptions of a hypothetical pension plan in order to gain a perspective on the relative importance of the various actuarial assumptions via a simulation analysis. Simulation analyses are used to examine the impact of actuarial assumptions on pension costs. There are two actuarial assumptions will be considered in this study which are mortality rates and interest rates. To calculate pension costs, Accrued Benefit Cost Method, constant amount (CA) modification, constant percentage of salary (CS) modification are used in the study. The mortality assumptions and the implied mortality experience of the plan can potentially have a significant impact on pension costs. While for interest rate assumptions, it is inversely related to the pension costs. Results of the study have important implications for analyst of pension costs.

  17. 76 FR 81362 - Regulations Governing the Performance of Actuarial Services Under the Employee Retirement Income...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-28

    ... JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES 20 CFR Part 901 [TD 9517] RIN 1545-BC82 Regulations...; Correction AGENCY: Joint Board for the Enrollment of Actuaries. ACTION: Correction to final regulations... Federal Register on Thursday, March 31, 2011 (76 FR 17762) relating to the enrollment of actuaries. DATES...

  18. 77 FR 12577 - Department of Defense (DoD) Board of Actuaries; Federal Advisory Committee Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-01

    ... DEPARTMENT OF DEFENSE Office of the Secretary Department of Defense (DoD) Board of Actuaries... that the following Federal advisory committee meeting of the DoD Board of Actuaries will take place... Actuaries meeting or make an oral presentation or submit a written statement for consideration at the...

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

    PubMed

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

    2018-01-01

    The purpose of this study is to analyze the clinical impact of radical nephrectomy on retroperitoneal liposarcoma near the kidney. Data of patients who underwent surgery for unilateral primary retroperitoneal liposarcoma near the kidney were retrospectively collected. Patients were divided into four groups according to whether they underwent nephrectomy and combined resection of other organs. Kaplan-Meier survival analysis was used to estimate disease-free survival and overall survival. Multivariable Cox analysis was used to analyze factors related to disease-free survival and overall survival. Nephrectomy (HR = 0.260, CI = 0.078-0.873, p = 0.029) had a beneficial effect on disease-free survival, while interaction model of nephrectomy*other organ resection (HR = 4.655, CI = 1.767-12.263, p = 0.002) showed poor disease-free survival. Other organ resection was not related to disease-free survival (HR = 1.543, CI = 0.146-16.251, p = 0.718). Operation method (p = 0.007) and FNCLCC grade (p < 0.001; G2, HR = 1.833, CI = 0.684-4.915, p = 0.228; G3, HR = 9.190, CI = 3.351-25.199, p < 0.001) were significant factors for disease-free survival. While combined organ resection without nephrectomy group (HR = 1.604, CI = 0.167-15.370, p = 0.682) and radical nephrectomy with combined organ resection group (HR = 1.309, CI = 0.448-3.825, p = 0.622) did not show significant difference in disease-free survival from the mass excision only group, radical nephrectomy without combined organ resection group (HR = 0.279, CI = 0.078-0.991, p = 0.048) showed superior disease-free survival. Radical nephrectomy of unilateral primary retroperitoneal liposarcoma near the kidney has a beneficial effect on disease-free survival.

  20. High-dose-rate interstitial brachytherapy for the treatment of high-volume locally recurrent endometrial carcinoma.

    PubMed

    Huang, Kitty; D'Souza, David; Patil, Nikhilesh; Velker, Vikram; Leung, Eric; Stitt, Larry; Whiston, Frances; Sugimoto, Akira; McGee, Jacob; Prefontaine, Michel

    2016-01-01

    Limited therapeutic options are available for the treatment of locally recurrent endometrial carcinoma. Our objective was to report an institutional experience using interstitial brachytherapy (IBT) to treat significant recurrent endometrial carcinoma, including previously irradiated disease. Between December 2004 and September 2012, 40 patients with high-volume locally recurrent endometrial cancer were treated by high-dose-rate IBT (± external beam radiation therapy EBRT). Sixteen patients had prior radiotherapy: EBRT alone (n = 5), intracavitary brachytherapy alone (n = 3), or EBRT with intracavitary brachytherapy boost (n = 8). Actuarial outcome rates were calculated using the Kaplan-Meier method and compared using the log-rank test. Median followup interval was 18 months. Median disease-free interval was 61 months. Actuarial local control, progression-free survival (PFS), and overall survival were 74% and 60%, 70% and 51%, and 83% and 72% at 12 and 24 months, respectively. p-Values for local control, progression-free survival, and overall survival between patient who had prior RT (n = 16) to no prior RT (n = 24) were p = 0.38, 0.32, and 0.90, respectively. Acute toxicities include Grade 1-2 pain (5%), genitourinary (7%), gastrointestinal (12%), soft tissue (5%), and dermatologic (12%). Four patients observed late Grade 3-4 toxicities, including rectal bleeding/fistula and soft tissue necrosis. High-dose-rate IBT is an effective treatment for locally recurrent endometrial carcinoma with an acceptable toxicity profile. Outcomes are similar between previously irradiated and nonirradiated patients. In women who have received prior radiotherapy and are often considered for palliative treatment, interstitial brachytherapy is a potentially curative option. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  1. Cetuximab treatment for metastatic colorectal cancer with KRAS p.G13D mutations improves progression-free survival

    PubMed Central

    OSUMI, HIROKI; SHINOZAKI, EIJI; OSAKO, MASAHIKO; KAWAZOE, YOSHIMASA; OBA, MASARU; MISAKA, TAKAHARU; GOTO, TAKASHI; KAMO, HITOMI; SUENAGA, MITSUKUNI; KUMEKAWA, YOSUKE; OGURA, MARIKO; OZAKA, MASATO; MATSUSAKA, SATOSHI; CHIN, KEISHO; HATAKE, KIYOHIKO; MIZUNUMA, NOBUYUKI

    2015-01-01

    A number of previous studies have reported that 30–50% of patients with colorectal cancer (CRC) harbor Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, which is a major predictive biomarker of resistance to epidermal growth factor (EGFR)-targeted therapy. Treatment with an anti-EGFR inhibitor is recommended for patients with KRAS wild-type metastatic colorectal cancer (mCRC). A recent retrospective study of cetuximab reported that patients with KRAS p.G13D mutations had better outcomes compared with those with other mutations. The aim of this retrospective study was to assess the prevalence of KRAS p.G13D mutations and evaluate the effectiveness of cetuximab in mCRC patients with KRAS p.G13D or other KRAS mutations. We reviewed the clinical records of 98 mCRC patients with KRAS mutations who were treated between August, 2004 and January, 2011 in four hospitals located in Tokyo and Kyushu Island. We also investigated KRAS mutation subtypes and patient characteristics. In the patients who received cetuximab, univariate and multivariate analyses were performed to assess the effect of KRAS p.G13D mutations on progression-free survival (PFS) and overall survival (OS). Of the 98 patients, 23 (23.5%) had KRAS p.G13D-mutated tumors, whereas 75 (76.5%) had tumors harboring other mutations. Of the 31 patients who received cetuximab, 9 (29.0%) had KRAS p.G13D mutations and 22 (71.0%) had other mutations. There were no significant differences in age, gender, primary site, pathological type, history of chemotherapy, or the combined use of irinotecan between either of the patient subgroups. The univariate analysis revealed no significant difference in PFS or OS between the patients with KRAS p.G13D mutations and those with other mutations (median PFS, 4.5 vs. 2.8 months, respectively; P=0.65; and median OS, 15.3 vs. 8.9 months, respectively; P=0.51). However, the multivariate analysis revealed a trend toward better PFS among patients harboring p.G13D mutations (PFS

  2. Relationship between venetoclax exposure, rituximab coadministration, and progression-free survival in patients with relapsed or refractory chronic lymphocytic leukemia: demonstration of synergy.

    PubMed

    Freise, Kevin J; Jones, Aksana K; Menon, Rajeev M; Verdugo, Maria E; Humerickhouse, Rod A; Awni, Walid M; Salem, Ahmed Hamed

    2017-12-01

    Venetoclax is indicated at a dosage of 400 mg daily (QD) for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion who have received at least 1 prior therapy. Ongoing trials are evaluating venetoclax in combination with CD20 targeting monoclonal antibodies, such as rituximab. The objective of this research was to characterize the relationship between venetoclax exposures and progression-free survival (PFS) and to evaluate the effect of rituximab coadministration on PFS in patients with relapsed or refractory (R/R) CLL/small lymphocytic lymphoma (SLL). A total of 323 patients from 3 clinical studies of venetoclax, with and without rituximab coadministration, were pooled for the analyses. A time-variant relative risk survival model was used to relate plasma venetoclax concentrations and rituximab administration to PFS. Demographics and baseline disease characteristics were evaluated for their effect on PFS. A concentration-dependent effect of venetoclax on PFS and a prolonged synergistic effect of 6 cycles of concomitant rituximab were identified. The 17p deletion chromosomal aberration was not identified to affect the PFS of patients treated with venetoclax. A venetoclax dose of 400 mg daily QD was estimated to result in a substantial median PFS of 1.8 years (95% confidence interval [CI], 1.7-2.1), whereas the addition of 6 cycles of rituximab was estimated to increase the median PFS to 3.9 years (95% CI, 2.8-5.6). The analysis demonstrates a concentration-dependent effect of venetoclax on PFS and also a synergistic effect with rituximab. Combining venetoclax with the CD20 targeting monoclonal antibody rituximab in R/R CLL/SLL patients provides substantial synergistic benefit compared with increasing the venetoclax monotherapy dose. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Overexpression of G6PD is associated with high risks of recurrent metastasis and poor progression-free survival in primary breast carcinoma.

    PubMed

    Pu, Haihong; Zhang, Qingyuan; Zhao, Chunbo; Shi, Lei; Wang, Yan; Wang, Jingxuan; Zhang, Minghui

    2015-11-25

    The present study aimed to investigate the expression of CYP27A1, CYP7B1, insulin-like growth factor-1 (IGF-1), glucose-6-phosphate-dehydrogenase (G6PD), glutathione S-transferase P1 (GSTP1), and pyruvate kinase isoform M2 (PKM2) in breast carcinoma tissue and evaluate their prognostic value for progression-free survival (PFS) and overall survival (OS). A total of 20 patients treated with surgery for primary breast carcinoma were enrolled: 10 cases diagnosed with recurrent metastasis (A), along with their corresponding metastases specimen (AM) and 10 cases with no evidence of recurrence or metastasis (B). Baseline characteristics of patients including age, lymph node metastasis, molecular subtypes, tumor staging and size, and pathological classification were all collected. Immunohistochemistry was performed to detect the protein expression in tumor specimens. Elevated G6PD protein levels were noted in group A compared with group AM and B (both P < 0.05), and PKM2 expression was also higher in group A when compared to group AM (P = 0.019), but similar with group B (P > 0.05). No association between clinicopathological parameters and the two proteins expression was observed. The G6PD protein expression was strongly associated with PFS of breast carcinoma patients (P = 0.021) but not for OS. According to the Kaplan-Meier analysis, mean PFS time of patients with G6PD-negative and G6PD-positive expression tumor were 71.36 ± 6.53 and 32.25 ± 5.67 months, respectively (P = 0.002). The G6PD protein could be served as a potential prognostic biomarker for primary breast carcinoma, and overexpression of G6PD protein predicted a high risk of recurrent metastasis and poor PFS during follow-up.

  4. Relationship between ornithine decarboxylase levels in anaplastic gliomas and progression-free survival in patients treated with DFMO-PCV chemotherapy.

    PubMed

    Levin, Victor A; Jochec, Jacob L; Shantz, Lisa M; Aldape, Kenneth D

    2007-11-15

    The purpose of this study was to assess the relationship between progression-free survival (PFS) in patients treated with DFMO + PCV (procarbazine, CCNU, vincristine) chemotherapy for malignant gliomas with tumor cell ornithine decarboxylase (ODC) activity. Formalin-fixed slides were obtained for study patients with anaplastic gliomas (AGs) and glioblastoma treated on protocol DM92-035. ODC levels were measured using an antibody to ODC coupled to Alexa 647 dye (Ab-ODC-Alexa 647). Ab-ODC-Alexa 647 intensity in transgenic murine hearts of differing ODC activity was used to calculate ODC activity in tumor cell nucleoplasm. In total, tumor specimens for 31 of 114 (27%) patients treated on the AG strata and 10 patients from the GBM strata were obtained. We found that tumor ODC level heterogeneity increased with increasing tumor malignancy. In a Cox proportional hazards model, PFS was found to be inversely related to median tumor ODC activity, with an unadjusted hazard ratio for median ODC group (>3.3 vs. 3.3 nmol/30 min/mug protein. Of AG tumors in which ODC activity was evaluated, 26% had ODC levels > 3.3 nmol/30 min/mug protein. This study shows that Ab-ODC-Alexa 647 fluorescence intensity can be used as a surrogate marker of ODC biochemical activity in AGs and can predict PFS to DFMO-based chemotherapy. (c) 2007 Wiley-Liss, Inc.

  5. Longitudinal Biological Exposure to Carotenoids is Associated with Breast Cancer-Free Survival in the Women’s Healthy Eating and Living Study

    PubMed Central

    Rock, Cheryl L.; Natarajan, Loki; Pu, Minya; Thomson, Cynthia A.; Flatt, Shirley W.; Caan, Bette J.; Gold, Ellen B.; Al-Delaimy, Wael K.; Newman, Vicky A.; Hajek, Richard A.; Stefanick, Marcia L.; Pierce, John P.

    2009-01-01

    In some cohort studies, a high-vegetable diet has been associated with greater likelihood of recurrence-free survival in women diagnosed with breast cancer. Carotenoids are obtained primarily from vegetables and fruit, and they exhibit biological activities that may specifically reduce the progression of mammary carcinogenesis. The present analysis examines the relationship between plasma carotenoids at enrollment and 1, 2 or 3, 4 and 6 years and breast cancer-free survival in the Women’s Healthy Eating and Living (WHEL) Study participants (n = 3043), who had been diagnosed with early stage breast cancer. The primary endpoint was time to a second breast cancer event (a recurrence or new primary breast cancer). An average carotenoid concentration over time was estimated for each participant as the average area under the plasma carotenoid curve (AUC) formed by the plasma carotenoid concentrations at scheduled clinic visits. Multiple regression Cox proportional hazards analysis with adjustment for prognostic and other factors was used to examine the association between carotenoids and breast cancer-free survival. A total of 508 (16.7%) breast cancer events occurred over a median 7.12 years follow-up. Compared to the lowest tertile, the hazard ratio for the medium/high plasma carotenoid tertiles was 0.67 (95% confidence interval 0.54–0.83) after adjustment. The interaction between study group and tertile of average carotenoid concentration over time was not significant (P = 0.23). Higher biological exposure to carotenoids, when assessed over the time frame of the study, was associated with greater likelihood of breast cancer-free survival regardless of study group assignment. PMID:19190138

  6. Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival

    PubMed Central

    Henkel, Jenny S; Beers, David R; Wen, Shixiang; Rivera, Andreana L; Toennis, Karen M; Appel, Joan E; Zhao, Weihua; Moore, Dan H; Powell, Suzanne Z; Appel, Stanley H

    2013-01-01

    In amyotrophic lateral sclerosis (ALS) mice, regulatory T-lymphocytes (Tregs) are neuroprotective, slowing disease progression. To address whether Tregs and FoxP3, a transcription factor required for Treg function, similarly influence progression rates of ALS patients, T-lymphocytes from patients were assessed by flow cytometry. Both numbers of Tregs and their FoxP3 protein expressions were reduced in rapidly progressing ALS patients and inversely correlated with progression rates. The mRNA levels of FoxP3, TGF-β, IL4 and Gata3, a Th2 transcription factor, were reduced in rapidly progressing patients and inversely correlated with progression rates. Both FoxP3 and Gata3 were accurate indicators of progression rates. No differences in IL10, Tbx21, a Th1 transcription factor or IFN-γ expression were found between slow and rapidly progressing patients. A 3.5-year prospective study with a second larger cohort revealed that early reduced FoxP3 levels were indicative of progression rates at collection and predictive of future rapid progression and attenuated survival. Collectively, these data suggest that Tregs and Th2 lymphocytes influence disease progression rates. Importantly, early reduced FoxP3 levels could be used to identify rapidly progressing patients. PMID:23143995

  7. Repeating platinum/bevacizumab in recurrent or progressive cervical cancer yields marginal survival benefits.

    PubMed

    Zamorano, Abigail S; Wan, Leping; Powell, Matthew A; Massad, L Stewart

    2017-11-01

    Our objective was to assess overall survival of cervical cancer patients following prior platinum/bevacizumab chemotherapy, comparing retreatment with platinum/bevacizumab with alternative therapies. A retrospective analysis was performed of women who received platinum/bevacizumab (PB) chemotherapy for cervical cancer at Washington University between July 1, 2005 and December 31, 2015. Wilcoxon rank-sum exact test and Fisher's exact test were used to compare the treatment groups, and Kaplan Meier curves were generated. Cox regression analyses were performed, with treatment free interval and prior therapy response included as covariates. Of 84 patients who received PB chemotherapy, 59 (70%) received no second line chemotherapy, as they did not recur, progressed without further chemotherapy, were lost to follow up, or expired. Of the remaining 25 patients, 9 were retreated with the combination of platinum/bevacizumab (PB), 6 were retreated with a platinum regimen without bevacizumab (P), and 10 were retreated with neither (not-P). The only long-term survivor was in the not-P group and was treated with an immunotherapy agent. Median overall survival of all patients was 7.1 months. There was a marginal difference in survival between women in the PB and not-PB groups (11.8 versus 5.7 months; HR 3.02, 95% CI, 0.98-9.28). There was no difference in survival based on platinum interval (HR 0.81; 95% CI, 0.27-2.45). Outcomes are grim for women retreated after platinum/bevacizumab therapy and are only marginally improved by retreatment with a platinum/bevacizumab regimen. Rather than additional PB therapy, women with cervical cancer who recur after platinum/bevacizumab should consider supportive care or clinical trials.

  8. Is the progression free survival advantage of concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin in patients with advanced cervical cancer worth the additional cost? A cost-effectiveness analysis.

    PubMed

    Smith, B; Cohn, D E; Clements, A; Tierney, B J; Straughn, J M

    2013-09-01

    The objective of this study is to determine whether concurrent and adjuvant chemoradiation with gemcitabine/cisplatin is cost-effective in patients with stage IIB to IVA cervical cancer. A cost-effectiveness model compared two arms of the trial performed by Duenas-Gonzalez et al. [1]: concurrent and adjuvant chemoradiation with gemcitabine/cisplatin (RT/GC+GC) versus concurrent radiation with cisplatin (RT/C). Major adverse events (AEs) and progression free survival (PFS) rates of each arm were incorporated in the model. AEs were defined as any hospitalization including grade 4 anemia, grade 4 neutropenia, and death. Medicare data and literature review were used to estimate costs. Incremental cost-effectiveness ratios (ICERs) per progression-free life-year saved (PF-LYS) were calculated. Sensitivity analyses were performed for pertinent uncertainties. For 10,000 women with locally advanced cervical cancer, the cost of therapy and AEs was $173.9 million (M) for RT/C versus $259.8M for RT/GC+GC. There were 879 additional 3-year progression-free survivors in the RT/GC+GC arm. The ICER for RT/GC+GC was $97,799 per PF-LYS. When the rate of hospitalization was equalized to 4.3%, the ICER for RT/GC+GC exceeded $80,000. The resultant ICER when increasing PFS in the RT/GC+GC arm by 5% was $62,605 per PF-LYS. When the cost of chemotherapy was decreased by 50%, the ICER was below $50,000 at $41,774 per PF-LYS. Radiation and gemcitabine/cisplatin for patients with stage IIB to IVA cervical cancer are not cost-effective. The increased financial burden of radiation with gemcitabine/cisplatin and associated toxicities appears to outweigh the benefit of increased 3-year PFS and is primarily dependent on chemotherapy drug costs. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Cannabinoids receptor type 2, CB2, expression correlates with human colon cancer progression and predicts patient survival.

    PubMed

    Martínez-Martínez, Esther; Gómez, Irene; Martín, Paloma; Sánchez, Antonio; Román, Laura; Tejerina, Eva; Bonilla, Félix; Merino, Antonio García; de Herreros, Antonio García; Provencio, Mariano; García, Jose M

    2015-01-01

    Many studies have demonstrated that the endocannabinoid system (ECS) is altered in different tumor types, including colon cancer. However, little is known about the role of the ECS in tumor progression. Here we report the correlation between CB 2 expression and pathological data in a series of 175 colorectal cancer patients, as well as the response of the HT29 colon cancer-derived cell line upon CB 2 activation. CB 2 mRNA was detected in 28.6% of samples tested. It was more frequent in N+ patients and predicts disease free survival and overall survival in colon cancer. In positive samples, CB 2 was expressed with great intensity in tumor epithelial cells and correlated with tumor growth. Treatment of HT29 with CB 2 agonist revealed membrane loss of E-cadherin and SNAIL1 overexpression. A direct correlation between CB 2 and SNAIL1 expression was also found in human tumors. CB 2 receptor expression is a poor prognostic marker for colon cancer and the activation of this receptor, with non-apoptotic doses of agonists, could be collaborating with disease progression. These results raise the question whether the activation of CB 2 should be considered as anti-tumoral therapy.

  10. Abiraterone and increased survival in metastatic prostate cancer.

    PubMed

    de Bono, Johann S; Logothetis, Christopher J; Molina, Arturo; Fizazi, Karim; North, Scott; Chu, Luis; Chi, Kim N; Jones, Robert J; Goodman, Oscar B; Saad, Fred; Staffurth, John N; Mainwaring, Paul; Harland, Stephen; Flaig, Thomas W; Hutson, Thomas E; Cheng, Tina; Patterson, Helen; Hainsworth, John D; Ryan, Charles J; Sternberg, Cora N; Ellard, Susan L; Fléchon, Aude; Saleh, Mansoor; Scholz, Mark; Efstathiou, Eleni; Zivi, Andrea; Bianchini, Diletta; Loriot, Yohann; Chieffo, Nicole; Kheoh, Thian; Haqq, Christopher M; Scher, Howard I

    2011-05-26

    Biosynthesis of extragonadal androgen may contribute to the progression of castration-resistant prostate cancer. We evaluated whether abiraterone acetate, an inhibitor of androgen biosynthesis, prolongs overall survival among patients with metastatic castration-resistant prostate cancer who have received chemotherapy. We randomly assigned, in a 2:1 ratio, 1195 patients who had previously received docetaxel to receive 5 mg of prednisone twice daily with either 1000 mg of abiraterone acetate (797 patients) or placebo (398 patients). The primary end point was overall survival. The secondary end points included time to prostate-specific antigen (PSA) progression (elevation in the PSA level according to prespecified criteria), progression-free survival according to radiologic findings based on prespecified criteria, and the PSA response rate. After a median follow-up of 12.8 months, overall survival was longer in the abiraterone acetate-prednisone group than in the placebo-prednisone group (14.8 months vs. 10.9 months; hazard ratio, 0.65; 95% confidence interval, 0.54 to 0.77; P<0.001). Data were unblinded at the interim analysis, since these results exceeded the preplanned criteria for study termination. All secondary end points, including time to PSA progression (10.2 vs. 6.6 months; P<0.001), progression-free survival (5.6 months vs. 3.6 months; P<0.001), and PSA response rate (29% vs. 6%, P<0.001), favored the treatment group. Mineralocorticoid-related adverse events, including fluid retention, hypertension, and hypokalemia, were more frequently reported in the abiraterone acetate-prednisone group than in the placebo-prednisone group. The inhibition of androgen biosynthesis by abiraterone acetate prolonged overall survival among patients with metastatic castration-resistant prostate cancer who previously received chemotherapy. (Funded by Cougar Biotechnology; COU-AA-301 ClinicalTrials.gov number, NCT00638690.).

  11. [Estimation of survival rates: technics used (author's transl)].

    PubMed

    Rodary, C; Laplanche, A; Comnougue, C; Flamant, R

    1979-01-01

    The direct method and life-table methods (actuarial and Kaplan-Meier) for estimating survival rates are described here. The difference between direct method and lifetable method is the use of information about the patients who are still alive. Practical examples of calculation are given with recommandations for graphical displays.

  12. High-dose-rate stereotactic body radiation therapy for postradiation therapy locally recurrent prostatic carcinoma: Preliminary prostate-specific antigen response, disease-free survival, and toxicity assessment.

    PubMed

    Fuller, Donald B; Wurzer, James; Shirazi, Reza; Bridge, Stephen S; Law, Jonathan; Mardirossian, George

    2015-01-01

    Patients with locally recurrent adenocarcinoma of the prostate following radiation therapy (RT) present a challenging problem. We prospectively evaluated the use of "high-dose-rate-like" prostate stereotactic body RT (SBRT) salvage for this circumstance, evaluating prostate-specific antigen response, disease-free survival, and toxicity. Between February 2009 and March 2014, 29 patients with biopsy-proven recurrent locally prostate cancer >2 years post-RT were treated. Median prior RT dose was 73.8 Gy and median interval to SBRT salvage was 88 months. Median recurrence Gleason score was 7 (79% was ≥7). Pre-existing RT toxicity >grade 1 was a reason for exclusion. Magnetic resonance imaging-defined prostate volume including any suspected extraprostatic extension, comprising the planning target volume. A total of 34 Gy/5 fractions was given, delivering a heterogeneous, high-dose-rate-like dose-escalation pattern. Toxicities were assessed using Common Terminology Criteria for Adverse Events, version 3.0, criteria. Twenty-nine treated patients had a median 24-month follow-up (range, 3-60 months). A median pre-SBRT salvage baseline prostate-specific antigen level of 3.1 ng/mL decreased to 0.65 ng/mL and 0.16 ng/mL at 1 and 2 years, respectively. Actuarial 2-year biochemical disease-free survival measured 82%, with no local failures. Toxicity >grade 1 was limited to the genitourinary domain, with 18% grade 2 or higher and 7% grade 3 or higher. No gastrointestinal toxicity >grade 1 occurred. Two-year disease-free survival is encouraging, and the prostate-specific antigen response kinetic appears comparable with that seen in de novo patients treated with SBRT, albeit still a preliminary finding. Grade ≥2 genitourinary toxicity was occasionally seen with no obvious predictive factor. Noting that our only brachytherapy case was 1 of the 2 cases with ≥grade 3 genitourinary toxicity, caution is recommended treating these patients. SBRT salvage of post-RT local recurrence

  13. Health-Related Quality of Life, Functional Status, and Cardiac Event-Free Survival in Patients With Heart Failure.

    PubMed

    Wu, Jia-Rong; Lennie, Terry A; Frazier, Susan K; Moser, Debra K

    2016-01-01

    Health-related quality of life (HRQOL), functional status, and cardiac event-free survival are outcomes used to assess the effectiveness of interventions in patients with heart failure (HF). However, the nature of the relationships among HRQOL, functional status, and cardiac event-free survival remains unclear. The purpose of this study is to examine the nature of the relationships among HRQOL, functional status, and cardiac event-free survival in patients with HF. This was a prospective, observational study of 313 patients with HF that was a secondary analysis from a registry. At baseline, patient demographic and clinical data were collected. Health-related quality of life was assessed using the Minnesota Living With Heart Failure Questionnaire and functional status was measured using the Duke Activity Status Index. Cardiac event-free survival data were obtained by patient interview, hospital database, and death certificate review. Multiple linear and Cox regressions were used to explore the relationships among HRQOL, functional status, and cardiac event-free survival while adjusting for demographic and clinical factors. Participants (n = 313) were men (69%), white (79%), and aged 62 ± 11 years. Mean left ventricular ejection fraction was 35% ± 14%. The mean HRQOL score of 32.3 ± 20.6 indicated poor HRQOL. The mean Duke Activity Status Index score of 16.2 ± 12.9 indicated poor functional status. Cardiac event-free survival was significantly worse in patients who had worse HRQOL or poorer functional status. Patients who had better functional status had better HRQOL (P < .001). Health-related quality of life was not a significant predictor of cardiac event-free survival after entering functional status in the model (P = .54), demonstrating that it was a mediator of the relationship between HRQOL and outcome. Functional status was a mediator between HRQOL and cardiac event-free survival. These data suggest that intervention studies to improve functional status

  14. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure.

    PubMed

    Lee, William M; Hynan, Linda S; Rossaro, Lorenzo; Fontana, Robert J; Stravitz, R Todd; Larson, Anne M; Davern, Timothy J; Murray, Natalie G; McCashland, Timothy; Reisch, Joan S; Robuck, Patricia R

    2009-09-01

    N-acetylcysteine (NAC), an antidote for acetaminophen poisoning, might benefit patients with non-acetaminophen-related acute liver failure. In a prospective, double-blind trial, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were stratified by site and coma grade and assigned randomly to groups that were given NAC or placebo (dextrose) infusion for 72 hours. The primary outcome was overall survival at 3 weeks. Secondary outcomes included transplant-free survival and rate of transplantation. A total of 173 patients received NAC (n = 81) or placebo (n = 92). Overall survival at 3 weeks was 70% for patients given NAC and 66% for patients given placebo (1-sided P = .283). Transplant-free survival was significantly better for NAC patients (40%) than for those given placebo (27%; 1-sided P = .043). The benefits of transplant-free survival were confined to the 114 patients with coma grades I-II who received NAC (52% compared with 30% for placebo; 1-sided P = .010); transplant-free survival for the 59 patients with coma grades III-IV was 9% in those given NAC and 22% in those given placebo (1-sided P = .912). The transplantation rate was lower in the NAC group but was not significantly different between groups (32% vs 45%; P = .093). Intravenous NAC generally was well tolerated; only nausea and vomiting occurred significantly more frequently in the NAC group (14% vs 4%; P = .031). Intravenous NAC improves transplant-free survival in patients with early stage non-acetaminophen-related acute liver failure. Patients with advanced coma grades do not benefit from NAC and typically require emergency liver transplantation.

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

    PubMed

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

    2018-03-01

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

  16. 77 FR 12577 - Department of Defense (DoD) Medicare-Eligible Retiree Health Care Board of Actuaries; Federal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-01

    ... Retiree Health Care Board of Actuaries; Federal Advisory Committee Meeting AGENCY: DoD. ACTION: Meeting... DoD Medicare-Eligible Retiree Health Care Board of Actuaries will take place. DATES: Friday, August 3... Contact: Persons desiring to attend the DoD Medicare- Eligible Retiree Health Care Board of Actuaries...

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

    PubMed

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

    2018-02-21

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

  18. MR imaging features associated with distant metastasis-free survival of patients with invasive breast cancer: a case-control study.

    PubMed

    Song, Sung Eun; Shin, Sung Ui; Moon, Hyeong-Gon; Ryu, Han Suk; Kim, Kwangsoo; Moon, Woo Kyung

    2017-04-01

    Preoperative breast magnetic resonance (MR) imaging features of primary breast cancers may have the potential to act as prognostic biomarkers by providing morphologic and kinetic features representing inter- or intra-tumor heterogeneity. Recent radiogenomic studies reveal that several radiologist-annotated image features are associated with genes or signal pathways involved in tumor progression, treatment resistance, and distant metastasis (DM). We investigate whether preoperative breast MR imaging features are associated with worse DM-free survival in patients with invasive breast cancer. Of the 3536 patients with primary breast cancers who underwent preoperative MR imaging between 2003 and 2009, 147 patients with DM were identified and one-to-one matched with control patients (n = 147) without DM according to clinical-pathologic variables. Three radiologists independently reviewed the MR images of 294 patients, and the association of DM-free survival with MR imaging and clinical-pathologic features was assessed using Cox proportional hazard models. Of MR imaging features, rim enhancement (hazard ratio [HR], 1.83 [95% confidence interval, CI 1.29, 2.51]; p = 0.001) and peritumoral edema (HR, 1.48 [95% CI 1.03, 2.11]; p = 0.032) were the significant features associated with worse DM-free survival. The significant MR imaging features, however, were different between breast cancer subtypes and stages. Preoperative breast MR imaging features of rim enhancement and peritumoral edema may be used as prognostic biomarkers that help predict DM risk in patients with breast cancer, thereby potentially enabling improved personalized treatment and monitoring strategies for individual patients.

  19. Reproductive Steroid Hormones and Recurrence-Free Survival in Women with a History of Breast Cancer

    PubMed Central

    Rock, Cheryl L.; Flatt, Shirley W.; Laughlin, Gail A.; Gold, Ellen B.; Thomson, Cynthia A.; Natarajan, Loki; Jones, Lovell A.; Caan, Bette J.; Stefanick, Marcia L.; Hajek, Richard A.; Al-Delaimy, Wael K.; Stanczyk, Frank Z.; Pierce, John P.

    2008-01-01

    Epidemiologic studies fairly consistently show in postmenopausal women that reproductive steroid hormones contribute to primary breast cancer risk, and this association is strongly supported by experimental studies using laboratory animals and model systems. Evidence linking sex hormone concentrations with risk for recurrence in women diagnosed with breast cancer is limited; however, beneficial effects of antiestrogenic therapy on recurrence-free survival suggest that these hormones affect progression and risk for recurrence. This study examined whether baseline serum concentrations of estradiol, testosterone, and sex hormone binding globulin were associated with recurrence-free survival in a nested case-control cohort of women from a randomized diet trial (Women's Healthy Eating and Living Study) who were followed for >7 years after diagnosis. In 153 case-control pairs of perimenopausal and postmenopausal women in this analysis, total estradiol [hazard ratio (HR), 1.41 per unit increase in log concentration; 95% confidence interval (95% CI), 1.01−1.97], bioavailable estradiol (HR, 1.26; 95% CI, 1.03−1.53), and free estradiol (HR, 1.31; 95% CI, 1.03−1.65) concentrations were significantly associated with risk for recurrence. Recurred women had an average total estradiol concentration that was double that of nonrecurred women (22.7 versus 10.8 pg/mL; P = 0.05). Testosterone and sex hormone binding globulin concentrations did not differ between cases and controls and were not associated with risk for recurrence. Although genetic and metabolic factors likely modulate the relationship between circulating sex hormones and risk, results from this study provide evidence that higher serum estrogen concentration contributes to risk for recurrence in women diagnosed with early stage breast cancer. PMID:18323413

  20. [Research progress on free radicals in human body].

    PubMed

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

    2016-08-10

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

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

    PubMed

    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

  2. Nonparametric Bayesian inference for mean residual life functions in survival analysis.

    PubMed

    Poynor, Valerie; Kottas, Athanasios

    2018-01-19

    Modeling and inference for survival analysis problems typically revolves around different functions related to the survival distribution. Here, we focus on the mean residual life (MRL) function, which provides the expected remaining lifetime given that a subject has survived (i.e. is event-free) up to a particular time. This function is of direct interest in reliability, medical, and actuarial fields. In addition to its practical interpretation, the MRL function characterizes the survival distribution. We develop general Bayesian nonparametric inference for MRL functions built from a Dirichlet process mixture model for the associated survival distribution. The resulting model for the MRL function admits a representation as a mixture of the kernel MRL functions with time-dependent mixture weights. This model structure allows for a wide range of shapes for the MRL function. Particular emphasis is placed on the selection of the mixture kernel, taken to be a gamma distribution, to obtain desirable properties for the MRL function arising from the mixture model. The inference method is illustrated with a data set of two experimental groups and a data set involving right censoring. The supplementary material available at Biostatistics online provides further results on empirical performance of the model, using simulated data examples. © The Author 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Choosing the 'best' plan in a health insurance exchange: actuarial value tells only part of the story.

    PubMed

    Lore, Ryan; Gabel, Jon R; McDevitt, Roland; Slover, Michael

    2012-08-01

    In the health insurance exchanges that will come online in 2014, consumers will be able to compare health plans with respect to actuarial value, or the percentage of health care costs that a plan would pay for a standard population. This analysis illustrates the out-of-pocket costs that might result from plans with various plan designs and actuarial values. We find that average out-of-pocket expense declines as actuarial values rise, but two plans with similar actuarial values can produce very different outcomes for a given person. The overall affordability of a plan also will be influenced by age rating, income-related premium subsidies, and out-of-pocket subsidies. Actuarial value is a useful starting point for selecting a plan, but it does not pinpoint which plan will produce the best overall value for a particular person.

  4. Insights into managed care--operational, legal and actuarial.

    PubMed

    Melek, S P; Johnson, B A; Schryver, D

    1997-01-01

    Understanding the operational, legal and actuarial dimensions of managed care is essential to developing managed care contracts between managed care organizations and individual health care providers or groups such as provider-sponsored organizations or independent practice associations. Operationally, it is important to understand managed care and its trends, emphasizing business issues, knowing your practice and defining acceptable levels of reimbursement and risk. Legally, there are a number of common themes or issues relevant to all managed care contracts, including primary care vs. specialist contracts, services offered, program policies and procedures, utilization review, physician reimbursement and compensation, payment schedule, terms and conditions, term and termination, continuation of care requirements, indemnification, amendment of contract and program policies, and stop-loss insurance. Actuarial issues include membership, geography, age-gender distribution, degree of health care management, local managed care utilization levels, historical utilization levels, health plan benefit design, among others.

  5. Conditional Disease-Free Survival After Surgical Resection of Gastrointestinal Stromal Tumors

    PubMed Central

    Bischof, Danielle A.; Kim, Yuhree; Dodson, Rebecca; Jimenez, M. Carolina; Behman, Ramy; Cocieru, Andrei; Fisher, Sarah B.; Groeschl, Ryan T.; Squires, Malcolm H.; Maithel, Shishir K.; Blazer, Dan G.; Kooby, David A.; Gamblin, T. Clark; Bauer, Todd W.; Quereshy, Fayez A.; Karanicolas, Paul J.; Law, Calvin H. L.; Pawlik, Timothy M.

    2015-01-01

    IMPORTANCE Gastrointestinal stromal tumors (GISTs) are the most commonly diagnosed mesenchymal tumors of the gastrointestinal tract. The risk of recurrence following surgical resection of GISTs is typically reported from the date of surgery. However, disease-free survival (DFS) over time is dynamic and changes based on disease-free time already accumulated following surgery. OBJECTIVES To assess the comparative performance of established GIST recurrence risk prognostic scoring systems and to characterize conditional DFS following surgical resection of GISTs. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study of 502 patients who underwent surgery for a primary, nonmetastatic GIST between January 1, 1998, and December 31, 2012, at 7 major academic cancer centers in the United States and Canada. MAIN OUTCOMES AND MEASURES Disease-free survival of the patients was classified according to 5 prognostic scoring systems, including the National Institutes of Health criteria, modified National Institutes of Health criteria, Memorial Sloan Kettering Cancer Center GIST nomogram, and American Joint Committee on Cancer gastric and nongastric categories. The concordance index (also known as the C statistic or the area under the receiver operating curve) of established GIST recurrence risk prognostic scoring systems. Conditional DFS estimates were calculated. RESULTS Overall 1-year, 3-year, and 5-year DFS following resection of GISTs was 95%, 83%, and 74%, respectively. All the prognostic scoring systems had fair prognostic ability. For all tumor sites, the American Joint Committee on Cancer gastric category demonstrated the best discrimination (C = 0.79). Using conditional DFS, the probability of remaining disease free for an additional 3 years given that a patient was disease free at 1 year, 3 years, and 5 years was 82%, 89%, and 92%, respectively. Patients with the highest initial recurrence risk demonstrated the greatest increase in conditional survival as time

  6. Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance.

    PubMed

    Sveistrup, Joen; af Rosenschöld, Per Munck; Deasy, Joseph O; Oh, Jung Hun; Pommer, Tobias; Petersen, Peter Meidahl; Engelholm, Svend Aage

    2014-02-04

    Image-guided radiotherapy (IGRT) facilitates the delivery of a very precise radiation dose. In this study we compare the toxicity and biochemical progression-free survival between patients treated with daily image-guided intensity-modulated radiotherapy (IG-IMRT) and 3D conformal radiotherapy (3DCRT) without daily image guidance for high risk prostate cancer (PCa). A total of 503 high risk PCa patients treated with radiotherapy (RT) and endocrine treatment between 2000 and 2010 were retrospectively reviewed. 115 patients were treated with 3DCRT, and 388 patients were treated with IG-IMRT. 3DCRT patients were treated to 76 Gy and without daily image guidance and with 1-2 cm PTV margins. IG-IMRT patients were treated to 78 Gy based on daily image guidance of fiducial markers, and the PTV margins were 5-7 mm. Furthermore, the dose-volume constraints to both the rectum and bladder were changed with the introduction of IG-IMRT. The 2-year actuarial likelihood of developing grade > = 2 GI toxicity following RT was 57.3% in 3DCRT patients and 5.8% in IG-IMRT patients (p < 0.001). For GU toxicity the numbers were 41.8% and 29.7%, respectively (p = 0.011). On multivariate analysis, 3DCRT was associated with a significantly increased risk of developing grade > = 2 GI toxicity compared to IG-IMRT (p < 0.001, HR = 11.59 [CI: 6.67-20.14]). 3DCRT was also associated with an increased risk of developing GU toxicity compared to IG-IMRT.The 3-year actuarial biochemical progression-free survival probability was 86.0% for 3DCRT and 90.3% for IG-IMRT (p = 0.386). On multivariate analysis there was no difference in biochemical progression-free survival between 3DCRT and IG-IMRT. The difference in toxicity can be attributed to the combination of the IMRT technique with reduced dose to organs-at-risk, daily image guidance and margin reduction.

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

    PubMed

    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.

  8. Disease Extent at Secondary Cytoreductive Surgery is Predictive of Progression-free and Overall Survival in Advanced Stage Ovarian Cancer: an NRG Oncology/Gynecologic Oncology Group study

    PubMed Central

    Rose, Peter G.; Java, James J.; Morgan, Mark A.; Secord, Angeles Alvarez; Kesterson, Joshua P.; Stehman, Frederick B.; Warshal, David P.; Creasman, William T.; Hanjani, Parviz; Morris, Robert T.; Copeland, Larry J.

    2017-01-01

    Purpose GOG 152 was a randomized trial of secondary cytoreductive surgery (SCS) in patients with suboptimal residual disease (residual tumor nodule >1 cm in greatest diameter) following primary cytoreductive surgery for advanced stage ovarian cancer. The current analysis was undertaken to evaluate the impact of disease findings at SCS on progression-free survival (PFS) and overall survival (OS). Methods Among the 550 patients enrolled on GOG-152, two-hundred-sixteen patients were randomly assigned following 3 cycles of cisplatin and paclitaxel to receive SCS. In 15 patients (7%) surgery was declined or contraindicated. In the remaining 201 patients the operative and pathology reports were utilized to classify their disease status at the beginning of SCS as; no gross disease/microscopically negative N= 40 (19.9%), no gross disease/microscopically positive N= 8 (4.0%), and gross disease N=153 (76.1%). Results The median PFS for patients with no gross disease/microscopically negative was 16.1 months, no gross disease/microscopically positive was 13.5 months and for gross disease was 11.7 months, p=0.002. The median OS for patients with no gross disease/microscopically negative was 51.5 months, no gross disease/microscopically positive was 42.6 months and for gross disease was 34.9 months, p=0.018. Conclusion Although as previously reported SCS did not change PFS or OS, for those who underwent the procedure, their operative and pathologic findings were predictive of PFS and OS. Surgical/pathological residual disease is a biomarker of response to chemotherapy and predictive of PFS and OS. PMID:27692669

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

    PubMed

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

    2016-02-15

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

  10. A Multi-state Model for Designing Clinical Trials for Testing Overall Survival Allowing for Crossover after Progression

    PubMed Central

    Xia, Fang; George, Stephen L.; Wang, Xiaofei

    2015-01-01

    In designing a clinical trial for comparing two or more treatments with respect to overall survival (OS), a proportional hazards assumption is commonly made. However, in many cancer clinical trials, patients pass through various disease states prior to death and because of this may receive treatments other than originally assigned. For example, patients may crossover from the control treatment to the experimental treatment at progression. Even without crossover, the survival pattern after progression may be very different than the pattern prior to progression. The proportional hazards assumption will not hold in these situations and the design power calculated on this assumption will not be correct. In this paper we describe a simple and intuitive multi-state model allowing for progression, death before progression, post-progression survival and crossover after progression and apply this model to the design of clinical trials for comparing the OS of two treatments. For given values of the parameters of the multi-state model, we simulate the required number of deaths to achieve a specified power and the distribution of time required to achieve the requisite number of deaths. The results may be quite different from those derived using the usual PH assumption. PMID:27239255

  11. Validation of serum amyloid α as an independent biomarker for progression-free and overall survival in metastatic renal cell cancer patients.

    PubMed

    Vermaat, Joost S; Gerritse, Frank L; van der Veldt, Astrid A; Roessingh, Wijnand M; Niers, Tatjana M; Oosting, Sjoukje F; Sleijfer, Stefan; Roodhart, Jeanine M; Beijnen, Jos H; Schellens, Jan H; Gietema, Jourik A; Boven, Epie; Richel, Dick J; Haanen, John B; Voest, Emile E

    2012-10-01

    We recently identified apolipoprotein A2 (ApoA2) and serum amyloid α (SAA) as independent prognosticators in metastatic renal cell carcinoma (mRCC) patients, thereby improving the accuracy of the Memorial-Sloan Kettering Cancer Center (MSKCC) model. Validate these results prospectively in a separate cohort of mRCC patients treated with tyrosine kinase inhibitors (TKIs). For training we used 114 interferon-treated mRCC patients (inclusion 2001-2006). For validation we studied 151 TKI-treated mRCC patients (inclusion 2003-2009). Using Cox proportional hazards regression analysis, SAA and ApoA2 were associated with progression-free survival (PFS) and overall survival (OS). In 72 TKI-treated patients, SAA levels were analyzed longitudinally as a potential early marker for treatment effect. Baseline ApoA2 and SAA levels significantly predicted PFS and OS in the training and validation cohorts. Multivariate analysis identified SAA in both separate patient sets as a robust and independent prognosticator for PFS and OS. In contrast to our previous findings, ApoA2 interacted with SAA in the validation cohort and did not contribute to a better predictive accuracy than SAA alone and was therefore excluded from further analysis. According to the tertiles of SAA levels, patients were categorized in three risk groups, demonstrating accurate risk prognostication. SAA as a single biomarker showed equal prognostic accuracy when compared with the multifactorial MSKCC risk mode. Using receiver operating characteristic analysis, SAA levels >71 ng/ml were designated as the optimal cut-off value in the training cohort, which was confirmed for its significant sensitivity and specificity in the validation cohort. Applying SAA >71 ng/ml as an additional risk factor significantly improved the predictive accuracy of the MSKCC model in both independent cohorts. Changes in SAA levels after 6-8 wk of TKI treatment had no value in predicting treatment outcome. SAA but not ApoA2 was shown to be

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

    PubMed

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

    2017-07-01

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

  13. Overall Survival and Updated Results for Sunitinib Compared With Interferon Alfa in Patients With Metastatic Renal Cell Carcinoma

    PubMed Central

    Motzer, Robert J.; Hutson, Thomas E.; Tomczak, Piotr; Michaelson, M. Dror; Bukowski, Ronald M.; Oudard, Stéphane; Negrier, Sylvie; Szczylik, Cezary; Pili, Roberto; Bjarnason, Georg A.; Garcia-del-Muro, Xavier; Sosman, Jeffrey A.; Solska, Ewa; Wilding, George; Thompson, John A.; Kim, Sindy T.; Chen, Isan; Huang, Xin; Figlin, Robert A.

    2009-01-01

    Purpose A randomized, phase III trial demonstrated superiority of sunitinib over interferon alfa (IFN-α) in progression-free survival (primary end point) as first-line treatment for metastatic renal cell carcinoma (RCC). Final survival analyses and updated results are reported. Patients and Methods Seven hundred fifty treatment-naïve patients with metastatic clear cell RCC were randomly assigned to sunitinib 50 mg orally once daily on a 4 weeks on, 2 weeks off dosing schedule or to IFN-α 9 MU subcutaneously thrice weekly. Overall survival was compared by two-sided log-rank and Wilcoxon tests. Progression-free survival, response, and safety end points were assessed with updated follow-up. Results Median overall survival was greater in the sunitinib group than in the IFN-α group (26.4 v 21.8 months, respectively; hazard ratio [HR] = 0.821; 95% CI, 0.673 to 1.001; P = .051) per the primary analysis of unstratified log-rank test (P = .013 per unstratified Wilcoxon test). By stratified log-rank test, the HR was 0.818 (95% CI, 0.669 to 0.999; P = .049). Within the IFN-α group, 33% of patients received sunitinib, and 32% received other vascular endothelial growth factor–signaling inhibitors after discontinuation from the trial. Median progression-free survival was 11 months for sunitinib compared with 5 months for IFN-α (P < .001). Objective response rate was 47% for sunitinib compared with 12% for IFN-α (P < .001). The most commonly reported sunitinib-related grade 3 adverse events included hypertension (12%), fatigue (11%), diarrhea (9%), and hand-foot syndrome (9%). Conclusion Sunitinib demonstrates longer overall survival compared with IFN-α plus improvement in response and progression-free survival in the first-line treatment of patients with metastatic RCC. The overall survival highlights an improved prognosis in patients with RCC in the era of targeted therapy. PMID:19487381

  14. Marketplace Plans Provide Risk Protection, But Actuarial Values Overstate Realized Coverage For Most Enrollees.

    PubMed

    Polyakova, Maria; Hua, Lynn Mei; Bundorf, M Kate

    2017-12-01

    The Affordable Care Act (ACA) has increased the number of Americans with health insurance. Yet many policy makers and consumers have questioned the value of Marketplace plan coverage because of the generally high levels of cost sharing. We simulated out-of-pocket spending for bronze, silver, or gold Marketplace plans (those having actuarial values of 60 percent, 70 percent, and 80 percent, respectively). We found that for the vast majority of consumers, the proportion of covered spending paid by the plans is likely to be far less than their actuarial values, the metric commonly used to convey plan generosity. Indeed, only when annual health care spending exceeds $16,500 for bronze plans, $19,500 for silver plans, and $21,500 for gold plans do plans in these metal tiers cover the proportion of costs matching their actuarial values. While Marketplace plans substantially reduce consumers' exposure to financial risk relative to being uninsured, the use of actuarial values to communicate plan generosity is likely to be misleading to consumers.

  15. 77 FR 24233 - Actuarial Advisory Committee With Respect to the Railroad Retirement Account; Notice of Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-23

    ... Actuary of the U.S. Railroad Retirement Board, 844 North Rush Street, Chicago, Illinois, on the conduct of... Actuary, U.S. Railroad Retirement Board, 844 North Rush Street, Chicago, Illinois 60611-2092. Dated: April...

  16. Complete surgical resection combined with aggressive adjuvant chemotherapy and bone marrow transplantation prolongs survival in children with advanced neuroblastoma.

    PubMed

    Chamberlain, R S; Quinones, R; Dinndorf, P; Movassaghi, N; Goodstein, M; Newman, K

    1995-03-01

    A multi-modality approach combining surgery with aggressive chemotherapy and radiation is used to treat advanced neuroblastoma. Despite this treatment, children with advanced disease have a 20% 2-year survival rate. Controversy has developed regarding the efficacy of combining aggressive chemotherapy with repeated surgical intervention aimed at providing a complete surgical resection (CSR) of the primary tumor and metastatic sites. Several prospective and retrospective studies have provided conflicting reports regarding the benefit of this approach on overall survival. Therefore, we evaluated the efficacy of CSR versus partial surgical resection (PSR) using a strategy combining surgery with aggressive chemotherapy, radiation, and bone marrow transplantation (BMT) for stage IV neuroblastoma. A retrospective study was performed with review of the medical records of 52 consecutive children with neuroblastoma treated between 1985 and 1993. Twenty-eight of these 52 children presented with advanced disease, 24 of which had sufficient data to allow for analysis. All children were managed with protocols designed by the Children's Cancer Group (CCG). Statistical analysis was performed using Student's t test, chi 2 test, and Kaplan-Meier survival curves. Mean survival (35.1 months) and progression-free survival (29.1 months) for the CSR children was statistically superior to that of the PSR children (20.36 and 16.5 months, p = 0.04 and 0.04, respectively). Similar significance was demonstrated using life table analysis of mean and progression-free survival of these two groups (p = 0.05 and < 0.01, respectively). One-, 2-, and 3-year survival rates for the CSR versus the PSR group were 100%, 80%, and 40% versus 77%, 38%, and 15%, respectively. An analysis of the BMT group compared with those children treated with aggressive conventional therapy showed improvement in mean and progression-free survival. Aggressive surgical resection aimed at removing all gross disease is

  17. Cytomegalovirus infection and disease reduce 10-year cardiac allograft vasculopathy-free survival in heart transplant recipients.

    PubMed

    Johansson, Inger; Andersson, Rune; Friman, Vanda; Selimovic, Nedim; Hanzen, Lars; Nasic, Salmir; Nyström, Ulla; Sigurdardottir, Vilborg

    2015-12-24

    Cytomegalovirus (CMV) is associated with an increased risk of cardiac allograft vasculopathy (CAV), the major limiting factor for long-term survival after heart transplantation (HTx). The purpose of this study was to evaluate the impact of CMV infection during long-term follow-up after HTx. A retrospective, single-centre study analyzed 226 HTx recipients (mean age 45 ± 13 years, 78 % men) who underwent transplantation between January 1988 and December 2000. The incidence and risk factors for CMV infection during the first year after transplantation were studied. Risk factors for CAV were included in an analyses of CAV-free survival within 10 years post-transplant. The effect of CMV infection on the grade of CAV was analyzed. Survival to 10 years post-transplant was higher in patients with no CMV infection (69 %) compared with patients with CMV disease (55 %; p = 0.018) or asymptomatic CMV infection (54 %; p = 0.053). CAV-free survival time was higher in patients with no CMV infection (6.7 years; 95 % CI, 6.0-7.4) compared with CMV disease (4.2 years; CI, 3.2-5.2; p < 0.001) or asymptomatic CMV infection (5.4 years; CI, 4.3-6.4; p = 0.013). In univariate analysis, recipient age, donor age, coronary artery disease (CAD), asymptomatic CMV infection and CMV disease were significantly associated with CAV-free survival. In multivariate regression analysis, CMV disease, asymptomatic CMV infection, CAD and donor age remained independent predictors of CAV-free survival at 10 years post-transplant. CAV-free survival was significantly reduced in patients with CMV disease and asymptomatic CMV infection compared to patients without CMV infection. These findings highlight the importance of close monitoring of CMV viral load and appropriate therapeutic strategies for preventing asymptomatic CMV infection.

  18. Research progress of free space coherent optical communication

    NASA Astrophysics Data System (ADS)

    Tan, Zhenkun; Ke, Xizheng

    2018-02-01

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

  19. Survival benefit for patients with diffuse intrinsic pontine glioma (DIPG) undergoing re-irradiation at first progression: A matched-cohort analysis on behalf of the SIOP-E-HGG/DIPG working group.

    PubMed

    Janssens, Geert O; Gandola, Lorenza; Bolle, Stephanie; Mandeville, Henry; Ramos-Albiac, Monica; van Beek, Karen; Benghiat, Helen; Hoeben, Bianca; Morales La Madrid, Andres; Kortmann, Rolf-Dieter; Hargrave, Darren; Menten, Johan; Pecori, Emilia; Biassoni, Veronica; von Bueren, Andre O; van Vuurden, Dannis G; Massimino, Maura; Sturm, Dominik; Peters, Max; Kramm, Christof M

    2017-03-01

    Overall survival (OS) of patients with diffuse intrinsic pontine glioma (DIPG) is poor. The purpose of this study is to analyse benefit and toxicity of re-irradiation at first progression. At first progression, 31 children with DIPG, aged 2-16 years, underwent re-irradiation (dose 19.8-30.0 Gy) alone (n = 16) or combined with systemic therapy (n = 15). At initial presentation, all patients had typical symptoms and characteristic MRI features of DIPG, or biopsy-proven high-grade glioma. An interval of ≥3 months after upfront radiotherapy was required before re-irradiation. Thirty-nine patients fulfilling the same criteria receiving radiotherapy at diagnosis, followed by best supportive care (n = 20) or systemic therapy (n = 19) at progression but no re-irradiation, were eligible for a matched-cohort analysis. Median OS for patients undergoing re-irradiation was 13.7 months. For a similar median progression-free survival after upfront radiotherapy (8.2 versus 7.7 months; P = .58), a significant benefit in median OS (13.7 versus 10.3 months; P = .04) was observed in favour of patients undergoing re-irradiation. Survival benefit of re-irradiation increased with a longer interval between end-of-radiotherapy and first progression (3-6 months: 4.0 versus 2.7; P < .01; 6-12 months: 6.4 versus 3.3; P = .04). Clinical improvement with re-irradiation was observed in 24/31 (77%) patients. No grade 4-5 toxicity was recorded. On multivariable analysis, interval to progression (corrected hazard ratio = .27-.54; P < .01) and re-irradiation (corrected hazard ratio = .18-.22; P < .01) remained prognostic for survival. A risk score (RS), comprising 5 categories, was developed to predict survival from first progression (ROC: .79). Median survival ranges from 1.0 month (RS-1) to 6.7 months (RS-5). The majority of patients with DIPG, responding to upfront radiotherapy, do benefit of re-irradiation with acceptable tolerability. Copyright © 2017 Elsevier Ltd

  20. Effect of Feitai Capsule () on quality of life and progression-free survival of patients with unresectable non-small cell lung cancer.

    PubMed

    Yu, Zong-Yang; Liu, Zhi-Zhen; Ouyang, Xue-Nong; Du, Jian; Dai, Xi-Hu; Chen, Xi; Zhao, Zhong-Quan; Wang, Wen-Wu; Li, Jie

    2012-02-01

    To examine the effect of a Chinese medicinal herbal formula (Feitai Capsule, ) on the quality of life (QOL) and progression-free survival (PFS) of patients with unresectable non-small cell lung cancer (NSCLC). Sixty-two patients were randomly divided into the treatment group (31 cases) and the control group (31 cases). For the treatment group, 4 capsules (1.2 g/capsule) of Feitai Capsule were administered 3 times a day after meals for 3 weeks; then no drug was administered for 1 week. This schedule was continued for at least 3 more cycles (12 weeks totally). If there were no obvious toxic reactions, the treatment was extended. The patients were evaluated at least once every 8 weeks until progressive disease (PD). For the control group, the regular follow-up and evaluation were performed at least once every 8 weeks until PD. Clinical symptoms, objective response, physical constitution and energy, QOL, and PFS were evaluated regularly. Analysis of variance (ANOVA), a non-parametric test, and analysis of covariance were used to compare clinical features, amelioration of clinical symptoms, physical constitution and energy, and QOL. Kaplan-Meier analysis was used to compare the two-group PFS. Sixty patients finished the final evaluation, with 30 patients in each group. Baseline characters between groups were not significantly different (P>0.05). The control group had a 36.7% improvement in clinical symptoms, while the treatment group had a 73.3% improvement. This difference was statistically significant (Z= -2.632, P=0.008). The control group had a 26.7% improvement in the Karnofsky performance status (KPS), while the treatment group had a 53.4% improvement. This was also significantly different (Z=-2.182, P=0.029). A comparative analysis indicated a positive correlation (r=0.917, P<0.001). Compared with the control group, QOL in the treatment group was significantly improved, except in the social/family condition and doctor-patient relationship indicators. The PFS of

  1. HIV-free survival at 12-24 months in breastfed infants of HIV-infected women on antiretroviral treatment.

    PubMed

    Chikhungu, Lana Clara; Bispo, Stephanie; Rollins, Nigel; Siegfried, Nandi; Newell, Marie-Louise

    2016-07-01

    To provide estimates of HIV-free survival at 12-24 months in breastfed children by maternal ART (6 months or lifelong) to inform WHO HIV and Infant Feeding guidelines. Eighteen studies published 2005-2015 were included in a systematic literature review (1295 papers identified, 156 abstracts screened, 55 full texts); papers were analysed by narrative synthesis and meta-analysis of HIV-free survival by maternal ART regimen in a random effects model. We also grouped studies by feeding modality. Study quality was assessed using a modified Newcastle-Ottawa Scale (NOS) and GRADE. The pooled estimates for 12-month HIV-free survival were 89.8% (95% confidence interval, CI: 86.5%, 93.2%) for infants of mothers on ART for 6 months post-natally (six studies) and 91.4% (95% CI 87.5%, 95.4%) for infants of mothers on lifelong ART (three studies). Eighteen-month HIV-free survival estimates were 89.0% (95% CI 83.9%, 94.2%) with 6 months ART (five studies) and 96.1% (95% CI 92.8%, 99.0%) with lifelong ART (three studies). Twenty-four-month HIV-free survival for infants whose mothers were on ART to 6 months post-natally (two studies) was 89.2% (95% CI 79.9%, 98.5%). Heterogeneity was considerable throughout. In four studies, HIV-free survival in breastfed infants ranged from 87% (95% CI 78%, 92%) to 96% (95% CI 91%, 98%) and in formula-fed infants from 67% (95% CI 35.5%, 87.9%) to 97.6% (95% CI 93.0%, 98.2%). Our results highlight the importance of breastfeeding for infant survival and of ART in reducing the risk of mother-to-child HIV transmission and support the WHO recommendation to initiate ART for life immediately after HIV diagnosis. © 2016 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ruella, Marco; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia; Filippi, Andrea Riccardo

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

  3. Human Papillomavirus and Overall Survival After Progression of Oropharyngeal Squamous Cell Carcinoma

    PubMed Central

    Fakhry, Carole; Zhang, Qiang; Nguyen-Tan, Phuc Felix; Rosenthal, David; El-Naggar, Adel; Garden, Adam S.; Soulieres, Denis; Trotti, Andy; Avizonis, Vilija; Ridge, John Andrew; Harris, Jonathan; Le, Quynh-Thu; Gillison, Maura

    2014-01-01

    Purpose Risk of cancer progression is reduced for patients with human papillomavirus (HPV) –positive oropharynx cancer (OPC) relative to HPV-negative OPC, but it is unknown whether risk of death after progression is similarly reduced. Patients and Methods Patients with stage III-IV OPC enrolled onto Radiation Therapy Oncology Group trials 0129 or RTOG 0522 who had known tumor p16 status plus local, regional, and/or distant progression after receiving platinum-based chemoradiotherapy were eligible for a retrospective analysis of the association between tumor p16 status and overall survival (OS) after disease progression. Rates were estimated by Kaplan-Meier method and compared by log-rank; hazard ratios (HRs) were estimated by Cox models. Tests and models were stratified by treatment protocol. Results A total of 181 patients with p16-positive (n = 105) or p16-negative (n = 76) OPC were included in the analysis. Patterns of failure and median time to progression (8.2 v 7.3 months; P = .67) were similar for patients with p16-positive and p16-negative tumors. After a median follow-up period of 4.0 years after disease progression, patients with p16-positive OPC had significantly improved survival rates compared with p16-negative patients (2-year OS, 54.6% v 27.6%; median, 2.6 v 0.8 years; P < .001). p16-positive tumor status (HR, 0.48; 95% CI, 0.31 to 0.74) and receipt of salvage surgery (HR, 0.48; 95% CI; 0.27 to 0.84) reduced risk of death after disease progression whereas distant versus locoregional progression (HR, 1.99; 95% CI, 1.28 to 3.09) increased risk, after adjustment for tumor stage and cigarette pack-years at enrollment. Conclusion Tumor HPV status is a strong and independent predictor of OS after disease progression and should be a stratification factor for clinical trials for patients with recurrent or metastatic OPC. PMID:24958820

  4. Racial differences in dietary antioxidant intake and cardiac event-free survival in patients with heart failure.

    PubMed

    Wu, Jia-Rong; Song, Eun Kyeung; Moser, Debra K; Lennie, Terry A

    2018-04-01

    Heart failure is a chronic, burdensome condition with higher re-hospitalization rates in African Americans than Whites. Higher dietary antioxidant intake is associated with lower oxidative stress and improved endothelial function. Lower dietary antioxidant intake in African Americans may play a role in the re-hospitalization disparity between African American and White patients with heart failure. The objective of this study was to examine the associations among race, dietary antioxidant intake, and cardiac event-free survival in patients with heart failure. In a secondary analysis of 247 patients with heart failure who completed a four-day food diary, intake of alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, zeaxanthin, lycopene, vitamins C and E, zinc, and selenium were assessed. Antioxidant deficiency was defined as intake below the estimated average requirement for antioxidants with an established estimated average requirement, or lower than the sample median for antioxidants without an established estimated average requirement. Patients were followed for a median of one year to determine time to first cardiac event (hospitalization or death). Survival analysis was used for data analysis. African American patients had more dietary antioxidant deficiencies and a shorter cardiac event-free survival compared with Whites ( p = .007 and p = .028, respectively). In Cox regression, race and antioxidant deficiency were associated with cardiac event-free survival before and after adjusting for covariates. African Americans with heart failure had more dietary antioxidant deficiencies and shorter cardiac event-free survival than Whites. This suggests that encouraging African American patients with heart failure to consume an antioxidant-rich diet may be beneficial in lengthening cardiac event-free survival.

  5. An analysis of possible applications of fuzzy set theory to the actuarial credibility theory

    NASA Technical Reports Server (NTRS)

    Ostaszewski, Krzysztof; Karwowski, Waldemar

    1992-01-01

    In this work, we review the basic concepts of actuarial credibility theory from the point of view of introducing applications of the fuzzy set-theoretic method. We show how the concept of actuarial credibility can be modeled through the fuzzy set membership functions and how fuzzy set methods, especially fuzzy pattern recognition, can provide an alternative tool for estimating credibility.

  6. Post-transplant survival in idiopathic pulmonary fibrosis patients concurrently listed for single and double lung transplantation.

    PubMed

    Chauhan, Dhaval; Karanam, Ashwin B; Merlo, Aurelie; Tom Bozzay, P A; Zucker, Mark J; Seethamraju, Harish; Shariati, Nazly; Russo, Mark J

    2016-05-01

    Lung transplantation is a widely accepted treatment for patients with end-stage lung disease related to idiopathic pulmonary fibrosis (IPF). However, there are conflicting data on whether double lung transplant (DLT) or single lung transplant (SLT) is the superior therapy in these patients. The purpose of this study was to determine whether actuarial post-transplant graft survival among IPF patients concurrently listed for DLT and SLT is greater for recipients undergoing the former or the latter. The United Network for Organ Sharing provided de-identified patient-level data. Analysis included lung transplant candidates with IPF listed between January 1, 2001 and December 31, 2009 (n = 3,411). The study population included 1,001 (29.3%) lung transplant recipients concurrently listed for DLT and SLT, all ≥18 years of age. The primary outcome measure was actuarial post-transplant graft survival, expressed in years. Among the study population, 433 (43.26%) recipients underwent SLT and 568 (56.74%) recipients underwent DLT. The analysis included 2,722.5 years at risk, with median graft survival of 5.31 years. On univariate (p = 0.317) and multivariate (p = 0.415) regression analyses, there was no difference in graft survival between DLT and SLT. Among IPF recipients concurrently listed for DLT and SLT, there is no statistical difference in actuarial graft survival between recipients undergoing DLT vs SLT. This analysis suggests that increased use of SLT for IPF patients may increase the availability of organs to other candidates, and thus increase the net benefit of these organs, without measurably compromising outcomes. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

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

    PubMed

    Takashima, Atsuo; Iizumi, Sakura; Boku, Narikazu

    2017-07-01

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

  8. Association Between Lung Microbiome and Disease Progression in IPF: A Prospective Cohort Study

    PubMed Central

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

    2014-01-01

    Background The lung microbiome’s contribution to IPF pathogenesisis unknown. Using COMET-IPF (Correlating Outcomes with biochemical Markers to Estimate Time-progression in Idiopathic Pulmonary Fibrosis), the goal of this study was to determine whether unique microbial signatures would associate with disease progression. Methods IPF subjects within four years of diagnosis aged 35–80 were eligible for inclusion. Subjects were followed for up to a maximum of 80 weeks. This completed observational study is registered with ClinicalTrials.gov, number NCT01071707. Progression-free survival was defined as death, acute exacerbation, lung transplant, or decline in FVC of 10% or DLCO of 15%.DNA was isolated from 55 bronchoscopic alveolar lavage (BAL) samples. 454 pyrosequencing was used to assign operational taxonomic units (OTUs) based on a 3% sequence divergence. Adjusted Cox models identified OTUs significantly associated with progression-free survival at a p<0·10 level. These OTUs were then used in principal components (PC) analysis. The association between PCs and microbes with high factor loadings from the PC analysis and progression-free survival were examined via Cox regression analyses. Findings Mean FVC was 70·1% and mean DLCO 42·3 %predicted. Significant associations with disease progression were noted with increased % relative abundance of two OTUs identified by PC analysis, a Streptococcus OTU. (p<0·0009) and a Staphylococcus OTU(p=0·01). Strength of associations using PCs versus two OTUs alone was similar. Threshold analysis helped define a cut point for % relative abundance for each OTU associated with progression-free survival, >3·9% for the Streptococcus OTU, HR 10·19 (95% CI 2·94, 35·35; p=0·0002) and >1·8% for the Staphylococcus OTU, HR 5·06 (1·71, 14·93; p=0·003). Interpretation These preliminary data suggest IPF disease progression is associated with presence of specific members within the Staphylococcus and Streptococcus genera. PMID

  9. Actuarial Science at One Four-Year Comprehensive University

    ERIC Educational Resources Information Center

    Charlwood, Kevin E.

    2014-01-01

    Building an Actuarial Science program designated as advanced requires dedicated faculty, support from the administration, and a core group of strong students. Washburn University may serve as a model for those wishing to start or enhance such a program at their institution. We face three main ongoing challenges: first, the hiring and retention of…

  10. A Comparison of Logistic Regression, Neural Networks, and Classification Trees Predicting Success of Actuarial Students

    ERIC Educational Resources Information Center

    Schumacher, Phyllis; Olinsky, Alan; Quinn, John; Smith, Richard

    2010-01-01

    The authors extended previous research by 2 of the authors who conducted a study designed to predict the successful completion of students enrolled in an actuarial program. They used logistic regression to determine the probability of an actuarial student graduating in the major or dropping out. They compared the results of this study with those…

  11. Improved survival with vemurafenib in melanoma with BRAF V600E mutation.

    PubMed

    Chapman, Paul B; Hauschild, Axel; Robert, Caroline; Haanen, John B; Ascierto, Paolo; Larkin, James; Dummer, Reinhard; Garbe, Claus; Testori, Alessandro; Maio, Michele; Hogg, David; Lorigan, Paul; Lebbe, Celeste; Jouary, Thomas; Schadendorf, Dirk; Ribas, Antoni; O'Day, Steven J; Sosman, Jeffrey A; Kirkwood, John M; Eggermont, Alexander M M; Dreno, Brigitte; Nolop, Keith; Li, Jiang; Nelson, Betty; Hou, Jeannie; Lee, Richard J; Flaherty, Keith T; McArthur, Grant A

    2011-06-30

    Phase 1 and 2 clinical trials of the BRAF kinase inhibitor vemurafenib (PLX4032) have shown response rates of more than 50% in patients with metastatic melanoma with the BRAF V600E mutation. We conducted a phase 3 randomized clinical trial comparing vemurafenib with dacarbazine in 675 patients with previously untreated, metastatic melanoma with the BRAF V600E mutation. Patients were randomly assigned to receive either vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg per square meter of body-surface area intravenously every 3 weeks). Coprimary end points were rates of overall and progression-free survival. Secondary end points included the response rate, response duration, and safety. A final analysis was planned after 196 deaths and an interim analysis after 98 deaths. At 6 months, overall survival was 84% (95% confidence interval [CI], 78 to 89) in the vemurafenib group and 64% (95% CI, 56 to 73) in the dacarbazine group. In the interim analysis for overall survival and final analysis for progression-free survival, vemurafenib was associated with a relative reduction of 63% in the risk of death and of 74% in the risk of either death or disease progression, as compared with dacarbazine (P<0.001 for both comparisons). After review of the interim analysis by an independent data and safety monitoring board, crossover from dacarbazine to vemurafenib was recommended. Response rates were 48% for vemurafenib and 5% for dacarbazine. Common adverse events associated with vemurafenib were arthralgia, rash, fatigue, alopecia, keratoacanthoma or squamous-cell carcinoma, photosensitivity, nausea, and diarrhea; 38% of patients required dose modification because of toxic effects. Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation. (Funded by Hoffmann-La Roche; BRIM-3 ClinicalTrials.gov number, NCT01006980.).

  12. 75 FR 68790 - Medicare Program; Medicare Part B Monthly Actuarial Rates, Premium Rate, and Annual Deductible...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-09

    ... 0938-AP81 Medicare Program; Medicare Part B Monthly Actuarial Rates, Premium Rate, and Annual... (SMI) program beginning January 1, 2011. In addition, this notice announces the monthly premium for... beneficiaries with modified adjusted gross income above certain threshold amounts. The monthly actuarial rates...

  13. 76 FR 67572 - Medicare Program; Medicare Part B Monthly Actuarial Rates, Premium Rate, and Annual Deductible...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-01

    ... 0938-AQ16 Medicare Program; Medicare Part B Monthly Actuarial Rates, Premium Rate, and Annual... (SMI) program beginning January 1, 2012. In addition, this notice announces the monthly premium for... beneficiaries with modified adjusted gross income above certain threshold amounts. The monthly actuarial rates...

  14. 78 FR 64943 - Medicare Program; Medicare Part B Monthly Actuarial Rates, Premium Rate, and Annual Deductible...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-30

    ... 0938-AR58 Medicare Program; Medicare Part B Monthly Actuarial Rates, Premium Rate, and Annual... (SMI) program beginning January 1, 2014. In addition, this notice announces the monthly premium for... beneficiaries with modified adjusted gross income above certain threshold amounts. The monthly actuarial rates...

  15. Real-world data on Len/Dex combination at second-line therapy of multiple myeloma: treatment at biochemical relapse is a significant prognostic factor for progression-free survival.

    PubMed

    Katroditou, Eirini; Kyrtsonis, Marie-Christine; Delimpasi, Sosana; Kyriakou, Despoina; Symeonidis, Argiris; Spanoudakis, Emmanouil; Vasilopoulos, Georgios; Anagnostopoulos, Achilles; Kioumi, Anna; Zikos, Panagiotis; Aktypi, Anthi; Briasoulis, Evangelos; Megalakaki, Aikaterini; Repousis, Panayiotis; Adamopoulos, Ioannis; Gogos, Dimitrios; Kotsopoulou, Maria; Pappa, Vassiliki; Papadaki, Eleni; Fotiou, Despoina; Nikolaou, Eftychia; Giannopoulou, Evlambia; Hatzimichael, Eleftheria; Giannakoulas, Nikolaos; Douka, Vassiliki; Kokoviadou, Kyriaki; Timotheatou, Despoina; Terpos, Evangelos

    2018-05-13

    We evaluated progression-free survival (PFS) rate of patients treated with lenalidomide/dexamethasone (Len/Dex), the efficacy of the combination, and the prognostic significance of treatment at biochemical vs. clinical relapse on PFS in 207 consecutive myeloma patients treated with Len/Dex in second line, according to routine clinical practice in Greece. First-line treatment included bortezomib-based (63.3%) or immunomodulatory drug-based (34.8%) therapies; 25% of patients underwent autologous stem cell transplantation. Overall response rate was 73.4% (17.8% complete response and 23.7% very good partial response); median time to best response was 6.7 months. Overall, median PFS and 12-month PFS rate was 19.2 months and 67.6%, respectively. 67.5% of patients had biochemical relapse and 32.5% had clinical relapse prior to initiation of Len/Dex. Median PFS was 24 months for patients treated at biochemical relapse vs. 13.2 months for those treated at clinical relapse (HR:0.63, p = 0.006) and the difference remained significant after adjustment for other prognostic factors. Type of relapse was the strongest prognostic factor for PFS in multivariate analysis. These real-world data confirm the efficacy of Len/Dex combination at first relapse; more importantly, it is demonstrated for the first time outside a clinical trial setting that starting therapy with Len/Dex at biochemical, rather than at clinical relapse, is a significant prognostic factor for PFS, inducing a 37% reduction of the probability of disease progression or death.

  16. Association between bacterial survival and free chlorine concentration during commercial fresh-cut produce wash operation

    USDA-ARS?s Scientific Manuscript database

    Determining minimal, effective free chlorine (FC) concentration for preventing pathogen survival and cross-contamination is critical for developing science- and risk-based food safety practices. The correlation between dynamic FC concentrations and bacterial survival was investigated under commerci...

  17. Recurrence and Survival Outcomes After Percutaneous Thermal Ablation of Oligometastatic Melanoma.

    PubMed

    White, Mariah L; Atwell, Thomas D; Kurup, A Nicholas; Schmit, Grant D; Carter, Rickey E; Geske, Jennifer R; Kottschade, Lisa A; Pulido, Jose S; Block, Matthew S; Jakub, James W; Callstrom, Matthew R; Markovic, Svetomir N

    2016-03-01

    To evaluate focal treatment of melanoma metastases and to explore whether any potential extended survival benefit exists in a select patient population. All patients who underwent image-guided local thermal ablation of metastatic melanoma over an 11-year period (January 1, 2002, to December 31, 2013) were retrospectively identified using an internally maintained clinical registry. Only patients with oligometastatic stage IV disease amenable to complete ablation of all clinical disease at the time of ablation were included in the analysis. Overall survival and median progression-free survival periods were calculated. Thirty-three patients with primary ocular or nonocular melanoma had 66 metastases treated in the lungs, liver, bones, or soft tissues. Eleven (33%) patients were on systemic medical therapy at the time of the procedure. The median survival time was 3.8 years (range, 0.5-10.5 years), with a 4-year estimated survival of 44.1% (95% CI, 28%-68%). Local recurrence at the ablation site developed in 15.1% (5 of 33) of the patients and 13.6% of the tumors (9 of 66). The median progression-free survival time was 4.4 months (95% CI, 1.4 months to 10.5 years), with an estimated 1-year progression-free survival of 30.3% (95% CI, 18%-51%). A subgroup analysis identified 11 patients with primary ocular melanoma and 22 with nonocular melanoma, with a median survival time of 3.9 years (range, 0.9-4.7 years) and 3.8 years (range, 0.5-10.5 years), respectively (P=.58). There were no major complications and no deaths within 30 days of the procedure. Selective use of image-guided thermal ablation of oligometastatic melanoma may provide results similar to surgical resection in terms of technical effectiveness and oncologic outcomes with minimal risk. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2012-01-01

    Background The antioxidant lycopene may be beneficial for patients with heart failure (HF). Processed tomato products are a major source of lycopene, although they are also high in sodium. Increased sodium intake may counter the positive antioxidant effect of lycopene. Methods This was a prospective study of 212 patients with HF. Dietary intake of lycopene and sodium was obtained from weighted 4-day food diaries. Patients were grouped by the median split of lycopene of 2471 μg/day and stratified by daily sodium levels above and below 3 g/day. Patients were followed for 1 year to collect survival and hospitalization data. Cox proportional hazards modeling was used to compare cardiac event-free survival between lycopene groups within each stratum of sodium intake. Results Higher lycopene intake was associated with longer cardiac event-free survival compared with lower lycopene intake (p = 0.003). The worst cardiac event-free survival was observed in the low lycopene intake group regardless of sodium intake (> 3 g/day HR = 3.01; p = 0.027 and ≤ 3 g/day HR= 3.34; p = 0.023). Conclusion These findings suggest that increased lycopene intake has the potential to improve cardiac event-free survival in patients with HF independent of sodium intake. PMID:23076979

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

    PubMed

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

    2013-08-01

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

  20. Real-World Treatment Patterns, Survival, and Prediction of CNS Progression in ALK-Positive Non-Small-Cell Lung Cancer Patients Treated with First-Line Crizotinib in Latin America Oncology Practices.

    PubMed

    Martín, Claudio; Cardona, Andrés F; Zatarain-Barrón, Zyanya Lucia; Ruiz-Patiño, Alejandro; Castillo, Omar; Oblitas, George; Corrales, Luis; Lupinacci, Lorena; Pérez, María Angelina; Rojas, Leonardo; González, Lisde; Chirinos, Luis; Ortíz, Carlos; Lema, Mauricio; Vargas, Carlos; Puparelli, Carmen; Carranza, Hernán; Otero, Jorge; Arrieta, Oscar

    2018-01-01

    This study describes the real-world characteristics, treatment sequencing, and outcomes among Hispanic patients with locally advanced/metastatic ALK-positive non-small-cell lung cancer (NSCLC) treated with crizotinib. A retrospective patient review was conducted for several centers in Latin America. Clinicians identified ALK-positive NSCLC patients who received crizotinib and reported their clinical characteristics, treatments, and survival. Overall survival and progression-free survival (PFS) were described. A Random Forest Tree (RFT) model was constructed to predict brain progression. A total of 73 patients were included; median age at diagnosis was 58 years, 60.3% were female, and 93.2% had adenocarcinoma. Eighty-nine percent of patients were never smokers/former smokers, 71.1% had ≥2 sites of metastasis, and 20.5% had brain metastases at diagnosis. The median PFS on first-line crizotinib was 7.07 months (95% CI 3.77-12.37) and the overall response rate was 52%. Of those who discontinued crizotinib, 55.9% progressed in the central nervous system (CNS). The RFT model reached a sensitivity of 100% and a specificity of 88% for prediction of CNS progression. The overall response rate and the PFS observed in Hispanic patients with ALK-positive NSCLC treated with first-line crizotinib were similar to those in previous reports. An RFT model is helpful in predicting CNS progression and can help clinicians tailor treatments in a resource-limited practice. © 2018 S. Karger AG, Basel.

  1. Is neoadjuvant chemoradiation with dose-escalation and consolidation chemotherapy sufficient to increase surgery-free and distant metastases-free survival in baseline cT3 rectal cancer?

    PubMed

    São Julião, Guilherme Pagin; Habr-Gama, Angelita; Vailati, Bruna Borba; Aguilar, Patricia Bailão; Sabbaga, Jorge; Araújo, Sérgio Eduardo Alonso; Mattacheo, Adrian; Alexandre, Flavia Andrea; Fernandez, Laura Melina; Gomes, Diogo Bugano; Gama-Rodrigues, Joaquim; Perez, Rodrigo Oliva

    2018-01-01

    Patients with cT3 rectal cancer are less likely to develop complete response to neoadjuvant chemoradiation (nCRT) and still face significant risk for systemic relapse. In this setting, radiation (RT) dose-escalation and consolidation chemotherapy in "extended" nCRT regimens have been suggested to improve primary tumor response and decrease the risks of systemic recurrences. For these reasons we compared surgery-free and distant-metastases free survival among cT3 patients undergoing standard or extended nCRT. Patients with distal and non-metastatic T3 rectal cancer managed by nCRT were retrospectively reviewed. Patients undergoing standard CRT (50.4 Gy and 2 cycles of 5FU-based chemotherapy) were compared to those undergoing extended CRT (54 Gy and 6 cycles of 5FU-based chemotherapy). Patients were assessed for tumor response at 8-10 weeks. Patients with complete clinical response (cCR) underwent organ-preservation strategy (Watch & Wait). Patients were referred to salvage surgery in the event of local recurrence during follow-up. Cox's logistic regression was performed to identify independent features associated with improved surgery-free survival after cCR and distant-metastases-free survival. 155 patients underwent standard and 66 patients extended CRT. Patients undergoing extended CRT were more likely to harbor larger initial tumor size (p = 0.04), baseline nodal metastases (cN+; p < 0.001) and higher tumor location (p = 0.02). Cox-regression analysis revealed that the type of nCRT regimen was not independently associated with distinct surgery-free survival after cCR or distant-metastases-free survival (p > 0.05). Dose-escalation and consolidation chemotherapy are insufficient to increase long-term surgery-free survival among cT3 rectal cancer patients and provides no advantage in distant metastases-free survival. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights

  2. Conversations with your actuary: getting to the right number.

    PubMed

    Frese, Richard C

    2013-05-01

    A healthcare finance leader can guarantee recognition of his or her organization's insurance program and better manage the program's liability by discussing changes in the following areas with an actuary: Claims management. Exposure. Coverage or retention Financial reporting of losses. Management goals. Other insurance and operational matters.

  3. 75 FR 6360 - Federal Advisory Committee; DoD Medicare-Eligible Retiree Health Care Board of Actuaries

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-09

    ... Retiree Health Care Board of Actuaries AGENCY: Department of Defense (DoD). ACTION: Meeting notice..., the Department of Defense announces that the DoD Medicare-Eligible Retiree Health Care Board of... actuarial methods and assumptions to be used in the valuation of benefits under DoD retiree health care...

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

    PubMed

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

    2007-03-01

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

  5. Target lesion response predicts survival of patients with hepatocellular carcinoma retreated with transarterial chemoembolization.

    PubMed

    Zhang, Yong-Fa; Guo, Rong-Ping; OuYang, Han-Yue; Shen, Jing-Xian; Zhao, Jing; Tan, Guo-Sheng; Le, Yong; Wei, Wei; Shi, Ming

    2016-10-01

    The discontinuation rules of transarterial chemoembolization (TACE) for patients who were assessed as progressive disease (PD) but stage progression-free (SP-free: still belongs to Barcelona Clinic Liver Cancer B) after TACE are unclear. We aimed to evaluate the impact of the PD-pattern on the survival of these patients retreated with TACE. In total, 115 consecutive patients who were assessed as PD but SP-free after TACE and then underwent at least one subsequent TACE session were included. Sixty patients were assessed as PD with target lesion progression (TP), and 55 patients were assessed as PD with target lesion non-progression (TNP). Survival and treatment-related adverse events were compared between the two groups. Additional external validation was performed using a data set (n = 103) from another institution. Patients with TNP had significantly longer median post-progression survival (PPS) than those with TP (21.0 vs. 11.9 months, P = 0.004). After TACE retreatment, the incidence of liver dysfunction was significantly higher for patients with TP than for patients with TNP (45% vs. 20%, P = 0.031). In the multivariate analysis, the target lesion response was one of the most significant prognostic factors for PPS (HR = 2.01; 95% confidence interval: 1.23-3.27; P = 0.005). The findings were supported by an independent external cohort. Compared to patients with TNP, patients with TP might exhibit no improvement in survival and even present damaged liver function after retreatment with TACE. Target lesion response is useful as a clinical decision for repeated TACE in these patients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    PubMed

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

    2017-09-01

    To investigate the association between NSUN2/IGF-II signature and ovarian cancer survival. Using a publicly accessible dataset of RNA sequencing and clinical follow-up data, we performed Classification and Regression Tree and survival analyses. Patients with NSUN2 high IGF-II low had significantly superior overall and disease progression-free survival, followed by NSUN2 low IGF-II low , NSUN2 high IGF-II high and NSUN2 low IGF-II high (p < 0.0001 for overall, p = 0.0024 for progression-free survival, respectively). The associations of NSUN2/IGF-II signature with the risks of death and relapse remained significant in multivariate Cox regression models. Random-effects meta-analyses show the upregulated NSUN2 and IGF-II expression in ovarian cancer versus normal tissues. The NSUN2/IGF-II signature associates with heterogeneous outcome and may have clinical implications in managing ovarian cancer.

  7. Effects of Early, Abrupt Weaning on HIV-free Survival of Children in Zambia

    PubMed Central

    Kuhn, Louise; Aldrovandi, Grace M.; Sinkala, Moses; Kankasa, Chipepo; Semrau, Katherine; Mwiya, Mwiya; Kasonde, Prisca; Scott, Nancy; Vwalika, Cheswa; Walter, Jan; Bulterys, Marc; Tsai, Wei-Yann; Thea, Donald M.

    2008-01-01

    Background In low-resource settings, many programs recommend that women who are infected with the human immunodeficiency virus (HIV) stop breast-feeding early. We conducted a randomized trial to evaluate whether abrupt weaning at 4 months as compared with the standard practice has a net benefit for HIV-free survival of children. Methods We enrolled 958 HIV-infected women and their infants in Lusaka, Zambia. All the women planned to breast-feed exclusively to 4 months; 481 were randomly assigned to a counseling program that encouraged abrupt weaning at 4 months, and 477 to a program that encouraged continued breast-feeding for as long as the women chose. The primary outcome was either HIV infection or death of the child by 24 months. Results In the intervention group, 69.0% of the mothers stopped breast-feeding at 5 months or earlier; 68.8% of these women reported the completion of weaning in less than 2 days. In the control group, the median duration of breast-feeding was 16 months. In the overall cohort, there was no significant difference between the groups in the rate of HIV-free survival among the children; 68.4% and 64.0% survived to 24 months without HIV infection in the intervention and control groups, respectively (P = 0.13). Among infants who were still being breast-fed and were not infected with HIV at 4 months, there was no significant difference between the groups in HIV-free survival at 24 months (83.9% and 80.7% in the intervention and control groups, respectively; P = 0.27). Children who were infected with HIV by 4 months had a higher mortality by 24 months if they had been assigned to the intervention group than if they had been assigned to the control group (73.6% vs. 54.8%, P = 0.007). Conclusions Early, abrupt cessation of breast-feeding by HIV-infected women in a low-resource setting, such as Lusaka, Zambia, does not improve the rate of HIV-free survival among children born to HIV-infected mothers and is harmful to HIV-infected infants

  8. A Single-Institutional Experience of 15 Years of Treating T3 Laryngeal Cancer With Primary Radiotherapy, With or Without Chemotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Al-Mamgani, Abrahim, E-mail: a.al-mamgani@erasmusmc.nl; Tans, Lisa; Rooij, Peter van

    2012-07-01

    Purpose: To retrospectively analyze the outcomes, toxicity, quality of life, and voice quality of patients with T3 laryngeal cancer treated with radiotherapy and to identify subgroups of patients in whom the addition of chemotherapy to radiotherapy is necessary. Methods and Materials: Between March 1996 and November 2009, 170 consecutive patients with T3 tumor were treated with (chemo)radiotherapy. Endpoints of the study were local control (LC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), late toxicity, quality of life, and voice handicap index. Results: After a median follow-up time of 32 months (range, 7-172), the 3-year actuarial rates of LC,more » LRC, DFS, and OS were 73%, 70%, 64%, and 61%, respectively, and the 5-year figures were 68%, 65%, 60%, and 49%, respectively. At last follow-up, 84 patients (49.5%) were still alive, 65 of them (77.3%) without local progression. Laryngectomy was performed in 16 patients, leaving 49 patients with anatomic organ preservation, corresponding to an actuarial laryngectomy-free survival of 58.3% at 3 years. The figures for patients treated with chemoradiotherapy and radiotherapy alone were 76.8% and 53.5%, respectively (p = 0.001). Chemoradiotherapy was the only significant predictor for LC on multivariate analysis. The overall 5-year cumulative incidence of late Grade {>=}2 toxicity was 28.2%. Chemoradiotherapy, compared with radiotherapy alone, resulted in slight increase in late toxicity and slight deterioration of quality of life and voice-handicap-index scores. However, the differences were statistically not significant. Conclusion: The addition of chemotherapy to radiotherapy in T3 laryngeal cancer significantly improved LC and laryngectomy-free survival without statistically significant increases in late toxicity or deterioration of quality of life or voice handicap index.« less

  9. Progress towards a Drag-free SmallSat

    NASA Astrophysics Data System (ADS)

    Saraf, Shailendhar

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

  10. Review of meta-analyses evaluating surrogate endpoints for overall survival in oncology.

    PubMed

    Sherrill, Beth; Kaye, James A; Sandin, Rickard; Cappelleri, Joseph C; Chen, Connie

    2012-01-01

    Overall survival (OS) is the gold standard in measuring the treatment effect of new drug therapies for cancer. However, practical factors may preclude the collection of unconfounded OS data, and surrogate endpoints are often used instead. Meta-analyses have been widely used for the validation of surrogate endpoints, specifically in oncology. This research reviewed published meta-analyses on the types of surrogate measures used in oncology studies and examined the extent of correlation between surrogate endpoints and OS for different cancer types. A search was conducted in October 2010 to compile available published evidence in the English language for the validation of disease progression-related endpoints as surrogates of OS, based on meta-analyses. We summarize published meta-analyses that quantified the correlation between progression-based endpoints and OS for multiple advanced solid-tumor types. We also discuss issues that affect the interpretation of these findings. Progression-free survival is the most commonly used surrogate measure in studies of advanced solid tumors, and correlation with OS is reported for a limited number of cancer types. Given the increased use of crossover in trials and the availability of second-/third-line treatment options available to patients after progression, it will become increasingly more difficult to establish correlation between effects on progression-free survival and OS in additional tumor types.

  11. Review of meta-analyses evaluating surrogate endpoints for overall survival in oncology

    PubMed Central

    Sherrill, Beth; Kaye, James A; Sandin, Rickard; Cappelleri, Joseph C; Chen, Connie

    2012-01-01

    Overall survival (OS) is the gold standard in measuring the treatment effect of new drug therapies for cancer. However, practical factors may preclude the collection of unconfounded OS data, and surrogate endpoints are often used instead. Meta-analyses have been widely used for the validation of surrogate endpoints, specifically in oncology. This research reviewed published meta-analyses on the types of surrogate measures used in oncology studies and examined the extent of correlation between surrogate endpoints and OS for different cancer types. A search was conducted in October 2010 to compile available published evidence in the English language for the validation of disease progression-related endpoints as surrogates of OS, based on meta-analyses. We summarize published meta-analyses that quantified the correlation between progression-based endpoints and OS for multiple advanced solid-tumor types. We also discuss issues that affect the interpretation of these findings. Progression-free survival is the most commonly used surrogate measure in studies of advanced solid tumors, and correlation with OS is reported for a limited number of cancer types. Given the increased use of crossover in trials and the availability of second-/third-line treatment options available to patients after progression, it will become increasingly more difficult to establish correlation between effects on progression-free survival and OS in additional tumor types. PMID:23109809

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

    PubMed Central

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

    2010-01-01

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

  13. Predicting Success for Actuarial Students in Undergraduate Mathematics Courses

    ERIC Educational Resources Information Center

    Smith, Richard Manning; Schumacher, Phyllis A.

    2005-01-01

    A study of undergraduate actuarial graduates found that math SAT scores, verbal SAT scores, percentile rank in high school graduating class, and percentage score on a college mathematics placement exam had some relevance to forecasting the students' grade point averages in their major. For both males and females, percentile rank in high school…

  14. A Model-Free Machine Learning Method for Risk Classification and Survival Probability Prediction.

    PubMed

    Geng, Yuan; Lu, Wenbin; Zhang, Hao Helen

    2014-01-01

    Risk classification and survival probability prediction are two major goals in survival data analysis since they play an important role in patients' risk stratification, long-term diagnosis, and treatment selection. In this article, we propose a new model-free machine learning framework for risk classification and survival probability prediction based on weighted support vector machines. The new procedure does not require any specific parametric or semiparametric model assumption on data, and is therefore capable of capturing nonlinear covariate effects. We use numerous simulation examples to demonstrate finite sample performance of the proposed method under various settings. Applications to a glioma tumor data and a breast cancer gene expression survival data are shown to illustrate the new methodology in real data analysis.

  15. Depressive Symptoms and Poor Social Support Have a Synergistic Effect on Event-Free Survival in Patients with Heart Failure

    PubMed Central

    Chung, Misook L.; Lennie, Terry A.; Dekker, Rebecca L; Wu, Jia-Rong; Moser, Debra K.

    2010-01-01

    Background Depressive symptoms and poor social support are predictors of increased morbidity and mortality in patients with heart failure (HF). However, the combined contribution of depressive symptoms and social support event-free survival of patients with HF has not been examined. Objective To compare event-free survival in four groups of patients with HF stratified by depressive symptoms and perceived social support. Method A total of 220 patients completed the Beck Depression Inventory-II and the Multidimensional Perceived Social Support Scale and were followed for up to 4 years to collect data on death and hospitalizations. Results Depressive symptoms (HR=1.73, P=.008) and perceived social support (PSS) (HR=1.51, P=.048) were independent predictors of event-free survival. Depressed patients with low PSS had 2.1 times higher risk of events than non-depressed patients with high PSS (P=.003). Conclusion Depressive symptoms and poor social support had a negative additive effect on event-free survival in patients with HF. PMID:21453972

  16. Depressive symptoms and poor social support have a synergistic effect on event-free survival in patients with heart failure.

    PubMed

    Chung, Misook L; Lennie, Terry A; Dekker, Rebecca L; Wu, Jia-Rong; Moser, Debra K

    2011-01-01

    Depressive symptoms and poor social support are predictors of increased morbidity and mortality in patients with heart failure (HF). However, the combined contribution of depressive symptoms and social support event-free survival of patients with HF has not been examined. To compare event-free survival in 4 groups of patients with HF stratified by depressive symptoms and perceived social support (PSS). A total of 220 patients completed the Beck Depression Inventory-II and the Multidimensional Perceived Social Support Scale and were followed for up to 4 years to collect data on death and hospitalizations. Depressive symptoms (hazard ratio = 1.73, P = .008) and PSS (hazard ratio = 1.51, P = .048) were independent predictors of event-free survival. Depressed patients with low PSS had 2.1 times higher risk of events than non-depressed patients with high PSS (P = .003). Depressive symptoms and poor social support had a negative additive effect on event-free survival in patients with HF. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schwarz, Julie K.; Siegel, Barry A.; Dehdashti, Farrokh

    2008-05-01

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

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

    NASA Astrophysics Data System (ADS)

    Borges, Ana; Sousa, Inês; Castro, Luis

    2017-06-01

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

  19. Deductibles in health insurance: can the actuarially fair premium reduction exceed the deductible?

    PubMed

    Bakker, F M; van Vliet, R C; van de Ven, W P

    2000-09-01

    The actuarially fair premium reduction in case of a deductible relative to full insurance is affected by: (1) out-of-pocket payments, (2) moral hazard, (3) administrative costs, and, in case of a voluntary deductible, (4) adverse selection. Both the partial effects and the total effect of these factors are analyzed. Moral hazard and adverse selection appear to have a substantial effect on the expected health care costs above a deductible but a small effect on the expected out-of-pocket expenditure. A premium model indicates that for a broad range of deductible amounts the actuarially fair premium reduction exceeds the deductible.

  20. Actuarial assessment of violence risk in hospital-based partner assault clinics.

    PubMed

    Hilton, N Zoe; Harris, Grant T; Holder, Norah

    2008-12-01

    Hospital-based partner assault clinics are a relatively recent addition to the community response to partner violence. In this study, 66% of 111 women attending hospital clinics for partner assault were physically injured and 43% reported death threats. Few concurrently used other services (shelters or police) and most relied on female friends and relatives for help. Many participants who currently lived with the perpetrator were contemplating leaving but only a third had made plans to do so. Participants faced an unusually high risk of future assault, according to both victim interview using the ODARA actuarial risk assessment and their own perceptions. Findings imply an important role for partner assault clinics and the feasibility of the victim service sector's using the same actuarial risk assessments as the criminal justice system.

  1. 18F-Fluoride PET/CT tumor burden quantification predicts survival in breast cancer.

    PubMed

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

    2017-05-30

    In bone-metastatic breast cancer patients, there are no current imaging biomarkers to identify which patients have worst prognosis. The purpose of our study was to investigate if skeletal tumor burden determined by 18F-Fluoride PET/CT correlates with clinical outcomes and may help define prognosis throughout the course of the disease. Bone metastases were present in 49 patients. On multivariable analysis, skeletal tumor burden was significantly and independently associated with overall survival (p < 0.0001) and progression free-survival (p < 0.0001). The simple presence of bone metastases was associated with time to bone event (p = 0.0448). We quantified the skeletal tumor burden on 18F-Fluoride PET/CT images of 107 female breast cancer patients (40 for primary staging and the remainder for restaging after therapy). Clinical parameters, primary tumor characteristics and skeletal tumor burden were correlated to overall survival, progression free-survival and time to bone event. The median follow-up time was 19.5 months. 18F-Fluoride PET/CT skeletal tumor burden is a strong independent prognostic imaging biomarker in breast cancer patients.

  2. Impact of histopathological transformation and overall survival in patients with progressive anaplastic glioma.

    PubMed

    Ho, Allen L; Koch, Matthew J; Tanaka, Shota; Eichler, April F; Batchelor, Tracy T; Tanboon, Jantima; Louis, David N; Cahill, Daniel P; Chi, Andrew S; Curry, William T

    2016-09-01

    Progression of anaplastic glioma (World Health Organization [WHO] grade III) is typically determined radiographically, and transformation to glioblastoma (GB) (WHO grade IV) is often presumed at that time. However, the frequency of actual histopathologic transformation of anaplastic glioma and the subsequent clinical impact is unclear. To determine these associations, we retrospectively reviewed all anaplastic glioma patients who underwent surgery at our center at first radiographic progression, and we examined the effects of histological diagnosis, clinical history, and molecular factors on transformation rate and survival. We identified 85 anaplastic glioma (39 astrocytoma, 24 oligodendroglioma, 22 oligoastrocytoma), of which 38.8% transformed to GB. Transformation was associated with shorter overall survival (OS) from the time of diagnosis (3.4 vs. 10.9years, p=0.0005) and second surgery (1.0 vs. 3.5years, p<0.0001). Original histologic subtype did not significantly impact the risk of transformation or OS. No other factors, including surgery, adjuvant therapy or molecular markers, significantly affected the risk of transformation. However, mutations in isocitrate dehydrogenase 1 (IDH1) was associated with longer time to progression (median 4.6 vs. 1.4years, p=0.008) and OS (median 10.0 vs. 4.2years, p=0.046). At radiographic progression, tissue diagnosis may be warranted as histologic grade may provide valuable prognostic information and affect therapeutic clinical trial selection criteria for this patient population. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Psychotherapy: theory, experience, and personalized actuarial tables.

    PubMed

    Leventhal, D B; Shemberg, K M

    1977-12-01

    This paper addresses the issue of the role of theory in the actual application of psychotherapeutic operations. Within the present framework, psychotherapeutic effectiveness is seen as an empirical, actuarial process which occurs in an interpersonal setting separate from theoretical considerations. The role of theory is discussed and a rationale for the coexistence of equally 'effective' contradictory theories is presented. Suggestions for future research in the area of behaviour change are made and an argument for the eventual development of a 'therapeutic cookbook' is presented.

  4. Starting an Actuarial Science Major at a Liberal Arts College

    ERIC Educational Resources Information Center

    Mills, Mark A.

    2014-01-01

    The article provides details of the process of starting an actuarial science major at a small, liberal arts college. Some critique of the major is included, as well as some challenges that may be faced by others wanting to start such a major at their institution.

  5. An actuarial approach to retrofit savings in buildings

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Subbarao, Krishnappa; Etingov, Pavel V.; Reddy, T. A.

    An actuarial method has been developed for determining energy savings from retrofits from energy use data for a number of buildings. This method should be contrasted with the traditional method of using pre- and post-retrofit data on the same building. This method supports the U.S. Department of Energy Building Performance Database of real building performance data and related tools that enable engineering and financial practitioners to evaluate retrofits. The actuarial approach derives, from the database, probability density functions (PDFs) for energy savings from retrofits by creating peer groups for the user’s pre post buildings. From the energy use distribution ofmore » the two groups, the savings PDF is derived. This provides the basis for engineering analysis as well as financial risk analysis leading to investment decisions. Several technical issues are addressed: The savings PDF is obtained from the pre- and post-PDF through a convolution. Smoothing using kernel density estimation is applied to make the PDF more realistic. The low data density problem can be mitigated through a neighborhood methodology. Correlations between pre and post buildings are addressed to improve the savings PDF. Sample size effects are addressed through the Kolmogorov--Smirnov tests and quantile-quantile plots.« less

  6. Pure versus follicular variant of papillary thyroid carcinoma: clinical features, prognostic factors, treatment, and survival.

    PubMed

    Zidan, Jamal; Karen, Drumea; Stein, Moshe; Rosenblatt, Edward; Basher, Walid; Kuten, Abraham

    2003-03-01

    The follicular variant of papillary thyroid carcinoma (FVPTC) is a common subtype of papillary thyroid carcinoma. Few studies have compared the clinical behavior and treatment outcome of patients with FVPTC with the outcome of patients with pure papillary carcinoma (PTC). A retrospective study was performed to identify the influence of FVPTC compared with PTC on therapeutic variables, prognostic variables, and survival. A clinicopathologic analysis of 243 patients with papillary carcinoma was performed. One hundred forty-three tumors were PTC, and 100 tumors were FVPTC. The following variables were evaluated: age at diagnosis, tumor size, stage of tumor, treatment, capsular invasion, and survival. The median follow-up was 11.5 years. The median age was 43 years in the PTC group and 44 years in the FVPTC group. The median tumor size, disease stage, and type of initial surgery and iodine 131 ablation were similar. More patients had capsular invasion by the tumor and less metastases to cervical lymph nodes in the FVPTC group. The actuarial survival of patients age < 40 years was higher compared with the survival of patients age > 50 years in both groups. The 21-year overall actuarial survival was 82% in patients with PTC and 86% in patients with FVPTC (P value not significant). The pathologic and clinical behaviors of PTC and FVPTC were comparable. Prognostic factors, treatment, and survival also were similar. Patients in both groups must be treated identically. Copyright 2003 American Cancer Society.

  7. Association of the Timing of Pregnancy With Survival in Women With Breast Cancer

    PubMed Central

    Iqbal, Javaid; Amir, Eitan; Rochon, Paula A.; Giannakeas, Vasily; Sun, Ping

    2017-01-01

    Importance Increasing numbers of women experience pregnancy around the time of, or after, a diagnosis of breast cancer. Understanding the effect of pregnancy on survival in women with breast cancer will help in the counseling and treatment of these women. Objective To compare the overall survival of women diagnosed with breast cancer during pregnancy or in the postpartum period with that of women who had breast cancer but did not become pregnant. Design, Setting, and Participants This population-based, retrospective cohort study linked health administrative databases in Ontario, Canada, comprising 7553 women aged 20 to 45 years at the time of diagnosis with invasive breast cancer, from January 1, 2003, to December 31, 2014. Exposures Any pregnancy in the period from 5 years before, until 5 years after, the index date of the diagnosis of breast cancer. Women were classified into the following 4 exposure groups: no pregnancy (the referent), pregnancy before breast cancer, pregnancy-associated breast cancer, and pregnancy following breast cancer. Main Outcomes and Measures Five-year actuarial survival rates for all exposure groups, age-adjusted and multivariable hazard ratios [HRs] of pregnancy for overall survival for all exposure groups, and time-dependent hazard ratios for women with pregnancy following breast cancer. Results Among the 7553 women in the study (mean age at diagnosis, 39.1 years; median, 40 years; range, 20-44 years) the 5-year actuarial survival rate was 87.5% (95% CI, 86.5%-88.4%) for women with no pregnancy, 85.3% (95% CI, 82.8%-87.8%) for women with pregnancy before breast cancer (age-adjusted hazard ratio, 1.03; 95% CI, 0.85-1.27; P = .73), and 82.1% (95% CI, 78.3%-85.9%) for women with pregnancy-associated breast cancer (age-adjusted hazard ratio, 1.18; 95% CI, 0.91-1.53; P = .20). The 5-year actuarial survival rate was 96.7% (95% CI, 94.1%-99.3%) for women who had pregnancy 6 months or more after diagnosis of breast cancer, vs 87

  8. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Edwards-Bennett, Sophia M., E-mail: edwards2@mskcc.org; Jacks, Lindsay M.; McCormick, Beryl

    Purpose: Population-based studies have reported that as many of 35% of black women do not undergo radiotherapy (RT) after breast conservation surgery (BCS). The objective of the present study was to determine whether this trend persisted at a large multidisciplinary cancer center, and to identify the factors that predict for noncompliance with RT and determine the outcomes for this subset of patients. Methods and Materials: Between January 2002 and December 2007, 83 black women underwent BCS at Memorial Sloan-Kettering Cancer Center and were therefore eligible for the present study. Of the 83 women, 38 (46%) had Stage I, 38 (46%)more » Stage II, and 7 (8%) Stage III disease. Of the study cohort, 31 (37%) had triple hormone receptor-negative tumors. RT was recommended for 81 (98%) of the 83 patients (median dose, 60 Gy). Results: Of the 81 women, 12 (15%) did not receive the recommended adjuvant breast RT. Nonreceipt of chemotherapy (p = .003) and older age (p = .009) were associated with nonreceipt of RT. With a median follow-up of 70 months, the 3-year local control, locoregional control, recurrence-free survival, disease-free survival, and overall survival rate was 99% (actuarial 5-year rate, 97%), 96% (actuarial 5-year rate, 93%), 95% (actuarial 5-year rate, 92%), 92% (actuarial 5-year rate, 89%), and 95% (actuarial 5-year rate, 91%), respectively. Conclusion: We found a greater rate of utilization adjuvant breast RT (85%) among black women after BCS than has been reported in recent studies, indicating that excellent outcomes are attainable for black women after BCS when care is administered in a multidisciplinary cancer center.« less

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

    PubMed

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

    2018-05-01

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

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

    PubMed Central

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

    2012-01-01

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

  11. Vemurafenib for BRAF V600 mutated advanced melanoma: results of treatment beyond progression.

    PubMed

    Scholtens, A; Geukes Foppen, M H; Blank, C U; van Thienen, J V; van Tinteren, H; Haanen, J B

    2015-03-01

    Selective BRAF inhibition (BRAFi) by vemurafenib or dabrafenib has become approved standard treatment in BRAF V600 mutated advanced stage melanoma. While the response rate is high, the response duration is limited with a progression-free survival (PFS) of 5-6months. Our observation of accelerated disease progression within some patients after stopping vemurafenib treatment has fostered the idea of treatment beyond progression (BRAFi TBP). In this retrospective study, we analysed 70 metastatic melanoma patients, treated at our institute, who experienced progression after prior objective response upon treatment with vemurafenib. Thirty-five patients that continued treatment beyond progression are compared with 35 patients who stopped BRAFi treatment at disease progression. Median overall survival beyond documented progression was found to be 5.2months versus 1.4months (95% confidence interval (CI): 3.8-7.4 versus 0.6-3.4; Log-Rank p=0.002) in favour of BRAFi TBP. In the multivariate survival analysis, stopping treatment at disease progression was significantly associated with shorter survival (hazard ratio: 1.92; 95% CI: 1.04-3.55; p=0.04). Our results suggest that continuing vemurafenib treatment beyond progression may be beneficial in advanced melanoma patients, who prior to progression responded to vemurafenib. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    PubMed

    Gorovets, Daniel; Rava, Paul; Ebner, Daniel K; Tybor, David J; Cielo, Deus; Puthawala, Yakub; Kinsella, Timothy J; DiPetrillo, Thomas A; Wazer, David E; Hepel, Jaroslaw T

    2015-01-01

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

  13. Cytoplasmic expression of Twist1, an EMT-related transcription factor, is associated with higher grades renal cell carcinomas and worse progression-free survival in clear cell renal cell carcinoma.

    PubMed

    Rasti, Arezoo; Madjd, Zahra; Abolhasani, Maryam; Mehrazma, Mitra; Janani, Leila; Saeednejad Zanjani, Leili; Asgari, Mojgan

    2018-05-01

    Twist1 is a key transcription factor, which confers tumor cells with cancer stem cell (CSC)-like characteristics and enhances epithelial-mesenchymal transition in pathological conditions including tumor malignancy and metastasis. This study aimed to evaluate the expression patterns and clinical significance of Twist1 in renal cell carcinoma (RCC). The cytoplasmic and nuclear expression of Twist1 were examined in 252 well-defined renal tumor tissues, including 173 (68.7%) clear cell renal cell carcinomas (ccRCC), 45 (17.9%) papillary renal cell carcinomas (pRCC) and 34 (13.5%) chromophobe renal cell carcinoma, by immunohistochemistry on a tissue microarray. The association between expression of this marker and clinicopathologic parameters and survival outcomes were then analyzed. Twist1 was mainly localized to the cytoplasm of tumor cells (98.8%). Increased cytoplasmic expression of Twist1 was associated with higher grade tumors (P = 0.045), renal vein invasion (P = 0.031) and microvascular invasion (P = 0.044) in RCC. It was positively correlated with higher grade tumors (P = 0.026), shorter progression-free survival time (P = 0.027) in patients with ccRCC, and also with higher stage in pRCC patients (P = 0.036). Significantly higher cytoplasmic expression levels of Twist1 were found in ccRCC and pRCC subtypes, due to their more aggressive tumor behavior. Increased cytoplasmic expression of Twist1 had a critical role in worse prognosis in ccRCC. These findings suggest that cytoplasmic, rather than nuclear expression of Twist1 can be considered as a prognostic and therapeutic marker for targeted therapy of RCC, especially for ccRCC patients.

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

    PubMed

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

    2014-07-01

    The role of the lung microbiome in the pathogenesis of idiopathic pulmonary fibrosis is unknown. We investigated whether unique microbial signatures were associated with progression of idiopathic pulmonary fibrosis. Patients (aged 35-80 years) with idiopathic pulmonary fibrosis within 4 years of diagnosis from the Correlating Outcomes with biochemical Markers to Estimate Time-progression (COMET) in idiopathic pulmonary fibrosis study were followed up for a maximum of 80 weeks. Progression-free survival was defined as time to death, acute exacerbation, lung transplant, or decrease in forced vital capacity (FVC) of 10% or greater or decrease in diffusion capacity of the lung (DLCO) of 15% or greater. DNA was isolated from 55 samples of bronchoscopic alveolar lavage. 454 pyrosequencing was used to assign operational taxonomic units (OTUs) to bacteria based on a 3% sequence divergence. Adjusted Cox models were used to identify OTUs that were significantly associated with progression-free survival at a p<0.10. These OTUs were then used in the analysis of the principal components. The association between principal components and microbes with high factor loadings and progression-free survival were assessed with Cox regression analyses. The COMET study is registered with ClinicalTrials.gov, number NCT01071707. Mean FVC was 70.1% (SD 17.0) and DLCO 42.3% (14.0) of predicted. Disease progression was significantly associated with increased relative abundance of two OTUs-Streptococcus OTU 1345 (relative risk 1.11, 95% CI 1.04-1.18; p=0.0009) and Staphylococcus OTU 1348 (1.16, 1.03-1.31, p=0.012). Thresholds for relative abundance of each OTU associated with progression-free survival were more than 3.9% for Streptococcus OTU 1345 (10.19, 2.94-35.35; p=0.0002) and more than 1.8% for Staphylococcus OTU 1348 (5.06, 1.71-14.93; p=0.003). These preliminary data suggest progression of idiopathic pulmonary fibrosis is associated with the presence of specific members within the

  15. An application of actuarial methods in psychiatric diagnosis.

    PubMed

    Overall, J E; Higgins, C W

    1977-10-01

    An actuarial program for psychiatric diagnosis is evaluated for agreement with final clinical diagnosis in a series of 288 patients. The acturial program provides a probability differential diagnosis based on an analysis of history and background data, symptom rating profiles, and MMPI clinical scale profiles. The observed agreement with final clinical diagnosis is approximately 50% higher than previously reported for psychological testing in this same setting. The results emphasize the importance for psychologists of clinical interview and observation skills.

  16. Reconstruction of the Foot and Ankle Using Pedicled or Free Flaps: Perioperative Flap Survival Analysis

    PubMed Central

    Li, Xiucun; Cui, Jianli; Maharjan, Suraj; Lu, Laijin; Gong, Xu

    2016-01-01

    Objective The purpose of this study is to determine the correlation between non-technical risk factors and the perioperative flap survival rate and to evaluate the choice of skin flap for the reconstruction of foot and ankle. Methods This was a clinical retrospective study. Nine variables were identified. The Kaplan-Meier method coupled with a log-rank test and a Cox regression model was used to predict the risk factors that influence the perioperative flap survival rate. The relationship between postoperative wound infection and risk factors was also analyzed using a logistic regression model. Results The overall flap survival rate was 85.42%. The necrosis rates of free flaps and pedicled flaps were 5.26% and 20.69%, respectively. According to the Cox regression model, flap type (hazard ratio [HR] = 2.592; 95% confidence interval [CI] (1.606, 4.184); P < 0.001) and postoperative wound infection (HR = 0.266; 95% CI (0.134, 0.529); P < 0.001) were found to be statistically significant risk factors associated with flap necrosis. Based on the logistic regression model, preoperative wound bed inflammation (odds ratio [OR] = 11.371,95% CI (3.117, 41.478), P < 0.001) was a statistically significant risk factor for postoperative wound infection. Conclusion Flap type and postoperative wound infection were both independent risk factors influencing the flap survival rate in the foot and ankle. However, postoperative wound infection was a risk factor for the pedicled flap but not for the free flap. Microvascular anastomosis is a major cause of free flap necrosis. To reconstruct complex or wide soft tissue defects of the foot or ankle, free flaps are safer and more reliable than pedicled flaps and should thus be the primary choice. PMID:27930679

  17. Stereotactic Fractionated Radiotherapy in the Treatment of Juxtapapillary Choroidal Melanoma: The McGill University Experience

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Al-Wassia, Rolina; Dal Pra, Alan; Shun, Kitty

    2011-11-15

    Purpose: To report our experience with linear accelerator-based stereotactic fractionated radiotherapy in the treatment of juxtapapillary choroidal melanoma. Methods and Materials: We performed a retrospective review of 50 consecutive patients diagnosed with juxtapapillary choroidal melanoma and treated with linear accelerator-based stereotactic fractionated radiotherapy between April 2003 and December 2009. Patients with small to medium sized lesions (Collaborative Ocular Melanoma Study classification) located within 2 mm of the optic disc were included. The prescribed radiation dose was 60 Gy in 10 fractions. The primary endpoints included local control, enucleation-free survival, and complication rates. Results: The median follow-up was 29 months (range,more » 1-77 months). There were 31 males and 29 females, with a median age of 69 years (range, 30-92 years). Eighty-four percent of the patients had medium sized lesions, and 16% of patients had small sized lesions. There were four cases of local progression (8%) and three enucleations (6%). Actuarial local control rates at 2 and 5 years were 93% and 86%, respectively. Actuarial enucleation-free survival rates at 2 and 5 years were 94% and 84%, respectively. Actuarial complication rates at 2 and 5 years were 33% and 88%, respectively, for radiation-induced retinopathy; 9.3% and 46.9%, respectively, for dry eye; 12% and 53%, respectively, for cataract; 30% and 90%, respectively, for visual loss [Snellen acuity (decimal equivalent), <0.1]; 11% and 54%, respectively, for optic neuropathy; and 18% and 38%, respectively, for neovascular glaucoma. Conclusions: Linear accelerator-based stereotactic fractionated radiotherapy using 60 Gy in 10 fractions is safe and has an acceptable toxicity profile. It has been shown to be an effective noninvasive treatment for juxtapapillary choroidal melanomas.« less

  18. Resection margin and recurrence-free survival after liver resection of colorectal metastases.

    PubMed

    Muratore, Andrea; Ribero, Dario; Zimmitti, Giuseppe; Mellano, Alfredo; Langella, Serena; Capussotti, Lorenzo

    2010-05-01

    Optimal margin width is uncertain because of conflicting results from recent studies using overall survival as the end-point. After recurrence, re-resection and aggressive chemotherapy heavily affect survival time; the potential confounding effect of such factors has not been investigated. Use of recurrence-free survival (RFS) may overcome this limitation. The aim of this study is to evaluate the impact of width of resection margin on RFS and site of recurrence after hepatic resection for colorectal metastases (CRM). From a prospectively maintained institutional database (1/1999-12/2007) we identified 314 patients undergone hepatectomy for CRM (1/1999-12/2007) with detailed pathologic analysis of the surgical margin and complete follow-up imaging studies documenting disease status and site of recurrence, which was categorized as: resection margin (M(arg)), other intra-hepatic ((other)IH), lung (L) or other extra-hepatic ((other)EH). Recurrence-free estimation was the survival end-point. Median follow-up was 56.5 months. Two hundred and fifteen patients (68.8%) recurred at 288 sites after a mean of 15.5 months. A positive resection margin was associated with an increased risk of M(arg) recurrence (P < 0.001). The presence of >or=2 metastases was the only factor increasing the risk of positive margins (P < 0.05). The width of the negative resection margin (>or=1 cm versus >1 cm) was not a prognostic factor of worse RFS (30.2% versus 37.3%, P = 0.6). Node status of the primary tumour, and size and number of CRM were independent predictors of RFS. Tumour biology and not the width of the negative resection margin affect RFS.

  19. Development of a Human Leukocyte Antigen Score to Predict Progression-Free Survival in Head and Neck Squamous Cell Carcinoma Patients.

    PubMed

    Wichmann, Gunnar; Lehmann, Claudia; Herchenhahn, Cindy; Kolb, Marlen; Hofer, Mathias; Wiegand, Susanne; Dietz, Andreas

    2018-01-01

    In personalized medicine and treatment stratification of head and neck squamous cell carcinoma (HNSCC), the heterogeneous genetic background of patients is not considered. Human leukocyte antigen (HLA) alleles and HLA haplotypes (HLA traits) are linked to development of HNSCC and affect progression-free survival (PFS) of HNSCC patients but most head and neck oncologists are not familiar with HLA typing. Hence, we developed an HLA-score abstracting from complexity of HLA-typing results to facilitate potential use of HLA-associated hazard ratios (HR) for prognostic stratification. The HR for PFS of 8 HLA traits shown to be independent predictors ( Pi ) of PFS in a test cohort (TC) of 90 HNSCC patients were used to build the HLA-score based on the natural logarithm (ln) of the Pi -associated HR. Crude ln-transformed HR of the eight Pi , alleles B*13 (2), B*35 (1), B*51 (2), DQB1*06 (1), homozygous Cw (1), homozygous DRB4 (2), and haplotypes A*01/B*08 (-6) and B*08/C*07 (4), were summed up to yield the individual patient's HLA-score. Receiver operating characteristic (ROC) and Kaplan-Meier curves were used to proof the suitability of the HLA-score as prognostic marker for PFS. An independent validation cohort (iVC) of 32 patients treated in the larynx-organ preservation trial DeLOS-II was utilized for validation. The individual HLA-scores (range -2 to 6) in TC classified HNSCC patients regarding PFS. ROC analysis (area under the curve = 0.750, 95% CI 0.665-0.836; P  = 0.0000034) demonstrated an optimum cutoff for the HLA-score at 0.5 (97.9% sensitivity, 34.7% specificity), and 70/90 patients in TC with HLA-score > 0 had significant reduced PFS ( P  = 0.001). Applying the same classifier (HLA-score > 0) confirmed these findings in the iVC revealing reduced PFS of 25/32 patients ( P  = 0.040). HLA traits constitute critical Pi . Considering the HLA-score may potentially facilitate the use of genetic information from HLA typing for prognostic

  20. Recent progress of dopant-free organic hole-transporting materials in perovskite solar cells

    NASA Astrophysics Data System (ADS)

    Dongxue, Liu; Liu, Yongsheng

    2017-01-01

    Organic-inorganic hybrid perovskite solar cells have undergone especially intense research and transformation over the past seven years due to their enormous progress in conversion efficiencies. In this perspective, we review the latest developments of conventional perovskite solar cells with a main focus on dopant-free organic hole transporting materials (HTMs). Regarding the rapid progress of perovskite solar cells, stability of devices using dopant-free HTMs are also discussed to help readers understand the challenges and opportunities in high performance and stable perovskite solar cells. Project supported by the Scientific Research Starting Foundation for Overseas Introduced Talents of College of Chemistry, Nankai University.

  1. Actuarial calculation for PSAK-24 purposes post-employment benefit using market-consistent approach

    NASA Astrophysics Data System (ADS)

    Effendie, Adhitya Ronnie

    2015-12-01

    In this paper we use a market-consistent approach to calculate present value of obligation of a companies' post-employment benefit in accordance with PSAK-24 (the Indonesian accounting standard). We set some actuarial assumption such as Indonesian TMI 2011 mortality tables for mortality assumptions, accumulated salary function for wages assumption, a scaled (to mortality) disability assumption and a pre-defined turnover rate for termination assumption. For economic assumption, we use binomial tree method with estimated discount rate as its average movement. In accordance with PSAK-24, the Projected Unit Credit method has been adapted to determine the present value of obligation (actuarial liability), so we use this method with a modification in its discount function.

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

    PubMed

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

    2016-09-01

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

  3. Differences in clinical characteristics and disease-free survival for Latino, African American, and non-Latino white men with localized prostate cancer: data from CaPSURE.

    PubMed

    Latini, David M; Elkin, Eric P; Cooperberg, Matthew R; Sadetsky, Natalia; Duchane, Janeen; Carroll, Peter R

    2006-02-15

    Few studies of ethnicity and prostate cancer have included Latino men in analyses of baseline clinical characteristics, treatment selection, and disease-free survival (DFS). The present study examines the impact of Latino ethnicity on these parameters in a large, multiinstitutional database of men with prostate cancer. We compared baseline disease characteristics and clinical outcomes for Latino (N = 138), non-Latino White (NLW, N = 5619), and African-American (AA, N = 608) men with localized prostate cancer by using chi-square and ANOVA for baseline variables and survival analysis to examine differences in time to recurrence. Latino men resembled AA men more than NLW on sociodemographic characteristics. AA men had higher Gleason scores and prostate-specific antigen (PSA) at diagnosis than Latino or NLW men (both P < 0.01). 10% of both Latino and AA men presented with advanced disease (T3b/T4/N+/M+) versus 4% of NLW (P < 0.01). Latino men did not receive different treatments than NLW or AA men after controlling for clinical and demographic factors; however, AA men were more likely to receive external beam radiation (OR = 1.51, 95% confidence interval [CI] = 0.99-2.31) and hormone treatment (OR = 1.56, 95% CI = 1.05-2.32) then NLW men. For prostatectomy patients, 3-year actuarial DFS rates were 83% for NLW men and 86% for Latino men versus 69% for AA men (P < 0.01). After controlling for clinical and sociodemographic variables, AA men were somewhat more likely than NLW to experience disease recurrence after radical prostatectomy (RP) (HR = 1.38, 95% CI = 0.98-1.94, P = 0.06). Latinos are more similar to African Americans on sociodemographic characteristics but more similar to NLW on clinical presentation, treatments received, and DFS. Copyright 2006 American Cancer Society.

  4. Throwing the baby out with the bath water: is it time for clinical judgment to supplement actuarial risk assessment?

    PubMed

    Abbott, Brian R

    2011-01-01

    The assessment of the potential for sexual violence is one of three prongs that must be met to satisfy the requirements for civil confinement of dangerous sex offenders in the 21 U.S. jurisdictions that have these laws. In a recent issue of The Journal, Sreenivasan et al. argued that, because of a host of methodological problems, actuarial risk assessment methods in general and the Static-99 and its progeny in particular are insufficient for accurate assessment of risk for dangerous sex offenders. They propose using a combination of clinical judgment with actuarial science as a solution. This analysis and review of Sreenivasan et al. reveals and corrects flaws in the arguments they employed to support their position and shows how the combination of actuarial science with clinical judgment is more error prone than the actuarial approach only, and cannot be forensically defended in court. Recommendations on reporting Static-99R data in expert testimony are provided, taking into account the limitations of the instrument.

  5. Of pacemakers and statistics: the actuarial method extended.

    PubMed

    Dussel, J; Wolbarst, A B; Scott-Millar, R N; Obel, I W

    1980-01-01

    Pacemakers cease functioning because of either natural battery exhaustion (nbe) or component failure (cf). A study of four series of pacemakers shows that a simple extension of the actuarial method, so as to incorporate Normal statistics, makes possible a quantitative differentiation between the two modes of failure. This involves the separation of the overall failure probability density function PDF(t) into constituent parts pdfnbe(t) and pdfcf(t). The approach should allow a meaningful comparison of the characteristics of different pacemaker types.

  6. Antidepressants Do Not Improve Event-free Survival in Patients with Heart Failure When Depressive Symptoms Remain

    PubMed Central

    Chung, Misook L.; Dekker, Rebecca L.; Lennie, Terry A.; Moser, Debra K.

    2012-01-01

    Objective The purpose of this secondary data analysis was to compare event-free survival among four groups of patients with heart failure (HF) that were stratified by presence of depressive symptoms and antidepressants. Methods We analyzed data from 209 outpatients (30.6% female, 62 ± 12 years, 54% NYHA Class III/IV) enrolled in a multicenter HF registry who had data on depressive symptoms, antidepressant use, and cardiac rehospitalization and death outcomes during 1 year follow up. Depressive symptoms were assessed using the Patient Health Questionnaire-9. Results Depressive symptoms, not antidepressant therapy, predicted event-free survival (HR=2.4, 95% CI = 1.2–4.6, p =.009). Depressed patients without antidepressants had 4.1 times higher risk of death and hospitalization than non-depressed patients on antidepressant (95% CI = 1.2–13.9, p=.022) after controlling for age, gender, NYHA class, body mass index, diabetes, medication of ACEI and beta blockers. Conclusion Antidepressant use was not a predictor of event-free survival outcomes when patients still reported depressive symptoms. Ongoing assessment of patients on antidepressants is needed to assure adequate treatment. PMID:23306168

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

    PubMed

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

    2017-12-20

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

  8. Significance of perioperative infection in survival of patients with ovarian cancer.

    PubMed

    Matsuo, Koji; Prather, Christina P; Ahn, Edward H; Eno, Michele L; Tierney, Katherine E; Yessaian, Annie A; Im, Dwight D; Rosenshein, Neil B; Roman, Lynda D

    2012-02-01

    Perioperative infectious diseases comprise some of the most common causes of surgical mortality in women with ovarian cancer. This study was aimed to evaluate the significance of perioperative infections in survival of patients with ovarian cancer. Patients who underwent primary cytoreductive surgery were included in the analysis (n = 276). The enumeration and speciation of pathogens, antimicrobial agents used, and sensitivity assay results were culled from medical records and correlated to clinicopathologic demographics and survival outcomes. Perioperative infection was determined as a positive microbiology result obtained within a 6-week postoperative period. The incidence of perioperative infection was 15.9% (common sites: urinary tract, 57.3%, and surgical wound, 21.4%). Commonly isolated pathogens were Enterococcus species (22.4%) and Escherichia coli (19.4%) in urinary tract infection, and Bacteroides fragilis, E. coli, and Klebsiella pneumoniae (all, 16%) in surgical wound infection. Imipenem represents one of the least resistant antimicrobial agents commonly seen in urinary tract and surgical wound infections in our institution. Perioperative infection was associated with diabetes, serous histology, lymph node metastasis, bowel resection, decreased bicarbonate, and elevated serum urea nitrogen in multivariate analysis. Perioperative infections were associated with increased surgical mortality, delay in chemotherapy treatment, decreased chemotherapy response, shorter progression-free survival (median time, 8.4 vs 17.6 months; P < 0.001), and decreased overall survival (29.0 vs 51.8 months; P = 0.011). Multivariate analysis showed that perioperative infections other than urinary tract infection remained a significant risk factor for decreased survival (progression-free survival, P = 0.02; and overall survival, P = 0.019). Perioperative infectious disease comprises an independent risk factor for survival of patients with ovarian cancer.

  9. 20 CFR 200.9 - Selection of members of Actuarial Advisory Committee.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Selection of members of Actuarial Advisory Committee. 200.9 Section 200.9 Employees' Benefits RAILROAD RETIREMENT BOARD GENERAL ADMINISTRATION GENERAL... railroad subject to the Interstate Commerce Act which own or control more than 50 percent of the total...

  10. Aberrant expression of cancer stem cell markers (CD44, CD90, and CD133) contributes to disease progression and reduced survival in hepatoblastoma patients: 4-year survival data.

    PubMed

    Bahnassy, Abeer A; Fawzy, Mohamed; El-Wakil, Mohamed; Zekri, Abdel-Rahman N; Abdel-Sayed, Ahmed; Sheta, Marwa

    2015-03-01

    Hepatoblastoma (HB) is an embryonal tumor of the liver in children. Prognosis and response to treatment in HB are highly variable. Cancer stem cells (CSCs) constitute a population of cells, which contribute to the development and progression of many tumors. However, their role in HB is not well defined yet. We assessed the prognostic and predictive values of some CSC markers in HB patients. Protein and messenger RNA expressions of the CSC markers CD133, CD90, and CD44 were assessed in 43 HB patients and 20 normal hepatic tissues using immunohistochemistry and quantitative real-time polymerase chain reaction. The expression levels of these markers were correlated to standard prognostic factors, patients' response to treatment, overall survival (OS), and disease-free survival (DFS). CD44, CD90, and CD133 proteins were detected in 48.8%, 32.6%, and 48.8% compared with 46.5%, 41.7%, and 58.1% RNA, respectively (concordance, 77.8%-96%). None of the normal tissue samples was positive for any of the markers. Significant correlations were reported between α-fetoprotein and both CD44 and CD133 (P = 0.02) as well as between tumor types CD90 and CD133 (P = 0.009). Reduced OS correlated with CD44, CD90, and CD133 expressions (P < 0.001), advanced stage (P < 0.001), response to treatment (P < 0.001), and total excision of the tumor. Reduced DFS correlated with CD44 and CD133 expressions (P < 0.001) only. In conclusion, CD133, CD44, and CD90 could be used as prognostic and predictive markers in HB. High expression of these markers is significantly associated with poor response to treatment and reduced survival. Moreover, complete surgical resection and systemic chemotherapy are essential to achieve good response and prolonged survival, especially in early stage patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Use of common analgesic medications and ovarian cancer survival: results from a pooled analysis in the Ovarian Cancer Association Consortium.

    PubMed

    Dixon, Suzanne C; Nagle, Christina M; Wentzensen, Nicolas; Trabert, Britton; Beeghly-Fadiel, Alicia; Schildkraut, Joellen M; Moysich, Kirsten B; deFazio, Anna; Risch, Harvey A; Rossing, Mary Anne; Doherty, Jennifer A; Wicklund, Kristine G; Goodman, Marc T; Modugno, Francesmary; Ness, Roberta B; Edwards, Robert P; Jensen, Allan; Kjær, Susanne K; Høgdall, Estrid; Berchuck, Andrew; Cramer, Daniel W; Terry, Kathryn L; Poole, Elizabeth M; Bandera, Elisa V; Paddock, Lisa E; Anton-Culver, Hoda; Ziogas, Argyrios; Menon, Usha; Gayther, Simon A; Ramus, Susan J; Gentry-Maharaj, Aleksandra; Pearce, Celeste Leigh; Wu, Anna H; Pike, Malcolm C; Webb, Penelope M

    2017-04-25

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with improved survival in some cancers, but evidence for ovarian cancer is limited. Pooling individual-level data from 12 Ovarian Cancer Association Consortium studies, we evaluated the association between self-reported, pre-diagnosis use of common analgesics and overall/progression-free/disease-specific survival among 7694 women with invasive epithelial ovarian cancer (4273 deaths). Regular analgesic use (at least once per week) was not associated with overall survival (pooled hazard ratios, pHRs (95% confidence intervals): aspirin 0.96 (0.88-1.04); non-aspirin NSAIDs 0.97 (0.89-1.05); acetaminophen 1.01 (0.93-1.10)), nor with progression-free/disease-specific survival. There was however a survival advantage for users of any NSAIDs in studies clearly defining non-use as less than once per week (pHR=0.89 (0.82-0.98)). Although this study did not show a clear association between analgesic use and ovarian cancer survival, further investigation with clearer definitions of use and information about post-diagnosis use is warranted.

  12. 5 CFR 839.1114 - Will OPM actuarially reduce my benefit if I elect to change my retirement coverage under these...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Will OPM actuarially reduce my benefit if... General Provisions § 839.1114 Will OPM actuarially reduce my benefit if I elect to change my retirement... Basic Employee Death Benefit (see § 839.1121). ...

  13. Five-year disease-free survival among stage II-IV breast cancer patients receiving FAC and AC chemotherapy in phase II clinical trials of Panagen.

    PubMed

    Proskurina, Anastasia S; Gvozdeva, Tatiana S; Potter, Ekaterina A; Dolgova, Evgenia V; Orishchenko, Konstantin E; Nikolin, Valeriy P; Popova, Nelly A; Sidorov, Sergey V; Chernykh, Elena R; Ostanin, Alexandr A; Leplina, Olga Y; Dvornichenko, Victoria V; Ponomarenko, Dmitriy M; Soldatova, Galina S; Varaksin, Nikolay A; Ryabicheva, Tatiana G; Uchakin, Peter N; Rogachev, Vladimir A; Shurdov, Mikhail A; Bogachev, Sergey S

    2016-08-18

    We report on the results of a phase II clinical trial of Panagen (tablet form of fragmented human DNA preparation) in breast cancer patients (placebo group n = 23, Panagen n = 57). Panagen was administered as an adjuvant leukoprotective agent in FAC and AC chemotherapy regimens. Pre-clinical studies clearly indicate that Panagen acts by activating dendritic cells and induces the development of adaptive anticancer immune response. We analyzed 5-year disease-free survival of patients recruited into the trial. Five-year disease-free survival in the placebo group was 40 % (n = 15), compared with the Panagen arm - 53 % (n = 51). Among stage III patients, disease-free survival was 25 and 52 % for placebo (n = 8) and Panagen (n = 25) groups, respectively. Disease-free survival of patients with IIIB + C stage was as follows: placebo (n = 6)-17 % vs Panagen (n = 18)-50 %. Disease-free survival rate (17 %) of patients with IIIB + C stage breast cancer receiving standard of care therapy is within the global range. Patients who additionally received Panagen demonstrate a significantly improved disease-free survival rate of 50 %. This confirms anticancer activity of Panagen. ClinicalTrials.gov NCT02115984 from 04/07/2014.

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

    PubMed

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

    2015-05-01

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

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

    PubMed

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

    2005-11-15

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

  16. Population projections for AIDS using an actuarial model.

    PubMed

    Wilkie, A D

    1989-09-05

    This paper gives details of a model for forecasting AIDS, developed for actuarial purposes, but used also for population projections. The model is only appropriate for homosexual transmission, but it is age-specific, and it allows variation in the transition intensities by age, duration in certain states and calendar year. The differential equations controlling transitions between states are defined, the method of numerical solution is outlined, and the parameters used in five different Bases of projection are given in detail. Numerical results for the population of England and Wales are shown.

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

    PubMed

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

    2017-05-01

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

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

    PubMed

    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.

  19. Anterior Aortic Plane Systolic Excursion: A Novel Indicator of Transplant-Free Survival in Systemic Light-Chain Amyloidosis.

    PubMed

    Ochs, Marco M; Riffel, Johannes; Kristen, Arnt V; Hegenbart, Ute; Schönland, Stefan; Hardt, Stefan E; Katus, Hugo A; Mereles, Derliz; Buss, Sebastian J

    2016-12-01

    Anterior aortic plane systolic excursion (AAPSE) was evaluated in the present pilot study as a novel echocardiographic indicator of transplant-free survival in patients with systemic light-chain amyloidosis. Eighty-nine patients with light-chain amyloidosis were included in the post-hoc analysis. A subgroup of 54 patients with biopsy-proven cardiac amyloid infiltration were compared with 41 healthy individuals to evaluate the discriminative ability of echocardiographic findings. AAPSE is defined as the systolic excursion of the anterior aortic margin. To quantify AAPSE, the M-mode cursor was placed on the aortic valve plane in parasternal long-axis view at end-diastole. Index echocardiography had been performed before chemotherapy. Median follow-up duration was 2.4 years. The primary combined end point was heart transplantation or overall death. Mean AAPSE was 14 ± 2 mm in healthy individuals (mean age=57 ± 10 years; 56% men; BMI=25 ± 4 kg/m 2 ). AAPSE < 11 mm separated patients from age-, gender-, and BMI-matched control subjects with 93% sensitivity and 97% specificity. Median transplant-free survival of patients with AAPSE < 5 mm was 0.7 versus 4.8 years (P = .0001). AAPSE was an independent indicator of transplant-free survival in multivariate Cox regression (echocardiographic model: hazard ratio=0.72 [P = .03]; biomarker model: hazard ratio=0.62 [P = .0001]). Sequential regression analysis suggested incremental power of AAPSE as a marker of transplant-free survival. An ejection fraction-based model with an overall χ 2 value of 22.8 was improved by the addition of log NT-proBNP (χ 2  = 32.6, P < .005), troponin-T (χ 2  = 39.6, P < .01), and AAPSE (χ 2  = 54.0, P < .0001). AAPSE is suggested as an indicator of transplant-free survival in patients with systemic light-chain amyloidosis. AAPSE provided significant incremental value to established staging models. Copyright © 2016 American Society of Echocardiography

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

    PubMed

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

    2016-12-01

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

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

    PubMed

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

    2018-03-30

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

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

    PubMed Central

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

    2005-01-01

    Background Median survival of metastatic malignant melanoma is 6.0 to 7.5 months, with a 5-year survival of ~6.0%. Although long-term complete remissions are rare, few reports describe cases after chemotherapy. Fifty-three patients with metastatic melanoma were treated with Cystemustine, a chloroethyl nitrosourea (CENU) (60 or 90 mg/m2). Case presentation We describe 5 cases, presenting with complete response with long-term disease-free survival of long-term remission of 14, 12, 9, 7 and 6 years after Cystemustine therapy alone. Conclusion Long-term survival has already been described in literature, but in all cases they have been obtained after chemotherapy associated with or followed by surgery. But despite these noteworthy and encouraging but also rare results, it appears essential to increase cystemustine efficiency. PMID:16287507

  3. Lack of active follow-up of cancer patients in Chennai, India: implications for population-based survival estimates

    PubMed Central

    Rama, Ranganathan; Shanta, Viswanathan

    2008-01-01

    Abstract Objective To measure the bias in absolute cancer survival estimates in the absence of active follow-up of cancer patients in developing countries. Methods Included in the study were all incident cases of the 10 most common cancers and corresponding subtypes plus all tobacco-related cancers not ranked among the top 10 that were registered in the population-based cancer registry in Chennai, India, during 1990–1999 and followed through 2001. Registered incident cases were first matched with those in the all-cause mortality database from the vital statistics division of the Corporation of Chennai. Unmatched incident cancer cases were then actively followed up to determine their survival status. Absolute survival was estimated by using an actuarial method and applying different assumptions regarding the survival status (alive/dead) of cases under passive and active follow-up. Findings Before active follow-up, matches between cases ranged from 20% to 66%, depending on the site of the primary tumour. Active follow-up of unmatched incident cases revealed that 15% to 43% had died by the end of the follow-up period, while the survival status of 4% to 38% remained unknown. Before active follow-up of cancer patients, 5-year absolute survival was estimated to be between 22% and 47% higher, than when conventional actuarial assumption methods were applied to cases that were lost to follow-up. The smallest survival estimates were obtained when cases lost to follow-up were excluded from the analysis. Conclusion Under the conditions that prevail in India and other developing countries, active follow-up of cancer patients yields the most reliable estimates of cancer survival rates. Passive case follow-up alone or applying standard methods to estimate survival is likely to result in an upward bias. PMID:18670662

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

    PubMed Central

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

    2014-01-01

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

  5. Exploring factors related to metastasis free survival in breast cancer patients using Bayesian cure models.

    PubMed

    Jafari-Koshki, Tohid; Mansourian, Marjan; Mokarian, Fariborz

    2014-01-01

    Breast cancer is a fatal disease and the most frequently diagnosed cancer in women with an increasing pattern worldwide. The burden is mostly attributed to metastatic cancers that occur in one-third of patients and the treatments are palliative. It is of great interest to determine factors affecting time from cancer diagnosis to secondary metastasis. Cure rate models assume a Poisson distribution for the number of unobservable metastatic-component cells that are completely deleted from the non-metastasis patient body but some may remain and result in metastasis. Time to metastasis is defined as a function of the number of these cells and the time for each cell to develop a detectable sign of metastasis. Covariates are introduced to the model via the rate of metastatic-component cells. We used non-mixture cure rate models with Weibull and log-logistic distributions in a Bayesian setting to assess the relationship between metastasis free survival and covariates. The median of metastasis free survival was 76.9 months. Various models showed that from covariates in the study, lymph node involvement ratio and being progesterone receptor positive were significant, with an adverse and a beneficial effect on metastasis free survival, respectively. The estimated fraction of patients cured from metastasis was almost 48%. The Weibull model had a slightly better performance than log-logistic. Cure rate models are popular in survival studies and outperform other models under certain conditions. We explored the prognostic factors of metastatic breast cancer from a different viewpoint. In this study, metastasis sites were analyzed all together. Conducting similar studies in a larger sample of cancer patients as well as evaluating the prognostic value of covariates in metastasis to each site separately are recommended.

  6. The impact of overall treatment time on outcomes in radiation therapy for non-small cell lung cancer.

    PubMed

    Chen, M; Jiang, G L; Fu, X L; Wang, L J; Qian, H; Chen, G Y; Zhao, S; Liu, T F

    2000-04-01

    A retrospective study was carried out to evaluate the impact of overall treatment time (OTT) on the results of radiation therapy for non-small cell lung cancer (NSCLC). From Jan. 1990 to Dec. 1996, 256 patients with stages I-IIIb NSCLC entered this analysis. All patients received definitive radiotherapy. Biologically effective dose (BED) was used to standardize the irradiation effects. The correlation between OTT and local progression-free survival was analyzed by linear-regression and Cox proportional hazard models. The prognostic variables for survival and distant metastasis were also briefly studied. OTT had been shortened in 64 patients because of an accelerated hyperfractioned irradiation, while OTT was prolonged i n 114 patients due to interruptions of irradiation courses. The main ca uses of interruption were machine breakdown or delayed preparations of c errobend block for boost fields (55%), holidays (11%) and treatment toxi city and side effects (34%). Patients tre ated with prolonged OTT (> 45 days) had significant poorer local progression-free survival than whom with OTT of actuarial local progression-free survivals being 49, 17 and 15% for the former, and 74, 35 and 25% for the latter, respectively (P<0.001). BED-T that contained the factor of OTT correlated directly to local controls, which implied that BED-T represented radiobiological effects accurately, in other words, OTT had played a role in determining the radiobiological effects. Linear-regression on 103 cases treated with BED of 80-85 Gy(10) showed that 3 year local progression-free survival decreased by 9% per week with prolongation of OTT, or vice versa it increased by 9% per week with shortening OTT in an OTT range of 30-76 days. Cox multivariate analyses confirmed that OTT was an independent prognostic factor for local controls. OTT may have played an important role in determining local controls in radiotherapy for NSCLC. One should always keep in mind to make

  7. Immunological network signatures of cancer progression and survival

    PubMed Central

    2011-01-01

    Background The immune contribution to cancer progression is complex and difficult to characterize. For example in tumors, immune gene expression is detected from the combination of normal, tumor and immune cells in the tumor microenvironment. Profiling the immune component of tumors may facilitate the characterization of the poorly understood roles immunity plays in cancer progression. However, the current approaches to analyze the immune component of a tumor rely on incomplete identification of immune factors. Methods To facilitate a more comprehensive approach, we created a ranked immunological relevance score for all human genes, developed using a novel strategy that combines text mining and information theory. We used this score to assign an immunological grade to gene expression profiles, and thereby quantify the immunological component of tumors. This immunological relevance score was benchmarked against existing manually curated immune resources as well as high-throughput studies. To further characterize immunological relevance for genes, the relevance score was charted against both the human interactome and cancer information, forming an expanded interactome landscape of tumor immunity. We applied this approach to expression profiles in melanomas, thus identifying and grading their immunological components, followed by identification of their associated protein interactions. Results The power of this strategy was demonstrated by the observation of early activation of the adaptive immune response and the diversity of the immune component during melanoma progression. Furthermore, the genome-wide immunological relevance score classified melanoma patient groups, whose immunological grade correlated with clinical features, such as immune phenotypes and survival. Conclusions The assignment of a ranked immunological relevance score to all human genes extends the content of existing immune gene resources and enriches our understanding of immune involvement in

  8. Cell-free DNA as a molecular tool for monitoring disease progression and response to therapy in breast cancer patients.

    PubMed

    Liang, Diana H; Ensor, Joe E; Liu, Zhe-Bin; Patel, Asmita; Patel, Tejal A; Chang, Jenny C; Rodriguez, Angel A

    2016-01-01

    Due to the spatial and temporal genomic heterogeneity of breast cancer, genomic sequencing obtained from a single biopsy may not capture the complete genomic profile of tumors. Thus, we propose that cell-free DNA (cfDNA) in plasma may be an alternate source of genomic information to provide comprehensive data throughout a patient's clinical course. We performed a retrospective chart review of 100 patients with stage 4 or high-risk stage 3 breast cancer. The degree of agreement between genomic alterations found in tumor DNA (tDNA) and cfDNA was determined by Cohen's Kappa. Clinical disease progression was compared to mutant allele frequency using a two-sided Fisher's exact test. The presence of mutations and mutant allele frequency was correlated with progression-free survival (PFS) using a Cox proportional hazards model and a log-rank test. The most commonly found genomic alterations were mutations in TP53 and PIK3CA, and amplification of EGFR and ERBB2. PIK3CA mutation and ERBB2 amplification demonstrated robust agreement between tDNA and cfDNA (Cohen's kappa = 0.64 and 0.77, respectively). TP53 mutation and EGFR amplification demonstrated poor agreement between tDNA and cfDNA (Cohen's kappa = 0.18 and 0.33, respectively). The directional changes of TP53 and PIK3CA mutant allele frequency were closely associated with response to therapy (p = 0.002). The presence of TP53 mutation (p = 0.0004) and PIK3CA mutant allele frequency [p = 0.01, HR 1.074 (95 % CI 1.018-1.134)] was excellent predictors of PFS. Identification of selected cancer-specific genomic alterations from cfDNA may be a noninvasive way to monitor disease progression, predict PFS, and offer targeted therapy.

  9. Use of common analgesic medications and ovarian cancer survival: results from a pooled analysis in the Ovarian Cancer Association Consortium

    PubMed Central

    Dixon, Suzanne C; Nagle, Christina M; Wentzensen, Nicolas; Trabert, Britton; Beeghly-Fadiel, Alicia; Schildkraut, Joellen M; Moysich, Kirsten B; deFazio, Anna; Risch, Harvey A; Rossing, Mary Anne; Doherty, Jennifer A; Wicklund, Kristine G; Goodman, Marc T; Modugno, Francesmary; Ness, Roberta B; Edwards, Robert P; Jensen, Allan; Kjær, Susanne K; Høgdall, Estrid; Berchuck, Andrew; Cramer, Daniel W; Terry, Kathryn L; Poole, Elizabeth M; Bandera, Elisa V; Paddock, Lisa E; Anton-Culver, Hoda; Ziogas, Argyrios; Menon, Usha; Gayther, Simon A; Ramus, Susan J; Gentry-Maharaj, Aleksandra; Pearce, Celeste Leigh; Wu, Anna H; Pike, Malcolm C; Webb, Penelope M

    2017-01-01

    Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with improved survival in some cancers, but evidence for ovarian cancer is limited. Methods: Pooling individual-level data from 12 Ovarian Cancer Association Consortium studies, we evaluated the association between self-reported, pre-diagnosis use of common analgesics and overall/progression-free/disease-specific survival among 7694 women with invasive epithelial ovarian cancer (4273 deaths). Results: Regular analgesic use (at least once per week) was not associated with overall survival (pooled hazard ratios, pHRs (95% confidence intervals): aspirin 0.96 (0.88–1.04); non-aspirin NSAIDs 0.97 (0.89–1.05); acetaminophen 1.01 (0.93–1.10)), nor with progression-free/disease-specific survival. There was however a survival advantage for users of any NSAIDs in studies clearly defining non-use as less than once per week (pHR=0.89 (0.82–0.98)). Conclusions: Although this study did not show a clear association between analgesic use and ovarian cancer survival, further investigation with clearer definitions of use and information about post-diagnosis use is warranted. PMID:28350790

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

    PubMed Central

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

    2016-01-01

    Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, P<0.0001) recovery, lower risk of grade II–IV acute graft-versus-host disease (HR=0.26, P<0.0001) and chronic graft-versus-host disease (HR=0.06, P<0.0001). Haplo-cord was associated with decreased risk of relapse (HR 0.48, P=0.001). Graft-versus-host disease-free, relapse-free survival was superior with haplo-cord (HR 0.63, P=0.002) but not overall survival (HR=0.97, P=0.85). Haplo-cord transplantation using fludarabine-melphalan-thymoglobulin conditioning hastens hematopoietic recovery with a lower risk of relapse relative to double umbilical cord blood transplantation using the commonly used fludarabine-cyclophosphamide-low-dose total body irradiation conditioning. Graft-versus-host disease-free and relapse-free survival is significantly improved. Haplo-cord is a readily available graft source that improves outcomes and access to transplant for those lacking HLA-matched donors. Trials registered at clinicaltrials.gov identifiers 00943800 and 01810588. PMID

  11. Usefulness of cancer-free survival in estimating the lifetime attributable risk of cancer incidence from radiation exposure.

    PubMed

    Seo, Songwon; Lee, Dal Nim; Jin, Young Woo; Lee, Won Jin; Park, Sunhoo

    2018-05-11

    Risk projection models estimating the lifetime cancer risk from radiation exposure are generally based on exposure dose, age at exposure, attained age, gender and study-population-specific factors such as baseline cancer risks and survival rates. Because such models have mostly been based on the Life Span Study cohort of Japanese atomic bomb survivors, the baseline risks and survival rates in the target population should be considered when applying the cancer risk. The survival function used in the risk projection models that are commonly used in the radiological protection field to estimate the cancer risk from medical or occupational exposure is based on all-cause mortality. Thus, it may not be accurate for estimating the lifetime risk of high-incidence but not life-threatening cancer with a long-term survival rate. Herein, we present the lifetime attributable risk (LAR) estimates of all solid cancers except thyroid cancer, thyroid cancer, and leukemia except chronic lymphocytic leukemia in South Korea for lifetime exposure to 1 mGy per year using the cancer-free survival function, as recently applied in the Fukushima health risk assessment by the World Health Organization. Compared with the estimates of LARs using an overall survival function solely based on all-cause mortality, the LARs of all solid cancers except thyroid cancer, and thyroid cancer evaluated using the cancer-free survival function, decreased by approximately 13% and 1% for men and 9% and 5% for women, respectively. The LAR of leukemia except chronic lymphocytic leukemia barely changed for either gender owing to the small absolute difference between its incidence and mortality. Given that many cancers have a high curative rate and low mortality rate, using a survival function solely based on all-cause mortality may cause an overestimation of the lifetime risk of cancer incidence. The lifetime fractional risk was robust against the choice of survival function.

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

    PubMed

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

    2009-12-15

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

  13. Long-term survival of a randomized phase III trial of head and neck cancer patients receiving concurrent chemoradiation therapy with or without low-level laser therapy (LLLT) to prevent oral mucositis.

    PubMed

    Antunes, Héliton S; Herchenhorn, Daniel; Small, Isabele A; Araújo, Carlos M M; Viégas, Celia Maria Pais; de Assis Ramos, Gabriela; Dias, Fernando L; Ferreira, Carlos G

    2017-08-01

    The impact of low-level laser therapy (LLLT) to prevent oral mucositis in patients treated with exclusive chemoradiation therapy remains unknown. This study evaluated the overall, disease-free and progression-free survival of these patients. Overall, disease-free and progression-free survival of 94 patients diagnosed with oropharynx, nasopharynx, and hypopharynx cancer, who participated on a phase III study, was evaluated from 2007 to 2015. The patients were subjected to conventional radiotherapy plus cisplatin every 3weeks. LLLT was applied with an InGaAlP diode (660nm-100mW-1J-4J/cm 2 ). With a median follow-up of 41.3months (range 0.7-101.9), patients receiving LLLT had a statistically significant better complete response to treatment than those in the placebo group (LG=89.1%; PG=67.4%; p=0.013). Patients subjected to LLLT also displayed increase in progression-free survival than those in the placebo group (61.7% vs. 40.4%; p=0.030; HR:1:93; CI 95%: 1.07-3.5) and had a tendency for better overall survival (57.4% vs. 40.4%; p=0.90; HR:1.64; CI 95%: 0.92-2.91). This is the first study to suggest that LLLT may improve survival of head and neck cancer patients treated with chemoradiotherapy. Further studies, with a larger sample, are necessary to confirm our findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2017-03-16

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

  15. The role of early magnetic resonance imaging in predicting survival on bevacizumab for recurrent glioblastoma: Results from a prospective clinical trial (CABARET).

    PubMed

    Field, Kathryn M; Phal, Pramit M; Fitt, Greg; Goh, Christine; Nowak, Anna K; Rosenthal, Mark A; Simes, John; Barnes, Elizabeth H; Sawkins, Kate; Cher, Lawrence M; Hovey, Elizabeth J; Wheeler, Helen

    2017-09-15

    Bevacizumab has been associated with prolonged progression-free survival for patients with recurrent glioblastoma; however, not all derive a benefit. An early indicator of efficacy or futility may allow early discontinuation for nonresponders. This study prospectively assessed the role of early magnetic resonance imaging (eMRI) and its correlation with subsequent routine magnetic resonance imaging (MRI) results and survival. Patients were part of a randomized phase 2 clinical trial (CABARET) comparing bevacizumab with bevacizumab plus carboplatin for recurrent glioblastoma. eMRI was conducted after 4 weeks in the trial (after 2 treatments with bevacizumab [10 mg/kg every 2 weeks]). The results were compared with the results of the subsequent 8-week MRI standard. For 119 of 122 patients, eMRI was available, and 111 had subsequent MRI for comparison. Thirty-six (30%) had an early radiological response, and 17 (14%) had progressive disease. The concordance between eMRI and 8-week MRI was moderate (κ = 0.56), with most providing the same result (n = 79 [71%]). There was strong evidence that progression-free survival and overall survival were predicted by the eMRI response (both P values < .001). The median survival was 8.6 months for an eMRI response, 6.6 months for stable disease, and 3.7 months for progressive disease; the hazard ratio (progressive disease vs stable disease) was 3.4 (95% confidence interval, 1.9-6.0). Landmark analyses showed that eMRI progression was a strong predictor of mortality independent of other potential baseline predictors. In this study, early progression on MRI appears to be a robust marker of a poor prognosis for patients on bevacizumab. Cancer 2017;123:3576-82. © 2017 American Cancer Society. © 2017 American Cancer Society.

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

    PubMed

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

    2018-06-01

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

  17. Use of various free flaps in progressive hemifacial atrophy.

    PubMed

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

    2011-11-01

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

  18. Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis.

    PubMed

    Alberts, Rudi; de Vries, Elisabeth M G; Goode, Elizabeth C; Jiang, Xiaojun; Sampaziotis, Fotis; Rombouts, Krista; Böttcher, Katrin; Folseraas, Trine; Weismüller, Tobias J; Mason, Andrew L; Wang, Weiwei; Alexander, Graeme; Alvaro, Domenico; Bergquist, Annika; Björkström, Niklas K; Beuers, Ulrich; Björnsson, Einar; Boberg, Kirsten Muri; Bowlus, Christopher L; Bragazzi, Maria C; Carbone, Marco; Chazouillères, Olivier; Cheung, Angela; Dalekos, Georgios; Eaton, John; Eksteen, Bertus; Ellinghaus, David; Färkkilä, Martti; Festen, Eleonora A M; Floreani, Annarosa; Franceschet, Irene; Gotthardt, Daniel Nils; Hirschfield, Gideon M; Hoek, Bart van; Holm, Kristian; Hohenester, Simon; Hov, Johannes Roksund; Imhann, Floris; Invernizzi, Pietro; Juran, Brian D; Lenzen, Henrike; Lieb, Wolfgang; Liu, Jimmy Z; Marschall, Hanns-Ulrich; Marzioni, Marco; Melum, Espen; Milkiewicz, Piotr; Müller, Tobias; Pares, Albert; Rupp, Christian; Rust, Christian; Sandford, Richard N; Schramm, Christoph; Schreiber, Stefan; Schrumpf, Erik; Silverberg, Mark S; Srivastava, Brijesh; Sterneck, Martina; Teufel, Andreas; Vallier, Ludovic; Verheij, Joanne; Vila, Arnau Vich; Vries, Boudewijn de; Zachou, Kalliopi; Chapman, Roger W; Manns, Michael P; Pinzani, Massimo; Rushbrook, Simon M; Lazaridis, Konstantinos N; Franke, Andre; Anderson, Carl A; Karlsen, Tom H; Ponsioen, Cyriel Y; Weersma, Rinse K

    2017-08-04

    Primary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications. We collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients-obtained using the Illumina immunochip-with their disease subphenotypes. Using logistic regression and Cox proportional hazards models, we identified genetic variants associated with binary and time-to-event PSC subphenotypes. We identified genetic variant rs853974 to be associated with liver transplant-free survival (p=6.07×10 -9 ). Kaplan-Meier survival analysis showed a 50.9% (95% CI 41.5% to 59.5%) transplant-free survival for homozygous AA allele carriers of rs853974 compared with 72.8% (95% CI 69.6% to 75.7%) for GG carriers at 10 years after PSC diagnosis. For the candidate gene in the region, RSPO3 , we demonstrated expression in key liver-resident effector cells, such as human and murine cholangiocytes and human hepatic stellate cells. We present a large international PSC cohort, and report genetic loci associated with PSC disease progression. For liver transplant-free survival, we identified a genome-wide significant signal and demonstrated expression of the candidate gene RSPO3 in key liver-resident effector cells. This warrants further assessments of the role of this potential key PSC modifier gene. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. 78 FR 773 - Hartford Financial Services Group, Inc., Commercial/Actuarial/Information Delivery Services (IDS...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-04

    ...., Commercial/ Actuarial/Information Delivery Services (IDS)/Corporate & Financial Reporting group, Hartford... financial reporting. The group develops databases for creating reports for corporate, regulatory, and... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-81,815] Hartford Financial...

  20. Tumor characteristics and survival outcomes of women with tamoxifen-related uterine carcinosarcoma.

    PubMed

    Matsuo, Koji; Ross, Malcolm S; Bush, Stephen H; Yunokawa, Mayu; Blake, Erin A; Takano, Tadao; Ueda, Yutaka; Baba, Tsukasa; Satoh, Shinya; Shida, Masako; Ikeda, Yuji; Adachi, Sosuke; Yokoyama, Takuhei; Takekuma, Munetaka; Takeuchi, Satoshi; Nishimura, Masato; Iwasaki, Keita; Yanai, Shiori; Klobocista, Merieme M; Johnson, Marian S; Machida, Hiroko; Hasegawa, Kosei; Miyake, Takahito M; Nagano, Tadayoshi; Pejovic, Tanja; Shahzad, Mian Mk; Im, Dwight D; Omatsu, Kohei; Ueland, Frederick R; Kelley, Joseph L; Roman, Lynda D

    2017-02-01

    To examine tumor characteristics and survival outcome of women with uterine carcinosarcoma who had a history of tamoxifen use. This is a multicenter retrospective study examining stage I-IV uterine carcinosarcoma cases based on history of tamoxifen use. Patient demographics, tumor characteristics, treatment pattern, and survival outcomes were compared between tamoxifen users and non-users. Sixty-six cases of tamoxifen-related uterine carcinosarcoma were compared to 1009 cases with no history of tamoxifen use. Tamoxifen users were more likely to be older (mean age, 69 versus 64, P<0.001) and had a past history of malignancy (100% versus 12.7%, P<0.001). Tamoxifen-related uterine carcinosarcoma was significantly associated with a higher proportion of stage IA disease (48.4% versus 29.9%) and a lower risk of stage IVB disease (7.8% versus 16.0%) compared to tamoxifen-unrelated carcinosarcoma (P=0.034). Deep myometrial tumor invasion was less common in uterine carcinosarcoma related to tamoxifen use (28.3% versus 48.8%, P=0.002). On univariate analysis, tamoxifen use was not associated with progression-free survival (5-year rates 44.5% versus 46.8%, P=0.48) and disease-specific survival (64.0% versus 59.1%, P=0.39). After adjusting for age, past history of malignancy, stage, residual disease status at surgery, and postoperative treatment patterns, tamoxifen use was not associated with progression-free survival (adjusted-hazard ratio 0.86, 95% confidence interval 0.50 to 1.50, P=0.60) and disease-specific survival (adjusted-hazard ratio 0.68, 95% confidence interval 0.36 to 1.29, P=0.24). Our study suggests that tamoxifen-related uterine carcinosarcoma may have favorable tumor characteristics but have comparable stage-specific survival outcomes compared to tamoxifen-unrelated uterine carcinosarcoma. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

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

    2018-05-01

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

  2. High expression of long non-coding RNA MALAT1 in breast cancer is associated with poor relapse-free survival.

    PubMed

    Wang, Zhanwei; Katsaros, Dionyssios; Biglia, Nicoletta; Shen, Yi; Fu, Yuanyuan; Loo, Lenora W M; Jia, Wei; Obata, Yuki; Yu, Herbert

    2018-05-29

    Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been identified as a prognostic marker for the metastasis of early-stage non-small cell lung cancer (NSCLCs). We studied MALAT1 expression in breast cancer in relation to disease features and patient survival. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to measure MALAT1 expression in tumor samples of 509 breast cancer patients. Hazards ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the association between MALAT1 expression and breast cancer survival using the Cox proportional hazards regression model, and the analysis was adjusted for age at surgery, tumor grade, disease stage, and hormone receptor status. Meta-analysis of multiple microarray datasets from online databases and our own study was performed to evaluate the association of MALAT1 with breast cancer survival. Patients with low-grade or ER-positive tumors had higher expression of MALAT1 compared to those with high-grade (p = 0.013) or ER-negative (p = 0.0002) tumors. Patients with PR-positive tumors also had higher MALAT1 expression than those with PR-negative tumors (p < 0.0001). In patients with positive hormone receptors or low tumor grade, tumors with high MALAT1 expression were more likely to recur. Survival analysis showed that patients with high expression of MALAT1 had a twofold increase in risk of relapse (p = 0.0083) compared to those with low expression. This association remained significant after adjustment for age at surgery, disease stage, tumor grade, and hormone receptor status. Meta-analysis showed that high MALAT1 expression was associated with poor relapse-free survival in patients with hormone receptor-positive tumors (HR 1.44, 95% CI 1.08-1.92). High expression of lncRNA MALAT1 is associated with breast cancer relapse and may play a role in tumor progression.

  3. Twenty-year follow-up study of long-term survival of limited-stage small-cell lung cancer and overview of prognostic and treatment factors.

    PubMed

    Tai, Patricia; Tonita, Jon; Yu, Edward; Skarsgard, David

    2003-07-01

    To predict the long-term survival results of clinical trials earlier than using actuarial methods and to assess the factors predictive of long-term cure in patients with limited-stage small-cell lung cancer. Between 1981 and 1998, 1417 new cases of small-cell lung cancer were diagnosed in Saskatchewan, Canada, of which 244 were limited stage and treated with curative intent. They were followed to the end of February 2002. A parametric lognormal statistical model was retrospectively validated to determine whether long-term survival rates could be estimated several years earlier than is possible using the standard life-table actuarial method. The survival time of the uncured group followed a lognormal distribution. Four 2-year periods of diagnosis were combined, and patients were followed as a cohort for an additional 2 years. The estimated 10-year cause-specific survival rate was 13% by the lognormal model. The Kaplan-Meier calculation for 10-year cause-specific survival rate was 15% +/- 3%. The data also showed that the absence of mediastinal lymphadenopathy and higher chest radiotherapy dose were significant prognostic factors on multivariate analysis (p < 0.05). Among the 163 patients given prophylactic cranial irradiation, a higher biologically effective dose to the brain did not improve survival or decrease the incidence of brain metastases. The lognormal model has been validated for the estimation of survival in patients with limited-stage small-cell lung cancer. A higher biologically effective dose to the brain did not improve survival or decrease the incidence of brain metastases.

  4. Should Actuarial Risk Assessments Be Used with Sex Offenders Who Are Intellectually Disabled?

    ERIC Educational Resources Information Center

    Harris, Andrew J. R.; Tough, Susan

    2004-01-01

    Background: Objective actuarial assessments are critical for making risk decisions, determining the necessary level of supervision and intensity of treatment ( Andrews & Bonta 2003). This paper reviews the history of organized risk assessment and discusses some issues in current attitudes towards sexual offenders with intellectual disabilities.…

  5. 78 FR 8596 - Hartford Financial Services Group, Inc., Commercial/Actuarial/ Information Delivery Services (IDS...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-06

    ... Delivery Services (IDS)/Corporate & Financial Reporting group, Hartford, Connecticut (The Hartford-IDS... technology applications for corporate, regulatory, and financial reporting. Pursuant to 29 CFR 90.18(c...., Commercial/Actuarial/Information Delivery Services (IDS)/ Corporate & Financial Reporting group, Hartford...

  6. Outcomes of Patients With Head-and-Neck Cancer of Unknown Primary Origin Treated With Intensity-Modulated Radiotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shoushtari, Asal; Saylor, Drew; Kerr, Kara-Lynne

    2011-11-01

    Purpose: To analyze survival, failure patterns, and toxicity in patients with head-and-neck carcinoma of unknown primary origin (HNCUP) treated with intensity-modulated radiotherapy (IMRT). Methods and materials: Records from 27 patients with HNCUP treated during the period 2002-2008 with IMRT were reviewed retrospectively. Nodal staging ranged from N1 to N3. The mean preoperative dose to gross or suspected disease, Waldeyer's ring, and uninvolved bilateral cervical nodes was 59.4, 53.5, and 51.0 Gy, respectively. Sixteen patients underwent neck dissection after radiation and 4 patients before radiation. Eight patients with advanced nodal disease (N2b-c, N3) or extracapsular extension received chemotherapy. Results: With amore » median follow-up of 41.9 months (range, 25.3-93.9 months) for nondeceased patients, the 5-year actuarial overall survival, disease-free survival, and nodal control rates were 70.9%, 85.2%, and 88.5%, respectively. Actuarial disease-free survival rates for N1, N2, and N3 disease were 100%, 94.1%, and 50.0%, respectively, at 5 years. When stratified by nonadvanced (N1, N2a nodal disease without extracapsular spread) vs. advanced nodal disease (N2b, N2c, N3), the 5-year actuarial disease-free survival rate for the nonadvanced nodal disease group was 100%, whereas for the advanced nodal disease group it was significantly lower at 66.7% (p = 0.017). Three nodal recurrences were observed: in 1 patient with bulky N2b disease and 2 in patients with N3 disease. No nodal failures occurred in patients with N1 or N2a disease who received only radiation and surgery. Conclusion: Definitive IMRT to 50-56 Gy followed by neck dissection results in excellent nodal control and overall and disease-free survival, with acceptable toxicity for patients with T0N1 or nonbulky T0N2a disease without extracapsular spread. Patients with extracapsular spread, advanced N2 disease, or N3 disease may benefit from concurrent chemotherapy, targeted therapeutic agents, or

  7. An Actuarial Model for Selecting Participants for a Special Medical Education Program.

    ERIC Educational Resources Information Center

    Walker-Bartnick, Leslie; And Others

    An actuarial model applied to the selection process of a special medical school program at the University of Maryland School of Medicine was tested. The 77 students in the study sample were admitted to the university's Fifth Pathway Program, which is designed for U.S. citizens who completed their medical school training, except for internship and…

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

    PubMed

    de Groot, Stefanie; Gelderblom, Hans; Fiocco, Marta; Bovée, Judith Vmg; van der Hoeven, Jacobus Jm; Pijl, Hanno; Kroep, Judith R

    2017-01-01

    Activation of the insulin-like growth factor 1 (IGF-1) pathway is involved in cell growth and proliferation and is associated with tumorigenesis, tumor progression, and therapy resistance in solid tumors. We examined whether variability in serum levels of IGF-1, IGF-2, and IGF-binding protein 3 (IGF-BP3) can predict event-free survival (EFS) and overall survival (OS) in Ewing sarcoma patients treated with chemotherapy. Serum levels of IGF-1, IGF-2, and IGF-BP3 of 22 patients with localized or metastasized Ewing sarcoma treated with six cycles of vincristine/ifosfamide/doxorubicin/etoposide (VIDE) chemotherapy were recorded. Baseline levels were compared with presixth cycle levels using paired t -tests and were tested for associations with EFS and OS. Continuous variables were dichotomized according to the Contal and O'Quigley procedure. Survival analyses were performed using Cox regression analysis. High baseline IGF-1 and IGF-BP3 serum levels were associated with EFS (hazard ratio [HR] 0.075, 95% confidence interval [CI] 0.009-0.602 and HR 0.090, 95% CI 0.011-0.712, respectively) in univariate and multivariate analyses (HR 0.063, 95% CI 0.007-0.590 and HR 0.057, 95% CI 0.005-0.585, respectively). OS was improved, but this was not statistically significant. IGF-BP3 and IGF-2 serum levels increased during treatment with VIDE chemotherapy ( P =0.055 and P =0.023, respectively). High circulating serum levels of IGF-1 and IGF-BP3 and the molar ratio of IGF-1:IGF-BP3 serum levels were associated with improved EFS and a trend for improved OS in Ewing sarcoma patients treated with VIDE chemotherapy. These findings suggest the need for further investigation of the IGF-1 pathway as a biomarker of disease progression in patients with Ewing sarcoma.

  9. A semi-quantitative World Health Organization grading scheme evaluating worst tumor differentiation predicts disease-free survival in oral squamous carcinoma patients.

    PubMed

    Jain, Dhruv; Tikku, Gargi; Bhadana, Pallavi; Dravid, Chandrashekhar; Grover, Rajesh Kumar

    2017-08-01

    We investigated World Health Organization (WHO) grading and pattern of invasion based histological schemes as independent predictors of disease-free survival, in oral squamous carcinoma patients. Tumor resection slides of eighty-seven oral squamous carcinoma patients [pTNM: I&II/III&IV-32/55] were evaluated. Besides examining various patterns of invasion, invasive front grade, predominant and worst (highest) WHO grade were recorded. For worst WHO grading, poor-undifferentiated component was estimated semi-quantitatively at advancing tumor edge (invasive growth front) in histology sections. Tumor recurrence was observed in 31 (35.6%) cases. The 2-year disease-free survival was 47% [Median: 656; follow-up: 14-1450] days. Using receiver operating characteristic curves, we defined poor-undifferentiated component exceeding 5% of tumor as the cutoff to assign an oral squamous carcinoma as grade-3, when following worst WHO grading. Kaplan-Meier curves for disease-free survival revealed prognostic association with nodal involvement, tumor size, worst WHO grading; most common pattern of invasion and invasive pattern grading score (sum of two most predominant patterns of invasion). In further multivariate analysis, tumor size (>2.5cm) and worst WHO grading (grade-3 tumors) independently predicted reduced disease-free survival [HR, 2.85; P=0.028 and HR, 3.37; P=0.031 respectively]. The inter-observer agreement was moderate for observers who semi-quantitatively estimated percentage of poor-undifferentiated morphology in oral squamous carcinomas. Our results support the value of semi-quantitative method to assign tumors as grade-3 with worst WHO grading for predicting reduced disease-free survival. Despite limitations, of the various histological tumor stratification schemes, WHO grading holds adjunctive value for its prognostic role, ease and universal familiarity. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma

    PubMed Central

    Taillibert, Sophie; Kanner, Andrew; Read, William; Steinberg, David M.; Lhermitte, Benoit; Toms, Steven; Idbaih, Ahmed; Ahluwalia, Manmeet S.; Fink, Karen; Di Meco, Francesco; Lieberman, Frank; Zhu, Jay-Jiguang; Stragliotto, Giuseppe; Tran, David D.; Brem, Steven; Hottinger, Andreas F.; Kirson, Eilon D.; Lavy-Shahaf, Gitit; Weinberg, Uri; Kim, Chae-Yong; Paek, Sun-Ha; Nicholas, Garth; Burna, Jordi; Hirte, Hal; Weller, Michael; Palti, Yoram; Hegi, Monika E.; Ram, Zvi

    2017-01-01

    Importance Tumor-treating fields (TTFields) is an antimitotic treatment modality that interferes with glioblastoma cell division and organelle assembly by delivering low-intensity alternating electric fields to the tumor. Objective To investigate whether TTFields improves progression-free and overall survival of patients with glioblastoma, a fatal disease that commonly recurs at the initial tumor site or in the central nervous system. Design, Setting, and Participants In this randomized, open-label trial, 695 patients with glioblastoma whose tumor was resected or biopsied and had completed concomitant radiochemotherapy (median time from diagnosis to randomization, 3.8 months) were enrolled at 83 centers (July 2009-2014) and followed up through December 2016. A preliminary report from this trial was published in 2015; this report describes the final analysis. Interventions Patients were randomized 2:1 to TTFields plus maintenance temozolomide chemotherapy (n = 466) or temozolomide alone (n = 229). The TTFields, consisting of low-intensity, 200 kHz frequency, alternating electric fields, was delivered (≥ 18 hours/d) via 4 transducer arrays on the shaved scalp and connected to a portable device. Temozolomide was administered to both groups (150-200 mg/m2) for 5 days per 28-day cycle (6-12 cycles). Main Outcomes and Measures Progression-free survival (tested at α = .046). The secondary end point was overall survival (tested hierarchically at α = .048). Analyses were performed for the intent-to-treat population. Adverse events were compared by group. Results Of the 695 randomized patients (median age, 56 years; IQR, 48-63; 473 men [68%]), 637 (92%) completed the trial. Median progression-free survival from randomization was 6.7 months in the TTFields-temozolomide group and 4.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.52-0.76; P < .001). Median overall survival was 20.9 months in the TTFields-temozolomide group vs 16.0 months in

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

    PubMed

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

    2015-01-01

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

  12. Applying a Forensic Actuarial Assessment (the Violence Risk Appraisal Guide) to Nonforensic Patients

    ERIC Educational Resources Information Center

    Harris, Grant T.; Rice, Marnie E.; Camilleri, Joseph A..

    2004-01-01

    The actuarial Violence Risk Appraisal Guide (VRAG) was developed for male offenders where it has shown excellent replicability in many new forensic samples using officially recorded outcomes. Clinicians also make decisions, however, about the risk of interpersonal violence posed by nonforensic psychiatric patients of both sexes. Could an actuarial…

  13. Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

    PubMed Central

    Wolchok, J.D.; Chiarion-Sileni, V.; Gonzalez, R.; Rutkowski, P.; Grob, J.-J.; Cowey, C.L.; Lao, C.D.; Wagstaff, J.; Schadendorf, D.; Ferrucci, P.F.; Smylie, M.; Dummer, R.; Hill, A.; Hogg, D.; Haanen, J.; Carlino, M.S.; Bechter, O.; Maio, M.; Marquez-Rodas, I.; Guidoboni, M.; McArthur, G.; Lebbé, C.; Ascierto, P.A.; Long, G.V.; Cebon, J.; Sosman, J.; Postow, M.A.; Callahan, M.K.; Walker, D.; Rollin, L.; Bhore, R.; Hodi, F.S.; Larkin, J.

    2017-01-01

    BACKGROUND Nivolumab combined with ipilimumab resulted in longer progression-free survival and a higher objective response rate than ipilimumab alone in a phase 3 trial involving patients with advanced melanoma. We now report 3-year overall survival outcomes in this trial. METHODS We randomly assigned, in a 1:1:1 ratio, patients with previously untreated advanced melanoma to receive nivolumab at a dose of 1 mg per kilogram of body weight plus ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses, followed by nivolumab at a dose of 3 mg per kilogram every 2 weeks; nivolumab at a dose of 3 mg per kilogram every 2 weeks plus placebo; or ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses plus placebo, until progression, the occurrence of unacceptable toxic effects, or withdrawal of consent. Randomization was stratified according to programmed death ligand 1 (PD-L1) status, BRAF mutation status, and metastasis stage. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group versus the ipilimumab group. RESULTS At a minimum follow-up of 36 months, the median overall survival had not been reached in the nivolumab-plus-ipilimumab group and was 37.6 months in the nivolumab group, as compared with 19.9 months in the ipilimumab group (hazard ratio for death with nivolumab plus ipilimumab vs. ipilimumab, 0.55 [P<0.001]; hazard ratio for death with nivolumab vs. ipilimumab, 0.65 [P<0.001]). The overall survival rate at 3 years was 58% in the nivolumab-plus-ipilimumab group and 52% in the nivolumab group, as compared with 34% in the ipilimumab group. The safety profile was unchanged from the initial report. Treatment-related adverse events of grade 3 or 4 occurred in 59% of the patients in the nivolumab-plus-ipilimumab group, in 21% of those in the nivolumab group, and in 28% of those in the ipilimumab group. CONCLUSIONS Among patients with advanced

  14. [Actuarial analysis of time-failure data and its rrelevance for interpretation of results. Audit of the journal "Strahlentherapie und Onkologie" (Radiotherapy and Oncology)].

    PubMed

    Dubben, H H; Beck-Bornholdt, H P

    2000-12-01

    The statistical quality of the contributions to "Strahlentherapie und Onkologie" is assessed, aiming for improvement of the journal and consequently its impact factor. All 181 articles published during 1998 and 1999 in the categories "review", "original contribution", and "short communication" were analyzed concerning actuarial analysis of time-failure data. One hundred and twenty-three publications without time-failure data were excluded from analysis. Forty-five of the remaining 58 publications with time-failure data were evaluated actuarially. This corresponds to 78% (95% confidence interval: 64 to 88%) of papers, in which data were adequately analyzed. Complications were reported in 16 of 58 papers, but in only 3 cases actuarially. The number of patients at risk during the course of follow-up was documented adequately in 22 of the 45 publications with actuarial analysis. Authors, peer reviewers, and editors could contribute to improve the quality of the journal by setting value on acturial analysis of time-failure data.

  15. Has actuarial aging “slowed” over the past 250 years? A comparison of small-scale subsistence populations and European cohorts

    PubMed Central

    Gurven, Michael; Fenelon, Andrew

    2012-01-01

    G.C. Williams’ 1957 hypothesis famously argues that higher age-independent, or “extrinsic”, mortality should select for faster rates of senescence. Long-lived species should therefore show relatively few deaths from extrinsic causes such as predation and starvation. Theoretical explorations and empirical tests of Williams’ hypothesis have flourished in the past decade but it has not yet been tested empirically among humans. We test Williams’ hypothesis using mortality data from subsistence populations and from historical cohorts from Sweden and England/Wales, and examine whether rates of actuarial aging declined over the past two centuries. We employ three aging measures: mortality rate doubling time (MRDT), Ricklef’s ω, and the slope of mortality hazard from ages sixty to seventy, m’60–70, and model mortality using both Weibull and Gompertz-Makeham hazard models. We find that (1) actuarial aging in subsistence societies is similar to that of early Europe, (2) actuarial senescence has slowed in later European cohorts, (3) reductions in extrinsic mortality associate with slower actuarial aging in longitudinal samples, and (4) men senesce more rapidly than women, especially in later cohorts. To interpret these results, we attempt to bridge population-based evolutionary analysis with individual-level proximate mechanisms. PMID:19220451

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

    PubMed Central

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

    2009-01-01

    Background: We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs). Methods: A total of 231 patients with GBM at first recurrence from 21 institutions in 10 countries were enrolled. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 600 mg per day for patients not on EIAEDs and at 500 mg twice a day if on EIAEDs. The primary end point was radiographic response rate and secondary end points were safety, progression-free survival at 6 months (PFS-6), and overall survival (OS). Results: The radiographic response rate after centralised review was 3.4%. Progression-free survival at 6 months and median OS were 10.6% and 26.0 weeks, respectively. Outcome did not appear to differ based on EIAED status. The most common grade 3 or greater adverse events were fatigue (7%), neutropaenia (7%), and thrombocytopaenia (7%). Conclusions: Imatinib in addition to hydroxyurea was well tolerated among patients with recurrent GBM but did not show clinically meaningful anti-tumour activity. PMID:19904263

  17. Pre-transplantation novel agent induction predicts progression-free survival for patients with immunoglobulin light-chain amyloidosis undergoing high-dose melphalan and autologous stem cell transplantation.

    PubMed

    Cowan, Andrew J; Klippel, Zandra K; Stevenson, Philip A; Hyun, Teresa S; Tuazon, Sherilyn; Becker, Pamela S; Green, Damian J; Holmberg, Leona A; Coffey, David G; Gopal, Ajay K; Libby, Edward N

    2016-12-01

    High-dose melphalan and autologous stem cell transplantation (HDM/SCT) is an effective treatment modality for immunoglobulin light-chain (AL) amyloidosis; however, its application remains restricted to patients with good performance status and limited organ involvement. In recent years, the paradigm for AL amyloidosis has changed with the introduction of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). We hypothesized that use of novel agent induction regimens has improved outcomes for patients with AL amyloidosis undergoing HDM/SCT at our center. All patients with AL amyloidosis, age ≥18 years who underwent HDM/SCT between 2001 and 2014 at the Fred Hutchinson Cancer Research Center and University of Washington Medical Center were included in this study. Any regimen administered within 6 months prior to HDM/SCT including an IMiD or a PI was considered a novel induction regimen. Use of induction regimen was evaluated in a Cox proportional hazard model for association with progression-free survival (PFS) and overall survival (OS). Forty-five patients with AL amyloidosis underwent HDM/SCT. The median age was 57.2 years (range 39-74.4), 15 (33.3%) were women. The median number of organs involved was 2 (range 1-5), with 20 patients having only 1 (44.4%), 10 patients having 2 (22.2%), and 15 patients (33.3%) having ≥ 3 organs involved. Novel agent induction regimens were used prior to HDM/SCT in 21 patients (46.7%); these comprised PI in 13/21 (57.1%), IMiD alone in 6/21 (28.6%), PI and cyclophosphamide (CyBorD) in 3/21 (14.3%), and IMiD and PI in 3/21 (14.3%). Use of a novel agent induction regimen was associated with improved, but not OS. The 3-year PFS for patients who received a novel agent induction was 79%, while for those who did not was 53% (hazard ratio [HR] = 0.317, p = 0.048). The 3-year OS for patients who received novel agent induction regimens was 95%, while for those who did not was 71% (HR = 0

  18. Surrogate endpoints for overall survival in lung cancer trials: a review.

    PubMed

    Fiteni, Frédéric; Westeel, Virginie; Bonnetain, Franck

    2017-05-01

    Intermediate endpoints are often used as primary endpoints instead of overall survival (OS) in lung cancer trials but they are not systematically validated as surrogate endpoints for OS. Areas covered: The aim of the study was to review the studies which assessed potential surrogate endpoints for OS in lung cancer trials. Expert commentary: Twenty studies were identified. In operable non-small cell lung cancer (NSCLC) (adjuvant trials) and locally advanced NSCLC (radiotherapy trials), one individual-patient data meta-analysis found a high correlation of disease-free survival (DFS) and progression-free survival (PFS) with OS at patient and trial level. In trials of adjuvant chemotherapy, correlation between disease-free survival DFS and OS were 0.83 at the individual level (95% CI 0.83-0.83) and 0.92 at trial level (95% CI 0.88-0.95). In locally advanced disease, correlation between PFS and OS was 0.77 to 0.85 at the individual level, and 0.89 to 0.97 at trial level. This study provides a 'proof' of the surrogacy of PFS and DFS on OS according to the IQWiG framework and the surrogacy of PFS and DFS on OS was classified level 2 according to Fleming hierarchy. In all the other setting, no endpoint was judged to be valid surrogate for OS.

  19. Construction of a North American Cancer Survival Index to Measure Progress of Cancer Control Efforts

    PubMed Central

    Weir, Hannah K; Mariotto, Angela; Wilson, Reda; Nishri, Diane

    2017-01-01

    Introduction Population-based cancer survival data provide insight into the effectiveness of health care delivery. Comparing survival for all cancer sites combined is challenging, because the primary cancer site and age distribution of patients may differ among areas or change over time. Cancer survival indices (CSIs) are summary measures of survival for cancers of all sites combined and are used in England and Europe to monitor temporal trends and examine geographic differences in survival. We describe the construction of the North American Cancer Survival Index and demonstrate how it can be used to compare survival by geographic area and by race. Methods We used data from 36 US cancer registries to estimate relative survival ratios for people diagnosed with cancer from 2006 through 2012 to create the CSI: the weighted sum of age-standardized, site-specific, relative survival ratios, with weights derived from the distribution of incident cases by sex and primary site from 2006 through 2008. The CSI was calculated for 32 registries for all races, 31 registries for whites, and 12 registries for blacks. Results The survival estimates standardized by age only versus age-, sex-, and site-standardized (CSI) were 64.1% (95% confidence interval [CI], 64.1%–64.2%) and 63.9% (95% CI, 63.8%–63.9%), respectively, for the United States for all races combined. The inter-registry ranges in unstandardized and CSI estimates decreased from 12.3% to 5.0% for whites, and from 5.4% to 3.9% for blacks. We found less inter-registry variation in CSI estimates than in unstandardized all-sites survival estimates, but disparities by race persisted. Conclusions CSIs calculated for different jurisdictions or periods are directly comparable, because they are standardized by age, sex, and primary site. A national CSI could be used to measure temporal progress in meeting public health objectives, such as Healthy People 2030. PMID:28910593

  20. Hypofractionated Proton Boost Combined with External Beam Radiotherapy for Treatment of Localized Prostate Cancer

    PubMed Central

    Johansson, Silvia; Åström, Lennart; Sandin, Fredrik; Isacsson, Ulf; Montelius, Anders; Turesson, Ingela

    2012-01-01

    Proton boost of 20 Gy in daily 5 Gy fractions followed by external beam radiotherapy (EBRT) of 50 Gy in daily 2 Gy fractions were given to 278 patients with prostate cancer with T1b to T4N0M0 disease. Fifty-three percent of the patients received neoadjuvant androgen deprivation therapy (N-ADT). The medium followup was 57 months. The 5-year PSA progression-free survival was 100%, 95%, and 74% for low-, intermediate-, and high-risk patients, respectively. The toxicity evaluation was supported by a patient-reported questionnaire before every consultant visit. Cumulative probability and actuarial prevalence of genitourinary (GU) and gastrointestinal (GI) toxicities are presented according to the RTOG classification. N-ADT did not influence curability. Mild pretreatment GU-symptoms were found to be a strong predictive factor for GU-toxicity attributable to treatment. The actuarial prevalence declined over 3 to 5 years for both GU and GI toxicities, indicating slow resolution of epithelial damage to the genitourinary and gastrointestinal tract. Bladder toxicities rather than gastrointestinal toxicities seem to be dose limiting. More than 5-year followup is necessary to reveal any sign of true progressive late side effects of the given treatment. Hypofractionated proton-boost combined with EBRT is associated with excellent curability of localized PC and acceptable frequencies of treatment toxicity. PMID:22848840

  1. [Survival is associated with time to reach PSA nadir (DAN) and the ratio DAN/nadir value after androgen deprivation for prostate cancer].

    PubMed

    Gagnat, A; Larré, S; Fromont, G; Pirès, C; Doré, B; Irani, J

    2011-05-01

    The objective of this study was to assess the prognostic decrease rate of PSA in patients treated with androgen suppression (AS) for prostate cancer (PCa). We identified in our database CaP patients with histologically documented, treated with SA alone and for whom vital status with a minimum follow-up of 6 months (except death beforehand) was established. Patient characteristics and CaP and PSA at baseline, PSA nadir, time of reaching the nadir PSA (DAN) and the ratio of the DAN/nadir value (ratio DAN/Nadir) were analyzed in relation to progression-free survival, specific and overall survival. One hundred ninety eight patients met the inclusion criteria and the median was 61.5 months (range 4.8 to 233). The median PSA at the start of the SA were 37.1 ng/mL and the median nadir PSA was 0.48 ng/mL. The median time to progression was 23.6 months. The median specific and overall survivals were 94 and 78 months, respectively. In univariate analysis, predictors of progression-free survival were PSA before SA, PSA nadir, DAN, DAN ratio/nadir, Gleason score, the percentage of core positive prostate biopsy and the status of bone scintigraphy. Except for PSA before SA which was no longer significant, predictors of specific and overall survival were similar and added the biochemical response (decrease of more than 50% of PSA) to a second hormonal manipulation during the biological progression. In multivariate analysis, the nadir PSA and the ratio DAN/Nadir remained significant predictors. These results have confirmed in one hand the predictive value of survival in patients DAN SA for CaP: achieving faster nadir PSA was associated with shorter survival. They have introduced in the other hand the new concept of DAN/Nadir PSA which provides independent prognostic information. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  2. Blood neutrophil-lymphocyte ratio predicts survival in locally advanced cancer stomach treated with neoadjuvant chemotherapy FOLFOX 4.

    PubMed

    el Aziz, Lamiss Mohamed Abd

    2014-12-01

    Accurate predictors of survival for patients with advanced gastric cancer treated with neoadjuvant chemotherapy are currently lacking. In this study, we aimed to evaluate the prognostic significance of the neutrophil-lymphocyte ratio (NLR) in patients with stage III-IV gastric cancer who received neoadjuvant chemotherapy FOLFOX 4 as neoadjuvant chemotherapy. We enrolled 70 patients with stage III-IV cancer stomach in this study. Patients received FOLFOX 4 as neoadjuvant chemotherapy. Blood sample was collected before chemotherapy. The NLR was divided into two groups: high (>3) and low (≤ 3). Univariate analysis on progression-free survival (PFS) and overall survival (OS) was performed using the Kaplan-Meier and log-rank tests, and multivariate analysis was conducted using the Cox proportional hazards regression model. The toxicity was evaluated according to National Cancer Institute Common Toxicity Criteria. The univariate analysis showed that PFS and OS were both worse for patients with high NLR than for those with low NLR before chemotherapy (median PFS 28 and 44 months, respectively, P = 0.001; median OS 30 and 48 months, P = 0.001). Multivariate analysis showed that NLRs before chemotherapy were independent prognostic factors of OS but not for progression-free survival. NLR may serve as a potential biomarker for survival prognosis in patients with stage III-IV gastric cancer receiving neoadjuvant chemotherapy. The FOLFOX 4 demonstrated an acceptable toxicity.

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

    PubMed Central

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

    2018-01-01

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

  4. A bundled care approach to patients with idiopathic pulmonary fibrosis improves transplant-free survival.

    PubMed

    Kulkarni, Tejaswini; Willoughby, John; Acosta Lara, Maria Del Pilar; Kim, Young-Il; Ramachandran, Rekha; Alexander, C Bruce; Luckhardt, Tracy; Thannickal, Victor J; de Andrade, Joao A

    2016-06-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with poor prognosis and limited therapeutic options. The 2011 ATS/ERS/JRS/ALAT consensus statement provided a number of recommendations for the management of IPF patients. The primary objective of this study was to determine if "bundling" these recommendations in the management of patients with IPF impacts clinical outcomes. We conducted a single center, retrospective cohort study of 284 patients diagnosed with IPF. The proposed bundle of care (BOC) components were: (1) visits to a specialized interstitial lung diseases clinic with evaluation of pulmonary function tests at least twice yearly; (2) referral to pulmonary rehabilitation yearly; (3) timed walk test yearly; (4) echocardiogram yearly; and (5) gastroesophageal reflux therapy. Each component of the BOC was given a score of "1" per year of follow up, and the average sum of the scores (ranging from 0 to 5) was determined for the entire period of follow-up (BOCS), as well as during the first year of follow-up (BOCY1). The primary outcome measure was transplant-free survival. Age, gender, smoking status, BMI, %FVC, %DLCO did not differ between levels of BOCS and BOCY1. Lowest BOCS (≤1) was associated with a lower transplant-free survival independent of age and %FVC compared to patients with the highest BOCS (>4) (HR 2.274, CI 1.12-4.64, p = 0.024). Lower BOCY1 was associated with a higher risk for transplant or death independent of age and %FVC in comparison to patients with highest BOCY1 (≤1 vs. >4, HR 2.23, p = 0.014; >1 to 2 vs. >4, HR 1.87, p = 0.011; >2 to 3 vs. >4, HR 1.72, p = 0.019). IPF patients with higher BOC scores had improved transplant-free survival. Prospective studies are needed to confirm these findings and determine the best strategies for the management of patients with IPF. Published by Elsevier Ltd.

  5. Treatment with Sunitinib for Patients with Progressive Metastatic Pheochromocytomas and Sympathetic Paragangliomas

    PubMed Central

    Ayala-Ramirez, Montserrat; Chougnet, Cecile N.; Habra, Mouhammed Amir; Palmer, J. Lynn; Leboulleux, Sophie; Cabanillas, Maria E.; Caramella, Caroline; Anderson, Pete; Al Ghuzlan, Abir; Waguespack, Steven G.; Deandreis, Desirée

    2012-01-01

    Context: Patients with progressive metastatic pheochromocytomas (PHEOs) or sympathetic paragangliomas (SPGLs) face a dismal prognosis. Current systemic therapies are limited. Objectives: The primary end point was progression-free survival determined by RECIST 1.1 criteria or positron emission tomography with [18F]fluorodeoxyglucose/computed tomography ([18F]FDG-PET/CT), in the absence of measurable soft tissue targets. Secondary endpoints were tumor response according to RECIST criteria version 1.1 or FDG uptake, blood pressure control, and safety. Design: We conducted a retrospective review of medical records of patients with metastatic PHEO/SPGL treated with sunitinib from December 2007 through December 2011. An intention-to-treat analysis was performed. Patients and Setting: Seventeen patients with progressive metastatic PHEO/SPGLs treated at the Institut Gustave-Roussy and MD Anderson Cancer Center. Interventions: Patients treated with sunitinib. Results: According to RECIST 1.1, eight patients experienced clinical benefit; three experienced partial response, and five had stable disease, including four with predominant skeletal metastases that showed a 30% or greater reduction in glucose uptake on [18F]FDG-PET/CT. Of 14 patients who had hypertension, six became normotensive and two discontinued antihypertensives. One patient treated with sunitinib and rapamycin experienced a durable benefit beyond 36 months. The median overall survival from the time sunitinib was initiated was 26.7 months with a progression-free survival of 4.1 months (95% confidence interval = 1.4–11.0). Most patients who experienced a clinical benefit were carriers of SDHB mutations. Conclusion: Sunitinib is associated with tumor size reduction, decreased [18F]FDG-PET/CT uptake, disease stabilization, and hypertension improvement in some patients with progressive metastatic PHEO/PGL. Prospective multi-institutional clinical trials are needed to determine the true benefits of sunitinib. PMID

  6. Cell-Free Plasma DNA-Guided Treatment With Osimertinib in Patients With Advanced EGFR-Mutated NSCLC.

    PubMed

    Buder, Anna; Hochmair, Maximilian J; Schwab, Sophia; Bundalo, Tatjana; Schenk, Peter; Errhalt, Peter; Mikes, Romana E; Absenger, Gudrun; Patocka, Kurt; Baumgartner, Bernhard; Setinek, Ulrike; Burghuber, Otto C; Prosch, Helmut; Pirker, Robert; Filipits, Martin

    2018-03-02

    Osimertinib is standard treatment for patients with advanced EGFR T790M-mutated non-small-cell lung cancer who have been pre-treated with EGFR-tyrosine kinase inhibitors (TKIs). We studied whether cell-free plasma DNA for T790M detection can be used to select patients for osimertinib treatment in the clinical routine. From April 2015 to November 2016, we included 119 patients with advanced EGFR-mutated non-small-cell lung cancer who had progressed under treatment with an EGFR-TKI. The T790M mutation status was assessed in cell-free plasma DNA by droplet digital polymerase chain reaction in all patients and by tissue analyses in selected patients. T790M mutations were detected in 85 (93%) patients by analyses of cell-free plasma DNA and in 6 (7%) plasma-negative patients by tumor re-biopsy. Eighty-nine of 91 T790M-positive patients received osimertinib. Median progression-free survival (PFS) was 10.1 months (95% confidence interval [CI]: 8.1-12.1). Median survival was not reached and the 1-year survival was 64%. The response rate was 70% in T790M-positive patients (n = 91) in the intention-to-treat population. PFS trended to be shorter in patients with high T790M copy number (≥10 copies/mL) compared to those with low T790M copy number (<10 copies/mL) (hazard ratio for PFS = 1.72, 95% CI: 0.92-3.2, p = 0.09). A comparable trend was observed for overall survival (hazard ratio for overall survival = 2.16, 95% CI: 0.89-5.25, p = 0.09). No difference in response rate was observed based on T790M copy numbers. Plasma genotyping using digital polymerase chain reaction is clinically useful for the selection of patients who had progressed during first-line EGFR-TKI therapy for treatment with osimertinib. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2013-01-01

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

  8. First-aid with warm water delays burn progression and increases skin survival.

    PubMed

    Tobalem, M; Harder, Y; Tschanz, E; Speidel, V; Pittet-Cuénod, B; Wettstein, R

    2013-02-01

    First aid treatment for thermal injuries with cold water removes heat and decreases inflammation. However, perfusion in the ischemic zone surrounding the coagulated core can be compromised by cold-induced vasoconstriction and favor burn progression. The aim of this study is to evaluate the effect of local warming on burn progression in the rat comb burn model. 24 male Wistar rats were randomly assigned to either no treatment (control) or application of cold (17 °C) or warm (37 °C) water applied for 20 min. Evolution of burn depth, interspace necrosis, and microcirculatory perfusion were assessed with histology, planimetry, respectively with Laser Doppler flowmetry after 1 h, as well as 1, 4, and 7 days. Consistent conversion from a superficial to a deep dermal burn within 24 h was obtained in control animals. Warm and cold water significantly delayed burn depth progression, however after 4 days the burn depth was similar in all groups. Interspace necrosis was significantly reduced by warm water treatment (62±4% vs. 69±5% (cold water) and 82±3% (control); p<0.05). This was attributed to the significantly improved perfusion after warming, which was present 1 h after burn induction and was maintained thereafter (103±4% of baseline vs. 91±3% for cold water and 80±2% for control, p<0.05). In order to limit damage after burn injury, burn progression has to be prevented. Besides delaying burn progression, the application of warm water provided an additional benefit by improving the microcirculatory perfusion, which translated into increased tissue survival. Copyright © 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

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

    PubMed Central

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

    2015-01-01

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

  10. The Overall Survival, Complication-Free Survival, and Related Complications of Combined Tooth-Implant Fixed Partial Dentures: A Literature Review

    PubMed Central

    Borg, Peter; Puryer, James; McNally, Lisa; O’Sullivan, Dominic

    2016-01-01

    This paper reviews the literature regarding possible complications, complication-free survival, and overall survival of fixed dental prostheses that use both implants and natural teeth as abutments. The paper also provides clinical guidelines for treatment based on this literature review. An electronic search utilizing the MEDLINE, BIOSIS Citation Index, and Web of Science™ Core Collection databases was undertaken, and a review of the 25 selected texts studying 22 different patient cohorts was carried out. From a total of 1610 implants reviewed, 40 were lost (33 due to loss of integration and 7 due to fracture), whereas, out of a total of 1301 teeth, 38 were lost, of which 16 were due to fracture. Seventy-three cases of tooth intrusion were detected. From a total of 676 frameworks reviewed (metal n = 645, Zirconia n = 31), 7 fractured, while veneer material fracture occurred in 70 out of 672 bridges. Overall, 502 out of 531 tooth-implant fixed prostheses (TIPFs) remained functional, and 336 out of 439 prostheses showed no technical or biological complications and remained functional. Rigid TIFPs permanently cemented to teeth with sufficient coronal structure and with limited use of prosthetic attachments offer a good long-term treatment option to patients with good oral hygiene following sound implant placement. This mode of treatment should be used when free-standing implant-supported options may not be possible. Larger randomized control studies and other clinical studies comparing tooth-to-implant-connected treatment with other forms of treatment are needed to better understand the place of TIFP treatment in oral rehabilitation. PMID:29563458

  11. Validation of a systems-actuarial computer process for multidimensional classification of child psychopathology.

    PubMed

    McDermott, P A; Hale, R L

    1982-07-01

    Tested diagnostic classifications of child psychopathology produced by a computerized technique known as multidimensional actuarial classification (MAC) against the criterion of expert psychological opinion. The MAC program applies series of statistical decision rules to assess the importance of and relationships among several dimensions of classification, i.e., intellectual functioning, academic achievement, adaptive behavior, and social and behavioral adjustment, to perform differential diagnosis of children's mental retardation, specific learning disabilities, behavioral and emotional disturbance, possible communication or perceptual-motor impairment, and academic under- and overachievement in reading and mathematics. Classifications rendered by MAC are compared to those offered by two expert child psychologists for cases of 73 children referred for psychological services. Experts' agreement with MAC was significant for all classification areas, as was MAC's agreement with the experts held as a conjoint reference standard. Whereas the experts' agreement with MAC averaged 86.0% above chance, their agreement with one another averaged 76.5% above chance. Implications of the findings are explored and potential advantages of the systems-actuarial approach are discussed.

  12. 29 CFR 2520.104-42 - Waiver of certain actuarial information in the annual report.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... ERISA that the annual report include as part of the actuarial statement (Schedule B) 1 the present value of all of the plan's liabilities for nonforfeitable pension benefits allocated by termination... report. 2520.104-42 Section 2520.104-42 Labor Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS...

  13. Concurrent Chemoradiotherapy with Temozolomide Followed by Adjuvant Temozolomide for Newly Diagnosed Glioblastoma Patients: A Retrospective Multicenter Observation Study in Korea.

    PubMed

    Kim, Byung Sup; Seol, Ho Jun; Nam, Do-Hyun; Park, Chul-Kee; Kim, Il Han; Kim, Tae Min; Kim, Jeong Hoon; Cho, Young Hyun; Yoon, Sang Min; Chang, Jong Hee; Kang, Seok-Gu; Kim, Eui Hyun; Suh, Chang-Ok; Jung, Tae-Young; Lee, Kyung-Hwa; Kim, Chae-Yong; Kim, In Ah; Hong, Chang-Ki; Yoo, Heon; Kim, Jin Hee; Kang, Shin-Hyuk; Kang, Min Kyu; Kim, Eun-Young; Kim, Sun-Hwan; Chung, Dong-Sup; Hwang, Sun-Chul; Song, Joon-Ho; Cho, Sung Jin; Lee, Sun-Il; Lee, Youn-Soo; Ahn, Kook-Jin; Kim, Se Hoon; Lim, Do Hun; Gwak, Ho-Shin; Lee, Se-Hoon; Hong, Yong-Kil

    2017-01-01

    The purpose of this study was to investigate the feasibility and survival benefits of combined treatment with radiotherapy and adjuvant temozolomide (TMZ) in a Korean sample. A total of 750 Korean patients with histologically confirmed glioblastoma multiforme, who received concurrent chemoradiotherapy with TMZ (CCRT) and adjuvant TMZ from January 2006 until June 2011, were analyzed retrospectively. After the first operation, a gross total resection (GTR), subtotal resection (STR), partial resection (PR), biopsy alone were achieved in 388 (51.7%), 159 (21.2%), 96 (12.8%), and 107 (14.3%) patients, respectively. The methylation status of O 6 -methylguanine-DNA methyltransferase (MGMT) was reviewed retrospectively in 217 patients. The median follow-up period was 16.3 months and the median overall survival (OS) was 17.5 months. The actuarial survival rates at the 1-, 3-, and 5-year OS were 72.1%, 21.0%, and 9.0%, respectively. The median progression-free survival (PFS) was 10.1 months, and the actuarial PFS at 1-, 3-, and 5-year PFS were 42.2%, 13.0%, and 7.8%, respectively. The patients who received GTR showed a significantly longer OS and PFS than those who received STR, PR, or biopsy alone, regardless of the methylation status of the MGMT promoter. Patients with a methylated MGMT promoter also showed a significantly longer OS and PFS than those with an unmethylated MGMT promoter. Patients who received more than six cycles of adjuvant TMZ had a longer OS and PFS than those who received six or fewer cycles. Hematologic toxicity of grade 3 or 4 was observed in 8.4% of patients during the CCRT period and in 10.2% during the adjuvant TMZ period. Patients treated with CCRT followed by adjuvant TMZ had more favorable survival rates and tolerable toxicity than those who did not undergo this treatment.

  14. Palliative chemotherapy with gemcitabine, paclitaxel, and cisplatin as first-line treatment following gemcitabine monotherapy for patients with transitional cell carcinoma of the urothelium.

    PubMed

    Ecke, T H; Gerullis, H; Bartel, P; Koch, S; Ruttloff, J

    2009-03-01

    Chemotherapeutic agents are active in transitional cell cancer of the urothelium, and combinations have shown promising results. The objective of this study was to evaluate the palliative chemotherapy with gemcitabine, paclitaxel, and cisplatin for transitional cell carcinoma. Thirty-four patients with advanced transitional cell carcinoma of the urothelium were treated between 2000 and 2007. All patients received chemotherapy with intravenous gemcitabine at a dose of 1000 mg/m2 on days I and VIII, intravenous paclitaxel at a dose of 80 mg/m2 on days I and VIII, and intravenous cisplatin at a dose of 50 mg/m2 on day II. Treatment courses were repeated every 21 days. After completion of four to six courses in this regimen an application of intravenous gemcitabine at a dose of 1000 mg/m2 followed repeating every 28 days. Twelve patients (35.3%) had 1 visceral sites of metastases. Twenty two patients (64.7%) had achieved objective responses to treatment (29.4% complete responses). The median actuarial survival was 18.5 months, and the actuarial one-year and two-year survival rates were 56% and 26% respectively. After a median follow-up of 16.3 months, 18 patients remained alive. The median progression-free survival was 7 months. Median survival time for patients with ECOG status 0, 1, and 2 was 45, 12, and 10.5 months respectively. Grade 3-4 neutropenia occurred in 41.2% of patients. The combination of gemcitabine, paclitaxel, and cisplatin is a highly effective and tolerable regimen for patients with advanced transitional cell carcinoma of the urothelium. This treatment should be considered as a suitable option that deserves further prospective evaluation. ECOG performance status and visceral metastases are important predictive factors for survival.

  15. Study design and data analysis considerations for the discovery of prognostic molecular biomarkers: a case study of progression free survival in advanced serous ovarian cancer.

    PubMed

    Qin, Li-Xuan; Levine, Douglas A

    2016-06-10

    Accurate discovery of molecular biomarkers that are prognostic of a clinical outcome is an important yet challenging task, partly due to the combination of the typically weak genomic signal for a clinical outcome and the frequently strong noise due to microarray handling effects. Effective strategies to resolve this challenge are in dire need. We set out to assess the use of careful study design and data normalization for the discovery of prognostic molecular biomarkers. Taking progression free survival in advanced serous ovarian cancer as an example, we conducted empirical analysis on two sets of microRNA arrays for the same set of tumor samples: arrays in one set were collected using careful study design (that is, uniform handling and randomized array-to-sample assignment) and arrays in the other set were not. We found that (1) handling effects can confound the clinical outcome under study as a result of chance even with randomization, (2) the level of confounding handling effects can be reduced by data normalization, and (3) good study design cannot be replaced by post-hoc normalization. In addition, we provided a practical approach to define positive and negative control markers for detecting handling effects and assessing the performance of a normalization method. Our work showcased the difficulty of finding prognostic biomarkers for a clinical outcome of weak genomic signals, illustrated the benefits of careful study design and data normalization, and provided a practical approach to identify handling effects and select a beneficial normalization method. Our work calls for careful study design and data analysis for the discovery of robust and translatable molecular biomarkers.

  16. Losartan Slows Pancreatic Tumor Progression and Extends Survival of SPARC-Null Mice by Abrogating Aberrant TGFβ Activation

    PubMed Central

    Arnold, Shanna A.; Rivera, Lee B.; Carbon, Juliet G.; Toombs, Jason E.; Chang, Chi-Lun; Bradshaw, Amy D.; Brekken, Rolf A.

    2012-01-01

    Pancreatic adenocarcinoma, a desmoplastic disease, is the fourth leading cause of cancer-related death in the Western world due, in large part, to locally invasive primary tumor growth and ensuing metastasis. SPARC is a matricellular protein that governs extracellular matrix (ECM) deposition and maturation during tissue remodeling, particularly, during wound healing and tumorigenesis. In the present study, we sought to determine the mechanism by which lack of host SPARC alters the tumor microenvironment and enhances invasion and metastasis of an orthotopic model of pancreatic cancer. We identified that levels of active TGFβ1 were increased significantly in tumors grown in SPARC-null mice. TGFβ1 contributes to many aspects of tumor development including metastasis, endothelial cell permeability, inflammation and fibrosis, all of which are altered in the absence of stromal-derived SPARC. Given these results, we performed a survival study to assess the contribution of increased TGFβ1 activity to tumor progression in SPARC-null mice using losartan, an angiotensin II type 1 receptor antagonist that diminishes TGFβ1 expression and activation in vivo. Tumors grown in SPARC-null mice progressed more quickly than those grown in wild-type littermates leading to a significant reduction in median survival. However, median survival of SPARC-null animals treated with losartan was extended to that of losartan-treated wild-type controls. In addition, losartan abrogated TGFβ induced gene expression, reduced local invasion and metastasis, decreased vascular permeability and altered the immune profile of tumors grown in SPARC-null mice. These data support the concept that aberrant TGFβ1-activation in the absence of host SPARC contributes significantly to tumor progression and suggests that SPARC, by controlling ECM deposition and maturation, can regulate TGFβ availability and activation. PMID:22348081

  17. 77 FR 69850 - Medicare Program; Medicare Part B Monthly Actuarial Rates, Premium Rate, and Annual Deductible...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-21

    ... percent reserve has been the normal target used to calculate the Part B premium. In view of the strong... 0938-AR16 Medicare Program; Medicare Part B Monthly Actuarial Rates, Premium Rate, and Annual...

  18. Detection and prognostic value of recurrent exportin 1 mutations in tumor and cell-free circulating DNA of patients with classical Hodgkin lymphoma.

    PubMed

    Camus, Vincent; Stamatoullas, Aspasia; Mareschal, Sylvain; Viailly, Pierre-Julien; Sarafan-Vasseur, Nasrin; Bohers, Elodie; Dubois, Sydney; Picquenot, Jean Michel; Ruminy, Philippe; Maingonnat, Catherine; Bertrand, Philippe; Cornic, Marie; Tallon-Simon, Valérie; Becker, Stéphanie; Veresezan, Liana; Frebourg, Thierry; Vera, Pierre; Bastard, Christian; Tilly, Hervé; Jardin, Fabrice

    2016-09-01

    Classical Hodgkin lymphoma is one of the most common lymphomas and shares clinical and genetic features with primary mediastinal B-cell lymphoma. In this retrospective study, we analyzed the recurrent hotspot mutation of the exportin 1 (XPO1, p.E571K) gene, previously identified in primary mediastinal B-cell lymphoma, in biopsies and plasma circulating cell-free DNA from patients with classical Hodgkin lymphoma using a highly sensitive digital PCR technique. A total of 94 patients were included in the present study. This widely expressed XPO1 E571K mutation is present in one quarter of classical Hodgkin lymphoma patients (24.2%). Mutated and wild-type classical Hodgkin lymphomas were similar regarding the main clinical features. Patients with a detectable XPO1 mutation at the end of treatment displayed a tendency toward shorter progression-free survival, as compared to patients with undetectable mutation in plasma cell-free DNA (2-year progression-free survival: 57.1%, 95% confidence interval: 30.1-100% versus 2-year progression-free survival: 90.5%, 95% confidence interval: 78.8-100%, respectively, P=0.0601). To conclude, the detection of the XPO1 E571K mutation in biopsy and plasma cell-free DNA by digital PCR may be used as a novel biomarker in classical Hodgkin lymphoma for both diagnosis and minimal residual disease, and pinpoints a crucial role of XPO1 in classical Hodgkin lymphoma pathogenesis. The detection of somatic mutation in the plasma cell-free DNA of patients represents a major technological advance in the context of liquid biopsies and noninvasive management of classical Hodgkin lymphoma. Copyright© Ferrata Storti Foundation.

  19. Long-Term Disease-Free Survival of Non-Metastatic Breast Cancer Patients in Iran: A Survival Model with Competing Risks Taking Cure Fraction and Frailty into Account

    PubMed

    Ghavami, Vahid; Mahmoudi, Mahmood; Rahimi Foroushani, Abbas; Baghishani, Hossein; Homaei Shandiz, Fatemeh; Yaseri, Mehdi

    2017-10-26

    Introduction: Survival modeling is a very important tool to detect risk factors and provide a basis for health care planning. However, cancer data may have properties leading to distorted results with routine methods. Therefore, this study aimed to cover specific factors (competing risk, cure fraction and heterogeneity) with a real dataset of Iranian breast cancer patients using a competing risk-cure-frailty model. Materials and methods: For this historical cohort study, information for 550 Iranian breast cancer patients who underwent surgery for tumor removal from 2001 to 2007 and were followed up to March 2017, was analyzed using R 3.2 software. Results: In contrast to T-stage and N-stage, hormone receptor status did not have any significant effect on the cure fraction (long-term disease-free survival). However, T-stage, N-stage and hormone receptor status all had a significant effect on short-term disease-free survival so that the hazard of loco-regional relapse or distant metastasis in cases positive for a hormone receptor was only 0.3 times that for their negative hormone receptor counterparts. The likelihood of locoregional relapse in the first quartile of follow up was nearly twice that of other quartiles. The least cumulative incidence of time to locoregional relapse was for cases with a positive hormone receptor, low N stage and low T stage. The effect of frailty term was significant in this study and a model with frailty appeared more appropriate than a model without, based on the Akaike information criterion (AIC); values for the frailty model and one without the frailty parameter were 1370.39 and 1381.46, respectively. Conclusions: The data from this study indicate ae necessity to consider competing risk, cure fraction and heterogeneity in survival modeling. The competing risk-cure-frailty model can cover complex situations with survival data. Creative Commons Attribution License

  20. Potential surrogate endpoints for overall survival in locoregionally advanced nasopharyngeal carcinoma: an analysis of a phase III randomized trial

    PubMed Central

    Chen, Yu-Pei; Chen, Yong; Zhang, Wen-Na; Liang, Shao-Bo; Zong, Jing-Feng; Chen, Lei; Mao, Yan-Ping; Tang, Ling-Long; Li, Wen-Fei; Liu, Xu; Guo, Ying; Lin, Ai-Hua; Liu, Meng-Zhong; Sun, Ying; Ma, Jun

    2015-01-01

    The gold standard endpoint in trials of locoregionally advanced nasopharyngeal carcinoma (NPC) is overall survival (OS). Using data from a phase III randomized trial, we evaluated whether progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) or locoregional failure-free survival (LR-FFS) could be reliable surrogate endpoints for OS. Between July 2002 and September 2005, 316 eligible patients with stage III-IVB NPC were randomly assigned to receive either radiotherapy alone or chemoradiotherapy. 2- and 3-year PFS, FFS, D-FFS, and LR-FFS were tested as surrogate endpoints for 5-year OS using Prentice’s four criteria. The Spearman’s rank correlation coefficient was calculated to assess the strength of the associations. After a median follow-up time of 5.8 years, 2- and 3-year D-FFS and LR-FFS were not significantly different between treatment arms, in rejection of Prentice’s second criterion. Being consistent with all Prentice’s criteria, 2- and 3-year PFS and FFS were valid surrogate endpoints for 5-year OS; the rank correlation coefficient was highest (0.84) between 3-year PFS and 5-year OS. In conclusion, PFS and FFS at 2 and 3 years may be candidate surrogate endpoints for OS at 5 years; 3-year PFS may be more appropriate for early assessment of long-term survival. PMID:26219568

  1. Potential surrogate endpoints for overall survival in locoregionally advanced nasopharyngeal carcinoma: an analysis of a phase III randomized trial.

    PubMed

    Chen, Yu-Pei; Chen, Yong; Zhang, Wen-Na; Liang, Shao-Bo; Zong, Jing-Feng; Chen, Lei; Mao, Yan-Ping; Tang, Ling-Long; Li, Wen-Fei; Liu, Xu; Guo, Ying; Lin, Ai-Hua; Liu, Meng-Zhong; Sun, Ying; Ma, Jun

    2015-07-29

    The gold standard endpoint in trials of locoregionally advanced nasopharyngeal carcinoma (NPC) is overall survival (OS). Using data from a phase III randomized trial, we evaluated whether progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) or locoregional failure-free survival (LR-FFS) could be reliable surrogate endpoints for OS. Between July 2002 and September 2005, 316 eligible patients with stage III-IVB NPC were randomly assigned to receive either radiotherapy alone or chemoradiotherapy. 2- and 3-year PFS, FFS, D-FFS, and LR-FFS were tested as surrogate endpoints for 5-year OS using Prentice's four criteria. The Spearman's rank correlation coefficient was calculated to assess the strength of the associations. After a median follow-up time of 5.8 years, 2- and 3-year D-FFS and LR-FFS were not significantly different between treatment arms, in rejection of Prentice's second criterion. Being consistent with all Prentice's criteria, 2- and 3-year PFS and FFS were valid surrogate endpoints for 5-year OS; the rank correlation coefficient was highest (0.84) between 3-year PFS and 5-year OS. In conclusion, PFS and FFS at 2 and 3 years may be candidate surrogate endpoints for OS at 5 years; 3-year PFS may be more appropriate for early assessment of long-term survival.

  2. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710

    PubMed Central

    Moser, Barry; Stock, Wendy; Gallagher, Robert E.; Willman, Cheryl L.; Stone, Richard M.; Rowe, Jacob M.; Coutre, Steven; Feusner, James H.; Gregory, John; Couban, Stephen; Appelbaum, Frederick R.; Tallman, Martin S.; Larson, Richard A.

    2010-01-01

    Arsenic trioxide (As2O3) is a highly effective treatment for patients with relapsed acute promyelocytic leukemia (APL); its role as consolidation treatment for patients in first remission has not been defined. We randomized 481 patients (age ≥ 15 years) with untreated APL to either a standard induction regimen of tretinoin, cytarabine, and daunorubicin, followed by 2 courses of consolidation therapy with tretinoin plus daunorubicin, or to the same induction and consolidation regimen plus two 25-day courses of As2O3 consolidation immediately after induction. After consolidation, patients were randomly assigned to one year of maintenance therapy with either tretinoin alone or in combination with methotrexate and mercaptopurine. Ninety percent of patients on each arm achieved remission and were eligible to receive their assigned consolidation therapy. Event-free survival, the primary end point, was significantly better for patients assigned to receive As2O3 consolidation, 80% compared with 63% at 3 years (stratified log-rank test, P < .0001). Survival, a secondary end point, was better in the As2O3 arm, 86% compared with 81% at 3 years (P = .059). Disease-free survival, a secondary end point, was significantly better in the As2O3 arm, 90% compared with 70% at 3 years (P < .0001). The addition of As2O3 consolidation to standard induction and consolidation therapy significantly improves event-free and disease-free survival in adults with newly diagnosed APL. This trial was registered at clinicaltrials.gov (NCT00003934). PMID:20705755

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

    PubMed

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

    2014-08-01

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

  4. MGMT expression levels predict disease stabilisation, progression-free and overall survival in patients with advanced melanomas treated with DTIC.

    PubMed

    Busch, Christian; Geisler, Jürgen; Lillehaug, Johan R; Lønning, Per Eystein

    2010-07-01

    Metastatic melanoma responds poorly to systemic treatment. We report the results of a prospective single institution study evaluating O(6)-methylguanine-DNA methyltransferase (MGMT) status as a potential predictive and/or prognostic marker among patients treated with dacarbazine (DTIC) 800-1000 mg/m(2) monotherapy administered as a 3-weekly schedule for advanced malignant melanomas. The study was approved by the Regional Ethical Committee. Surgical biopsies from metastatic or loco-regional deposits obtained prior to DTIC treatment were snap-frozen immediately upon removal and stored in liquid nitrogen up to processing. Median time from enrolment to end of follow-up was 67 months. MGMT expression levels evaluated by qRT-PCR correlated significantly to DTIC benefit (CR/PR/SD; p=0.005), time to progression (TTP) (p=0.005) and overall survival (OS) (p=0.003). MGMT expression also correlated to Breslow thickness in the primary tumour (p=0.014). While MGMT promoter hypermethylation correlated to MGMT expression, MGMT promoter hypermethylation did not correlate to treatment benefit, TTP or OS, suggesting that other factors may be critical in determining MGMT expression levels in melanomas. In a Cox proportional regression analysis, serum lactate dehydrogenase (LDH, p<0.001), MGMT expression (p=0.022) and p16(INK4a) expression (p=0.037) independently predicted OS, while TTP correlated to DTIC benefit after 6 weeks only (p=0.001). Our data reveal MGMT expression levels to be associated with disease stabilisation and prognosis in patients receiving DTIC monotherapy for advanced melanoma. The role of MGMT expression as a predictor to DTIC sensitivity versus a general prognostic factor in advanced melanomas warrants further evaluation. Copyright 2010 Elsevier Ltd. All rights reserved.

  5. 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

    PubMed Central

    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

  6. Surrogate endpoints for overall survival in advanced non-small-cell lung cancer patients with mutations of the epidermal growth factor receptor gene.

    PubMed

    Yoshino, Reiko; Imai, Hisao; Mori, Keita; Takei, Kousuke; Tomizawa, Mai; Kaira, Kyoichi; Yoshii, Akihiro; Tomizawa, Yoshio; Saito, Ryusei; Yamada, Masanobu

    2014-09-01

    Subsequent therapies confound the ability to discern the effect of first-line chemotherapy on overall survival (OS). We investigated whether progression-free survival (PFS), post-progression survival (PPS) and tumor response were valid surrogate endpoints for OS following first-line chemotherapy in individual patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive epidermal growth factor receptor gene mutations. We retrospectively analyzed 35 patients with advanced NSCLC treated with first-line gefitinib. The associations of PFS, PPS and tumor response with OS were analyzed. PPS was found to be strongly correlated with OS, unlike PFS and tumor shrinkage. The factors significantly associated with PPS were performance status (PS) after first-line treatment, best response to second-line treatment and number of regimens used after disease progression. PPS may be a surrogate for OS in this patient population and further therapy after disease progression following first-line chemotherapy may significantly affect OS. However, a larger study is required to validate these results.

  7. Hepatic retransplantation in New England--a regional experience and survival model.

    PubMed

    Powelson, J A; Cosimi, A B; Lewis, W D; Rohrer, R J; Freeman, R B; Vacanti, J P; Jonas, M; Lorber, M I; Marks, W H; Bradley, J

    1993-04-01

    Hepatic retransplantation (reTx) offers the only alternative to death for patients who have failed primary hepatic transplantation (PTx). Assuming a finite number of donor organs, reTx also denies the chance of survival for some patients awaiting PTx. The impact of reTx on overall survival (i.e., the survival of all candidates for transplantation) must therefore be clarified. Between 1983 and 1991, 651 patients from the New England Organ Bank underwent liver transplantation, and 73 reTx were performed in 71 patients (11% reTx rate). The 1-year actuarial survival for reTx (48%) was significantly less than for PTx (70%, P < 0.05). This survival varied, dependent on the interval of time following PTx in which the reTx was performed (0-3 days, 57% survival; 4-30 days, 24%; 30-365 days, 54%; and > 365 days, 83%). Patients on the regional waiting list had an 18% mortality rate while awaiting transplantation. These results were incorporated into a mathematical model describing survival as a function of reTx rate, assuming a limited supply of donor livers. ReTx improves the 1-year survival rate for patients undergoing PTx but decreases overall survival (survival of all candidates) for liver transplantation. In the current era of persistently insufficient donor numbers, strategies based on minimizing the use of reTx, especially in the case of patients in whom chances of success are minimal, will result in the best overall rate of patient survival.

  8. [Liver and lung metastases of colorectal cancer. Long-term survival and prognostic factors].

    PubMed

    Sponholz, S; Bölükbas, S; Schirren, M; Oguzhan, S; Kudelin, N; Schirren, J

    2016-02-01

    The resection of liver and lung metastases from colorectal cancer has not yet been completely investigated. The aim of this study was to investigate the overall survival and prognostic factors for patients with liver and lung metastases from colorectal cancer. A retrospective review of a prospective database of 52 patients with liver and lung metastases from colorectal cancer, undergoing metastasectomy with curative intent from 1999-2009 at a single institution was carried out. The mean overall survival (OS) was 64 months. For synchronous liver and lung metastases the mean overall survival was 63 months (5-year survival 54 %) and for metachronous liver and lung metastases 74 months (5-year survival 58 %, p = 0.451). A poor prognostic outcome was observed in cases of localization of the primary tumor in the rectum (OS 81 vs. 38 months, p = 0.004), with multiple lung metastases (≥ 2 metastases, OS 74 vs. 59 months, p = 0.032) and with disease progression after premetastasectomy chemotherapy (OS 74 vs. 63 vs. 15 months, p < 0.001). No influence on overall survival was detected for bilateral lung metastases, thoracic lymph node metastases, disease recurrence and disease-free interval < 36 months. Metastasectomy for liver and lung metastases of colorectal cancer is associated with a good overall survival in selected cases. Patients with liver and lung metastases should not be routinely excluded from metastasectomy and patients with thoracic lymph node metastases should also not be routinely excluded. Negative prognostic factors for survival are localization of the tumor in the rectum, multiple metastases and disease progression after premetastasectomy chemotherapy. Patients with disease progression after premetastasectomy chemotherapy should be excluded from metastasectomy.

  9. A clinical study of 407 cases of nasopharyngeal carcinoma in Hong Kong

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Teo, P.; Tsao, S.Y.; Shiu, W.

    Four hundred and seven cases of nasopharyngeal carcinoma were analyzed retrospectively; 403/407 were evaluable for recurrence and survival. Parapharyngeal boost significantly decreased local recurrences in parapharyngeal diseases without base of skull involvement (T2p), but not with base of skull involvement (T3p). Enhanced local control of T2p with boost was significant without neoadjuvant chemotherapy. Tumors localized within the nasopharynx (T1) and tumors with nasal involvement (T2n) suffering from local persistences after external radiation therapy were treated with an intracavitary afterloading method. They had survival and recurrence rates comparable to complete responders to external radiation therapy. Patients with bulky cervical nodes (maximalmore » diameter greater than or equal to 4 cm, N1-N3), treated with neoadjuvant chemotherapy with cis-diamminedichloroplatinum II and 5-fluorouracil, had a regional failure rate, distant metastasis rate, actuarial survival rate, and disease-free survival rate comparable to those with smaller nodes treated with external radiation therapy alone. A simple modification of the Ho's classification by regrouping the T-stages into 'early T-stages' and 'advanced T-stages' and by combining the N1 and the N2 has greatly increased the power of the system in predicting local recurrence and distant metastasis, respectively. There was an overall improvement of the actuarial survival rate and disease-free survival rate over the historical control, and its significance is discussed.« less

  10. Survival | Cancer Trends Progress Report

    Cancer.gov

    The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

  11. A mathematical proof and example that Bayes's Theorem is fundamental to actuarial estimates of sexual recidivism risk.

    PubMed

    Donaldson, Theodore; Wollert, Richard

    2008-06-01

    Expert witnesses in sexually violent predator (SVP) cases often rely on actuarial instruments to make risk determinations. Many questions surround their use, however. Bayes's Theorem holds much promise for addressing these questions. Some experts nonetheless claim that Bayesian analyses are inadmissible in SVP cases because they are not accepted by the relevant scientific community. This position is illogical because Bayes's Theorem is simply a probabilistic restatement of the way that frequency data are combined to arrive at whatever recidivism rates are paired with each test score in an actuarial table. This article presents a mathematical proof and example validating this assertion. The advantages and implications of a logic model that combines Bayes's Theorem and the null hypothesis are also discussed.

  12. Cerebellar medulloblastoma: the importance of posterior fossa dose to survival and patterns of failure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Silverman, C.L.; Simpson, J.R.

    1982-11-01

    Fifty patients with biopsy-proven cerebellar medulloblastoma were retrospectively analyzed for prognostic factors, survival and patterns of failure. Five- and ten-year actuarial survivals for the entire group were 51% and 42%. Survival and local control were significantly better for the 21 patients who received doses greater than 5000 rad to the posterior fossa (85% and 80% respectively) than for the remaining patients (38% and 38%, respectively). Significant prognostic factors included achievement of local control in the posterior fossa (p = .0001) and dose to the posterior fossa (p = .0005). Sex, age, duration of symptoms, extent of surgery and initial T-stagemore » of disease were not significant. Posterior fossa was the predominant site of failure (71% of failures), but 10% of patients failed in the cerebrum and 12% outside the CNS. This experience confirms that survival rates of 70-80% are achievable with current treatment policies but accurate and consistent dose delivery to the posterior fossa is essential.« less

  13. Cerebellar medulloblastoma: the importance of posterior fossa dose to survival and patterns of failure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Silverman, C.L.; Simpson, J.R.

    1982-11-01

    Fifty patients with biopsy-proven cerebellar medulloblastoma were retrospectively analyzed for prognostic factors, survival and patterns of failure. Five- and ten-year actuarial survivals for the entire group were 51% and 42%. Survival and local control were significantly better for the 21 patients who received doses greater that 5000 rad to the posterior fossa (85% and 80% respectively) than for the remaining patients (38% and 38%, respectively). Significant prognostic factors included achievement of local control in the posterior fossa (p = .0001) and dose to the posterior fossa (p = .0005). Sex, age, duration of symptoms, extent of surgery and initial T-stagemore » of disease were not significant. Posterior fossa was the predominant site of failure (71% of failures), but 10% of patients failed in the cerebrum and 12% outside the CNS. This experience confirms that survival rates of 70-80% are achievable with current treatment policies but accurate and consistent dose delivery to the posterior fossa is essential.« less

  14. Results and survival after photodynamic therapy in early-stage esophageal carcinoma

    NASA Astrophysics Data System (ADS)

    Spinelli, Pasquale; Mancini, Andrea; Dal Fante, Marco; Meroni, Emmanuele; Jasinskas, Algirdas

    1996-01-01

    From January 1985 to December 1994, 23 early stage carcinomas of the esophagus were treated by photodynamic therapy in 21 patients. The stage of the tumors was assessed by esophagoscopy with multiple biopsies, CT scan and, from June 1991, also by endoscopic ultrasonography: 7 lesions were classified as carcinoma in situ (Tis) and 16 as invasive (T1). The photosensitizers used for PDT were hematoporphyrin derivative 3 mg/kg in 4 patients and dihematoporphyrin ether 2 mg/kg in 17. Light irradiation was performed using an Argon-dye laser system at a wavelength of 630 nm with an average energy of 50 J/cm2 and 70 J/cm2 for the treatment of Tis and T1, respectively. A complete response was achieved in 17/23 (74%) tumors, 15/21 (71%) patients. In the follow-up period from 6 to 78 months (median 36 months) 3 recurrences occurred 6, 12, and 14 months after PDT, respectively. Seven patients died due to concomitant diseases, not related to tumor progression. The actuarial survival rate was 95%, 75% and 37% at 1, 3, and 5 years, respectively. Complications included 1 case of sunburn and 2 cases of esophageal stenosis at the treatment site, that gradually responded to endoscopic bougienage.

  15. Prognostic significance of electrical alternans versus signal averaged electrocardiography in predicting the outcome of electrophysiological testing and arrhythmia-free survival

    NASA Technical Reports Server (NTRS)

    Armoundas, A. A.; Rosenbaum, D. S.; Ruskin, J. N.; Garan, H.; Cohen, R. J.

    1998-01-01

    OBJECTIVE: To investigate the accuracy of signal averaged electrocardiography (SAECG) and measurement of microvolt level T wave alternans as predictors of susceptibility to ventricular arrhythmias. DESIGN: Analysis of new data from a previously published prospective investigation. SETTING: Electrophysiology laboratory of a major referral hospital. PATIENTS AND INTERVENTIONS: 43 patients, not on class I or class III antiarrhythmic drug treatment, undergoing invasive electrophysiological testing had SAECG and T wave alternans measurements. The SAECG was considered positive in the presence of one (SAECG-I) or two (SAECG-II) of three standard criteria. T wave alternans was considered positive if the alternans ratio exceeded 3.0. MAIN OUTCOME MEASURES: Inducibility of sustained ventricular tachycardia or fibrillation during electrophysiological testing, and 20 month arrhythmia-free survival. RESULTS: The accuracy of T wave alternans in predicting the outcome of electrophysiological testing was 84% (p < 0.0001). Neither SAECG-I (accuracy 60%; p < 0.29) nor SAECG-II (accuracy 71%; p < 0.10) was a statistically significant predictor of electrophysiological testing. SAECG, T wave alternans, electrophysiological testing, and follow up data were available in 36 patients while not on class I or III antiarrhythmic agents. The accuracy of T wave alternans in predicting the outcome of arrhythmia-free survival was 86% (p < 0.030). Neither SAECG-I (accuracy 65%; p < 0.21) nor SAECG-II (accuracy 71%; p < 0.48) was a statistically significant predictor of arrhythmia-free survival. CONCLUSIONS: T wave alternans was a highly significant predictor of the outcome of electrophysiological testing and arrhythmia-free survival, while SAECG was not a statistically significant predictor. Although these results need to be confirmed in prospective clinical studies, they suggest that T wave alternans may serve as a non-invasive probe for screening high risk populations for malignant ventricular

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

    PubMed

    Brenner, Hermann; Jansen, Lina

    2016-02-01

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

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

    PubMed Central

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

    2014-01-01

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

  18. Association between bacterial survival and free chlorine concentration during commercial fresh-cut produce wash operation.

    PubMed

    Luo, Yaguang; Zhou, Bin; Van Haute, Sam; Nou, Xiangwu; Zhang, Boce; Teng, Zi; Turner, Ellen R; Wang, Qin; Millner, Patricia D

    2018-04-01

    Determining the minimal effective free chlorine (FC) concentration for preventing pathogen survival and cross-contamination during produce washing is critical for developing science- and risk-based food safety practices. The correlation between dynamic FC concentrations and bacterial survival was investigated during commercial washing of chopped Romaine lettuce, shredded Iceberg lettuce, and diced cabbage as pathogen inoculation study during commercial operation is not feasible. Wash water was sampled every 30 min and assayed for organic loading, FC, and total aerobic mesophilic bacteria after chlorine neutralization. Water turbidity, chemical oxygen demand, and total dissolved solids increased significantly over time, with more rapid increases in diced cabbage water. Combined chlorine increased consistently while FC fluctuated in response to rates of chlorine dosing, product loading, and water replenishment. Total bacterial survival showed a strong correlation with real-time FC concentration. Under approximately 10 mg/L, increasing FC significantly reduced the frequency and population of surviving bacteria detected. Increasing FC further resulted in the reduction of the aerobic plate count to below the detection limit (50 CFU/100 mL), except for a few sporadic positive samples with low cell counts. This study confirms that maintaining at least 10 mg/L FC in wash water strongly reduced the likelihood of bacterial survival and thus potential cross contamination of washed produce. Published by Elsevier Ltd.

  19. Two-Tiered Violence Risk Estimates: a validation study of an integrated-actuarial risk assessment instrument.

    PubMed

    Mills, Jeremy F; Gray, Andrew L

    2013-11-01

    This study is an initial validation study of the Two-Tiered Violence Risk Estimates instrument (TTV), a violence risk appraisal instrument designed to support an integrated-actuarial approach to violence risk assessment. The TTV was scored retrospectively from file information on a sample of violent offenders. Construct validity was examined by comparing the TTV with instruments that have shown utility to predict violence that were prospectively scored: The Historical-Clinical-Risk Management-20 (HCR-20) and Lifestyle Criminality Screening Form (LCSF). Predictive validity was examined through a long-term follow-up of 12.4 years with a sample of 78 incarcerated offenders. Results show the TTV to be highly correlated with the HCR-20 and LCSF. The base rate for violence over the follow-up period was 47.4%, and the TTV was equally predictive of violent recidivism relative to the HCR-20 and LCSF. Discussion centers on the advantages of an integrated-actuarial approach to the assessment of violence risk.

  20. Survival and aging of a small laboratory population of a marine mollusc, Aplysia californica.

    PubMed

    Hirsch, H R; Peretz, B

    1984-09-01

    In an investigation of the postmetamorphic survival of a population of 112 Aplysia californica, five animals died before 100 days of age and five after 200 days. The number of survivors among the 102 animals which died between 100 and 220 days declined approximately linearly with age. The median age at death was 155 days. The animals studied were those that died of natural causes within a laboratory population that was established to provide Aplysia for sacrifice in an experimental program. Actuarial separation of the former group from the latter was justified by theoretical consideration. Age-specific mortality rates were calculated from the survival data. Statistical fluctuation arising from the small size of the population was reduced by grouping the data in bins of unequal age duration. The durations were specified such that each bin contained approximately the same number of data points. An algorithm for choosing the number of data bins was based on the requirement that the precision with which the age of a group is determined should equal the precision with which the number of deaths in the groups is known. The Gompertz and power laws of mortality were fitted to the age-specific mortality-rate data with equally good results. The positive values of slope associated with the mortality-rate functions as well as the linear shape of the curve of survival provide actuarial evidence that Aplysia age. Since Aplysia grow linearly without approaching a limiting size, the existence of senescence indicates especially clearly the falsity of Bidder's hypothesis that aging is a by-product of the cessation of growth.

  1. NF-κB gene signature predicts prostate cancer progression

    PubMed Central

    Jin, Renjie; Yi, Yajun; Yull, Fiona E.; Blackwell, Timothy S.; Clark, Peter E.; Koyama, Tatsuki; Smith, Joseph A.; Matusik, Robert J.

    2014-01-01

    In many prostate cancer (PCa) patients, the cancer will be recurrent and eventually progress to lethal metastatic disease after primary treatment, such as surgery or radiation therapy. Therefore, it would be beneficial to better predict which patients with early-stage PCa would progress or recur after primary definitive treatment. In addition, many studies indicate that activation of NF-κB signaling correlates with PCa progression; however, the precise underlying mechanism is not fully understood. Our studies show that activation of NF-κB signaling via deletion of one allele of its inhibitor, IκBα, did not induce prostatic tumorigenesis in our mouse model. However, activation of NF-κB signaling did increase the rate of tumor progression in the Hi-Myc mouse PCa model when compared to Hi-Myc alone. Using the non-malignant NF-κB activated androgen depleted mouse prostate, a NF-κB Activated Recurrence Predictor 21 (NARP21) gene signature was generated. The NARP21 signature successfully predicted disease-specific survival and distant metastases-free survival in patients with PCa. This transgenic mouse model derived gene signature provides a useful and unique molecular profile for human PCa prognosis, which could be used on a prostatic biopsy to predict indolent versus aggressive behavior of the cancer after surgery. PMID:24686169

  2. Prognosis and Conditional Disease-Free Survival Among Patients With Ovarian Cancer

    PubMed Central

    Kurta, Michelle L.; Edwards, Robert P.; Moysich, Kirsten B.; McDonough, Kathleen; Bertolet, Marnie; Weissfeld, Joel L.; Catov, Janet M.; Modugno, Francesmary; Bunker, Clareann H.; Ness, Roberta B.; Diergaarde, Brenda

    2014-01-01

    Purpose Traditional disease-free survival (DFS) does not reflect changes in prognosis over time. Conditional DFS accounts for elapsed time since achieving remission and may provide more relevant prognostic information for patients and clinicians. This study aimed to estimate conditional DFS among patients with ovarian cancer and to evaluate the impact of patient characteristics. Patients and Methods Patients were recruited as part of the Hormones and Ovarian Cancer Prediction case-control study and were included in the current study if they had achieved remission after a diagnosis of cancer of the ovary, fallopian tube, or peritoneum (N = 404). Demographic and lifestyle information was collected at enrollment; disease, treatment, and outcome information was abstracted from medical records. DFS was calculated using the Kaplan-Meier method. Conditional DFS estimates were computed using cumulative DFS estimates. Results Median DFS was 2.54 years (range, 0.03-9.96 years) and 3-year DFS was 48.2%. The probability of surviving an additional 3 years without recurrence, conditioned on having already survived 1, 2, 3, 4, and 5 years after remission, was 63.8%, 80.5%, 90.4%, 97.0%, and 97.7%, respectively. Initial differences in 3-year DFS at time of remission between age, stage, histology, and grade groups decreased over time. Conclusion DFS estimates for patients with ovarian cancer improved dramatically over time, in particular among those with poorer initial prognoses. Conditional DFS is a more relevant measure of prognosis for patients with ovarian cancer who have already achieved a period of remission, and time elapsed since remission should be taken into account when making follow-up care decisions. PMID:25403208

  3. Disease-free survival in patients with non-metastatic breast cancer.

    PubMed

    Diniz, Roberta Wolp; Guerra, Maximiliano Ribeiro; Cintra, Jane Rocha Duarte; Fayer, Vívian Assis; Teixeira, Maria Teresa Bustamante

    2016-01-01

    Breast cancer is the second most common malignancy in the world and the one with highest incidence in the female population; it is also a major cause of death from cancer among women. To analyze the disease-free survival (DFS) at 5 years and prognostic factors in women with non-metastatic invasive breast cancer treated at a referral center for cancer care located in a medium-sized city in the Southeast of Brazil. Patients diagnosed with the disease between 2003 and 2005 and identified through the institution's cancer hospital records were analyzed. The follow-up of cases was carried out through hospital records, and complemented by search in the database of the Mortality Information System (SIM) as well as telephone contact. The variables analyzed were distributed in the following blocks: socio-demographic data, tumor-related characteristics, and treatment-related characteristics. Survival functions were calculated using the Kaplan-Meier method and the prognostic factors were analyzed based on Cox proportional hazard model. The study showed a DFS at 5 years of 72% (95CI 67.6-75.9). The main variables independently associated with DFS were lymph node involvement, use of hormone therapy, and education level. This study reinforces the importance of early diagnosis for DFS, pointing to the role of social aspects in this regard. The relevance of this research in the country is also highlighted, given the scarcity of studies on DFS in the Brazilian population.

  4. 76 FR 81362 - Regulations Governing the Performance of Actuarial Services Under the Employee Retirement Income...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-28

    ... Governing the Performance of Actuarial Services Under the Employee Retirement Income Security Act of 1974... regulations (TD 9517) that are the subject of this correction are under section 3042 of the Employee... EMPLOYEE RETIREMENT INCOME SECURITY ACT OF 1974 0 Paragraph 1. The authority citation for part 901...

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

    PubMed

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

    2017-10-01

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

  6. 18 years' experience with high dose rate strontium-90 brachytherapy of small to medium sized posterior uveal melanoma.

    PubMed

    van Ginderdeuren, R; van Limbergen, E; Spileers, W

    2005-10-01

    To analyse local tumour control, radiation related complications, visual acuity, enucleation rate, and survival after brachytherapy of small to medium sized choroidal melanoma (CM) with a high dose rate (HDR) strontium-90 (Sr-90) applicator. From 1983 until 2000, 98 eyes with CM were treated with Sr-90 brachytherapy. The main outcome measures were actuarial rates of the patients' survival, ocular conservation rate, tumour regression, complication rates, and preservation of visual acuity. End point rates were estimated using Kaplan-Meier analysis. The median follow up time was 6.7 years (0.5-18.8 years). Actuarial melanoma free patient survival rate was 85% (SE 4.8%) after 18 years. Actuarial rate of ocular conservation and complete tumour regression was 90% (SE 3.8%) after 15 years. In 93% local tumour control was achieved, 88% showed a stable scar. Recurrence of the tumour on the border caused enucleation of six eyes (7%). In three cases (4%) retinal detachment was the end point. No cases of optic atrophy or of sight impairing retinopathy outside the treated area were found. Actuarial rate of preservation of visual acuity of 1/10 was 65% at 5 years and 45% at 15 years of follow up (SE 5.9% and 8.8%). Sr-90 brachytherapy is as effective as iodine or ruthenium brachytherapy for small to medium sized CM but causes fewer complications. The preservation of vision is better than with all other described radioisotopes. HDR Sr-90 brachytherapy can therefore safely be recommended for small to medium sized CM.

  7. 18 Years’ experience with high dose rate strontium-90 brachytherapy of small to medium sized posterior uveal melanoma

    PubMed Central

    van Ginderdeuren, R; van Limbergen, E; Spileers, W

    2005-01-01

    Aim: To analyse local tumour control, radiation related complications, visual acuity, enucleation rate, and survival after brachytherapy of small to medium sized choroidal melanoma (CM) with a high dose rate (HDR) strontium-90 (Sr-90) applicator. Methods: From 1983 until 2000, 98 eyes with CM were treated with Sr-90 brachytherapy. The main outcome measures were actuarial rates of the patients’ survival, ocular conservation rate, tumour regression, complication rates, and preservation of visual acuity. End point rates were estimated using Kaplan-Meier analysis. Results: The median follow up time was 6.7 years (0.5–18.8 years). Actuarial melanoma free patient survival rate was 85% (SE 4.8%) after 18 years. Actuarial rate of ocular conservation and complete tumour regression was 90% (SE 3.8%) after 15 years. In 93% local tumour control was achieved, 88% showed a stable scar. Recurrence of the tumour on the border caused enucleation of six eyes (7%). In three cases (4%) retinal detachment was the end point. No cases of optic atrophy or of sight impairing retinopathy outside the treated area were found. Actuarial rate of preservation of visual acuity of 1/10 was 65% at 5 years and 45% at 15 years of follow up (SE 5.9% and 8.8%). Conclusions: Sr-90 brachytherapy is as effective as iodine or ruthenium brachytherapy for small to medium sized CM but causes fewer complications. The preservation of vision is better than with all other described radioisotopes. HDR Sr-90 brachytherapy can therefore safely be recommended for small to medium sized CM. PMID:16170122

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

    PubMed

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

    2016-03-11

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

  9. Combined-modality therapy for primary central nervous system lymphoma: Long-term data from a Phase II multicenter study (Trans-Tasman Radiation Oncology Group)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    O'Brien, Peter C.; Roos, Daniel E.; Pratt, Gary

    2006-02-01

    Purpose: To assess, in a multicenter setting, the long-term outcomes of a brief course of high-dose methotrexate followed by radiotherapy for patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Forty-six patients were entered in a Phase II protocol consisting of methotrexate (1 g/m{sup 2} on Days 1 and 8), followed by whole-brain irradiation (45-50.4 Gy). The median follow-up time was 7 years, with a minimum follow-up of 5 years. Results: The 5-year survival estimate was 37% ({+-}14%, 95% confidence interval [CI]), with progression-free survival being 36% ({+-}15%, 95% CI), and median survival 36 months. Of the originalmore » 46 patients, 10 were alive, all without evidence of disease recurrence. A total of 11 patients have developed neurotoxicity, with the actuarial risk being 30% ({+-}18%, 95% CI) at 5 years but continuing to increase. For patients aged >60 years the risk of neurotoxicity at 7 years was 58% ({+-}30%, 95% CI). Conclusion: Combined-modality therapy, based on high-dose methotrexate, results in improved survival outcomes in PCNSL. The risk of neurotoxicity for patients aged >60 years is unacceptable with this regimen, although survival outcomes for patients aged >60 years were higher than in many other series.« less

  10. Quantitative T2 mapping of recurrent glioblastoma under bevacizumab improves monitoring for non-enhancing tumor progression and predicts overall survival

    PubMed Central

    Hattingen, Elke; Jurcoane, Alina; Daneshvar, Keivan; Pilatus, Ulrich; Mittelbronn, Michel; Steinbach, Joachim P.; Bähr, Oliver

    2013-01-01

    Background Anti-angiogenic treatment in recurrent glioblastoma patients suppresses contrast enhancement and reduces vasogenic edema while non-enhancing tumor progression is common. Thus, the importance of T2-weighted imaging is increasing. We therefore quantified T2 relaxation times, which are the basis for the image contrast on T2-weighted images. Methods Conventional and quantitative MRI procedures were performed on 18 patients with recurrent glioblastoma before treatment with bevacizumab and every 8 weeks thereafter until further tumor progression. We segmented the tumor on conventional MRI into 3 subvolumes: enhancing tumor, non-enhancing tumor, and edema. Using coregistered quantitative maps, we followed changes in T2 relaxation time in each subvolume. Moreover, we generated differential T2 maps by a voxelwise subtraction using the first T2 map under bevacizumab as reference. Results Visually segmented areas of tumor and edema did not differ in T2 relaxation times. Non-enhancing tumor volume did not decrease after commencement of bevacizumab treatment but strikingly increased at progression. Differential T2 maps clearly showed non-enhancing tumor progression in previously normal brain. T2 relaxation times decreased under bevacizumab without re-increasing at tumor progression. A decrease of <26 ms in the enhancing tumor following exposure to bevacizumab was associated with longer overall survival. Conclusions Combining quantitative MRI and tumor segmentation improves monitoring of glioblastoma patients under bevacizumab. The degree of change in T2 relaxation time under bevacizumab may be an early response parameter predictive of overall survival. The sustained decrease in T2 relaxation times toward values of healthy tissue masks progressive tumor on conventional T2-weighted images. Therefore, quantitative T2 relaxation times may detect non-enhancing progression better than conventional T2-weighted imaging. PMID:23925453

  11. Cyclophosphamide's addition in relapsed/refractory multiple myeloma patients with biochemical progression during lenalidomide-dexamethasone treatment.

    PubMed

    Cesini, Laura; Siniscalchi, Agostina; Grammatico, Sara; Andriani, Alessandro; Fiorini, Alessia; De Rosa, Luca; Za, Tommaso; Rago, Angela; Caravita, Tommaso; Petrucci, Maria Teresa

    2018-05-02

    The aim of this study was to evaluate the addition of cyclophosphamide in relapsed-refractory multiple myeloma patients (RRMM) who experienced biochemical relapse or progression without CRAB, during treatment with lenalidomide and dexamethasone (Rd), to slow down the progression in active relapse. This analysis included 31 patients with RRMM treated with Rd who received cyclophosphamide (CRd) at biochemical relapse. The CRd regimen was continued until disease progression. The median number of CRd cycles administered was 8 (range: 1-35). A response was observed in 9 (29%) patients. After a median observation time of 11 months, the median overall survival (OS) from the beginning of CRd was 17.7 months. The median progression-free survival (PFS) from the beginning of CRd was 13.1 months. The addition of cyclophosphamide delays the progression in patients who present a biochemical relapse during Rd treatment. The response rate and the duration of PFS obtained with minimal toxicities and low costs induced us to setting up a randomized clinical trial. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Intensity modulated radiotherapy for elderly bladder cancer patients

    PubMed Central

    2011-01-01

    Background To review our experience and evaluate treatment planning using intensity-modulated radiotherapy (IMRT) and helical tomotherapy (HT) for the treatment of elderly patients with bladder cancer. Methods From November 2006 through November 2009, we enrolled 19 elderly patients with histologically confirmed bladder cancer, 9 in the IMRT and 10 in the HT group. The patients received 64.8 Gy to the bladder with or without concurrent chemotherapy. Conventional 4-field "box" pelvic radiation therapy (2DRT) plans were generated for comparison. Results The median patient age was 80 years old (range, 65-90 years old). The median survival was 21 months (5 to 26 months). The actuarial 2-year overall survival (OS) for the IMRT vs. the HT group was 26.3% vs .37.5%, respectively; the corresponding values for disease-free survival were 58.3% vs. 83.3%, respectively; for locoregional progression-free survival (LRPFS), the values were 87.5% vs. 83.3%, respectively; and for metastases-free survival, the values were 66.7% vs. 60.0%, respectively. The 2-year OS rates for T1, 2 vs. T3, 4 were 66.7% vs. 35.4%, respectively (p = 0.046). The 2-year OS rate was poor for those whose RT completion time greater than 8 weeks when compared with the RT completed within 8 wks (37.9% vs. 0%, p = 0.004). Conclusion IMRT and HT provide good LRPFS with tolerable toxicity for elderly patients with invasive bladder cancer. IMRT and HT dosimetry and organ sparing capability were superior to that of 2DRT, and HT provides better sparing ability than IMRT. The T category and the RT completion time influence OS rate. PMID:21679408

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

    PubMed

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

    2009-01-01

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

  14. The effect of completeness of revascularization on event-free survival at one year in the ARTS trial.

    PubMed

    van den Brand, Marcel J B M; Rensing, Benno J W M; Morel, Marie-angèle M; Foley, David P; de Valk, Vincent; Breeman, Arno; Suryapranata, Harry; Haalebos, Maximiliaan M P; Wijns, William; Wellens, Francis; Balcon, Rafael; Magee, Patrick; Ribeiro, Expedito; Buffolo, Enio; Unger, Felix; Serruys, Patrick W

    2002-02-20

    We sought to assess the relationship between completeness of revascularization and adverse events at one year in the ARTS (Arterial Revascularization Therapies Study) trial. There is uncertainty to what extent degree of completeness of revascularization, using up-to-date techniques, influences medium-term outcome. After consensus between surgeon and cardiologist regarding the potential for equivalence in the completeness of revascularization, 1,205 patients with multivessel disease were randomly assigned to either bypass surgery or stent implantation. All baseline and procedural angiograms and surgical case-record forms were centrally assessed for completeness of revascularization. Of 1,205 patients randomized, 1,172 underwent the assigned treatment. Complete data for review were available in 1,143 patients (97.5%). Complete revascularization was achieved in 84.1% of the surgically treated patients and 70.5% of the angioplasty patients (p < 0.001). After one year, the stented angioplasty patients with incomplete revascularization showed a significantly lower event-free survival than stented patients with complete revascularization (i.e., freedom from death, myocardial infarction, cerebrovascular accident and repeat revascularization) (69.4% vs. 76.6%; p < 0.05). This difference was due to a higher incidence of subsequent bypass procedures (10.0% vs. 2.0%; p < 0.05). Conversely, at one year, bypass surgery patients with incomplete revascularization showed only a marginally lower event-free survival rate than those with complete revascularization (87.8% vs. 89.9%). Complete revascularization was more frequently accomplished by bypass surgery than by stent implantation. One year after bypass, there was no significant difference in event-free survival between surgically treated patients with complete revascularization and those with incomplete revascularization, but patients randomized to stenting with incomplete revascularization had a greater need for subsequent

  15. 24-month HIV-free survival among infants born to HIV-positive women enrolled in Option B+ program in Kigali, Rwanda: The Kabeho Study.

    PubMed

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

    2017-12-01

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

  16. Are psychological measures and actuarial data equally effective in discriminating among the prison population? Analysis by crimes

    PubMed Central

    Burneo-Garcés, Carlos; Marín-Morales, Agar; Pérez-García, Miguel

    2018-01-01

    The ability of a wide range of psychological and actuarial measures to characterize crimes in the prison population has not yet been compared in a single study. Our main objective was to determine if the discriminant capacity of psychological measures (PM) and actuarial data (AD) varies according to the crime. An Ecuadorian sample of 576 men convicted of Robbery, Murder, Rape and Drug Possession crimes was evaluated through an ad hoc questionnaire, prison files and the Spanish adaptation of the Personality Assessment Inventory. Discriminant analysis was used to establish, for each crime, the discriminant capacity and the classification accuracy of a model composed of AD (socio-demographic and judicial measures) and a second model incorporating PM. The AD showed a superior discriminant capacity, whilst the contribution of both types of measures varied according to the crime. The PM generated some increase in the correct classification percentages for Murder, Rape and Drug Possession, but their contribution was zero for the crime of Robbery. Specific profiles of each crime were obtained from the strongest significant correlations between the value of each explanatory variable and the probability of belonging to the crime. The AD model is more robust when these four crimes are characterized. The contribution of AD and PM depends on the crime, and the inclusion of PM in actuarial models moderately optimizes the classification accuracy of Murder, Rape, and Drug Possession crimes. PMID:29874264

  17. Aortic elasticity indices by magnetic resonance predict progression of ascending aorta dilation.

    PubMed

    Aquaro, Giovanni Donato; Briatico Vangosa, Alessandra; Toia, Patrizia; Barison, Andrea; Ait-Ali, Lamia; Midiri, Massimo; Cotroneo, Antonio Raffaele; Emdin, Michele; Festa, Pierluigi

    2017-04-01

    Aortic distensibility and pulse-wave velocity (PWV) are under investigation as parameters by which to evaluate the indication for ascending aorta (AA) replacement. The maximum rate of systolic distension (MRSD) was proposed as a new index of aortic elasticity. The aim of this study was to assess the role of aortic elasticity parameters to predict AA growth rates in patients with AA dilation (AAD). Magnetic resonance imaging (MRI) was performed annually in 65 patients with AA dilation (median follow-up 17 months; 25-75th percentile; range 12-30 months). A significant increase in AA diameter was defined as a ≥2-mm increase. An increase in AA diameter was found in 42 (68 %) patients (AAD+ group) and absent in 20. Median increase was 0.16 (25-75th percentile; range 0.32-0.7) mm/month. The AAD+ group had a lower MRSD (4.6 ± 2.2 vs 7.4 ± 2.0, p < 0.001) but the same PWV and distensibility. MRSD showed 93.7 % specificity and 75.6 % sensitivity for prediction of increase. Patients with MRSD ≤ 6 had lower progression-free survival times (p < 0.002). After a follow-up of 4.1 years, patients who underwent surgical therapy had lower MRSD and distensibility than others. MRSD is an index of aorta elastic properties and is a valuable predictor for progression in AAD. • MRI-derived parameters of aortic wall elasticity predict progression of ascending aorta dilation. • Maximal rate of systolic distension (MRSD) was the best predictor of progression. • Patients with MRSD ≤ 6 had lower progression-free survival (PFS) times. • Patients who underwent surgical therapy had lower MRSD and distensibility. • MRI-derived parameters identify patients with fast progression of Ascending Aorta Dilation.

  18. Single center experience of aortic bypass graft for aortic arch obstruction in children.

    PubMed

    Shinkawa, Takeshi; Chipman, Carl; Holloway, Jessica; Tang, Xinyu; Gossett, Jeffrey M; Imamura, Michiaki

    2017-01-01

    The purpose of this study is to access the outcomes of aortic bypass graft placement in children. This is a retrospective review of all children having aortic bypass graft placement for aortic arch obstruction for the first time between 1982 and 2013 at a single institution. The actuarial survival and the freedom from aortic arch reoperation were calculated and compared between the groups. Seventy consecutive children underwent aortic bypass graft placements. The median age and body weight at the operation were 14 days and 3.6 kg. There were 7 early deaths, 6 late deaths, and 7 heart transplants during the median follow-up of 10.8 years (0.0-31.5 years). The actuarial transplant free survival was 64.7 % at 20 years and the freedom from aortic arch reoperation was 50.5 % at 10 years. Between the children younger than 1 year old and older than 1 year old, there were significant differences in actuarial transplant free survival (56.4 vs. 100 % at 15 years, p = 0.0042) and in the freedom from aortic arch reoperation (18.7 vs. 100 % at 10 years, p < 0.001). The children who received aortic bypass graft larger than 16 mm in size had no aortic arch reoperation at 15 years. The aortic bypass graft placement for aortic arch obstruction can be done with low mortality and morbidity for children who can receive bypass graft larger than 16 mm in size. However, it should be avoided for the neonates and infants except selected situations.

  19. Clinical Outcomes and Survival Following Treatment of Metastatic Castrate-Refractory Prostate Cancer With Docetaxel Alone or With Strontium-89, Zoledronic Acid, or Both: The TRAPEZE Randomized Clinical Trial.

    PubMed

    James, Nicholas D; Pirrie, Sarah J; Pope, Ann M; Barton, Darren; Andronis, Lazaros; Goranitis, Ilias; Collins, Stuart; Daunton, Adam; McLaren, Duncan; O'Sullivan, Joe; Parker, Christopher; Porfiri, Emilio; Staffurth, John; Stanley, Andrew; Wylie, James; Beesley, Sharon; Birtle, Alison; Brown, Janet; Chakraborti, Prabir; Hussain, Syed; Russell, Martin; Billingham, Lucinda J

    2016-04-01

    Bony metastatic castrate-refractory prostate cancer (CRPC) has a poor prognosis and high morbidity. Zoledronic acid (ZA) is commonly combined with docetaxel in practice but lacks evidence that combining is effective, and strontium-89 (Sr89) is generally used palliatively in patients unfit for chemotherapy. Phase 2 analysis of the TRAPEZE trial confirmed combining the agents was safe and feasible, and the objectives of phase 3 include assessment of the treatments on survival. To determine clinical effectiveness and cost-effectiveness of combining docetaxel, ZA, and Sr89, all having palliative benefits and used in bony metastatic CRPC to control bone symptoms and, for docetaxel, to prolong survival. The TRAPEZE trial is a 2 × 2 factorial trial comparing docetaxel alone or with ZA, Sr89, or both. A cohort of 757 participants were recruited between February 2005 and February 2012 from hospitals in the United Kingdom. Overall, 169 participants (45%) had received palliative radiotherapy, and the median (IQR) prostate-specific antigen level was 146 (51-354). Follow-ups were performed for at least 12 months. Up to 10 cycles of docetaxel alone; docetaxel with ZA; docetaxel with a single Sr89 dose after 6 cycles; or docetaxel with both ZA and Sr89. Primary outcomes included clinical progression-free survival (CPFS) (pain progression, skeletal-related events [SREs], or death) and cost-effectiveness. Secondary outcomes included SRE-free interval, pain progression-free interval, total SREs, and overall survival (OS). Overall, of 757 participants, 349 (46%) completed docetaxel treatment. Median (IQR) age was 68 (63-73) years. Clinical progression-free survival did not reach statistical significance for either Sr89 or ZA. Cox regression analysis adjusted for all stratification variables showed benefit of Sr89 on CPFS (hazard ratio [HR], 0.85; 95% CI, 0.73-0.99; P = .03) and confirmed no effect of ZA (HR, 0.98; 95% CI, 0.85-1.14; P = .81); ZA had a significant effect

  20. Low levels of serum n-3 polyunsaturated fatty acids are associated with worse heart failure-free survival in patients after acute myocardial infarction.

    PubMed

    Hara, Masahiko; Sakata, Yasuhiko; Nakatani, Daisaku; Suna, Shinichiro; Usami, Masaya; Matsumoto, Sen; Hamasaki, Toshimitsu; Doi, Yasuji; Nishino, Masami; Sato, Hiroshi; Kitamura, Tetsuhisa; Nanto, Shinsuke; Hori, Masatsugu; Komuro, Issei

    2013-01-01

    Intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), is associated with a lower risk of atherosclerotic cardiovascular events, particularly acute myocardial infarction (AMI). However, limited data are available regarding the association between serum n-3 PUFA levels and heart failure (HF) events in survivors of AMI. We evaluated whether serum DHA and EPA levels were associated with HF-free survival and HF hospitalization rates after AMI. A total of 712 patients were divided into 3 groups according to their tertile serum levels of DHA and EPA (Low, Middle, and High). Propensity-score-stratified Cox regression analysis revealed that DHA- and EPA-Low groups presented statistically significant worse HF-free survival (hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.03-2.72, P=0.0358, and HR 1.69, 95% CI 1.05-2.72, P=0.0280, respectively), with the EPA-Low group having a higher risk of HF hospitalization (HR 2.40, 95% CI 1.21-4.75, P=0.0097) than the DHA-Low group (HR 1.72, 95% CI 0.86-3.45, P=0.1224). The relationship between a low DHA or EPA level and decreased HF-free survival was almost common to all subgroups; however, the effect of low serum EPA on HF hospitalization was prominent in male patients, and those with low levels of high-density lipoprotein cholesterol or without statin therapy. Low levels of circulating n-3 PUFA are associated with decreased HF-free survival in post-AMI patients.

  1. Exposure to ACEI/ARB and β-Blockers Is Associated with Improved Survival and Decreased Tumor Progression and Hospitalizations in Patients with Advanced Colon Cancer1

    PubMed Central

    Engineer, Diana R; Burney, Basil O; Hayes, Teresa G; Garcia, Jose M

    2013-01-01

    BACKGROUND: Advanced colon cancer is associated with weight loss and decreased survival. Studies suggest that angiotensin and β-adrenergic blockade decrease colon cancer progression and ameliorate weight loss. This study aims to determine whether exposure to β-adrenoceptor blockers (BBs), angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) is associated with decreased mortality, tumor progression, number of hospitalizations, or weight loss in colorectal cancer. METHODS: Retrospective chart review included patients with advanced colorectal cancer. Survival, stage, hospitalization, cancer progression, cancer treatment, and body weight history were collected. RESULTS: Two hundred sixty-two of 425 new stage III to IV colorectal cancer cases reviewed met the study criteria. Those exposed to ACEI/ARB, BB, or both were more likely to have diabetes, hypertension, and stage III colorectal cancer. Adjusting for age, presence of hypertension and diabetes, and stage, ACEI/ARB + BB exposure was associated with decreased mortality compared to unexposed individuals [hazard ratio (HR) = 0.5, confidence interval (CI) = 0.29–0.85; Cox regression, P = .01]. Fewer total and cancer-related hospitalizations and decreased cancer progression in the ACEI/ARB + BB group versus the unexposed group (HR = 0.59, CI = 0.36–0.99, P = .047) were seen. Exposure did not affect weight changes; furthermore, body weight changes from both prediagnosis and at diagnosis to 6, 12, 18, and 24 months postdiagnosis predicted survival. CONCLUSIONS: We have observed an association between exposure to a combination of ACEI/ARB + BB and increased survival, decreased hospitalizations, and decreased tumor progression in advanced colorectal cancer. Future studies will be needed to replicate these results and generalize them to broader populations. Determination of causality will require a randomized controlled trial. PMID:24151534

  2. Phase II trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4(Dpc4) immunostaining with pattern of disease progression.

    PubMed

    Crane, Christopher H; Varadhachary, Gauri R; Yordy, John S; Staerkel, Gregg A; Javle, Milind M; Safran, Howard; Haque, Waqar; Hobbs, Bridgett D; Krishnan, Sunil; Fleming, Jason B; Das, Prajnan; Lee, Jeffrey E; Abbruzzese, James L; Wolff, Robert A

    2011-08-01

    This phase II trial was designed to assess the efficacy and safety of cetuximab, gemcitabine, and oxaliplatin followed by cetuximab, capecitabine, and radiation therapy in locally advanced pancreatic cancer (LAPC). Treatment-naive eligible patients (n = 69) received intravenous gemcitabine (1,000 mg/m(2)) and oxaliplatin (100 mg/m(2)) every 2 weeks for four doses, followed by radiation (50.4 Gy to the gross tumor only) with concurrent capecitabine (825 mg/m(2) twice daily on radiation treatment days). Cetuximab (500 mg/m(2)) was started on day 1 of chemotherapy and was continued every 2 weeks during chemotherapy and chemoradiotherapy. Diagnostic cytology specimens were immunostained for Smad4(Dpc4) expression. Median overall survival time was 19.2 months (95% CI, 14.2 to 24.2 months), and 1-year, 2-year, and 4-year actuarial overall survival rates were 66.0%, 25.02%, and 11.3%, respectively. Acneiform rash correlated with improved survival (P = .001), but initial CA19-9, borderline resectable initial stage, and surgical resection (n = 7) did not. The 1-year and 2-year radiographic local progression rates were 22.8% and 61.0%, respectively. The worst acute toxic effects were GI toxicity (32% and 10% for grades 2 and 3, respectively); fatigue (26% and 6% for grades 2 and 3, respectively); sensory neuropathy (9% and 1% for grades 2 and 3, respectively); and acneiform rash (54% and 3% for grades 2 and 3, respectively). Smad4(Dpc4) expression correlated with a local rather than a distant dominant pattern of disease progression (P = .016). This regimen appears effective and has acceptable toxicity. The primary end point (1-year overall survival rate > 45%) was met, with encouraging survival duration. Smad4(Dpc4) immunostaining correlated with the pattern of disease progression. Prospective validation of Smad4(Dpc4) expression in cytology specimens as a predictive biomarker is warranted and may lead to personalized treatment strategies for patients with localized

  3. 26 CFR 1.412(c)(2)-1 - Valuation of plan assets; reasonable actuarial valuation methods.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... market value by making use of the— (i) Fair market value (determined under paragraph (c) of this section... requirements of section 412(c)(2)(A) solely on the basis of their fair market value (under paragraph (c) of... reasonble actuarial valuation methods designed to mitigate short-run changes in the fair market value of...

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

    PubMed

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

    2015-10-20

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

  5. Restoring platinum sensitivity in recurrent ovarian cancer by extending the platinum-free interval: Myth or reality?

    PubMed

    Tomao, Federica; D'Incalci, Maurizio; Biagioli, Elena; Peccatori, Fedro A; Colombo, Nicoletta

    2017-09-15

    The platinum-free interval is the most important predictive factor of a response to subsequent lines of chemotherapy and the most important prognostic factor for progression-free and overall survival in patients with recurrent epithelial ovarian cancer. A nonplatinum regimen is generally considered the most appropriate approach when the disease recurs very early after the end of chemotherapy, whereas platinum-based chemotherapy is usually adopted when the platinum-free interval exceeds 12 months. However, the therapeutic management of patients with intermediate sensitivity (ie, when the relapse occurs between 6 and 12 months) remains debatable. Preclinical and clinical data suggest that the extension of platinum-free interval (using a nonplatinum-based regimen) might restore platinum sensitivity, thus allowing survival improvement. The objective of this review was to critically analyze preclinical and clinical evidences supporting this hypothesis. Cancer 2017;123:3450-9. © 2017 American Cancer Society. © 2017 American Cancer Society.

  6. Long-term actuarial survivorship analysis of an interspinous stabilization system

    PubMed Central

    Sénégas, Jacques; Pointillart, Vincent; Mangione, Paolo

    2007-01-01

    In 1986, an interspinous dynamic stabilization system (the prototype of the current Wallis implant) was designed to stiffen unstable operated degenerate lumbar segments with a hard interspinous blocker to limit extension and a tension band around the spinous processes to secure the implant and limit flexion. Restoring physiological mechanical conditions to the treated level(s) while preserving some intervertebral mobility was intended to treat low-back pain related to degenerative instability without increasing stress forces in the adjacent segments. The procedure was easily reversible. If low back pain persisted or recurred, the device was removed and stability was achieved using fusion. The intermediate-term results were promising, but the long-term safety and efficacy of this dynamic interspinous stabilization device has not been previously documented. We retrospectively reviewed the hospital files of all the patients (n = 241) who had this dynamic stabilization system implanted between 1987 and 1995, contacting as many as possible to determine the actuarial survivorship of the system. In this manner, 142 of the 241 patients (58.9%) were contacted by telephone. The endpoints used for the survivorship analysis were ‘any subsequent lumbar operation’ and ‘implant removal’. At 14 years follow-up, values of actuarial survivorship with 95% confidence interval were 75.9 ± 8.3 and 81.3 ± 6.8% for the endpoints ‘any subsequent lumbar operation’ and ‘implant removal’, respectively. There was no difference in survivorship of multiple-level implants with respect to single-level devices. Although the conclusions of the present study must be tempered by the 41% attrition rate, these findings support the long-term safety of this system, and possibly long-term protective action against adjacent-level degeneration by motion preservation. Outcomes at least equivalent to those of fusion were observed without the primary drawbacks of fusion. PMID:17426988

  7. Prognostic Implications of Multiplex Detection of KRAS Mutations in Cell-Free DNA from Patients with Pancreatic Ductal Adenocarcinoma.

    PubMed

    Kim, Min Kyeong; Woo, Sang Myung; Park, Boram; Yoon, Kyong-Ah; Kim, Yun-Hee; Joo, Jungnam; Lee, Woo Jin; Han, Sung-Sik; Park, Sang-Jae; Kong, Sun-Young

    2018-04-01

    Cell-free DNA (cfDNA) is known to provide potential biomarkers for predicting clinical outcome, but its value in pancreatic ductal adenocarcinoma (PDAC) has not been fully evaluated. The aim of this study was to evaluate the clinical applicability of quantitative analysis of multiplex KRAS mutations in cell-free DNA from patients with PDAC. A total of 106 patients with PDAC were enrolled in this prospective study. The concentration and fraction of KRAS mutations were determined through multiplex detection of KRAS mutations in plasma samples by use of a droplet digital PCR kit (Bio-Rad). KRAS mutations were detected in 96.1% of tissue samples. Eighty patients (80.5%) harbored KRAS mutations in cfDNA, with a median KRAS mutation concentration of 0.165 copies/μL and a median fractional abundance of 0.415%. Multivariable analyses demonstrated that the KRAS mutation concentration [hazard ratio (HR), 2.08; 95% CI, 1.20-3.63] and KRAS fraction (HR, 1.73; 95% CI, 1.02-2.95) were significant factors for progression-free survival. KRAS mutation concentration (HR, 1.97; 95% CI, 1.05-3.67) also had prognostic implications for overall survival. Subgroup analyses showed that KRAS mutation concentration and fractional abundance significantly affected progression-free survival in resectable PDAC ( P = 0.016). Moreover, when combined with the cancer biomarker CA19-9, the KRAS mutation concentration in cfDNA showed additive benefits for the prediction of overall survival. This study demonstrates that multiplex detection of KRAS mutations in plasma cfDNA is clinically relevant, providing a potential candidate biomarker for prognosis of PDAC. © 2018 American Association for Clinical Chemistry.

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

    PubMed

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

    2016-06-01

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

  9. Academic Attributes of College Freshmen that Lead to Success in Actuarial Studies in a Business College

    ERIC Educational Resources Information Center

    Smith, Richard Manning; Schumacher, Phyllis

    2006-01-01

    The authors studied beginning undergraduate actuarial concentrators in a business college. They identified four variables (math Scholastic Aptitude Test [SAT] score, verbal SAT score, percentile rank in high school graduating class, and percentage score on a college mathematics placement exam) that were available for entering college students that…

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

    PubMed

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

    2017-06-01

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

  11. Ultrasound-based follow-up does not increase survival in early-stage melanoma patients: A comparative cohort study.

    PubMed

    Ribero, S; Podlipnik, S; Osella-Abate, S; Sportoletti-Baduel, E; Manubens, E; Barreiro, A; Caliendo, V; Chavez-Bourgeois, M; Carrera, C; Cassoni, P; Malvehy, J; Fierro, M T; Puig, S

    2017-11-01

    Different protocols have been used to follow up melanoma patients in stage I-II. However, there is no consensus on the complementary tests that should be requested or the appropriate intervals between visits. Our aim is to compare an ultrasound-based follow-up with a clinical follow-up. Analysis of two prospectively collected cohorts of melanoma patients in stage IB-IIA from two tertiary referral centres in Barcelona (clinical-based follow-up [C-FU]) and Turin (ultrasound-based follow-up [US-FU]). Kaplan-Meier curves were used to evaluate distant metastases-free survival (DMFS), disease-free interval (DFI), nodal metastases-free survival (NMFS) and melanoma-specific survival (MSS). A total of 1149 patients in the American Joint Committee on Cancer stage IB and IIA were included in this study, of which 554 subjects (48%) were enrolled for a C-FU, and 595 patients (52%) received a protocolised US-FU. The median age was 53.8 years (interquartile range [IQR] 41.5-65.2) with a median follow-up time of 4.14 years (IQR 1.2-7.6). During follow-up, 69 patients (12.5%) in C-FU and 72 patients (12.1%) in US-FU developed disease progression. Median time to relapse for the first metastatic site was 2.11 years (IQR 1.14-4.04) for skin metastases, 1.32 (IQR 0.57-3.29) for lymph node metastases and 2.84 (IQR 1.32-4.60) for distant metastases. The pattern of progression and the total proportion of metastases were not significantly different (P = .44) in the two centres. No difference in DFI, DMFS, NMFS and MSS was found between the two cohorts. Ultrasound-based follow-up does not increase the survival of melanoma patients in stage IB-IIA. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  13. Regression and Sentinel Lymph Node Status in Melanoma Progression

    PubMed Central

    Letca, Alina Florentina; Ungureanu, Loredana; Şenilă, Simona Corina; Grigore, Lavinia Elena; Pop, Ştefan; Fechete, Oana; Vesa, Ştefan Cristian

    2018-01-01

    Background The purpose of this study was to assess the role of regression and other clinical and histological features for the prognosis and the progression of cutaneous melanoma. Material/Methods Between 2005 and 2016, 403 patients with melanoma were treated and followed at our Department of Dermatology. Of the 403 patients, 173 patients had cutaneous melanoma and underwent sentinel lymph node (SLN) biopsy and thus were included in this study. Results Histological regression was found in 37 cases of melanoma (21.3%). It was significantly associated with marked and moderate tumor-infiltrating lymphocyte (TIL) and with negative SLN. Progression of the disease occurred in 42 patients (24.2%). On multivariate analysis, we found that a positive lymph node and a Breslow index higher than 2 mm were independent variables associated with disease free survival (DFS). These variables together with a mild TIL were significantly correlated with overall survival (OS). The presence of regression was not associated with DFS or OS. Conclusions We could not demonstrate an association between regression and the outcome of patients with cutaneous melanoma. Tumor thickness greater than 2 mm and a positive SLN were associated with recurrence. Survival was influenced by a Breslow thickness >2 mm, the presence of a mild TIL and a positive SLN status. PMID:29507279

  14. [Application of selection criteria in sequential double lung transplantation].

    PubMed

    Borro, J M; Tarazona, V; Vicente, R; Cafarena, J M; Ramos, F; Sales, G; Galán, G; Lozano, C; Morant, P; Calvo, V; Morcillo, A; París, F

    1999-03-01

    Since the first sequential double lung transplant was performed in 1986, such procedures have been increasing in number and the criteria used as indications for this type of surgery have broadened. Our aim was to reflect on the application of selection criteria and to describe the anesthetic and surgical techniques and postoperative follow-up of 72 patients who underwent this type of transplant surgery between March 1993 and December 1998. Actuarial survival five years after surgery was 74.4%. Among patients requiring transplantation after septic disease, actuarial survival was 90.8% for cystic fibrosis and 88.2% for bronchiectasis. Of the preoperative risk factors analyzed (prior surgery, pachypleuritis, multiresistant germs, poor nutrition, mechanical ventilation and corticoid therapy), only prior treatment with high doses of corticoids proved significant. Eleven patients have been diagnosed of bronchiolitis obliterans, four have died and only two continue to experience difficulties in daily living. The high survival rate and the restriction-free life after recovery lead us to consider sequential double lung transplantation to be the treatment of choice for all pulmonary diseases.

  15. Anthropometric characteristics and ovarian cancer risk and survival.

    PubMed

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

    2018-02-01

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

  16. 5 CFR 839.1121 - What is the Actuarial Reduction for the Basic Employee Death Benefit (BEDB)?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... will be the amount of the BEDB divided by the present value factor for your age at the time of the... Basic Employee Death Benefit (BEDB)? 839.1121 Section 839.1121 Administrative Personnel OFFICE OF... Benefits § 839.1121 What is the Actuarial Reduction for the Basic Employee Death Benefit (BEDB)? If you...

  17. Extended Survival and Prognostic Factors for Patients With ALK-Rearranged Non–Small-Cell Lung Cancer and Brain Metastasis

    PubMed Central

    Johung, Kimberly L.; Yeh, Norman; Desai, Neil B.; Williams, Terence M.; Lautenschlaeger, Tim; Arvold, Nils D.; Ning, Matthew S.; Attia, Albert; Lovly, Christine M.; Goldberg, Sarah; Beal, Kathryn; Yu, James B.; Kavanagh, Brian D.; Chiang, Veronica L.; Camidge, D. Ross

    2016-01-01

    Purpose We performed a multi-institutional study to identify prognostic factors and determine outcomes for patients with ALK-rearranged non–small-cell lung cancer (NSCLC) and brain metastasis. Patients and Methods A total of 90 patients with brain metastases from ALK-rearranged NSCLC were identified from six institutions; 84 of 90 patients received radiotherapy to the brain (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]), and 86 of 90 received tyrosine kinase inhibitor (TKI) therapy. Estimates for overall (OS) and intracranial progression-free survival were determined and clinical prognostic factors were identified by Cox proportional hazards modeling. Results Median OS after development of brain metastases was 49.5 months (95% CI, 29.0 months to not reached), and median intracranial progression-free survival was 11.9 months (95% CI, 10.1 to 18.2 months). Forty-five percent of patients with follow-up had progressive brain metastases at death, and repeated interventions for brain metastases were common. Absence of extracranial metastases, Karnofsky performance score ≥ 90, and no history of TKIs before development of brain metastases were associated with improved survival (P = .003, < .001, and < .001, respectively), whereas a single brain metastasis or initial treatment with SRS versus WBRT were not (P = .633 and .666, respectively). Prognostic factors significant by multivariable analysis were used to describe four patient groups with 2-year OS estimates of 33%, 59%, 76%, and 100%, respectively (P < .001). Conclusion Patients with brain metastases from ALK-rearranged NSCLC treated with radiotherapy (SRS and/or WBRT) and TKIs have prolonged survival, suggesting that interventions to control intracranial disease are critical. The refinement of prognosis for this molecular subtype of NSCLC identifies a population of patients likely to benefit from first-line SRS, close CNS observation, and treatment of emergent CNS disease. PMID:26438117

  18. Surgical management in patients with coexistent coronary and cerebrovascular disease. Long-term results.

    PubMed

    Kaul, T K; Fields, B L; Wyatt, D A; Jones, C R; Kahn, D R

    1994-11-01

    Between January 1980 and December 1992, 3% (210/6,862) of our patients undergoing myocardial revascularization (CABG) had high grade (> 80%) internal carotid stenosis (CS). One hundred seventy-five of these patients with complete follow up for a minimum of 18 months were studied. Bilateral internal CS was present in 60%, and 75% had other vascular lesions, mainly as peripheral vascular disease (PVD) of the lower limb (50.8%). All patients underwent CAE (carotid endarterectomy) followed by CABG under the same anesthesia. Peripheral vascular lesions, contralateral internal CS and recurrent (n = 43) and progressive vascular lesions (n = 50), were subsequently treated as staged procedures. Hospital mortality was 3.42%. By univariate analysis significant predictors of late mortality were congestive heart failure, COPD, PVD, postoperative myocardial infarction, postoperative stroke, and ischemic cardiomyopathy. Only the latter two were also significant by multivariate analysis. At 12 years, actuarial survival in the presence of these risk factors were 46%, 49%, 22%, 37%, 53%, and 27% respectively. All are significantly lower as compared with the corresponding subsets of patients with the risk factor absent. At 12 years, actuarial survival for the entire series was 65%. Cumulative incidence of postoperative strokes was higher in patients with bilateral internal CS than in patients with unilateral internal CS (p < 0.07) and in patients with neurologic symptoms than asymptomatic patients. At 12 years, actuarial freedom from all cardiac related events, postoperative stroke, and symptomatic PVD were 49%, 82%, and 76% respectively. After successful revascularization these patients should be carefully followed for recurrent and progressive vascular lesions.

  19. Lymph node ratio may predict relapse free survival and overall survival in patients with stage II & III colorectal carcinoma.

    PubMed

    Zekri, Jamal; Ahmad, Imran; Fawzy, Ehab; Elkhodary, Tawfik R; Al-Gahmi, Aboelkhair; Hassouna, Ashraf; El Sayed, Mohamed E; Ur Rehman, Jalil; Karim, Syed M; Bin Sadiq, Bakr

    2015-01-01

    Lymph node ratio (LNR) defined as the number of lymph nodes (LNs) involved with metastases divided by number of LNs examined, has been shown to be an independent prognostic factor in breast, stomach and various other solid tumors. Its significance as a prognostic determinant in colorectal cancer (CRC) is still under investigation. This study investigated the prognostic value of LNR in patients with resected CRC. We retrospectively ex- amined 145 patients with stage II & III CRC diagnosed and treated at a single institution during 9 years pe- riod. Patients were grouped according to LNR in three groups. Group 1; LNR < 0.05, Group 2; LNR = 0.05-0.19 & Group 3 > 0.19. Chi square, life table analysis and multivariate Cox regression were used for statistical analysis. On multivariate analysis, number of involved LNs (NILN) (HR = 1.15, 95% CI 1.055-1.245; P = 0.001) and pathological T stage (P = 0.002) were statistically significant predictors of relapse free survival (RFS). LNR as a continuous variable (but not as a categorical variable) was statistically significant predictor of RFS (P = 0.02). LNR was also a statistically significant predictor of overall survival (OS) (P = 0.02). LNR may predict RFS and OS in patients with resected stage II & III CRC. Studies with larger cohorts and longer follow up are needed to further examine and validate theprognostic value of LNR.

  20. Sequential FOLFIRI.3 + Gemcitabine Improves Health-Related Quality of Life Deterioration-Free Survival of Patients with Metastatic Pancreatic Adenocarcinoma: A Randomized Phase II Trial

    PubMed Central

    Anota, Amélie; Mouillet, Guillaume; Trouilloud, Isabelle; Dupont-Gossart, Anne-Claire; Artru, Pascal; Lecomte, Thierry; Zaanan, Aziz; Gauthier, Mélanie; Fein, Francine; Dubreuil, Olivier; Paget-Bailly, Sophie; Taieb, Julien; Bonnetain, Franck

    2015-01-01

    Background A randomized multicenter phase II trial was conducted to assess the sequential treatment strategy using FOLFIRI.3 and gemcitabine alternately (Arm 2) compared to gemcitabine alone (Arm 1) in patients with metastatic non pre-treated pancreatic adenocarcinoma. The primary endpoint was the progression-free survival (PFS) rate at 6 months. It concludes that the sequential treatment strategy appears to be feasible and effective with a PFS rate of 43.5% in Arm 2 at 6 months (26.1% in Arm 1). This paper reports the results of the longitudinal analysis of the health-related quality of life (HRQoL) as a secondary endpoint of this study. Methods HRQoL was evaluated using the EORTC QLQ-C30 at baseline and every two months until the end of the study or death. HRQoL deterioration-free survival (QFS) was defined as the time from randomization to a first significant deterioration as compared to the baseline score with no further significant improvement, or death. A propensity score was estimated comparing characteristics of partial and complete responders. Analyses were repeated with inverse probability weighting method using the propensity score. Multivariate Cox regression analyses were performed to identify independent factors influencing QFS. Results 98 patients were included between 2007 and 2011. Adjusting on the propensity score, patients of Arm 2 presented a longer QFS of Global Health Status (Hazard Ratio: 0.52 [0.31-0.85]), emotional functioning (0.35 [0.21–0.59]) and pain (0.50 [0.31 – 0.81]) than those of Arm 1. Conclusion Patients of Arm 2 presented a better HRQoL with a longer QFS than those of Arm 1. Moreover, the propensity score method allows to take into account the missing data depending on patients’ characteristics. Trial registration information Eudract N° 2006-005703-34. (Name of the Trial: FIRGEM). PMID:26010884

  1. Microsomal PGE2 synthase-1 regulates melanoma cell survival and associates with melanoma disease progression

    PubMed Central

    Kim, Sun-Hee; Hashimoto, Yuuri; Cho, Sung-Nam; Roszik, Jason; Milton, Denái R.; Dal, Fulya; Kim, Sangwon F.; Menter, David G.; Yang, Peiying; Ekmekcioglu, Suhendan; Grimm, Elizabeth A.

    2016-01-01

    Summary COX-2 and its product PGE2 enhance carcinogenesis and tumor progression, which has been previously reported in melanoma. As most COX inhibitors cause much toxicity, the downstream microsomal PGE2 synthase-1 (mPGES1) is a consideration for targeting. Human melanoma TMAs were employed for testing mPGES1 protein staining intensity and percentage levels and both increased with clinical stage; employing a different Stage III TMA, mPGES1 intensity (not percentage) associated with reduced patient survival. Our results further show that iNOS was also highly expressed in melanoma tissues with high mPGES1 levels, and iNOS-mediated NO promoted mPGES1 expression and PGE2 production. An mPGES1specific inhibitor (CAY10526) as well as siRNA attenuated cell survival and increased apoptosis. CAY10526 significantly suppressed tumor growth and increased apoptosis in melanoma xenografts. Our findings support the value of a prognostic and predictive role for mPGES1, and suggest targeting this molecule in the PGE2 pathway as another avenue toward improving melanoma therapy. PMID:26801201

  2. Survival Analysis of Papillary Thyroid Carcinoma in Relation to Stage and Recurrence Risk: A 20-Year Experience in Pakistan.

    PubMed

    Hassan, Aamna; Razi, Mairah; Riaz, Saima; Khalid, Madeeha; Nawaz, M Khalid; Syed, Aamir Ali; Bashir, Humayun

    2016-08-01

    The aim of this study was to evaluate the overall and progression-free survival of papillary thyroid carcinoma (PTC), comparing the American Thyroid Association (ATA) guideline for risk of recurrence with the TNM staging system with dynamic assessment at 2 years. This study is a retrospective analysis of 689 PTC patients over a 20-year period at a single center. Disease-free survival based on the TNM staging and ATA recurrence risk was calculated using Kaplan-Meier curves. Dynamic response assessment during the first 2 years was compared for both systems. Survival was calculated based on age, baseline resectability, and postthyroidectomy serum tumor marker levels. Six hundred eighty-nine (72.2%) of the total thyroid cancer patients had PTC. Four hundred sixty-nine patients were females, and 220 patients were males. The age range was 6 to 87 years. Five hundred thirty-five patients were resectable, and 56 patients were unresectable. One hundred fifty-one patients were excluded due to insufficient information on recurrence risk. By ATA categorization, 39% had low risk, no disease-related mortality; 44% had intermediate risk, 3 died; and 17% had high risk, 32 died. The 5-year disease-free survival was 54%, 26%, and 5% in low-, intermediate-, and high-risk groups, respectively. The log-rank test showed a significant difference in the percent survival (P < 0.01). TNM stage wise, in terms of survival, 1.3% in stage I, 2.2% in stage II, 0% in stage III, and 37.5% in stage IV died. The 20-year disease-free survival showed the following: stage I, 43%; stage II, 28%; stage III, 18%; and stage IV, 2%. There is significant difference in survival rate (P < 0.01). Both ATA risk classification and TNM staging were significant predictors of disease-free survival. On bivariate analysis, ATA classification (hazards ratio, 2.1; 95% confidence interval, 1.64-2.67; P = 0.001) was better predictive of overall survival versus TNM classification (hazards ratio, 1.3; 95% confidence

  3. Should high risk patients with Hodgkin's disease be singled out for heavier therapeutic regimens while low risk patients are spared such therapies?

    PubMed

    Reece, D

    1995-01-01

    In order to optimize the use of intensive therapy and autologous transplantation in patients with progressive Hodgkin's disease, we have examined the outcome of our initial 100 patients entered into autograft studies between 1985 and 1992. At a median follow-up of 3.6 (range 1.6-8.2) years, the actuarial progression free survival (PFS) was 46% (95% confidence intervals 33%-57%). The most significant determinant of PFS was the disease status at the time of protocol entry. Patients entered into transplant studies at the time of first untested relapse had a PFS of 61% compared with 38% in those who had failed induction chemotherapy, 25% in patients treated in > or = second untested relapse and 0% in those in a chemoresistant relapse. The reasons for failure differed, however, in that a high non-relapse mortality was seen in the > or = second untested relapse and resistant relapse groups while a high probability of relapse was observed in the induction failures and resistant relapse group. The most obvious group to target with more intensive therapeutic regimens consists of patients who have failed induction chemotherapy.

  4. BRAF Mutation is Associated with an Improved Survival in Glioma-a Systematic Review and Meta-analysis.

    PubMed

    Vuong, Huy Gia; Altibi, Ahmed M A; Duong, Uyen N P; Ngo, Hanh T T; Pham, Thong Quang; Fung, Kar-Ming; Hassell, Lewis

    2018-05-01

    Newly emerged molecular markers in gliomas provide prognostic values beyond the capabilities of histologic classification. BRAF mutation, especially BRAF V600E, is common in a subset of gliomas and may represent a potential prognostic marker. The aim of our study is to investigate the potential use of BRAF mutations on prognosis of glioma patients. Four electronic databases were searched for potential articles, including PubMed, Scopus, ISI Web of Science, and Virtual Health Library (VHL). Data of hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were directly obtained from original papers or indirectly estimated from Kaplan Meier curve (KMC). A random effect model weighted by inverse variance method was used to calculate the pooled HR. From 705 articles, we finally included 11 articles with 1308 glioma patients for the final analysis. The overall estimates showed that BRAF V600E was associated with an improved overall survival (OS) in glioma patients (HR = 0.60; 95% CI = 0.44-0.80). Results for progression-free survival (PFS), however, were not statistically significant (HR = 1.39; 95% CI = 0.82-2.34). In subgroup analyses, BRAF V600E showed its effect in improving survival in pediatric and young adult gliomas (under 35 years) but did not have prognostic value in old adult. Additionally, BRAF V600E was only associated with a favorable prognosis in lower grade glioma. Our meta-analysis provides evidence that BRAF mutation has a favorable prognostic impact in gliomas and its prognostic value might be dependent on patient age and tumor grade. This mutation can be used as a prognostic factor in glioma but additional studies are required to clarify its prognostic value taking into account other confounding factors.

  5. Biochemical Response to Ursodeoxycholic Acid Predicts Survival in a North American Cohort of Primary Biliary Cirrhosis Patients

    PubMed Central

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

    2014-01-01

    Background Biochemical response to Ursodeoxycholic Acid among patients with Primary Biliary Cirrhosis remains variable and there is no agreement of an ideal model. Novel assessment of response coupled to histologic progression was recently defined by the Toronto criteria. We retrospectively assessed transplant-free survival and clinical outcomes associated with Ursodeoxycholic Acid response to evaluate the Toronto criteria using a large North American cohort of PBC patients. Methods 398 PBC patients from the Mayo Clinic PBC Genetic Epidemiology (MCPGE) Registry were assessed for Ursodeoxycholic Acid treatment and biochemical response per the Toronto criteria. Responders were defined by reduction in alkaline phosphatase to less than or equal to 1.67 times the upper normal limit by 2 years of treatment, whereas non-responders had alkaline phosphatase values greater than 1.67 times the upper normal limit. Probability of survival was estimated using the Kaplan-Meier method. Results 302 (76%) patients were responders and 96 (24%) were non-responders. Significantly more non-responders developed adverse events related to chronic liver disease compared to responders (Hazard Ratio (HR): 2.77, P = 0.001). Biochemical responders and early-stage disease at treatment start was associated with improved overall transplant-free survival compared to non-responders (HR: 1.9) and patients with late stage disease (HR: 2.7) after age and sex adjustment. Conclusions The Toronto criteria are capable of identifying Ursodeoxycholic Acid-treated Primary Biliary Cirrhosis patients at risk of poor transplant-free survival and adverse clinical outcomes. Our data reveal that despite advanced disease at diagnosis, biochemical response per the Toronto criteria associates with improved overall transplant-free survival. PMID:24317935

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

    PubMed

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

    2014-10-01

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

  7. Toxicity and outcome of a phase II trial of taxane-based neoadjuvant chemotherapy and 3-dimensional, conformal, accelerated radiotherapy in locally advanced nonsmall cell lung cancer.

    PubMed

    Rojas, Ana M; Lyn, Basil E; Wilson, Elena M; Williams, Frances J; Shah, Nihal; Dickson, Jeanette; Saunders, Michele I

    2006-09-15

    The objective of this study was to evaluate prospectively the acute and late adverse effects of taxane/carboplatin neoadjuvant chemotherapy and 3-dimensional, conformal radiotherapy in patients with locally advanced nonsmall cell lung cancer (NSCLC). Forty-two patients were entered into a nonrandomized Phase II study of continuous, hyperfractionated, accelerated radiotherapy (CHART) week-end less (CHARTWEL) to a dose of 60 grays (Gy). Three cycles of chemotherapy were given over 9 weeks before radiotherapy. Dose escalation with paclitaxel was from 150 mg/m2 to 225 mg/m2. Systemic toxicity to chemotherapy was monitored throughout. Radiation-induced, early, adverse effects were assessed during the first 9 weeks from the start of radiotherapy, and late effects were assessed from 3 months onward. Overall survival, disease-free survival, and locoregional tumor control also were monitored. Twenty percent of patients failed to receive chemotherapy as planned, primarily because of neutropenia. The incidence of Dische Dictionary Grade >or=2 and Grade >or=3 dysphagia was 57.5% and 10%, respectively, with an average duration of 1.2 weeks and 1.5 days, respectively. By 9 weeks, <3% of patients were symptomatic; and, eventually, all acute reactions were healed, and there has been no evidence of consequential damage. At 6 months, the actuarial incidence of moderate-to-severe pneumonitis was 10%. During this time, all patients were free of severe pulmonary complications. Actuarial estimates of Grade >or=2 late lung dysfunction were 3% at 1 year, 10% at 2 years, and remained at this level thereafter. The actuarial 3-year locoregional control and overall survival rates were 54% and 45%, respectively. Neoadjuvant chemotherapy followed by 3-dimensional, conformal CHARTWEL 60-Gy radiotherapy in patients with advanced NSCLC was feasible and was tolerated well. Historic comparisons indicated that locoregional tumor control is not compromised by the use of conformal techniques. (c) 2006

  8. Radiation therapy in the treatment of cervical cancer: The University of Chicago/Michael Reese Hospital experience

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rader, J.S.; Haraf, D.J.; Halpern, H.J.

    1990-07-01

    A retrospective analysis was conducted on 307 patients referred for radiation therapy at The University of Chicago and Michael Reese Hospital between 1971 and 1986. Median follow-up was 6.4 years. Treatment techniques varied during the time of the study. Actuarial disease-free survivals were 78%, 64%, 55%, 33%, 41%, and 60% for stage IB, IIA, IIB, IIIA, IIIB, and IVA, respectively. Stage, size of the cervical lesion, and hemoglobin level during treatment were prognostic factors. Treatment technique as well as time dose factors were analyzed with respect to survival, failures, and complications.

  9. LINC00472 expression is regulated by promoter methylation and associated with disease-free survival in patients with grade 2 breast cancer

    PubMed Central

    Shen, Yi; Wang, Zhanwei; Loo, Lenora WM; Ni, Yan; Jia, Wei; Fei, Peiwen; Risch, Harvey A.; Katsaros, Dionyssios; Yu, Herbert

    2015-01-01

    Long non-coding RNAs (lncRNAs) are a class of newly recognized DNA transcripts that have diverse biological activities. Dysregulation of lncRNAs may be involved in many pathogenic processes including cancer. Recently, we found an intergenic lncRNA, LINC00472, whose expression was correlated with breast cancer progression and patient survival. Our findings were consistent across multiple clinical datasets and supported by results from in vitro experiments. To evaluate further the role of LINC00472 in breast cancer, we used various online databases to investigate possible mechanisms that might affect LINC00472 expression in breast cancer. We also analyzed associations of LINC00472 with estrogen receptor, tumor grade, and molecular subtypes in additional online datasets generated by microarray platforms different from the one we investigated previously. We found that LINC00472 expression in breast cancer was regulated more possibly by promoter methylation than by the alteration of gene copy number. Analysis of additional datasets confirmed our previous findings of high expression of LINC00472 associated with ER-positive and low-grade tumors and favorable molecular subtypes. Finally, in nine datasets, we examined the association of LINC00472 expression with disease-free survival in patients with grade 2 tumors. Meta-analysis of the datasets showed that LINC00472 expression in breast tumors predicted the recurrence of breast cancer in patients with grade 2 tumors. In summary, our analyses confirm that LINC00472 is functionally a tumor suppressor, and that assessing its expression in breast tumors may have clinical implications in breast cancer management. PMID:26564482

  10. LINC00472 expression is regulated by promoter methylation and associated with disease-free survival in patients with grade 2 breast cancer.

    PubMed

    Shen, Yi; Wang, Zhanwei; Loo, Lenora W M; Ni, Yan; Jia, Wei; Fei, Peiwen; Risch, Harvey A; Katsaros, Dionyssios; Yu, Herbert

    2015-12-01

    Long non-coding RNAs (lncRNAs) are a class of newly recognized DNA transcripts that have diverse biological activities. Dysregulation of lncRNAs may be involved in many pathogenic processes including cancer. Recently, we found an intergenic lncRNA, LINC00472, whose expression was correlated with breast cancer progression and patient survival. Our findings were consistent across multiple clinical datasets and supported by results from in vitro experiments. To evaluate further the role of LINC00472 in breast cancer, we used various online databases to investigate possible mechanisms that might affect LINC00472 expression in breast cancer. We also analyzed associations of LINC00472 with estrogen receptor, tumor grade, and molecular subtypes in additional online datasets generated by microarray platforms different from the one we investigated previously. We found that LINC00472 expression in breast cancer was regulated more possibly by promoter methylation than by the alteration of gene copy number. Analysis of additional datasets confirmed our previous findings of high expression of LINC00472 associated with ER-positive and low-grade tumors and favorable molecular subtypes. Finally, in nine datasets, we examined the association of LINC00472 expression with disease-free survival in patients with grade 2 tumors. Meta-analysis of the datasets showed that LINC00472 expression in breast tumors predicted the recurrence of breast cancer in patients with grade 2 tumors. In summary, our analyses confirm that LINC00472 is functionally a tumor suppressor, and that assessing its expression in breast tumors may have clinical implications in breast cancer management.

  11. KATP Channel Expression and Genetic Polymorphisms Associated with Progression and Survival in Amyotrophic Lateral Sclerosis.

    PubMed

    Vidal-Taboada, José M; Pugliese, Marco; Salvadó, Maria; Gámez, Josep; Mahy, Nicole; Rodríguez, Manuel J

    2018-02-28

    The ATP-sensitive potassium (K ATP ) channel directly regulates the microglia-mediated inflammatory response following CNS injury. To determine the putative role of the K ATP channel in amyotrophic lateral sclerosis (ALS) pathology, we investigated whether ALS induces changes in K ATP channel expression in the spinal cord and motor cortex. We also characterized new functional variants of human ABCC8, ABCC9, KCNJ8, and KCNJ11 genes encoding for the K ATP channel and analyzed their association with ALS risk, rate of progression, and survival in a Spanish ALS cohort. The expression of ABCC8 and KCNJ8 genes was enhanced in the spinal cord of ALS samples, and KCNJ11 increased in motor cortex of ALS samples, as determined by real-time polymerase chain reaction. We then sequenced the exons and regulatory regions of K ATP channel genes from a subset of 28 ALS patients and identified 50 new genetic variants. For the case-control association analysis, we genotyped five selected polymorphisms with predicted functional relevance in 185 Spanish ALS (134 spinal ALS and 51 bulbar ALS) patients and 493 controls. We found that bulbar ALS patients presenting the G/G genotype of the rs4148646 variant of ABCC8 and the T/T genotype of the rs5219 variant of KCNJ11 survived longer than other ALS patients presenting other genotypes. Also, the C/C genotype of the rs4148642 variant of ABCC8 and the T/C genotype of the rs148416760 variant of ABCC9 modified the progression rate in spinal ALS patients. Our results suggest that the K ATP channel plays a role in the pathophysiological mechanisms of ALS.

  12. Everolimus for the Treatment of Advanced Pancreatic Neuroendocrine Tumors: Overall Survival and Circulating Biomarkers From the Randomized, Phase III RADIANT-3 Study.

    PubMed

    Yao, James C; Pavel, Marianne; Lombard-Bohas, Catherine; Van Cutsem, Eric; Voi, Maurizio; Brandt, Ulrike; He, Wei; Chen, David; Capdevila, Jaume; de Vries, Elisabeth G E; Tomassetti, Paola; Hobday, Timothy; Pommier, Rodney; Öberg, Kjell

    2016-11-10

    Purpose Everolimus improved median progression-free survival by 6.4 months in patients with advanced pancreatic neuroendocrine tumors (NET) compared with placebo in the RADIANT-3 study. Here, we present the final overall survival (OS) data and data on the impact of biomarkers on OS from the RADIANT-3 study. Methods Patients with advanced, progressive, low- or intermediate-grade pancreatic NET were randomly assigned to everolimus 10 mg/day (n = 207) or placebo (n = 203). Crossover from placebo to open-label everolimus was allowed on disease progression. Ongoing patients were unblinded after final progression-free survival analysis and could transition to open-label everolimus at the investigator's discretion (extension phase). OS analysis was performed using a stratified log-rank test in the intent-to-treat population. The baseline levels of chromogranin A, neuron-specific enolase, and multiple soluble angiogenic biomarkers were determined and their impact on OS was explored. Results Of 410 patients who were enrolled between July 2007 and March 2014, 225 received open-label everolimus, including 172 patients (85%) randomly assigned initially to the placebo arm. Median OS was 44.0 months (95% CI, 35.6 to 51.8 months) for those randomly assigned to everolimus and 37.7 months (95% CI, 29.1 to 45.8 months) for those randomly assigned to placebo (hazard ratio, 0.94; 95% CI, 0.73 to 1.20; P = .30). Elevated baseline chromogranin A, neuron-specific enolase, placental growth factor, and soluble vascular endothelial growth factor receptor 1 levels were poor prognostic factors for OS. The most common adverse events included stomatitis, rash, and diarrhea. Conclusion Everolimus was associated with a median OS of 44 months in patients with advanced, progressive pancreatic NET, the longest OS reported in a phase III study for this population. Everolimus was associated with a survival benefit of 6.3 months, although this finding was not statistically significant. Crossover of

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

    PubMed

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

    2018-01-02

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

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

    PubMed

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

    2018-04-01

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

  15. A Brief Actuarial Assessment for the Prediction of Wife Assault Recidivism: The Ontario Domestic Assault Risk Assessment

    ERIC Educational Resources Information Center

    Hilton, N. Zoe; Harris, Grant T.; Rice, Marnie E.; Lang, Carol; Cormier, Catherine A.; Lines, Kathryn J.

    2004-01-01

    An actuarial assessment to predict male-to-female marital violence was constructed from a pool of potential predictors in a sample of 589 offenders identified in police records and followed up for an average of almost 5 years. Archival information in several domains (offender characteristics, domestic violence history, nondomestic criminal…

  16. Effects of Anorectic Drugs on Food Intake under Progressive-Ratio and Free-Access Conditions in Rats

    ERIC Educational Resources Information Center

    LeSage, Mark G.; Stafford, David; Glowa, John R.

    2004-01-01

    The effects of two anorectic drugs, dexfenfluramine and phentermine, on food intake under different food-access conditions were examined. Experiment 1 compared the effects of these drugs on food intake under a progressive-ratio (PR) schedule and free-access conditions. Dexfenfluramine decreased food intake under both conditions, but the doses…

  17. Meta-analysis of gene expression profiles associated with histological classification and survival in 829 ovarian cancer samples.

    PubMed

    Fekete, Tibor; Rásó, Erzsébet; Pete, Imre; Tegze, Bálint; Liko, István; Munkácsy, Gyöngyi; Sipos, Norbert; Rigó, János; Györffy, Balázs

    2012-07-01

    Transcriptomic analysis of global gene expression in ovarian carcinoma can identify dysregulated genes capable to serve as molecular markers for histology subtypes and survival. The aim of our study was to validate previous candidate signatures in an independent setting and to identify single genes capable to serve as biomarkers for ovarian cancer progression. As several datasets are available in the GEO today, we were able to perform a true meta-analysis. First, 829 samples (11 datasets) were downloaded, and the predictive power of 16 previously published gene sets was assessed. Of these, eight were capable to discriminate histology subtypes, and none was capable to predict survival. To overcome the differences in previous studies, we used the 829 samples to identify new predictors. Then, we collected 64 ovarian cancer samples (median relapse-free survival 24.5 months) and performed TaqMan Real Time Polimerase Chain Reaction (RT-PCR) analysis for the best 40 genes associated with histology subtypes and survival. Over 90% of subtype-associated genes were confirmed. Overall survival was effectively predicted by hormone receptors (PGR and ESR2) and by TSPAN8. Relapse-free survival was predicted by MAPT and SNCG. In summary, we successfully validated several gene sets in a meta-analysis in large datasets of ovarian samples. Additionally, several individual genes identified were validated in a clinical cohort. Copyright © 2011 UICC.

  18. Predictors of survival in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery based on the pooled analysis of an international collaborative cohort

    PubMed Central

    Zang, R Y; Harter, P; Chi, D S; Sehouli, J; Jiang, R; Tropé, C G; Ayhan, A; Cormio, G; Xing, Y; Wollschlaeger, K M; Braicu, E I; Rabbitt, C A; Oksefjell, H; Tian, W J; Fotopoulou, C; Pfisterer, J; du Bois, A; Berek, J S

    2011-01-01

    Background: This study aims to identify prognostic factors and to develop a risk model predicting survival in patients undergoing secondary cytoreductive surgery (SCR) for recurrent epithelial ovarian cancer. Methods: Individual data of 1100 patients with recurrent ovarian cancer of a progression-free interval at least 6 months who underwent SCR were pooled analysed. A simplified scoring system for each independent prognostic factor was developed according to its coefficient. Internal validation was performed to assess the discrimination of the model. Results: Complete SCR was strongly associated with the improvement of survival, with a median survival of 57.7 months, when compared with 27.0 months in those with residual disease of 0.1–1 cm and 15.6 months in those with residual disease of >1 cm, respectively (P<0.0001). Progression-free interval (⩽23.1 months vs >23.1 months, hazard ratio (HR): 1.72; score: 2), ascites at recurrence (present vs absent, HR: 1.27; score: 1), extent of recurrence (multiple vs localised disease, HR: 1.38; score: 1) as well as residual disease after SCR (R1 vs R0, HR: 1.90, score: 2; R2 vs R0, HR: 3.0, score: 4) entered into the risk model. Conclusion: This prognostic model may provide evidence to predict survival benefit from secondary cytoreduction in patients with recurrent ovarian cancer. PMID:21878937

  19. Combined vemurafenib and fotemustine in patients with BRAF V600 melanoma progressing on vemurafenib.

    PubMed

    Queirolo, Paola; Spagnolo, Francesco; Picasso, Virginia; Spano, Laura; Tanda, Enrica; Fontana, Valeria; Giorello, Laura; Merlo, Domenico Franco; Simeone, Ester; Grimaldi, Antonio Maria; Curvietto, Marcello; Del Vecchio, Michele; Bruzzi, Paolo; Ascierto, Paolo Antonio

    2018-02-23

    BRAF inhibitor vemurafenib achieves high response rate and an improvement in survival in patients with BRAF-mutated metastatic melanoma. However, median progression-free survival is only 6.9 months in the phase 3 study. Retrospective analyses suggest that treatment with BRAF inhibitors beyond initial progression might be associated with improved overall survival. We aimed to prospectively investigate the activity of prolonged treatment with vemurafenib and the addition of fotemustine in patients with systemic progression on prior single-agent BRAF inhibitor. In this two-centres, single-arm Phase 2 trial, we enrolled patients with systemic progressive disease during single-agent vemurafenib treatment. Participants received vemurafenib 960 mg twice daily or dose administered at time of disease progression with vemurafenib previous treatment and fotemustine 100 mg/m2 intravenously every three weeks. The primary endpoint was PFS. Thirty-one patients were enrolled in the study; 16 patients had brain metastases at baseline. Median PFS was 3.9 months and 19 patients (61.3%) achieved disease control (1 CR, 4 PR, 14 SD). For patients achieving disease control, median duration of treatment was 6 months. Median OS was 5.8 months from enrolment and 15.4 months from start of previous vemurafenib. Five patients (16.1%) had a G3-4 AE, the most common being thrombocytopenia, which occurred in 3 patients.This trial is registered with ClinicalTrials.gov number NCT01983124. The combination of vemurafenib plus fotemustine has clinical activity and an acceptable safety profile in BRAF-refractory patients.

  20. Survival impact of rituximab combined with ACVBP and upfront consolidation autotransplantation in high-risk diffuse large B-cell lymphoma for GELA

    PubMed Central

    Fitoussi, Olivier; Belhadj, Karim; Mounier, Nicolas; Parrens, Marie; Tilly, Hervé; Salles, Gilles; Feugier, Pierre; Ferme, Christophe; Ysebaert, Loic; Gabarre, Jean; Herbrecht, Raoul; Janvier, Maud; Van Den Neste, Eric; Morschhauser, Franck; Casasnovas, Olivier; Ghesquieres, Hervé; Anglaret, Bruno; Brechignac, Sabine; Haioun, Corinne; Gisselbrecht, Christian

    2011-01-01

    Background As rituximab combined with CHOP improves complete remission and overall survival in diffuse large B-cell lymphoma, intensified chemotherapy followed by autologous stem-cell transplantation has also been advocated for high-risk patients. The aim of this study was to establish whether or not combining rituximab with high-dose chemotherapy and auto-transplantation also benefits patient survival. Design and Methods The LNH2003-3 study was a phase II trial including diffuse large B-cell lymphoma patients with 2 or 3 International Prognostic Index factors. They received four cycles of intensive biweekly chemotherapy with rituximab, doxorubicine, cyclophosphamide, vindesine, bleomycine, prednisolone (R-ACVBP) followed by auto-transplantation in responding patients. Two hundred and nine patients under 60 years of age were included in the study and 155 responding patients underwent auto-transplantation. In addition, a case-control study was performed by matching (1:1) 181 patients treated with R-ACVBP with ACVBP patients not given rituximab but submitted to auto-transplantation from the previous LNH1998-3 trial. Results With a median follow up of 45 months, 4-year progression-free survival and overall survival were estimated at 76% (CI: 69–81) and 78% (CI: 72–83), respectively. There was no difference between patients with 2 or 3 International Prognostic Index factors. Four year progression-free survival was significantly higher in R-ACVBP than ACVBP patients (74% vs. 58%; P=0.0005). There was also a significant increase in 4-year overall survival (76% vs. 68%; P=0.0494). Conclusions In high-risk diffuse large B-cell lymphoma patients, treatment with R-ACVBP followed by auto-transplantation results in a 78% 4-year overall survival which should be compared to other approaches. (Clinicaltrials.gov identifier: NCT00144807) PMID:21546499

  1. Conditional survival analysis of hepatocellular carcinoma patients treated with radiofrequency ablation.

    PubMed

    Facciorusso, Antonio; Del Prete, Valentina; Antonino, Matteo; Neve, Viviana; Amoruso, Annabianca; Crucinio, Nicola; Di Leo, Alfredo; Barone, Michele

    2015-10-01

    Survival estimates are commonly reported as survival from the first observation, but future survival probability changes based on the survival time already accumulated after therapy, otherwise known as conditional survival (CS). The aim of the study was to describe CS according to different prognostic variables in hepatocellular carcinoma (HCC) patients treated with radiofrequency ablation (RFA). Data on 125 very early/early HCC patients treated with RFA between 1999 and 2007 were analyzed. Actuarial survival estimates were computed by means of Kaplan-Meier method and compared by log-rank test. The 5-year CS was calculated with stratification by several predictors for patients who had already survived up to 5 years from diagnosis. Median overall survival (OS) was 72 months (95% confidence interval [CI], 58-86). Age, Child-Pugh (CP), α-fetoprotein (AFP), Cancer of the Liver Italian Program (CLIP) score and type of recurrence (early vs late) were significant predictors of OS. The 5-year CS rates of the entire study cohort assessed at 1, 2, 3 and 5 years from the treatment were 49%, 48%, 30% and 34%, respectively. Subgroup analysis confirmed age and CP as significant predictors of CS at all time points, while the CS of subgroups stratified by AFP and CLIP did not differ significantly from the 3rd year after RFA onward, as more advanced patients had probably escaped early recurrence. CS analysis showed that the impact of different variables influencing OS is not linear over time after RFA. Information derived from the study can improve the current management of HCC patients. © 2014 The Japan Society of Hepatology.

  2. Failure to Achieve a PSA Level {<=}1 ng/mL After Neoadjuvant LHRHA Therapy Predicts for Lower Biochemical Control Rate and Overall Survival in Localized Prostate Cancer Treated With Radiotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mitchell, Darren M.; McAleese, Jonathan; Park, Richard M.

    2007-12-01

    Purpose: To investigate whether failure to suppress the prostate-specific antigen (PSA) level to {<=}1 ng/mL after {>=}2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy in patients scheduled to undergo external beam radiotherapy for localized prostate carcinoma is associated with reduced biochemical failure-free survival. Methods and Materials: A retrospective case note review of consecutive patients with intermediate- or high-risk localized prostate cancer treated between January 2001 and December 2002 with neoadjuvant hormonal deprivation therapy, followed by concurrent hormonal therapy and radiotherapy was performed. Patient data were divided for analysis according to whether the PSA level in Week 1 of radiotherapymore » was {<=}1.0 ng/mL. Biochemical failure was determined using the American Society for Therapeutic Radiology and Oncology (Phoenix) definition. Results: A total of 119 patients were identified. The PSA level after neoadjuvant hormonal deprivation therapy was {<=}1 ng/mL in 67 patients and >1 ng/mL in 52. At a median follow-up of 49 months, the 4-year actuarial biochemical failure-free survival rate was 84% vs. 60% (p = 0.0016) in favor of the patients with a PSA level after neoadjuvant hormonal deprivation therapy of {<=}1 ng/mL. The overall survival rate was 94% vs. 77.5% (p = 0.0045), and the disease-specific survival rate at 4 years was 98.5% vs. 82.5%. Conclusions: The results of our study have shown that patients with a PSA level >1 ng/mL at the beginning of external beam radiotherapy after {>=}2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy have a significantly greater rate of biochemical failure and lower survival rate compared with those with a PSA level of {<=}1 ng/mL. Patients without adequate PSA suppression should be considered a higher risk group and considered for dose escalation or the use of novel treatments.« less

  3. Survival of adult Steller sea lions in Alaska: senescence, annual variation and covariation with male reproductive success.

    PubMed

    Hastings, Kelly K; Jemison, Lauri A; Pendleton, Grey W

    2018-01-01

    Population dynamics of long-lived vertebrates depend critically on adult survival, yet factors affecting survival and covariation between survival and other vital rates in adults remain poorly examined for many taxonomic groups of long-lived mammals (e.g. actuarial senescence has been examined for only 9 of 34 extant pinniped species using longitudinal data). We used mark-recapture models and data from 2795 Steller sea lion ( Eumetopias jubatus ) pups individually marked at four of five rookeries in southeastern Alaska (SEAK) and resighted for 21 years to examine senescence, annual variability and covariation among life-history traits in this long-lived, sexually dimorphic pinniped. Sexes differed in age of onset (approx. 16-17 and approx. 8-9 years for females and males, respectively), but not rate (-0.047 and -0.046/year of age for females and males) of senescence. Survival of adult males from northern SEAK had greatest annual variability (approx. ±0.30 among years), whereas survival of adult females ranged approximately ±0.10 annually. Positive covariation between male survival and reproductive success was observed. Survival of territorial males was 0.20 higher than that of non-territorial males, resulting in the majority of males alive at oldest ages being territorial.

  4. Survival of adult Steller sea lions in Alaska: senescence, annual variation and covariation with male reproductive success

    PubMed Central

    Jemison, Lauri A.; Pendleton, Grey W.

    2018-01-01

    Population dynamics of long-lived vertebrates depend critically on adult survival, yet factors affecting survival and covariation between survival and other vital rates in adults remain poorly examined for many taxonomic groups of long-lived mammals (e.g. actuarial senescence has been examined for only 9 of 34 extant pinniped species using longitudinal data). We used mark–recapture models and data from 2795 Steller sea lion (Eumetopias jubatus) pups individually marked at four of five rookeries in southeastern Alaska (SEAK) and resighted for 21 years to examine senescence, annual variability and covariation among life-history traits in this long-lived, sexually dimorphic pinniped. Sexes differed in age of onset (approx. 16–17 and approx. 8–9 years for females and males, respectively), but not rate (−0.047 and −0.046/year of age for females and males) of senescence. Survival of adult males from northern SEAK had greatest annual variability (approx. ±0.30 among years), whereas survival of adult females ranged approximately ±0.10 annually. Positive covariation between male survival and reproductive success was observed. Survival of territorial males was 0.20 higher than that of non-territorial males, resulting in the majority of males alive at oldest ages being territorial. PMID:29410794

  5. If You Build It, Will They Come? Tales of Developing a New Degree Program in Actuarial Science

    ERIC Educational Resources Information Center

    Marano, Lisa E.

    2014-01-01

    In 2007, the B.S. in Applied Mathematics program consisting of five concentrations, including Actuarial Science, began at West Chester University of Pennsylvania, and we graduated our first class (of one) that December. We describe our program, some ideas to consider when planning your own program, and share some of the successes of our program…

  6. 78 FR 9890 - DoD Medicare-Eligible Retiree Health Care Board of Actuaries; Notice of Federal Advisory...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ... DEPARTMENT OF DEFENSE Office of the Secretary DoD Medicare-Eligible Retiree Health Care Board of... Retiree Health Care Board of Actuaries will take place. DATES: Friday, August 2, 2013, from 10:00 a.m. to... assumptions to be used in the valuation of benefits under DoD retiree health care programs for Medicare...

  7. Microsomal PGE2 synthase-1 regulates melanoma cell survival and associates with melanoma disease progression.

    PubMed

    Kim, Sun-Hee; Hashimoto, Yuuri; Cho, Sung-Nam; Roszik, Jason; Milton, Denái R; Dal, Fulya; Kim, Sangwon F; Menter, David G; Yang, Peiying; Ekmekcioglu, Suhendan; Grimm, Elizabeth A

    2016-05-01

    COX-2 and its product PGE2 enhance carcinogenesis and tumor progression, which has been previously reported in melanoma. As most COX inhibitors cause much toxicity, the downstream microsomal PGE2 synthase-1 (mPGES1) is a consideration for targeting. Human melanoma TMAs were employed for testing mPGES1 protein staining intensity and percentage levels, and both increased with clinical stage; employing a different Stage III TMA, mPGES1 intensity (not percentage) associated with reduced patient survival. Our results further show that iNOS was also highly expressed in melanoma tissues with high mPGES1 levels, and iNOS-mediated NO promoted mPGES1 expression and PGE2 production. An mPGES1-specific inhibitor (CAY10526) as well as siRNA attenuated cell survival and increased apoptosis. CAY10526 significantly suppressed tumor growth and increased apoptosis in melanoma xenografts. Our findings support the value of a prognostic and predictive role for mPGES1, and suggest targeting this molecule in the PGE2 pathway as another avenue toward improving melanoma therapy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. [Technical advancement improves survival in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiotherapy].

    PubMed

    Wang, J B; Jiang, W; Ji, Z; Cao, J Z; Liu, L P; Men, Y; Xu, C; Wang, X Z; Hui, Z G; Liang, J; Lyu, J M; Zhou, Z M; Xiao, Z F; Feng, Q F; Chen, D F; Zhang, H X; Yin, W B; Wang, L H

    2016-08-01

    This study aimed to evaluate the impact of technical advancement of radiation therapy in patients with LA-NSCLC receiving definitive radiotherapy (RT). Patients treated with definitive RT (≥50 Gy) between 2000 and 2010 were retrospectively reviewed. Overall survival (OS), cancer specific survival (CSS), locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) were calculated and compared among patients irradiated with different techniques. Radiation-induced lung injury (RILI) and esophageal injury (RIEI) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events 3.0 (NCI-CTCAE 3.0). A total of 946 patients were eligible for analysis, including 288 treated with two-dimensional radiotherapy (2D-RT), 209 with three-dimensional conformal radiation therapy (3D-CRT) and 449 with intensity-modulated radiation therapy (IMRT) respectively. The median follow-up time for the whole population was 84.1 months. The median OS of 2D-RT, 3D-CRT and IMRT groups were 15.8, 19.7 and 23.3 months, respectively, with the corresponding 5-year survival rate of 8.7%, 13.0% and 18.8%, respectively (P<0.001). The univariate analysis demonstrated significantly inferior OS, LRPFS, DMFS and PFS of 2D-RT than those provided by 3D-CRT or IMRT. The univariate analysis also revealed that the IMRT group had significantly loger LRPFS and a trend toward better OS and DMFS compared with 3D-CRT. Multivariate analysis showed that TNM stage, RT technique and KPS were independent factors correlated with all survival indexes. Compared with 2D-RT, the utilization of IMRT was associated with significantly improved OS, LRPFS, DMFS as well as PFS. Compared with 3D-CRT, IMRT provided superior DMFS (P=0.035), a trend approaching significance with regard to LRPFS (P=0.073) but no statistically significant improvement on OS, CSS and PFS in multivariate analysis. The incidence rates of RILI were

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

    PubMed

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

    2011-06-14

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

  10. NDRG2 correlated with favorable recurrence-free survival inhibits metastasis of mouse breast cancer cells via attenuation of active TGF-β production.

    PubMed

    Oh, Sang-seok; Kim, Donghyeok; Kim, Dong-Hee; Chang, Hong Hee; Sohn, Kyung-Cheol; Kim, Kyo Hyun; Jung, Sung Hoo; Lee, Byoung Kil; Kim, Joo Heon; Kim, Kwang Dong

    2012-10-01

    N-myc downstream-regulated gene 2 (NDRG2) has been studied for its inhibitory effects against growth and metastasis of many tumor cell types. In this study, we showed NDRG2 expression was correlated with favorable recurrence-free survival of patients with breast cancer and inhibited metastasis of breast cancer cells (4T1). NDRG2 expression was examined in 189 breast carcinoma tissues and paired normal breast tissues using immunohistochemistry. Histological and clinicopathological data were correlated using Pearson's chi-square test of independence. NDRG2 expression in human breast cancer tissues was inversely associated with lymph node metastasis and pTNM stage. Furthermore, patients with breast cancer with a high level of NDRG2 expression showed favorable recurrence-free survival (P = 0.038). To study the effect of NDRG2 on metastasis in vivo, we established an NDRG2-overexpressing mouse breast cancer cell line (4T1-NDRG2) and measured the metastasis and survival of 4T1-NDRG2 tumor-bearing mice. To test whether transforming growth factor β (TGF-β)- mediated metastasis of 4T1 was inhibited by NDRG2 expression, TGF-Smad-binding element (SBE)-luciferase activity and/or measurement of active TGF-β were performed in cell or tumor tissue level. 4T1-NDRG2 cells grew gradually and showed less metastatic activity in vivo and low invasiveness in vitro. 4T1-NDRG2 cells showed lower SBE-luciferase activity and lower level of active autocrine TGF-β than 4T1-Mock did. Correctly, our data show that NDRG2 significantly suppress tumor metastasis by attenuating active autocrine TGF-β production, and the attenuation might be typically associated with the favorable recurrence-free survival of patients clinically.

  11. Advances in surgical techniques for resection of childhood cerebellopontine angle ependymomas are key to survival.

    PubMed

    Sanford, Robert A; Merchant, Thomas E; Zwienenberg-Lee, Marike; Kun, Larry E; Boop, Frederick A

    2009-10-01

    Childhood cerebellopontine angle (CPA) ependymoma is an uncommon anatomical variant of posterior fossa ependymoma. In infants and young children, the tumor often goes undetected until it causes hydrocephalus. As CPA ependymomas grow, they distort the anatomy and encase cranial nerves and vessels, thereby making resection a formidable surgical challenge. The purpose of this paper is to describe the surgical technique used to achieve gross total resection (GTR) of CPA ependymomas and demonstrate improved survival in these patients. Surgical techniques used for GTR in 45 patients with CPA ependymoma treated from 1997 to 2008 are described. Results of those procedures are compared with data from 11 patients who previously underwent surgical resection (1985-1995). We achieved GTR in 43 (95.6%) patients and near-total resection in two (4.4%); the probability of progression-free survival was 53.8%, and that of overall survival was 64%. Our novel surgical techniques greatly improve central nervous system function and survival among pediatric patients with CPA ependymoma.

  12. Long-term survival in a patient with glioblastoma on antipsychotic therapy for schizophrenia: a case report and literature review

    PubMed Central

    Faraz, Shahdabul; Pannullo, Susan; Rosenblum, Marc; Smith, Andrew; Wernicke, A. Gabriella

    2016-01-01

    Glioblastoma is not only the most common primary brain tumor, but also the most aggressive. Currently, the most effective treatment of surgery, chemotherapy and radiation therapy allows for a modest median survival of 15 months. Here, we report a case of a 57-year-old male with histologically confirmed glioblastoma with unfavorable prognostic characteristics (poor performance status and persistent neurological symptoms after surgery), whose expected 5-year survival is 0%. Further genetic analysis offered a mixed prognostic picture with positive methylation of 0-6-methylguinine-DNA (deoxyribonucleic acid) methyltransferase (MGMT; favorable prognosis) and wild-type isocitrate dehydrogenase 1 (IDH-1; unfavorable prognosis). Remarkably, the patient showed a progression-free survival of 5.5 years and a total survival of 6.5 years. In the context of recently published literature, the authors hypothesize that the patient’s use of the antipsychotic medication risperidone may have had a potential antitumor effect. Risperidone antagonizes the dopamine-2 receptor and the serotonin-7 receptor, both of which have been individually implicated in the growth and progression of glioblastoma. To the authors’ knowledge, this is the first clinical case in the literature to explore this association. PMID:27800031

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

    PubMed

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

    2017-07-01

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

  14. Burden of potentially pathologic copy number variants is higher in children with isolated congenital heart disease and significantly impairs covariate-adjusted transplant-free survival.

    PubMed

    Kim, Daniel Seung; Kim, Jerry H; Burt, Amber A; Crosslin, David R; Burnham, Nancy; Kim, Cecilia E; McDonald-McGinn, Donna M; Zackai, Elaine H; Nicolson, Susan C; Spray, Thomas L; Stanaway, Ian B; Nickerson, Deborah A; Heagerty, Patrick J; Hakonarson, Hakon; Gaynor, J William; Jarvik, Gail P

    2016-04-01

    Copy number variants (CNVs) are duplications or deletions of genomic regions. Large CNVs are potentially pathogenic and are overrepresented in children with congenital heart disease (CHD). We sought to determine the frequency of large CNVs in children with isolated CHD, and to evaluate the relationship of these potentially pathogenic CNVs with transplant-free survival. These cases are derived from a prospective cohort of patients with nonsyndromic CHD (n = 422) identified before first surgery. Healthy pediatric controls (n = 500) were obtained from the electronic Medical Records and Genetic Epidemiology Network, and CNV frequency was contrasted for CHD cases and controls. CNVs were determined algorithmically; subsequently screened for >95% overlap between 2 methods, size (>300 kb), quality score, overlap with a gene, and novelty (absent from databases of known, benign CNVs); and separately validated by quantitative polymerase chain reaction. Survival likelihoods for cases were calculated using Cox proportional hazards modeling to evaluate the joint effect of CNV burden and known confounders on transplant-free survival. Children with nonsyndromic CHD had a higher burden of potentially pathogenic CNVs compared with pediatric controls (12.1% vs 5.0%; P = .00016). Presence of a CNV was associated with significantly decreased transplant-free survival after surgery (hazard ratio, 3.42; 95% confidence interval, 1.66-7.09; P = .00090) with confounder adjustment. We confirm that children with isolated CHD have a greater burden of rare/large CNVs. We report a novel finding that these CNVs are associated with an adjusted 2.55-fold increased risk of death or transplant. These data suggest that CNV burden is an important modifier of survival after surgery for CHD. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  15. Independent association between time to prostate-specific antigen (PSA) nadir and PSA progression-free survival in patients with docetaxel-naïve, metastatic castration-resistant prostate cancer receiving abiraterone acetate, but not enzalutamide.

    PubMed

    Miyake, Hideaki; Hara, Takuto; Tamura, Keita; Sugiyama, Takayuki; Furuse, Hiroshi; Ozono, Seiichiro; Fujisawa, Masato

    2017-06-01

    The objective of this study was to compare the prognostic effect of time to prostate-specific antigen (PSA) nadir (TTPN) after treatment with abiraterone acetate (AA) and enzalutamide (Enz) in patients with docetaxel-naïve, metastatic castration-resistant prostate cancer (mCRPC). This study included a total of 297 consecutive patients with mCRPC, of whom 125 and 172 received AA and Enz, respectively, without previous treatment with docetaxel and subsequently achieved any degree of PSA reduction after the administration of either agent. The mean values of TTPN in the AA and Enz groups were 19 and 14 weeks, respectively. Despite the lack of significant differences in several parameters according to the mean TTPN in the Enz group, patients with TTPN>19 weeks were characterized by longer duration of androgen deprivation therapy, better performance status, lower incidence of bone metastasis, lower value of nadir PSA, and higher incidence of PSA response than those with TTPN ≤19 weeks in the AA group. The PSA progression-free survival (PFS) in patients with TTPN >19 weeks was significantly superior when compared with TTPN ≤19 weeks in the AA group; however, there was no significant effect of the mean TTPN on the PSA-PFS in the Enz group. Furthermore, TTPN was identified as one of the independent predictors of PSA-PFS in the AA group but not in Enz group. A longer time to reach a PSA nadir after treatment with AA, but not Enz, appeared to be associated with favorable disease control in patients with docetaxel-naïve mCRPC. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2018-03-02

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

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

    PubMed Central

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

    2018-01-01

    Background Prostaglandin E2 (PGE2) receptor 3 (EP3) regulates tumor cell proliferation, migration, and invasion in numerous cancers. The role of EP3 as a prognostic biomarker in endometrial cancer remains unclear. The primary aim of this study was to analyze the prognostic significance of EP3 expression in endometrial cancer. Methods We analyzed the EP3 expression of 140 endometrial carcinoma patients by immunohistochemistry. RL95-2 endometrial cancer cell line was chosen from four endometrial cancer cell lines (RL95-2, Ishikawa, HEC-1-A, and HEC-1-B) according to EP3 expression level. Treated with PGE2 and EP3 antagonist, RL95-2 cells were investigated by MTT, BrdU, and wound healing assay for functional assessment of EP3. Results EP3 staining differed significantly according to WHO tumor grading in both whole cohort (p = 0.01) and the subgroup of endometrioid carcinoma (p = 0.01). Patients with high EP3 expression in their respective tumors had impaired progression-free survival as well as overall survival in both cohorts above. EP3 expression in the overall cohort was identified as an independent prognostic marker for progression-free survival (HR 1.014, 95%CI 1.003-1.024, p = 0.01) when adjusted for age, stage, grading, and recurrence. Treatment with EP3 antagonists induced upregulation of estrogen receptor β and decreased activity of Ras and led to attenuated proliferation and migration of RL95-2 cells. Conclusions EP3 seems to play a crucial role in endometrial cancer progression. In the context of limited systemic treatment options for endometrial cancer, this explorative analysis identifies EP3 as a potential target for diagnostic workup and therapy. PMID:29416671

  18. The factor structure of static actuarial items: its relation to prediction.

    PubMed

    Barbaree, Howard E; Langton, Calvin M; Peacock, Edward J

    2006-04-01

    Principal components analysis was conducted on items contained in actuarial instruments used with adult sex offenders, including: the Rapid Assessment of Sex Offender Risk for Recidivism (RASORR), the Static-99, the Violence Risk Appraisal Guide (VRAG), the Sex Offender Risk Appraisal Guide (SORAG), and the Minnesota Sex Offender Screening Tool-Revised (MnSOST-R). In a data set that included child molesters and rapists (N = 311), six interpretable components were identified: Antisocial Behavior, Child Sexual Abuse, Persistence, Detached Predatory Behavior, Young and Single, and Male Victim(s). The RRASOR was highly correlated with Persistence, and the VRAG and SORAG were highly correlated with Antisocial Behavior. Antisocial Behavior was a significant predictor of violent recidivism, while Persistence and Child Sexual Abuse were significant predictors of sexual recidivism.

  19. Long-term outcome in BRAF(V600E) melanoma patients treated with vemurafenib: Patterns of disease progression and clinical management of limited progression.

    PubMed

    Puzanov, Igor; Amaravadi, Ravi K; McArthur, Grant A; Flaherty, Keith T; Chapman, Paul B; Sosman, Jeffrey A; Ribas, Antoni; Shackleton, Mark; Hwu, Patrick; Chmielowski, Bartosz; Nolop, Keith B; Lin, Paul S; Kim, Kevin B

    2015-07-01

    Vemurafenib induces tumour regression in most patients with BRAF(V600E)-mutant melanoma; eventually, most experience progressive disease (PD). Long-term follow-up of patients with BRAF(V600E) melanoma treated in the phase 1 vemurafenib trial is reported. Patients received vemurafenib 240-1120 mg (dose escalation cohort) or 960 mg (extension cohort) orally twice daily. Clinical response was evaluated every 8 weeks by Response Evaluation Criteria In Solid Tumors (RECIST). Patients with PD amenable to local therapy (surgery or radiotherapy) were allowed to continue vemurafenib after progression. Overall survival (OS) from time of treatment initiation and from PD was estimated. Sites of PD were recorded. Forty-eight patients (escalation cohort, n = 16; extension cohort, n = 32) received therapeutic doses of vemurafenib (⩾ 240 mg twice daily). Forty-four patients had PD by the time of this analysis and four remained progression free (follow-up time, 1.2-56.1 months). Median OS was 14 months (range, 1.2-56.1); 3- and 4-year melanoma-specific survival rate in the extension cohort was 26% and 19%, respectively. Median OS was 26.0 months (range, 7.7-56.1) among 20 patients who continued vemurafenib after local therapy. Median treatment duration beyond initial PD was 3.8 months (range, 1.1-26.6). In the extension cohort, six and five patients were alive after 3 and 4 years, respectively, on vemurafenib monotherapy. Some patients with melanoma achieved long-term survival with vemurafenib monotherapy. Continuation of vemurafenib after PD might be beneficial in some patients because remaining disease might continue to respond to BRAF inhibition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. [Multi-disciplinary treatment increases the survival rate of late stage pharyngeal, laryngeal or cervical esophageal cancers treated by free jejunal flap reconstruction after cancer resection].

    PubMed

    Zhu, Y M; Zhang, H; Ni, S; Wang, J; Li, D Z; Liu, S Y

    2016-05-23

    To investigate the survival status of patients with pharyngeal, laryngeal or cervical esophageal cancers, who received free jejunal flap (FJF) to repair the defects following tumor resection, and to analyze the effect of multi-disciplinary treatment on their survival. Fifty-eight patients with pharyngeal, laryngeal or cervical esophageal cancer underwent free jejunal flap (FJF) reconstruction after cancer resection between 2010 and 2013. All their clinical records were reviewed and analyzed. The success rate of flap transplantation was 91.4% (53/58). The 2-year overall survival rates (OSR) of cervical esophageal cancer and hypopharyngeal cancer patients were 67.5% and 49.3%, respectively, both were significantly better than that of laryngeal cancer. The main causes of death were local recurrence and distant metastases. The group with no short-term complications had a better two-year OSR (59.0%) than the group with short-term complications (46.6%), however, the difference between them was not significant (P=0.103). The 2-year survival rate of the initial treatment group was 65.0%, better than that of the salvage treatment group (49.4%), but the difference was not significant (P=0.051). For the stage III and IV patients, the multi-disciplinary treatment group had a significantly better 2-year OSR (64.7%) than the single or sequential treatment group (37.0%, P=0.016). Free jejunal flap reconstruction is an ideal option for repairing the cervical digestive tract circumferential defects caused by tumor resection with a high success rate and a low mortality. Compared with the single or sequential treatment, multi-disciplinary treatment can significantly improve the survival rate of late-stage hypopharyngeal and cervical esophageal cancer patients.