Sample records for year disease-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. 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.

  3. 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.

  4. 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

  5. Anti-Heat Shock Protein-27 Antibody Levels in Women with Breast Cancer: Association with Disease Complications and Two-Year Disease-Free Survival

    PubMed Central

    Homaei-Shandiz, Fatemeh; Mehrad-Majd, Hassan; Tasbandi, Mojtaba; Aledavood, Amir; Afshari, Jalil Tavakol; Ghavami, Vahid; Ghayour-Mobarhan, Majid

    2016-01-01

    Background and Aim: Breast cancer is a major healthcare problem in women. There are many reports about up-regulation of Hsp27 in cancer tissues but less is known about the potential relationship between Hsp27 antibody levels and breast cancer complications. We here investigated concentrations of serum Hsp27 antigen and antibodies in subjects with and without breast cancer and assessed potential associations with two-year disease-free survival, histological grade and number of lymph nodes. Materials and Methods: Specifically, serum Hsp27 antigen and antibody levels from 97 patients with breast cancer, and 65 healthy controls were determined by enzyme-linkedimmunosorbent assays (ELISAs). Results: Serum Hsp27 and antibody levels were significantly (p<0.001) higher in patients with breast cancer compared to the control group, but no relationship were found with two-year disease free survival, histological grade or number of lymph nodes (p> 0.6, 0.2 and 0.9 respectively). Conclusions: Elevated levels of Hsp27 antibody occur with women with breast cancer but do not appear to be associated with the presence of disease clinical complications. PMID:27892679

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. Prognostic factors for survival after salvage total laryngectomy following radiotherapy or chemoradiation failure: a 10-year retrospective longitudinal study in eastern Denmark.

    PubMed

    Wulff, N B; Andersen, E; Kristensen, C A; Sørensen, C H; Charabi, B; Homøe, P

    2017-04-01

    The primary aims were to determine the rates of and prognostic factors for overall survival, disease-specific survival and disease-free survival following salvage total laryngectomy. Retrospective longitudinal study. Tertiary medical centres. A total of 142 patients in eastern Denmark undergoing salvage total laryngectomy for squamous cell carcinoma of the larynx or hypopharynx. 5-year overall survival, 5-year disease-specific survival, 5-year disease-free survival and prognostic factors for these outcomes. 5-year overall survival, disease-specific survival and disease-free survival were 37.7%, 54.9% and 55.3%, respectively. N classification at primary diagnosis, lymph node excision and postoperative complications within 1 year after salvage total laryngectomy were prognostic factors for shorter overall survival, disease-specific survival and disease-free survival. Residual tumour/recurrence was negatively associated with overall survival, close or involved resection margins with disease-specific survival, and second primary cancer was associated with longer disease-specific survival and disease-free survival. Nine per cent of all patients had residual tumour and 33.8% developed a recurrence. Our overall survival, disease-specific survival and disease-free survival findings are in accordance with previous studies. With the purpose of identifying recurrent tumour, we suggest extra attention being given to patients with higher N classification and need for lymph node excision during salvage total laryngectomy along with use of frozen sections. The high number of patients with recurrence within 1 year after salvage total laryngectomy occurred although thorough and regular follow-up visits were performed. © 2016 John Wiley & Sons Ltd.

  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. Pathologic complete response and disease-free survival are not surrogate endpoints for 5-year survival in rectal cancer: an analysis of 22 randomized trials.

    PubMed

    Petrelli, Fausto; Borgonovo, Karen; Cabiddu, Mary; Ghilardi, Mara; Lonati, Veronica; Barni, Sandro

    2017-02-01

    We performed a literature-based analysis of randomized clinical trials to assess the pathologic complete response (pCR) (ypT0N0 after neoadjuvant therapy) and 3-year disease-free survival (DFS) as potential surrogate endpoints for 5-year overall survival (OS) in rectal cancer treated with neoadjuvant (chemo)radiotherapy (CT)RT. A systematic literature search of PubMed, EMBASE, the Web of Science, SCOPUS, CINAHL, and the Cochrane Library was performed. Treatment effects on 3-year DFS and 5-year OS were expressed as rates of patients alive (%), and those on pCR as differences in pCR rates (∆ pCR% ). A weighted regression analysis was performed at individual- and trial-level to test the association between treatment effects on surrogate (∆ pCR% and ∆ 3yDFS ) and the main clinical outcome (∆ 5yOS ). Twenty-two trials involving 10,050 patients, were included in the analysis. The individual level surrogacy showed that the pCR% and 3-year DFS were poorly correlated with 5-year OS (R=0.52; 95% CI, 0.31-0.91; P=0.002; and R=0.60; 95% CI, 0.36-1; P=0.002). The trial-level surrogacy analysis confirmed that the two treatment effects on surrogates (∆ pCR% and ∆ 3yDFS ) are not strong surrogates for treatment effects on 5-year OS % (R=0.2; 95% CI, -0.29-0.78; P=0.5 and R=0.64; 95% CI, 0.29-1; P=0.06). These findings were confirmed in neoadjuvant CTRT studies but not in phase III trials were 3-year DFS could still represent a valid surrogate. This analysis does not support the use of pCR and 3-year DFS% as appropriate surrogate endpoints for 5-year OS% in patients with rectal cancer treated with neoadjuvant therapy.

  15. 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.

  16. Survival in Alzheimer disease

    PubMed Central

    Helzner, E P.; Scarmeas, N; Cosentino, S; Tang, M X.; Schupf, N; Stern, Y

    2008-01-01

    Objective: To describe factors associated with survival in Alzheimer disease (AD) in a multiethnic, population-based longitudinal study. Methods: AD cases were identified in the Washington Heights Inwood Columbia Aging Project, a longitudinal, community-based study of cognitive aging in Northern Manhattan. The sample comprised 323 participants who were initially dementia-free but developed AD during study follow-up (incident cases). Participants were followed for an average of 4.1 (up to 12.6) years. Possible factors associated with shorter lifespan were assessed using Cox proportional hazards models with attained age as the time to event (time from birth to death or last follow-up). In subanalyses, median postdiagnosis survival durations were estimated using postdiagnosis study follow-up as the timescale. Results: The mortality rate was 10.7 per 100 person-years. Mortality rates were higher among those diagnosed at older ages, and among Hispanics compared to non-Hispanic whites. The median lifespan of the entire sample was 92.2 years (95% CI: 90.3, 94.1). In a multivariable-adjusted Cox model, history of diabetes and history of hypertension were independently associated with a shorter lifespan. No differences in lifespan were seen by race/ethnicity after multivariable adjustment. The median postdiagnosis survival duration was 3.7 years among non-Hispanic whites, 4.8 years among African Americans, and 7.6 years among Hispanics. Conclusion: Factors influencing survival in Alzheimer disease include race/ethnicity and comorbid diabetes and hypertension. GLOSSARY AD = Alzheimer disease; NDI = National Death Index; WHICAP = Washington Heights Inwood Columbia Aging Project. PMID:18981370

  17. 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

  18. 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

  19. 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

  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. Pediatric differentiated thyroid carcinoma in stage I: risk factor analysis for disease free survival

    PubMed Central

    2009-01-01

    Background To examine the outcomes and risk factors in pediatric differentiated thyroid carcinoma (DTC) patients who were defined as TNM stage I because some patients develop disease recurrence but treatment strategy for such stage I pediatric patients is still controversial. Methods We reviewed 57 consecutive TNM stage I patients (15 years or less) with DTC (46 papillary and 11 follicular) who underwent initial treatment at Ito Hospital between 1962 and 2004 (7 males and 50 females; mean age: 13.1 years; mean follow-up: 17.4 years). Clinicopathological results were evaluated in all patients. Multivariate analysis was performed to reveal the risk factors for disease-free survival (DFS) in these 57 patients. Results Extrathyroid extension and clinical lymphadenopathy at diagnosis were found in 7 and 12 patients, respectively. Subtotal/total thyroidectomy was performed in 23 patients, modified neck dissection in 38, and radioactive iodine therapy in 10. Pathological node metastasis was confirmed in 37 patients (64.9%). Fifteen patients (26.3%) exhibited local recurrence and 3 of them also developed metachronous lung metastasis. Ten of these 15 achieved disease-free after further treatments and no patients died of disease. In multivariate analysis, male gender (p = 0.017), advanced tumor (T3, 4a) stage (p = 0.029), and clinical lymphadenopathy (p = 0.006) were risk factors for DFS in stage I pediatric patients. Conclusion Male gender, tumor stage, and lymphadenopathy are risk factors for DFS in stage I pediatric DTC patients. Aggressive treatment (total thyroidectomy, node dissection, and RI therapy) is considered appropriate for patients with risk factors, whereas conservative or stepwise approach may be acceptable for other patients. PMID:19723317

  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. Preoperative magnetic resonance imaging assessment of circumferential resection margin predicts disease-free survival and local recurrence: 5-year follow-up results of the MERCURY study.

    PubMed

    Taylor, Fiona G M; Quirke, Philip; Heald, Richard J; Moran, Brendan J; Blomqvist, Lennart; Swift, Ian R; Sebag-Montefiore, David; Tekkis, Paris; Brown, Gina

    2014-01-01

    The prognostic relevance of preoperative high-resolution magnetic resonance imaging (MRI) assessment of circumferential resection margin (CRM) involvement is unknown. This follow-up study of 374 patients with rectal cancer reports the relationship between preoperative MRI assessment of CRM staging, American Joint Committee on Cancer (AJCC) TNM stage, and clinical variables with overall survival (OS), disease-free survival (DFS), and time to local recurrence (LR). Patients underwent protocol high-resolution pelvic MRI. Tumor distance to the mesorectal fascia of ≤ 1 mm was recorded as an MRI-involved CRM. A Cox proportional hazards model was used in multivariate analysis to determine the relationship of MRI assessment of CRM to survivorship after adjusting for preoperative covariates. Surviving patients were followed for a median of 62 months. The 5-year OS was 62.2% in patients with MRI-clear CRM compared with 42.2% in patients with MRI-involved CRM with a hazard ratio (HR) of 1.97 (95% CI, 1.27 to 3.04; P < .01). The 5-year DFS was 67.2% (95% CI, 61.4% to 73%) for MRI-clear CRM compared with 47.3% (95% CI, 33.7% to 60.9%) for MRI-involved CRM with an HR of 1.65 (95% CI, 1.01 to 2.69; P < .05). Local recurrence HR for MRI-involved CRM was 3.50 (95% CI, 1.53 to 8.00; P < .05). MRI-involved CRM was the only preoperative staging parameter that remained significant for OS, DFS, and LR on multivariate analysis. High-resolution MRI preoperative assessment of CRM status is superior to AJCC TNM-based criteria for assessing risk of LR, DFS, and OS. Furthermore, MRI CRM involvement is significantly associated with distant metastatic disease; therefore, colorectal cancer teams could intensify treatment and follow-up accordingly to improve survival outcomes.

  4. 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

  5. Influence of complete administration of adjuvant chemotherapy cycles on overall and disease-free survival in locally advanced rectal cancer: post hoc analysis of a randomized, multicenter, non-inferiority, phase 3 trial.

    PubMed

    Sandra-Petrescu, Flavius; Herrle, Florian; Burkholder, Iris; Kienle, Peter; Hofheinz, Ralf-Dieter

    2018-04-03

    A randomized trial demonstrated that capecitabine is at least as effective as fluorouracil in the adjuvant treatment of patients with locally advanced rectal cancer. However, not all patients receive all planned cycles of chemotherapy. Therefore it is of interest how complete or partial administration of chemotherapy influences oncological outcome. A post hoc analysis of a trial with 401 randomized patients, nine being excluded because of missing data, was performed. 392 patients (197 - capecitabine, 195 - fluorouracil) could be analyzed regarding the number of administered adjuvant chemotherapy cycles. In the subgroup of 361 patients with an overall survival of at least six months, five-year overall and disease-free survival were analyzed in respect to completion (complete vs. incomplete) of chemotherapy cycles. Survival rates and curves were calculated and compared using the log-rank test. The effect of completion of chemotherapy was adjusted for relevant confounding factors. Two hundred fifty-one (64.0%) of analyzed patients received all postoperative scheduled cycles. Five-year overall survival was significantly better in these patients compared to the incomplete group (76.0 vs. 60.6%, p < 0.0001). Of 361 patients with an overall survival of at least six months, 251(69.5%) patients received all cycles. Five-year overall survival was also significantly better than in the incomplete group (76.0 vs. 66.4%, p = 0.0073). Five-year disease free survival was numerically better (64.9 vs. 58.7%, p = 0.0646; HR [not all cycles vs. all cycles] = 1.42 95% CI: [0.98, 2.07]). Cox regression models show a non-significant better OS (p = 0.061) and DFS (p = 0.083), if chemotherapy cycles were administered completely. Complete administration of chemotherapy cycles was associated with improved five-year overall and disease-free survival in patients with locally advanced rectal cancer.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. Ten-year Biochemical Disease-free Survival After High-intensity Focused Ultrasound (HIFU) for Localized Prostate Cancer: Comparison with Four Different Generation Devices

    NASA Astrophysics Data System (ADS)

    Uchida, T.; Nakano, M.; Shoji, S.; Omata, T.; Harano, Y.; Nagata, Y.; Usui, Y.; Terachi, T.

    2010-03-01

    HIFU has been recognized as a minimally invasive treatment option for localized prostate cancer. The purpose of the study was to assess with a long-term outcome of HIFU for prostate cancer. From January 1999, a total of 657 patients who had HIFU with at least 2 year follow-up were treated with four different types of Sonablate® (Focus Surgery, Indianapolis, USA) devices. Thirty-three patients were treated with Sonablate® 200 (S200) from 1999 to 2001, 406 patients with Sonablate® 500 (S500) from 2001 to 2005, 200 patients with Sonablate® 500 version 4 (V4) from 2005-2008 and 19 patients with Sonablate® 500 TCM (TCM) from 2007. Biochemical disease-free survival rate (bDFS) in all patients was 59% in 8 years. bDFS in 8 years in patients with S200 and S500 groups were 55% and 56%, and bDFS in 4 and 2 years in patients with V4 and TCM group were 72% and 84%, respectively. bDFS in low, intermediate, and high risk groups were 75%, 54%, and 43% in S200/S500 and 93%, 72%, and 58% in V4/TCM group. Negative prostate biopsy rate after HIFU was 97% in S200, 79% in S500, 94% in V4 and 100% in TCM group. HIFU as primary therapy for prostate cancer is indicated in patients with low- and intermediate-risk (T1-T2b N0M0 disease, a Gleason score of ⩽7, a PSA level of <20 ng/mL) and a prostate volume of less than 40 mL. The rate of clinical outcome has significantly improved over the years due to technical improvements in the device.

  12. 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.

  13. 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.

  14. 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

  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. [Disease-free survival related factors in breast cancer].

    PubMed

    Dávila-Arias, Cristina; Ocón, Olga; Fernández, Mariana F; Arrebola, Juan Pedro; Sánchez, María José; Aneiros, José; Torné, Pablo; Olea, Nicolás

    2014-10-07

    To evaluate the relationship between the clinical and pathological parameters of the primary tumor and disease-free survival (DFS) in a sample of hospital cases of invasive breast cancer. We performed a retrospective cohort study in 635 patients recruited at San Cecilio University Hospital in Granada (Spain) between 1994 and 2006. Information on the primary tumor and the outcomes of patients was collected by reviewing the medical records. Predictors of recurrence and/or metastasis and DFS (follow up of 3, 5 and 10 years) were analyzed by using Cox regression analysis. Multivariate models adjusted for age, tumor size, lymph nodal status, histological grade and estrogen and progesterone receptor expression showed a higher risk of recurrence and/or metastasis and lower DFS (adjusted relative risk, 95% confidence intervals) with tumor size (3 yrs: 3.00, 1.79-5.03; 5 yrs: 2.56, 1.65-3.98; 10 yrs: 2.16, 1.44-3.24), lymph nodal status (3 yrs: 4.58, 2.42-8.65; 5 yrs: 3.84, 2.35-6.30; 10 yrs: 3.08, 2.05-4.61), lymphovascular invasion (5 yrs: 1.88, 1.16-3.04; 10 yrs: 2.19, 1.43-3.35), multifocal and/or multicenter tumors (3 yrs: 2.69, 1.46-4.96; 5 yrs: 1.90, 1.08-3.35) and p53 protein expression (3 yrs: 2.03, 1.00-4.09). DFS was positively associated with an increased expression of progesterone receptor (3 yr: 0.48, 0.26-0.89; 5 yrs: 0.58, 0.35-0.97; 10 yrs: 0.59, 0.38-0.90). The biological characteristics of the primary tumor can be used to identify patients with distinctive prognoses and DFS, and could be helpful in making individual follow up strategies. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  17. 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

  18. Two-year survival of severe chronic obstructive pulmonary disease subjects requiring invasive mechanical ventilation and the factors affecting survival.

    PubMed

    Asker, Selvi; Ozbay, Bulent; Ekin, Selami; Yildiz, Hanifi; Sertogullarindan, Bunyamin

    2016-05-01

    To investigate two-year survival rates and the factors affecting survival in patients of severe chronic obstructive pulmonary disease requiring invasive mechanical ventilation. The retrospective study was conducted at Yuzuncuy?l University, Van, Turkey, and comprised record of in-patients with moderate to severe chronic obstructive pulmonary disease who required invasive mechanical ventilation in the intensive care unit of the Pulmonary Diseases Department between January 2007 and December 2010. Correlation between survival and parameters such as age, gender, duration of illness, history of smoking, arterial blood gas values, pulmonary artery pressure, left ventricular ejection fraction, body mass index and laboratory findings were investigated. SPSS 19 was used for statistical analysis. Of the 69 severe COPD subjects available, 20 (29%) were excluded as they did not meet the inclusion criteria. Overall in-hospital mortality rate was 42% (n:29). Of the remaining 20 (29%) who comprised the study group, 14(70%) were men and 6(30%) were women. The mortality rates at the end of 3rd, 6th, 12th and 24th months were 61%, 76%, 84% and 85.5% respectively. There was no correlation between gender and survival in time point (p>0.05). The only factor that affected the rate of mortality at the end of the 3rd month was age (p<0.05). Mortality was high in subjects with advanced ages (p<0.05). Duration of illness affected the survival at the end of the six month (p<0.05). Survival rates were high in subjects with longer illness durations (p<0.05). Haematocrit level was the only factor that affected mortality rates at the end of 12th and 24th months (p<0.05). Subjects with higher haematocrit levels had higher survival rates (p<0.05). Age, duration of illness and haematocrit levels were the most important factors that affected survival in chronic obstructive pulmonary disease patients requiring mechanical ventilation.

  19. 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

  20. 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.

  1. Free disease long-term survival in primary thoracic spine leiomyosarcoma after total en bloc spondylectomy: A case report.

    PubMed

    Ramirez-Villaescusa, José; Canosa-Fernández, Adriana; Martin-Benlloch, Antonio; Ruiz-Picazo, David; López-Torres Hidalgo, Jesús

    2017-01-01

    To describe an unusual primary vertebral leiomyosarcoma in thoracic spine. An isolated lesion of the T11 vertebra in a 62-year-old woman with no neurologic deficit is reported. Imaging findings indicated a nonspecific high-grade malignant lesion. TC-guided biopsy failed thus open incisional biopsy was needed. A diagnosis of low-intermediate mesenchymal sarcoma was made. A total en bloc spondylectomy of T11 was performed with three-column reconstruction. The histology and immunostaining showed the appearance of leiomyosarcoma. After diagnosis, post-operative radiation therapy was performed. Metastatic lesion was ruled out by CT scans of the chest, abdomen and pelvis, in addition to total body radionuclide scanning and 18-F-FDG-PET. After five years of follow-up, no signs of local recurrence, metastasis or distant lesions suggesting a primary lesion were observed. Vertebral primary leiomyosarcoma is exceedingly rare. Primary vertebral leiomyosarcoma diagnosis must be performed when the metastatic origin is excluded. For the treatment of primary tumors, total en bloc spondylectomy (TES) is the technique of choice to achieve marginal or wide tumor resection, decrease the risk of local recurrence and remote lesions and increase survival. A well-planned pre-operative study and a wide surgical excision can result in local tumor control and long-term survival. This case presents the longest disease-free survival period of a primary leiomyosarcoma in spinal location after total en bloc spondylectomy. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  2. 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

  3. 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

  4. 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.

  5. Survival after initial diagnosis of Alzheimer disease.

    PubMed

    Larson, Eric B; Shadlen, Marie-Florence; Wang, Li; McCormick, Wayne C; Bowen, James D; Teri, Linda; Kukull, Walter A

    2004-04-06

    Alzheimer disease is an increasingly common condition in older people. Knowledge of life expectancy after the diagnosis of Alzheimer disease and of associations of patient characteristics with survival may help planning for future care. To investigate the course of Alzheimer disease after initial diagnosis and examine associations hypothesized to correlate with survival among community-dwelling patients with Alzheimer disease. Prospective observational study. An Alzheimer disease patient registry from a base population of 23 000 persons age 60 years and older in the Group Health Cooperative, Seattle, Washington. 521 newly recognized persons with Alzheimer disease enrolled from 1987 to 1996 in an Alzheimer disease patient registry. Baseline measurements included patient demographic features, Mini-Mental State Examination score, Blessed Dementia Rating Scale score, duration since reported onset of symptoms, associated symptoms, comorbid conditions, and selected signs. Survival was the outcome of interest. The median survival from initial diagnosis was 4.2 years for men and 5.7 years for women with Alzheimer disease. Men had poorer survival across all age groups compared with females. Survival was decreased in all age groups compared with the life expectancy of the U.S. population. Predictors of mortality based on proportional hazards models included a baseline Mini-Mental State Examination score of 17 or less, baseline Blessed Dementia Rating Scale score of 5.0 or greater, presence of frontal lobe release signs, presence of extrapyramidal signs, gait disturbance, history of falls, congestive heart failure, ischemic heart disease, and diabetes at baseline. The base population, although typical of the surrounding Seattle community, may not be representative of other, more diverse populations. In this sample of community-dwelling elderly persons who received a diagnosis of Alzheimer disease, survival duration was shorter than predicted on the basis of U.S. population

  6. Zoonotic diseases associated with free-roaming cats.

    PubMed

    Gerhold, R W; Jessup, D A

    2013-05-01

    Free-roaming cat populations have been identified as a significant public health threat and are a source for several zoonotic diseases including rabies, toxoplasmosis, cutaneous larval migrans because of various nematode parasites, plague, tularemia and murine typhus. Several of these diseases are reported to cause mortality in humans and can cause other important health issues including abortion, blindness, pruritic skin rashes and other various symptoms. A recent case of rabies in a young girl from California that likely was transmitted by a free-roaming cat underscores that free-roaming cats can be a source of zoonotic diseases. Increased attention has been placed on trap-neuter-release (TNR) programmes as a viable tool to manage cat populations. However, some studies have shown that TNR leads to increased immigration of unneutered cats into neutered populations as well as increased kitten survival in neutered groups. These compensatory mechanisms in neutered groups leading to increased kitten survival and immigration would confound rabies vaccination campaigns and produce naïve populations of cats that can serve as source of zoonotic disease agents owing to lack of immunity. This manuscript is a review of the various diseases of free-roaming cats and the public health implications associated with the cat populations. © 2012 Blackwell Verlag GmbH.

  7. 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...

  8. 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

  9. 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.

  10. 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

  11. 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.

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

    PubMed

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

    2017-10-12

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

  13. Prostate-Specific Antigen at 4 to 5 Years After Low-Dose-Rate Prostate Brachytherapy Is a Strong Predictor of Disease-Free Survival

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

    Lo, Andrea C.; Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia; Morris, W. James, E-mail: JMorris@bccancer.bc.ca

    2014-01-01

    Purpose: To determine (1) the prognostic utility of prostate-specific antigen (PSA) concentration at 45 to 60 months (48mPSA) after low-dose-rate prostate brachytherapy (LDR-PB); (2) the predictors of 48mPSA; and (3) the prognostic utility of directional trends between PSA levels at 24, 36, and 48 months after LDR-PB. Methods and Materials: Between 1998 and 2008, 2223 patients with low- and intermediate-risk prostate cancer received LDR-PB monotherapy. A cohort of 1434 of these patients was identified with a documented 48mPSA and no evidence of disease relapse prior to the 48mPSA. In addition, a subset of this cohort (n=585) was identified with ≥72more » months of follow-up and documented PSA values at both 24 and 36 months after implantation. Results: Median follow-up time was 76 months. Eight-year Kaplan-Meier disease-free survival (DFS) rates were 100% vs 73.4% for patients with 48mPSA ≤0.2 vs those with >0.2 ng/mL; 99.1% versus 53.8% for a 48mPSA threshold of ≤0.4 versus >0.4 ng/mL, respectively; and 97.3% versus 0% for a threshold of ≤1.0 versus >1.0 ng/mL, respectively. On multivariate analysis, the only factor predictive of DFS was 48mPSA (P<.0001). On subset analysis (n=585), 29 patients had a PSA rise (defined as >0.2 ng/mL) between 24 and 36 months, 24 patients had a rise between 36 and 48 months, and 11 patients had rises over both intervals. Failure rates in these patients were 52%, 79%, and 100%, respectively. On multivariate analysis, initial PSA, androgen deprivation therapy, and dose to 90% of the prostate significantly correlated with 48mPSA but together accounted for only ∼5% of its total variance. Conclusions: The 48mPSA after LDR-PB is highly predictive of long-term DFS. Patients with 48mPSA ≤0.4 ng/mL had a <1% risk of disease relapse at 8 years, whereas all patients with 48mPSA >1.0 ng/mL relapsed. Consecutive PSA rises of >0.2 ng/mL from 24 to 36 months and from 36 to 48 months were also highly predictive of subsequent failure.« less

  14. 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.

  15. 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

  16. Relapse and disease specific survival in 1143 Danish women diagnosed with borderline ovarian tumours (BOT).

    PubMed

    Karlsen, Nikoline Marie Schou; Karlsen, Mona Aarenstrup; Høgdall, Estrid; Nedergaard, Lotte; Christensen, Ib Jarle; Høgdall, Claus

    2016-07-01

    The aim of the study was to evaluate the rate of relapse as well as disease-free, overall, and disease-specific survival in women with borderline ovarian tumour (BOT). Furthermore, the study aims to identify the clinical parameters correlated to relapse. National clinical data of women diagnosed with BOT from January 2005 to January 2013 constituted the basis for our study population. The prognostic influence of clinical variables was evaluated using univariate and multivariate analyses. A total of 1143 women were eligible for analysis, with 87.9% in FIGO stage I and 12.1% in FIGO stages II-IV. Relapse of BOT was detected in 3.7%, hereof 40.5% with malignant transformation. The five-year disease-free survival was 97.6% in FIGO stage I and 87.3% in FIGO stages II-IV. Younger age, laparoscopic surgical approach, fertility sparing surgery, FIGO stages II-IV, bilateral tumour presence, serous histology, implants and microinvasion of the tumour were significantly associated with relapse in univariate analyses. The overall five-year survival rate was 92.2% in FIGO stage I and 89.0% in FIGO stages II-IV. Out of 77 deaths in total, only seven women died from BOT. A general favourable prognosis in women with BOT was confirmed in our study. Our findings indicate that systematic, long-term follow-up does not seem necessary in women treated for FIGO stage IA BOT with no residual disease or microinvasion. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed

    Gill, Sharlene; Sargent, Daniel

    2006-06-01

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

  18. Survival of patients with Ewing's sarcoma in Yazd-Iran.

    PubMed

    Akhavan, Ali; Binesh, Fariba; Shamshiri, Hadi; Ghanadi, Fazllolah

    2014-01-01

    The Ewing's sarcoma family is a group of small round cell tumors which accounts for 10-15% of all primary bone neoplasms. The aim of this study was to evaluate the survival of Ewing's sarcoma patients in our province and to determine of influencing factors. All patients with documented Ewing's sarcoma/ primitive neuroectodermal tumor(PNET) family pathology were enrolled in this study during a period of eight years. For all of them local and systemic therapy were carried out. Overall and event free survival and prognostic factors were evaluated. Thirty two patients were enrolled in the study. The median age was 17.5 years. Twenty (65.2%) were male and 9 (28.1%) were aged 14 years or less. Mean disease free survival was 26.8 (95%CI; 13.8-39.9) months and five year disease free survival was 26%. Mean overall survival was 38.7 months (95%CI; 25.9-50.6) and median overall survival was 24 months. Five year overall survival was 25%. From the variables evaluated , only presence of metastatic disease at presentation (p value=0. 028) and complete response (p value =0. 006) had significant relations to overall survival. Survival of Ewing's sarcoma in our province is disappointing. It seems to be mostly due to less effective treatment. Administration of adequate chemotherapy dosage, resection of tumor with negative margins and precise assessment of irradiation volume may prove helpful.

  19. 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

  20. 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.

  1. Complete embedding and close step-sectioning of radical prostatectomy specimens both increase detection of extra-prostatic extension, and correlate with increased disease-free survival by stage of prostate cancer patients.

    PubMed

    Desai, A; Wu, H; Sun, L; Sesterhenn, I A; Mostofi, F K; McLeod, D; Amling, C; Kusuda, L; Lance, R; Herring, J; Foley, J; Baldwin, D; Bishoff, J T; Soderdahl, D; Moul, J W

    2002-01-01

    The objectives of this work were to evaluate the efficacy of controlled close step-sectioned and whole-mounted radical prostatectomy specimen processing in prediction of clinical outcome as compared to the traditional processing techniques. Two-hundred and forty nine radical prostatectomy (RP) specimens were whole-mounted and close step-sectioned at caliper-measured 2.2-2.3 mm intervals. A group of 682 radical prostatectomy specimens were partially sampled as control. The RPs were performed during 1993-1999 with a mean follow-up of 29.3 months, pretreatment PSA of 0.1-40, and biopsy Gleason sums of 5-8. Disease-free survival based on biochemical or clinical recurrence and secondary intervention were computed using a Kaplan-Meier analysis. There were no significant differences in age at diagnosis, age at surgery, PSA at diagnosis, or biopsy Gleason between the two groups (P<0.05). Compared with the non-close step-sectioned group, the close step-sectioned group showed higher detection rates of extra-prostatic extension (215 (34.1%) vs, 128 (55.4%), P<0.01), and seminal vesicle invasion (50 (7.6%) vs 35 (14.7%), P<0.01). The close step-sectioned group correlated with greater 3-y disease-free survival in organ-confined (P<0.01) and specimen-confined (P<0.01) cases, over the non-uniform group. The close step-sectioned group showed significantly higher disease-free survival for cases with seminal vesicle invasion (P=0.046). No significant difference in disease-free survival was found for the positive margin group (P=0.39) between the close step-sectioned and non-uniform groups. The close step-sectioned technique correlates with increased disease-free survival rates for organ and specimen confined cases, possibly due to higher detection rates of extra-prostatic extension and seminal vesicle invasion. Close step-sectioning provides better assurance of organ-confined disease, resulting in enhanced prediction of outcome by pathological (TNM) stage.

  2. Primary cutaneous marginal zone B-cell lymphoma: response to treatment and disease-free survival in a series of 137 patients.

    PubMed

    Servitje, Octavio; Muniesa, Cristina; Benavente, Yolanda; Monsálvez, Verónica; Garcia-Muret, M Pilar; Gallardo, Fernando; Domingo-Domenech, Eva; Lucas, Anna; Climent, Fina; Rodriguez-Peralto, Jose L; Ortiz-Romero, Pablo L; Sandoval, Juan; Pujol, Ramon M; Estrach, M Teresa

    2013-09-01

    Primary cutaneous marginal zone B-cell lymphomas are low-grade lymphomas running an indolent course. Skin relapses have been frequently reported but little information about disease-free survival (DFS) is available. We sought to evaluate relapse rate and DFS in patients with primary cutaneous marginal zone B-cell lymphomas. Clinical features, European Organization for Research and Treatment of Cancer/International Society for Cutaneous Lymphomas stage, light chain restriction, clonality, treatments, skin relapses, DFS, stage progression, extracutaneous disease, and outcome are analyzed in a series of 137 patients. Patients were classified as solitary lesion (T1) (n = 70; 51%), regional skin involvement (T2) (n = 40; 29%), and generalized skin lesions (T3) (n = 27; 20%). Surgical excision, local radiotherapy, or a combination were the initial treatment in 118 patients (86%). In 121 of 137 patients (88%) a complete remission was observed after initial treatment, including 99 of 106 patients (93%) with solitary or localized disease and 22 of 31 patients (71%) with multifocal lesions. Cutaneous relapses were observed in 53 patients (44%). Median DFS was 47 months. Patients with multifocal lesions or T3 disease showed higher relapse rate and shorter DFS. No significant differences were observed between surgery and radiotherapy, but surgery alone was associated with more recurrences at initial site. Overall survival at 5 and 10 years was 93%. Six patients (4%) developed extracutaneous disease during follow-up. This was a case series retrospective study. Our results support long-term follow-up in patients with primary cutaneous marginal zone B-cell lymphomas. Disseminated skin lesions have higher relapse rate and shorter DFS suggesting further investigation on systemic therapies in such a group of patients. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  3. 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

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

    PubMed

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

    2015-09-01

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

  5. Magnetic resonance imaging in breast cancer treated with neoadjuvant chemotherapy: radiologic-pathologic correlation of the response and disease-free survival depending on molecular subtype.

    PubMed

    Cruz Ciria, S; Jiménez Aragón, F; García Mur, C; Esteban Cuesta, H; Gros Bañeres, B

    2014-01-01

    To evaluate the radiologic and pathologic responses to neoadjuvant chemotherapy and their correlation in the molecular subtypes of breast cancer and to analyze their impact in disease-free survival. We included 205 patients with breast cancer treated with neoadjuvant chemotherapy. We evaluated the radiologic response by comparing MRI images acquired before and after chemotherapy. The pathologic response was classified on the Miller and Payne scale. For each subtype (HER2+, TN, luminal A, luminal B HER2-, and luminal B HER2+), we used the χ(2) test, Student's t-test, ANOVA, and Kendall's Tau-b to evaluate the radiologic response and the pathologic response, the radiologic-pathologic correlation, and the disease-free survival. The subtypes HER2+ (62.1%) and TN (45.2%) had higher rates of complete radiologic response. The pathologic response was 65.5% in the HER2+ subtype, 38.1% in the TN subtype, 2.6% in the luminal A subtype, 8.2% in the luminal B HER2- subtype, and 31% in the luminal B HER2+ subtype. The rate of radiologic-pathologic correlation was significant in all subtypes, higher in TN and HER2 (Tau-b coefficients 0.805 and 0.717, respectively). Disease-free survival was higher in HER2+ (91.9±3.3 months) and lower in TN (69.5±6.3 months), with significant differences between the cases with poor and good radiologic responses (P=.040). Survival was greater in cases with good radiologic response, except in cases with luminal A subtype. MRI can be a useful tool that provides information about the evolution of breast cancer treated with neoadjuvant chemotherapy, which varies with the immunohistochemical subtype. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

  6. Performance evaluation of 4 measuring methods of ground-glass opacities for predicting the 5-year relapse-free survival of patients with peripheral nonsmall cell lung cancer: a multicenter study.

    PubMed

    Kakinuma, Ryutaro; Kodama, Ken; Yamada, Kouzo; Yokoyama, Akira; Adachi, Shuji; Mori, Kiyoshi; Fukuyama, Yasuro; Fukuda, Yasuro; Kuriyama, Keiko; Oda, Junichi; Oda, Junji; Noguchi, Masayuki; Matsuno, Yoshihiro; Yokose, Tomoyuki; Ohmatsu, Hironobu; Nishiwaki, Yutaka

    2008-01-01

    To evaluate the performance of 4 methods of measuring the extent of ground-glass opacities as a means of predicting the 5-year relapse-free survival of patients with peripheral nonsmall cell lung cancer (NSLC). Ground-glass opacities on thin-section computed tomographic images of 120 peripheral NSLCs were measured at 7 medical institutions by the length, area, modified length, and vanishing ratio (VR) methods. The performance (Az) of each method in predicting the 5-year relapse-free survival was evaluated using receiver operating characteristic analysis. The mean Az value obtained by the length, area, modified length, and VR methods in the receiver operating characteristic analyses was 0.683, 0.702, 0.728, and 0.784, respectively. The differences between the mean Az value obtained by the VR method and by the other 3 methods were significant. Vanishing ratio method was the most accurate predictor of the 5-year relapse-free survival of patients with peripheral NSLC.

  7. Survival and Late Effects after Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancy at Less than Three Years of Age.

    PubMed

    Vrooman, Lynda M; Millard, Heather R; Brazauskas, Ruta; Majhail, Navneet S; Battiwalla, Minoo; Flowers, Mary E; Savani, Bipin N; Akpek, Görgün; Aljurf, Mahmoud; Bajwa, Rajinder; Baker, K Scott; Beitinjaneh, Amer; Bitan, Menachem; Buchbinder, David; Chow, Eric; Dandoy, Christopher; Dietz, Andrew C; Diller, Lisa; Gale, Robert Peter; Hashmi, Shahrukh K; Hayashi, Robert J; Hematti, Peiman; Kamble, Rammurti T; Kasow, Kimberly A; Kletzel, Morris; Lazarus, Hillard M; Malone, Adriana K; Marks, David I; O'Brien, Tracey A; Olsson, Richard F; Ringden, Olle; Seo, Sachiko; Steinberg, Amir; Yu, Lolie C; Warwick, Anne; Shaw, Bronwen; Duncan, Christine

    2017-08-01

    Very young children undergoing hematopoietic cell transplantation (HCT) are a unique and vulnerable population. We analyzed outcomes of 717 patients from 117 centers who survived relapse free for ≥1 year after allogeneic myeloablative HCT for hematologic malignancy at <3 years of age, between 1987 and 2012. The median follow-up was 8.3 years (range, 1.0 to 26.4 years); median age at follow-up was 9 years (range, 2 to 29 years). Ten-year overall and relapse-free survival were 87% (95% confidence interval [CI], 85% to 90%) and 84% (95% CI, 81% to 87%). Ten-year cumulative incidence of relapse was 11% (95% CI, 9% to 13%). Of 84 deaths, relapse was the leading cause (43%). Chronic graft-versus-host-disease 1 year after HCT was associated with increased risk of mortality (hazard ratio [HR], 2.1; 95% CI, 1.3 to 3.3; P = .0018). Thirty percent of patients experienced ≥1 organ toxicity/late effect >1 year after HCT. The most frequent late effects included growth hormone deficiency/growth disturbance (10-year cumulative incidence, 23%; 95% CI, 19% to 28%), cataracts (18%; 95% CI, 15% to 22%), hypothyroidism (13%; 95% CI, 10% to 16%), gonadal dysfunction/infertility requiring hormone replacement (3%; 95% CI, 2% to 5%), and stroke/seizure (3%; 95% CI, 2% to 5%). Subsequent malignancy was reported in 3.6%. In multivariable analysis, total body irradiation (TBI) was predictive of increased risk of cataracts (HR, 17.2; 95% CI, 7.4 to 39.8; P < .001), growth deficiency (HR, 3.5; 95% CI, 2.2 to 5.5; P < .001), and hypothyroidism (HR, 5.3; 95% CI, 3.0 to 9.4; P < .001). In summary, those who survived relapse free ≥1 year after HCT for hematologic malignancy at <3 years of age had favorable overall survival. Chronic graft-versus-host-disease and TBI were associated with adverse outcomes. Future efforts should focus on reducing the risk of relapse and late effects after HCT at early age. Copyright © 2017 The American Society for Blood and Marrow Transplantation

  8. Overexpression of chemokine receptor CXCR2 and ligand CXCL7 in liver metastases from colon cancer is correlated to shorter disease-free and overall survival

    PubMed Central

    Desurmont, Thibault; Skrypek, Nicolas; Duhamel, Alain; Jonckheere, Nicolas; Millet, Guillaume; Leteurtre, Emmanuelle; Gosset, Pierre; Duchene, Belinda; Ramdane, Nassima; Hebbar, Mohamed; Van Seuningen, Isabelle; Pruvot, François-René; Huet, Guillemette; Truant, Stéphanie

    2015-01-01

    Our aim was to analyze the potential role of chemokine receptors CXCR2 and CXCR4 signalling pathways in liver metastatic colorectal cancer (CRC) relapse. CXCR2, CXCR4, and their chemokine ligands were evaluated in liver metastases of colorectal cancer in order to study their correlation with overall and disease-free survival of patients having received, or not received, a neoadjuvant chemotherapy regimen. Quantitative RT-PCR and CXCR2 immunohistochemical staining were carried out using CRC liver metastasis samples. Expression levels of CXCR2, CXCR4, and their ligands were statistically analyzed according to treatment with neoadjuvant chemotherapy and patients’ outcome. CXCR2 and CXCL7 overexpression are correlated to shorter overall and disease-free survival. By multivariate analysis, CXCR2 and CXCL7 expressions are independent factors of overall and disease-free survival. Neoadjuvant chemotherapy increases significantly the expression of CXCR2: treated group 1.89 (0.02–50.92) vs 0.55 (0.07–3.22), P = 0.016. CXCL7 was overexpressed close to significance, 0.40 (0.00–7.85) vs 0.15 (0.01–7.88), P = 0.12. We show the involvement of CXCL7/CXCR2 signalling pathways as a predictive factor of poor outcome in metastatic CRC. 5-Fluorouracil-based chemotherapy regimens increase the expression of these genes in liver metastasis, providing one explanation for aggressiveness of relapsed drug-resistant tumors. Selective blockage of CXCR2/CXCL7 signalling pathways could provide new potential therapeutic opportunities. PMID:25580640

  9. Failure-free survival after second-line systemic treatment of chronic graft-versus-host disease

    PubMed Central

    Storer, Barry E.; Lee, Stephanie J.; Carpenter, Paul A.; Sandmaier, Brenda M.; Flowers, Mary E. D.; Martin, Paul J.

    2013-01-01

    This study attempted to characterize causes of treatment failure, identify associated prognostic factors, and develop shorter-term end points for trials testing investigational products or regimens for second-line systemic treatment of chronic graft-versus-host disease (GVHD). The study cohort (312 patients) received second-line systemic treatment of chronic GVHD. The primary end point was failure-free survival (FFS) defined by the absence of third-line treatment, nonrelapse mortality, and recurrent malignancy during second-line treatment. Treatment change was the major cause of treatment failure. FFS was 56% at 6 months after second-line treatment. Lower steroid doses at 6 months correlated with subsequent withdrawal of immunosuppressive treatment. Multivariate analysis showed that high-risk disease at transplantation, lower gastrointestinal involvement at second-line treatment, and severe NIH global score at second-line treatment were associated with increased risks of treatment failure. These three factors were used to define risk groups, and success rates at 6 months were calculated for each risk group either without or with various steroid dose limits at 6 months as an additional criterion of success. These success rates could be used as the basis for a clinically relevant and efficient shorter-term end point in clinical studies that evaluate agents for second-line systemic treatment of chronic GVHD. PMID:23321253

  10. Overexpression of chemokine receptor CXCR2 and ligand CXCL7 in liver metastases from colon cancer is correlated to shorter disease-free and overall survival.

    PubMed

    Desurmont, Thibault; Skrypek, Nicolas; Duhamel, Alain; Jonckheere, Nicolas; Millet, Guillaume; Leteurtre, Emmanuelle; Gosset, Pierre; Duchene, Belinda; Ramdane, Nassima; Hebbar, Mohamed; Van Seuningen, Isabelle; Pruvot, François-René; Huet, Guillemette; Truant, Stéphanie

    2015-03-01

    Our aim was to analyze the potential role of chemokine receptors CXCR2 and CXCR4 signalling pathways in liver metastatic colorectal cancer (CRC) relapse. CXCR2, CXCR4, and their chemokine ligands were evaluated in liver metastases of colorectal cancer in order to study their correlation with overall and disease-free survival of patients having received, or not received, a neoadjuvant chemotherapy regimen. Quantitative RT-PCR and CXCR2 immunohistochemical staining were carried out using CRC liver metastasis samples. Expression levels of CXCR2, CXCR4, and their ligands were statistically analyzed according to treatment with neoadjuvant chemotherapy and patients' outcome. CXCR2 and CXCL7 overexpression are correlated to shorter overall and disease-free survival. By multivariate analysis, CXCR2 and CXCL7 expressions are independent factors of overall and disease-free survival. Neoadjuvant chemotherapy increases significantly the expression of CXCR2: treated group 1.89 (0.02-50.92) vs 0.55 (0.07-3.22), P = 0.016. CXCL7 was overexpressed close to significance, 0.40 (0.00-7.85) vs 0.15 (0.01-7.88), P = 0.12. We show the involvement of CXCL7/CXCR2 signalling pathways as a predictive factor of poor outcome in metastatic CRC. 5-Fluorouracil-based chemotherapy regimens increase the expression of these genes in liver metastasis, providing one explanation for aggressiveness of relapsed drug-resistant tumors. Selective blockage of CXCR2/CXCL7 signalling pathways could provide new potential therapeutic opportunities. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  11. Presence of bone marrow micro-metastases in stage I-III colon cancer patients is associated with worse disease-free and overall survival.

    PubMed

    Viehl, Carsten T; Weixler, Benjamin; Guller, Ulrich; Dell-Kuster, Salome; Rosenthal, Rachel; Ramser, Michaela; Banz, Vanessa; Langer, Igor; Terracciano, Luigi; Sauter, Guido; Oertli, Daniel; Zuber, Markus

    2017-05-01

    The prognostic significance of bone marrow micro-metastases (BMM) in colon cancer patients remains unclear. We conducted a prospective cohort study with long-term follow-up to evaluate the relevance of BMM as a prognostic factor for disease free (DFS) and overall survival (OS) in stage I-III colon cancer patients. In this prospective multicenter cohort study 144 stage I-III colon cancer patients underwent bone marrow aspiration from both iliac crests prior to open oncologic resection. The bone marrow aspirates were stained with the pancytokeratin antibody A45-B/B3 and analyzed for the presence of epithelial tumor cells. DFS and OS were analyzed using a Cox proportional hazard model and robust standard errors to account for clustering in the multicenter setting. Median overall follow-up was 6.2 years with no losses to follow-up, and 7.3 years in patients who survived. BMM were found in 55 (38%) patients. In total, 30 (21%) patients had disease recurrence and 56 (39%) patients died. After adjusting for known prognostic factors, BMM positive patients had a significantly worse DFS (hazard ratio [HR] 1.33; 95% confidence interval [95% CI]: 1.02-1.73; P = 0.037) and OS (HR 1.30; 95% CI: 1.09-1.55; P = 0.003) compared to BMM negative patients. Bone marrow micro-metastases occur in over one third of stage I-III colon cancer patients and are a significant, independent negative prognostic factor for DFS and OS. Future trials should evaluate whether node-negative colon cancer patients with BMM benefit from adjuvant chemotherapy. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  12. The effects of geography on survival in patients with oral cavity squamous cell carcinoma.

    PubMed

    Zhang, Han; Dziegielewski, Peter T; Jean Nguyen, T T; Jeffery, Caroline C; O'Connell, Daniel A; Harris, Jeffrey R; Seikaly, Hadi

    2015-06-01

    To assess the survival outcomes of oral cavity squamous cell carcinoma (OCSCC) by differing geographical location. Demographic, pathologic, treatment, and survival data was obtained from OCSCC patients from 1998-2010 in Alberta, Canada. 554 patients were included from 660 OCSCC patients. Overall, disease-specific, and disease-free survivals were estimated with Kaplan-Meier and Cox regression analyses. Patients were grouped by geographic locations. Patients from urban locations had improved overall, disease-specific, and disease-free survival compared to rural locations (p<0.05). Two and five year estimates of overall survival were significantly higher in the urban cohort at 84% and 78%, versus rural with 48% and 44%, respectively (p<0.05). Disease-specific and disease-free survival rates were also superior in the urban group (p<0.05). Diagnosis to treatment time for all 3 geographical groups was not found to be statistically significant (p>0.05). This study shows that patients with OCSCC living in urban settings have improved survival compared to rural groups. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Lymphovascular invasion in clear cell renal cell carcinoma--association with disease-free and cancer-specific survival.

    PubMed

    Belsante, Michael; Darwish, Oussama; Youssef, Ramy; Bagrodia, Aditya; Kapur, Payal; Sagalowsky, Arthur I; Lotan, Yair; Margulis, Vitaly

    2014-01-01

    The objective is to evaluate the effect of lymphovascular invasion (LVI) on disease-free survival (DFS) and cancer-specific survival (CSS) in patients with clinically localized clear cell renal cell carcinoma (ccRCC). Patients with ccRCC who were treated surgically in 1997 to 2010 were identified. Retrospective chart review was performed to identify clinical outcomes. Independent pathologic re-review was performed by a single pathologist to confirm LVI status. Pathologic features were correlated with clinical outcomes using Kaplan-Meier and Cox regression analyses. Four hundred and nineteen patients with nonmetastatic ccRCC comprised the study cohort. Three hundred and thirty-three of these patients had an organ-confined (pT1-2, N any, and M0) disease. LVI was present in 14.3% of all nonmetastatic patients. In all patients with nonmetastatic ccRCC, presence of LVI was correlated with significantly shorter DFS (P <0.001) and CSS (P = 0.001) on Kaplan-Meier analysis. In cases of organ-confined, nonmetastatic ccRCC, presence of LVI was a significant predictor of DFS (hazard ratio = 4.0, P = 0.026) and CSS (hazard ratio = 12.7, P = 0.01) on multivariate analysis. Patients with organ-confined RCC who were LVI positive had similar DFS (P = 0.957) and CSS (P = 0.799) to patients with locally advanced tumors (pT3-pT4, N any, and M0) on Kaplan-Meier analysis. The presence of LVI is an independent predictor of both DFS and CSS in organ-confined, nonmetastatic ccRCC. LVI positivity in patients with otherwise pathologically organ-confined ccRCC confers oncologic outcomes similar to those of patients with locally advanced disease. If confirmed by others, future revisions to the tumor-node-metastasis staging system may incorporate LVI status into the prognostic algorithm of patients with RCC. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. 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.

  15. 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

  16. Factors Influencing Relapse-Free Survival in Merkel Cell Carcinoma of the Lower Limb-A Review of 60 Cases

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

    Poulsen, Michael, E-mail: michael_poulsen@health.qld.gov.a; Round, Caroline; Keller, Jacqui

    2010-02-01

    Purpose: Factors affecting relapse-free survival (RFS) in patients with Merkel cell carcinoma (MCC) of the lower limb were reviewed. Methods and Materials: The records of 60 patients from 1986 to 2005 with a diagnosis of MCC of the lower limb or buttock were retrospectively reviewed. The patients were treated with curative intent with surgery, radiation, or chemotherapy. Results: The 5-year overall survival, disease-specific survival, and RFS were 53%, 61%, and 20%, respectively. Factors influencing RFS were analyzed using univariate analysis. It appeared that recurrent disease worsened RFS (p = 0.03) and the addition of any radiotherapy improved RFS (p <0.001),more » as did radiotherapy to the inguinal nodes (p = 0.01) or primary site and inguinal nodes (p = 0.003). Age, surgical margins, and stage were not statistically significant. On multivariate analysis, the only significant factor was the addition of radiotherapy (hazard ratio = 0.51 p = 0.03). Conclusion: The addition of radiotherapy improves RFS compared with surgery alone. Elective treatment should be given to the inguinal nodes to reduce the risk of relapse.« less

  17. A randomized controlled trial of cognitive-behavioral stress management in breast cancer: survival and recurrence at 11-year follow-up.

    PubMed

    Stagl, Jamie M; Lechner, Suzanne C; Carver, Charles S; Bouchard, Laura C; Gudenkauf, Lisa M; Jutagir, Devika R; Diaz, Alain; Yu, Qilu; Blomberg, Bonnie B; Ironson, Gail; Glück, Stefan; Antoni, Michael H

    2015-11-01

    Non-metastatic breast cancer patients often experience psychological distress which may influence disease progression and survival. Cognitive-behavioral stress management (CBSM) improves psychological adaptation and lowers distress during breast cancer treatment and long-term follow-ups. We examined whether breast cancer patients randomized to CBSM had improved survival and recurrence 8-15 years post-enrollment. From 1998 to 2005, women (N = 240) 2-10 weeks post-surgery for non-metastatic Stage 0-IIIb breast cancer were randomized to a 10-week, group-based CBSM intervention (n = 120) or a 1-day psychoeducational seminar control (n = 120). In 2013, 8-15 years post-study enrollment (11-year median), recurrence and survival data were collected. Cox Proportional Hazards Models and Weibull Accelerated Failure Time tests were used to assess group differences in all-cause mortality, breast cancer-specific mortality, and disease-free interval, controlling for biomedical confounders. Relative to the control, the CBSM group was found to have a reduced risk of all-cause mortality (HR = 0.21; 95 % CI [0.05, 0.93]; p = .040). Restricting analyses to women with invasive disease revealed significant effects of CBSM on breast cancer-related mortality (p = .006) and disease-free interval (p = .011). CBSM intervention delivered post-surgery may provide long-term clinical benefit for non-metastatic breast cancer patients in addition to previously established psychological benefits. Results should be interpreted with caution; however, the findings contribute to the limited evidence regarding physical benefits of psychosocial intervention post-surgery for non-metastatic breast cancer. Additional research is necessary to confirm these results and investigate potential explanatory mechanisms, including physiological pathways, health behaviors, and treatment adherence changes.

  18. CT and 3-T MRI accurately identify T3c disease in colon cancer, which strongly predicts disease-free survival.

    PubMed

    Hunter, C; Siddiqui, M; Georgiou Delisle, T; Blake, H; Jeyadevan, N; Abulafi, M; Swift, I; Toomey, P; Brown, G

    2017-04-01

    To compare the preoperative staging accuracy of computed tomography (CT) and 3-T magnetic resonance imaging (MRI) in colon cancer, and to investigate the prognostic significance of identified risk factors. Fifty-eight patients undergoing primary resection of their colon cancer were prospectively recruited, with 53 patients included for final analysis. Accuracy of CT and MRI were compared for two readers, using postoperative histology as the reference standard. Patients were followed-up for a median of 39 months. Risk factors were compared by modality and reader in terms of metachronous metastases and disease-free survival (DFS), stratified for adjuvant chemotherapy. Accuracy for the identification of T3c+ disease was non-significantly greater on MRI (75% and 79%) than CT (70% and 77%). Differences in the accuracy of MRI and CT for identification of T3+ disease (MRI 75% and 57%, CT 72% and 66%) and N+ disease (MRI 62% and 63%, CT 62% and 56%) were also non-significant. Identification of extramural venous invasion (EMVI+) disease was significantly greater on MRI (75% and 75%) than CT (79% and 54%) for one reader (p=0.029). T3c+ disease at histopathology was the only risk factor that demonstrated a significant difference in rate of metachronous metastases (odds ratio [OR] 8.6, p=0.0044) and DFS stratified for adjuvant therapy (OR=4, p=0.048). T3c or greater disease is the strongest risk factor for predicting DFS in colon cancer, and is accurately identified on imaging. T3c+ disease may therefore be the best imaging entry criteria for trials of neoadjuvant treatment. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  19. 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.

  20. Long-term survival in an adolescent with widely metastatic renal cell carcinoma with rhabdoid features.

    PubMed

    Ettinger, L J; Goodell, L A; Javidian, P; Hsieh, Y; Amenta, P

    2000-01-01

    Renal cell carcinoma is rarely seen in children and adolescents. Patients with widespread disease at diagnosis have a particularly poor survival rate. Currently, all known chemotherapy has been ineffective in improving the median survival in patients with advanced disease. A 13-year-old black boy with stage IV renal cell carcinoma with rhabdoid features is a long-term disease-free survivor after aggressive multiagent chemotherapy. After the initial evaluation and histologic diagnosis of renal cell carcinoma, the patient received three courses of an aggressive chemotherapy regimen consisting of vincristine, doxorubicin, cyclophosphamide with mesna uroprotection, granulocyte colony-stimulating factor and erythropoietin (Epogen). After an almost complete response, a radical nephrectomy was performed and results demonstrated a solitary small nodule with viable tumor. After surgery, he received floxuridine infusion for 14 days by circadian schedule at 28-day intervals for a total of 1 year. The patient is well and free of disease 5 years after initial presentation. The dramatic response to treatment and long-term disease-free survival of this patient suggest this chemotherapeutic approach warrants additional investigation.

  1. Ten-year survival after epithelial ovarian cancer is not associated with BRCA mutation status.

    PubMed

    Kotsopoulos, Joanne; Rosen, Barry; Fan, Isabel; Moody, Joel; McLaughlin, John R; Risch, Harvey; May, Taymaa; Sun, Ping; Narod, Steven A

    2016-01-01

    After a diagnosis of ovarian cancer, positive BRCA mutation status confers a transient mortality benefit that diminishes with time. The majority of women who survive for 10-12 years are effectively cured of their disease. Thus, it is important to estimate the probability of long-term survival by BRCA mutation status and treatment-related factors. We included unselected epithelial ovarian cancers diagnosed in Ontario, Canada from 1995 to 1999 and from 2002 to 2004. Clinical information was obtained from medical records. Survival status was determined by linkage to the Ontario Cancer Registry. We estimated the annual mortality for these patients. We compared women who did and did not survive 10 years for a range of factors including BRCA mutation status and extent of residual disease post-surgery. Of the 1421 patients, 109 (7.7%) had BRCA1 mutations and 68 (4.8%) had BRCA2 mutations. A status of no residual disease was achieved by 39% of non-carriers and 19% of mutation carriers (P<0.0001). By 10-years of follow-up, 43% of non-carriers, 57% of BRCA1 mutation carriers and 69% of BRCA2 mutation carriers had died from ovarian cancer. Among women with stage III/IV serous cancers and no residual disease, the 10-year actuarial survival was 42% for non-carriers and 29% for mutation carriers (P=0.40). The initial survival advantage among women with BRCA mutations may reflect a higher initial sensitivity of BRCA carriers to chemotherapy, but this response does not predict long-term survival. The strongest predictor of long-term survival is status of no residual disease at resection. Copyright © 2015. Published by Elsevier Inc.

  2. [Prognostic factors for survival in patients with resectable advanced gastric adenocarcinoma].

    PubMed

    Medrano-Guzmán, Rafael; Valencia-Mercado, Daniel; Luna-Castillo, Marisol; García-Ríos, Luis Enrique; González-Rodríguez, Domingo

    Patients under 45 years with gastric cancer are associated with a poor prognosis. Recent studies report that the 5-year survival is better in younger patients after curative resection. To determine if prognostic factors such as age under 45 years old, anaemia, weight loss, tumour differentiation, histological sub-type, depth of invasion, and lymph node involvement, reduce the survival of patients with resectable advanced gastric adenocarcinoma undergoing gastrectomy with limited and extended lymphadenectomy. This study included a cohort of consecutive cases treated in the Sarcomas Department of the Oncology Hospital of the Centro Médico Nacional Siglo XXI, of the Instituto Mexicano del Seguro Social, during the period between January 2000 and December 2006. Of the total of 588 patients evaluated, 112 (19%) were under 45 years, 43% classified as Borrmann IV, and 36% as Borrmann III. Metastatic disease was present in 39.3%, localised diffuse in 12.5%; lower resectability 52.7 vs. 61.3% in older than 45 years. At the end of the study 29.5% of patients under 45 years were alive; no recurrence in 26.8%, with an overall survival of 58.6±4.3 months, compared with 18.3% of patients alive over 45 years, 17.9% disease-free, and with overall survival 35.2±4.3 months resectable disease. Patients under 45 years have a better survival after a two-year disease-free period. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  3. 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.

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

    PubMed

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

    2017-11-01

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

  5. 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

  6. Twenty-year survival after coronary artery surgery: an institutional perspective from Emory University.

    PubMed

    Weintraub, William S; Clements, Stephen D; Crisco, L Van-Thomas; Guyton, Robert A; Craver, Joseph M; Jones, Ellis L; Hatcher, Charles R

    2003-03-11

    Coronary artery bypass graft (CABG) surgery has been performed frequently for symptomatic coronary atherosclerotic heart disease for more than 30 years. However, uncertainty exists regarding the relationship between long-term survival after CABG and readily available clinical correlates of mortality. We studied outcome at 20 years by age, sex, and other variables in 3939 patients who had CABG surgery from 1973 to 1979 in the Emory University System of Healthcare. Twenty-year survival, freedom from myocardial infarction, and freedom from repeat CABG were 35.6% (95% confidence interval [CI], 33.9% to 37.3%), 66.6% (95% CI, 64.6% to 68.6%), and 59.1% (95% CI, 56.9% to 61.5%). Multivariate correlates of late mortality were age (hazard ratio [HR], 1.46 per 10 years), female sex (HR, 1.21), hypertension (HR, 1.44), angina class (HR, 1.07 per class increase of 1), prior CABG (HR, 1.72), ejection fraction (HR, 1.07 per 10-point decrease), number of vessels diseased (HR, 1.11 per 1-vessel increase), and weight (HR, 1.04 per 10 kg). Twenty-year survival by age was 55%, 38%, 22%, and 11% for age <50, 50 to 59, 60 to 69, and >70 years at the time of initial surgery. Survival at 20 years after surgery with and without hypertension was 27% and 41%, respectively. Similarly, 20-year survival was 37% and 29% for men and women. Symptomatic coronary atherosclerotic heart disease requiring surgical revascularization is progressive with continuing events and mortality. Clinical correlates of mortality significantly impact survival over time and may help identify long-term benefits after CABG.

  7. Survival of Alzheimer's disease patients in Korea.

    PubMed

    Go, Seok Min; Lee, Kang Soo; Seo, Sang Won; Chin, Juhee; Kang, Sue J; Moon, So Young; Na, Duk L; Cheong, Hae-Kwan

    2013-01-01

    The natural history of Alzheimer's disease (AD) has rarely been studied in the Korean population. Our study on survival analyses in Korean AD patients potentially provides a basis for cross-cultural comparisons. We studied 724 consecutive patients from a memory disorder clinic in a tertiary hospital in Seoul, who were diagnosed as having AD between April 1995 and December 2005. Deaths were identified by the Statistics Korea database. The Kaplan-Meier method was used for survival analysis, and a Cox proportional hazard model was used to assess factors related to patient survival. The overall median survival from the onset of first symptoms and from the time of diagnosis was 12.6 years (95% confidence interval 11.7-13.4) and 9.3 years (95% confidence interval 8.7-9.9), respectively. The age of onset, male gender, history of diabetes mellitus, lower Mini-Mental State Examination score, and higher Clinical Dementia Rating score were negatively associated with survival. There was a reversal of risk of AD between early-onset and later-onset AD, 9.1 years after onset. The results of our study show a different pattern of survival compared to those studies carried out with western AD populations. Mortality risk of early-onset AD varied depending on the duration of follow-up. Copyright © 2013 S. Karger AG, Basel.

  8. Substantia Nigra Free Water Increases Longitudinally in Parkinson Disease.

    PubMed

    Guttuso, T; Bergsland, N; Hagemeier, J; Lichter, D G; Pasternak, O; Zivadinov, R

    2018-02-01

    Free water in the posterior substantia nigra obtained from a bi-tensor diffusion MR imaging model has been shown to significantly increase over 1- and 4-year periods in patients with early-stage idiopathic Parkinson disease compared with healthy controls, which suggests that posterior substantia nigra free water may be an idiopathic Parkinson disease progression biomarker. Due to the known temporal posterior-to-anterior substantia nigra degeneration in idiopathic Parkinson disease, we assessed longitudinal changes in free water in both the posterior and anterior substantia nigra in patients with later-stage idiopathic Parkinson disease and age-matched healthy controls for comparison. Nineteen subjects with idiopathic Parkinson disease and 19 age-matched healthy control subjects were assessed on the same 3T MR imaging scanner at baseline and after approximately 3 years. Baseline mean idiopathic Parkinson disease duration was 7.1 years. Both anterior and posterior substantia nigra free water showed significant intergroup differences at baseline ( P < .001 and P = .014, respectively, idiopathic Parkinson disease versus healthy controls); however, only anterior substantia nigra free water showed significant longitudinal group × time interaction increases ( P = .021, idiopathic Parkinson disease versus healthy controls). There were no significant longitudinal group × time interaction differences found for conventional diffusion tensor imaging or free water-corrected DTI assessments in either the anterior or posterior substantia nigra. Results from this study provide further evidence supporting substantia nigra free water as a promising disease-progression biomarker in idiopathic Parkinson disease that may help to identify disease-modifying therapies if used in future clinical trials. Our novel finding of longitudinal increases in anterior but not posterior substantia nigra free water is potentially a result of the much longer disease duration of our cohort compared

  9. Disease-related costs of care and survival among Medicare-enrolled patients with myelodysplastic syndromes.

    PubMed

    Zeidan, Amer M; Wang, Rong; Davidoff, Amy J; Ma, Shuangge; Zhao, Yinjun; Gore, Steven D; Gross, Cary P; Ma, Xiaomei

    2016-05-15

    Although newer treatments for myelodysplastic syndromes (MDS), particularly hypomethylating agents (HMAs), are expensive, it is unclear whether MDS-related costs of care are associated with overall survival. This study evaluated the relation between MDS-related costs and survival among Medicare beneficiaries with MDS. Eligible patients were identified from the Surveillance, Epidemiology, and End Results-Medicare database with codes for MDS from International Classification of Diseases for Oncology, 3rd edition. The patients were diagnosed between January 1, 2005 and December 31, 2011, were 66 years old or older, and were followed through death or the end of study (December 31, 2012). Medicare payments were used to estimate costs. Cumulative costs in a propensity score-matched group of cancer-free Medicare beneficiaries were subtracted from costs in the MDS cohort in each registry to estimate MDS-related costs. Hazard ratios (HRs) and 95% confidence intervals (CIs) were derived from multivariate Cox proportional hazards models adjusted for patient and disease characteristics. There were 8580 eligible patients, and 1,267 (14.7%) received HMAs. The overall 2-year survival rate was 48.7%, and the 2-year registry-specific MDS-related cost per patient ranged from $40,793 to $78,156 across 16 registries. The 2-year MDS-related cost was not associated with survival in the overall study population (first tertile, reference; second tertile, HR, 0.96; 95% CI, 0.89-1.04; P = .29; third tertile, HR, 0.98; 95% CI, 0.91-1.06; P = .64) or in subgroups of patients who did or did not receive HMAs. Medicare expenditures for elderly patients with MDS varied across registries but were not associated with survival. A lack of an association between costs and outcomes warrants additional research because it may help to identify potential areas for cost-saving interventions without compromising patient outcomes. Cancer 2016;122:1598-607. © 2016 American Cancer Society. © 2016 American

  10. 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

  11. Does overall environmental quality affect end-stage renal disease survival?

    EPA Science Inventory

    Prevalence of end-stage renal disease (ESRD) in the U.S. increased by 74% from 2000 to 2013, with a 5-year survival of only 42%. To investigate associations between environmental quality and ESRD survival time, we used the Environmental Quality Index (EQI), an aggregate measure o...

  12. Maximal exercise testing variables and 10-year survival: fitness risk score derivation from the FIT Project.

    PubMed

    Ahmed, Haitham M; Al-Mallah, Mouaz H; McEvoy, John W; Nasir, Khurram; Blumenthal, Roger S; Jones, Steven R; Brawner, Clinton A; Keteyian, Steven J; Blaha, Michael J

    2015-03-01

    To determine which routinely collected exercise test variables most strongly correlate with survival and to derive a fitness risk score that can be used to predict 10-year survival. This was a retrospective cohort study of 58,020 adults aged 18 to 96 years who were free of established heart disease and were referred for an exercise stress test from January 1, 1991, through May 31, 2009. Demographic, clinical, exercise, and mortality data were collected on all patients as part of the Henry Ford ExercIse Testing (FIT) Project. Cox proportional hazards models were used to identify exercise test variables most predictive of survival. A "FIT Treadmill Score" was then derived from the β coefficients of the model with the highest survival discrimination. The median age of the 58,020 participants was 53 years (interquartile range, 45-62 years), and 28,201 (49%) were female. Over a median of 10 years (interquartile range, 8-14 years), 6456 patients (11%) died. After age and sex, peak metabolic equivalents of task and percentage of maximum predicted heart rate achieved were most highly predictive of survival (P<.001). Subsequent addition of baseline blood pressure and heart rate, change in vital signs, double product, and risk factor data did not further improve survival discrimination. The FIT Treadmill Score, calculated as [percentage of maximum predicted heart rate + 12(metabolic equivalents of task) - 4(age) + 43 if female], ranged from -200 to 200 across the cohort, was near normally distributed, and was found to be highly predictive of 10-year survival (Harrell C statistic, 0.811). The FIT Treadmill Score is easily attainable from any standard exercise test and translates basic treadmill performance measures into a fitness-related mortality risk score. The FIT Treadmill Score should be validated in external populations. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. Survival significance of coexisting chronic obstructive pulmonary disease in patients with early lung cancer after curative surgery

    PubMed Central

    Miyazawa, Tomoyuki; Sakai, Hiroki; Kimura, Yusuke; Tsuda, Masataka; Wakiyama, Yoichi; Marushima, Hideki; Kojima, Koji; Nakamura, Haruhiko

    2017-01-01

    Background The impact of chronic obstructive pulmonary disease (COPD) severity on survival after curative resection of early‐stage lung cancer (NSCLC) has not been sufficiently elucidated. Methods We retrospectively reviewed 250 consecutive patients who underwent lobectomy with lymph nodal dissection for pathological stage I–II NSCLC. Results Among the COPD patients, 28 were classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1, 21 as GOLD 2, and one as GOLD 3. The cumulative overall survival (OS) of the non‐COPD, GOLD 1, and GOLD 2–3 groups at five years was 90.7%, 85.7%, and 55.3%, respectively, (P < 0.0001), while recurrence‐free survival (RFS) between the groups at five years was 84.7%, 80.7%, and 72.9%, respectively. Although RFS in the GOLD 2–3 group tended to indicate a poor prognosis, there was no statistical difference between the groups (P = 0.385). In multivariate analysis, age ≥75 years, pN1, and GOLD 2–3 COPD were independent factors for a poor prognosis (P = 0.034, P = 0.010, and P = 0.030, respectively). Conclusions Our results indicate that early stage NSCLC patients with COPD had a significantly increased risk of poorer OS and potentially an increased risk of poor RFS. PMID:28976075

  18. 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

  19. A scoring system based on artificial neural network for predicting 10-year survival in stage II A colon cancer patients after radical surgery.

    PubMed

    Peng, Jian-Hong; Fang, Yu-Jing; Li, Cai-Xia; Ou, Qing-Jian; Jiang, Wu; Lu, Shi-Xun; Lu, Zhen-Hai; Li, Pei-Xing; Yun, Jing-Ping; Zhang, Rong-Xin; Pan, Zhi-Zhong; Wan, De Sen

    2016-04-19

    Nearly 20% patients with stage II A colon cancer will develop recurrent disease post-operatively. The present study aims to develop a scoring system based on Artificial Neural Network (ANN) model for predicting 10-year survival outcome. The clinical and molecular data of 117 stage II A colon cancer patients from Sun Yat-sen University Cancer Center were used for training set and test set; poor pathological grading (score 49), reduced expression of TGFBR2 (score 33), over-expression of TGF-β (score 45), MAPK (score 32), pin1 (score 100), β-catenin in tumor tissue (score 50) and reduced expression of TGF-β in normal mucosa (score 22) were selected as the prognostic risk predictors. According to the developed scoring system, the patients were divided into 3 subgroups, which were supposed with higher, moderate and lower risk levels. As a result, for the 3 subgroups, the 10-year overall survival (OS) rates were 16.7%, 62.9% and 100% (P < 0.001); and the 10-year disease free survival (DFS) rates were 16.7%, 61.8% and 98.8% (P < 0.001) respectively. It showed that this scoring system for stage II A colon cancer could help to predict long-term survival and screen out high-risk individuals for more vigorous treatment.

  20. Progression marker of Parkinson's disease: a 4-year multi-site imaging study.

    PubMed

    Burciu, Roxana G; Ofori, Edward; Archer, Derek B; Wu, Samuel S; Pasternak, Ofer; McFarland, Nikolaus R; Okun, Michael S; Vaillancourt, David E

    2017-08-01

    Progression markers of Parkinson's disease are crucial for successful therapeutic development. Recently, a diffusion magnetic resonance imaging analysis technique using a bitensor model was introduced allowing the estimation of the fractional volume of free water within a voxel, which is expected to increase in neurodegenerative disorders such as Parkinson's disease. Prior work demonstrated that free water in the posterior substantia nigra was elevated in Parkinson's disease compared to controls across single- and multi-site cohorts, and increased over 1 year in Parkinson's disease but not in controls at a single site. Here, the goal was to validate free water in the posterior substantia nigra as a progression marker in Parkinson's disease, and describe the pattern of progression of free water in patients with a 4-year follow-up tested in a multicentre international longitudinal study of de novo Parkinson's disease (http://www.ppmi-info.org/). The analyses examined: (i) 1-year changes in free water in 103 de novo patients with Parkinson's disease and 49 controls; (ii) 2- and 4-year changes in free water in a subset of 46 patients with Parkinson's disease imaged at baseline, 12, 24, and 48 months; (iii) whether 1- and 2-year changes in free water predict 4-year changes in the Hoehn and Yahr scale; and (iv) the relationship between 4-year changes in free water and striatal binding ratio in a subgroup of Parkinson's disease who had undergone both diffusion and dopamine transporter imaging. Results demonstrated that: (i) free water level in the posterior substantia nigra increased over 1 year in de novo Parkinson's disease but not in controls; (ii) free water kept increasing over 4 years in Parkinson's disease; (iii) sex and baseline free water predicted 4-year changes in free water; (iv) free water increases over 1 and 2 years were related to worsening on the Hoehn and Yahr scale over 4 years; and (v) the 4-year increase in free water was associated with the 4-year

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. Predicting Survival After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Appendix Adenocarcinoma.

    PubMed

    Aziz, Omer; Jaradat, Ihab; Chakrabarty, Bipasha; Selvasekar, Chelliah R; Fulford, Paul E; Saunders, Mark P; Renehan, Andrew G; Wilson, Malcolm S; O'Dwyer, Sarah T

    2018-05-15

    Appendix adenocarcinomas are rare tumors with propensity for peritoneal metastasis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is an established treatment with curative intent, but, to date, studies reporting survival have been heterogeneous with regard to their patient groups (including other tumor types), interventions (not all patients receiving intraperitoneal chemotherapy), and follow-up (varying surveillance protocols). The aim of this study is to quantify the impact of this intervention on survival in a homogeneous group of patients with appendix adenocarcinoma receiving standardized treatment and follow-up, and to determine the impact of prognostic indicators on survival. This is a retrospective analysis of a prospective database at a national peritoneal tumor center where all patients had their appendix pathology reviewed and management planned by a specialized peritoneal tumor multidisciplinary team. Data were extracted on prognostic indicators including peritoneal cancer index, completeness of cytoreduction score, preoperative tumor markers, and histological features. Overall and disease event-free survival from the date of intervention were evaluated using Kaplan Meier curves and univariate Cox proportional hazards regression analysis. A total of 65 patients underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for appendix adenocarcinoma between 2005 and 2015. Median follow-up was 44.3 months. The overall survival was 55.5% and disease event-free survival was 36.1% (5-year rate). Peritoneal Cancer Index <7, complete cytoreduction score of 0, and preoperative CEA of <6 were all associated with significantly higher overall and disease event-free survival. CA19-9 <38 and CA125 <31 were not associated with a significantly higher overall or disease event-free survival. The sample size was limited because of the rarity of this tumor type. This study quantifies the impact of cytoreductive surgery with

  7. In Papillary Thyroid Cancer, Preoperative Central Neck Ultrasound Detects Only Macroscopic Surgical Disease, But Negative Findings Predict Excellent Long-Term Regional Control and Survival

    PubMed Central

    Moreno, Mauricio A.; Edeiken-Monroe, Beth S.; Siegel, Eric R.; Sherman, Steven I.

    2012-01-01

    Background Ultrasound (US) of the central neck compartment (CNC) is considered of limited sensitivity for nodal spread in papillary thyroid cancer (PTC); elective neck dissection is commonly advocated even in the absence of sonographic abnormalities. We hypothesized that US is an accurate predictor for long-term disease-free survival, regardless of the use of elective central neck dissection in patients with PTC. Methods A retrospective chart review of 331 consecutive PTC patients treated with total thyroidectomy at M.D. Anderson Cancer Center between 1996 and 2003 was performed. Information retrieved included preoperative sonographic status of the CNC, surgical treatment of the neck, demographics, cancer staging, histopathological variables and use of adjuvant treatment. The endpoints for the study were nodal recurrence and survival. Results There were 112 males and 219 females with a median age of 44 years (range 11–87). The median follow-up time for the series was 71.5 months (range 12.7–148.7). There were 151 (45.6%) patients with a T1, 58 (17.5%) with a T2, 70 (21.1%) with a T3, and 52 (15.7%) with a T4. Preoperative sonographic abnormalities were present in the CNC in 79 (23.9%) patients. During the surveillance period, 11 (3.2%) patients recurred in the central neck, with an average time for recurrence of 22.8 months. Advanced T stage (T3/T4) and abnormal US were independent prognostic factors for recurrence in the central neck (p=0.013 and p=0.005 respectively). There were 119 (35%) patients with a sonographically negative central compartment who underwent elective central neck dissection; 85 of them (71.4%) were found to be histopathologically N(+) while 34 (28.6%) were pN0. There were no differences in overall survival (p=0.32), disease specific survival (DSS; p=0.49), and recurrence-free survival (p=0.32) between these two groups. Preoperative US of the CNC was an age-independent predictor for overall survival (p<0.001), DSS (p=0.0097), and disease-free

  8. Survival outcomes following aggressive treatment of oligometastatic breast cancer: a systematic review protocol.

    PubMed

    Coombe, Robyn; Lisy, Karolina; Campbell, Jared; Perry, Gajen; Prasannan, Subhita

    2017-08-01

    The objective of this systematic review is to assess the effectiveness of aggressive treatment of oligometastatic breast cancer (OMBC) on survival outcomes by conducting a meta-analysis of current available evidence.More specifically, the objectives are to identify the effectiveness of intensified multidisciplinary treatment with aggressive locoregional therapies on survival time, five-year survival rates and disease free survival. The population is adult women (18 years and over) with OMBC defined as single or few (five or less) metastases limited to a single organ and the comparative group is conventional palliative treatment aimed at disease control. Secondary objectives to be assessed will be adverse outcomes associated with intensified treatment regimes.

  9. Genetic variants of cell cycle pathway genes predict disease-free survival of hepatocellular carcinoma.

    PubMed

    Liu, Shun; Yang, Tian-Bo; Nan, Yue-Li; Li, An-Hua; Pan, Dong-Xiang; Xu, Yang; Li, Shu; Li, Ting; Zeng, Xiao-Yun; Qiu, Xiao-Qiang

    2017-07-01

    Disruption of the cell cycle pathway has previously been related to development of human cancers. However, associations between genetic variants of cell cycle pathway genes and prognosis of hepatocellular carcinoma (HCC) remain largely unknown. In this study, we evaluated the associations between 24 potential functional single nucleotide polymorphisms (SNPs) of 16 main cell cycle pathway genes and disease-free survival (DFS) of 271 HCC patients who had undergone radical surgery resection. We identified two SNPs, i.e., SMAD3 rs11556090 A>G and RBL2 rs3929G>C, that were independently predictive of DFS in an additive genetic model with false-positive report probability (FPRP) <0.2. The SMAD3 rs11556090G allele was associated with a poorer DFS, compared with the A allele [hazard ratio (HR) = 1.46, 95% confidential interval (95% CI) = 1.13-1.89, P = 0.004]; while the RBL2 rs3929 C allele was associated with a superior DFS, compared with the G allele (HR = 0.74, 95% CI = 0.57-0.96, P = 0.023). Additionally, patients with an increasing number of unfavorable genotypes (NUGs) of these loci had a significant shorter DFS (P trend  = 0.0001). Further analysis using receiver operating characteristic (ROC) curves showed that the model including the NUGs and known prognostic clinical variables demonstrated a significant improvement in predicting the 1-year DFS (P = 0.011). Moreover, the RBL2 rs3929 C allele was significantly associated with increased mRNA expression levels of RBL2 in liver tissue (P = 1.8 × 10 -7 ) and the whole blood (P = 3.9 × 10 -14 ). Our data demonstrated an independent or a joint effect of SMAD3 rs11556090 and RBL2 rs3929 in the cell cycle pathway on DFS of HCC, which need to be validated by large cohort and biological studies. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  10. MRE11-deficiency associated with improved long-term disease free survival and overall survival in a subset of stage III colon cancer patients in randomized CALGB 89803 trial.

    PubMed

    Pavelitz, Thomas; Renfro, Lindsay; Foster, Nathan R; Caracol, Amber; Welsch, Piri; Lao, Victoria Valinluck; Grady, William B; Niedzwiecki, Donna; Saltz, Leonard B; Bertagnolli, Monica M; Goldberg, Richard M; Rabinovitch, Peter S; Emond, Mary; Monnat, Raymond J; Maizels, Nancy

    2014-01-01

    Colon cancers deficient in mismatch repair (MMR) may exhibit diminished expression of the DNA repair gene, MRE11, as a consequence of contraction of a T11 mononucleotide tract. This study investigated MRE11 status and its association with prognosis, survival and drug response in patients with stage III colon cancer. Cancer and Leukemia Group B 89803 (Alliance) randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly adjuvant bolus 5-fluorouracil/leucovorin (FU/LV) or irinotecan+FU/LV (IFL), with 8 year follow-up. Tumors from these patients were analyzed to determine stability of a T11 tract in the MRE11 gene. The primary endpoint was overall survival (OS), and a secondary endpoint was disease-free survival (DFS). Non-proportional hazards were addressed using time-dependent covariates in Cox analyses. Of 625 tumor cases examined, 70 (11.2%) exhibited contraction at the T11 tract in one or both MRE11 alleles and were thus predicted to be deficient in MRE11 (dMRE11). In pooled treatment analyses, dMRE11 patients showed initially reduced DFS and OS but improved long-term DFS and OS compared with patients with an intact MRE11 T11 tract. In the subgroup of dMRE11 patients treated with IFL, an unexplained early increase in mortality but better long-term DFS than IFL-treated pMRE11 patients was observed. Analysis of this relatively small number of patients and events showed that the dMRE11 marker predicts better prognosis independent of treatment in the long-term. In subgroup analyses, dMRE11 patients treated with irinotecan exhibited unexplained short-term mortality. MRE11 status is readily assayed and may therefore prove to be a useful prognostic marker, provided that the results reported here for a relatively small number of patients can be generalized in independent analyses of larger numbers of samples. ClinicalTrials.gov NCT00003835.

  11. MRE11-Deficiency Associated with Improved Long-Term Disease Free Survival and Overall Survival in a Subset of Stage III Colon Cancer Patients in Randomized CALGB 89803 Trial

    PubMed Central

    Pavelitz, Thomas; Renfro, Lindsay; Foster, Nathan R.; Caracol, Amber; Welsch, Piri; Lao, Victoria Valinluck; Grady, William B.; Niedzwiecki, Donna; Saltz, Leonard B.; Bertagnolli, Monica M.; Goldberg, Richard M.; Rabinovitch, Peter S.; Emond, Mary; Monnat, Raymond J.; Maizels, Nancy

    2014-01-01

    Purpose Colon cancers deficient in mismatch repair (MMR) may exhibit diminished expression of the DNA repair gene, MRE11, as a consequence of contraction of a T11 mononucleotide tract. This study investigated MRE11 status and its association with prognosis, survival and drug response in patients with stage III colon cancer. Patients and Methods Cancer and Leukemia Group B 89803 (Alliance) randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly adjuvant bolus 5-fluorouracil/leucovorin (FU/LV) or irinotecan+FU/LV (IFL), with 8 year follow-up. Tumors from these patients were analyzed to determine stability of a T11 tract in the MRE11 gene. The primary endpoint was overall survival (OS), and a secondary endpoint was disease-free survival (DFS). Non-proportional hazards were addressed using time-dependent covariates in Cox analyses. Results Of 625 tumor cases examined, 70 (11.2%) exhibited contraction at the T11 tract in one or both MRE11 alleles and were thus predicted to be deficient in MRE11 (dMRE11). In pooled treatment analyses, dMRE11 patients showed initially reduced DFS and OS but improved long-term DFS and OS compared with patients with an intact MRE11 T11 tract. In the subgroup of dMRE11 patients treated with IFL, an unexplained early increase in mortality but better long-term DFS than IFL-treated pMRE11 patients was observed. Conclusions Analysis of this relatively small number of patients and events showed that the dMRE11 marker predicts better prognosis independent of treatment in the long-term. In subgroup analyses, dMRE11 patients treated with irinotecan exhibited unexplained short-term mortality. MRE11 status is readily assayed and may therefore prove to be a useful prognostic marker, provided that the results reported here for a relatively small number of patients can be generalized in independent analyses of larger numbers of samples. Trial Registration ClinicalTrials.gov NCT00003835 PMID:25310185

  12. 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.

  13. Comparison of survival between radiation therapy and trans-oral laser microsurgery for early glottic cancer patients; a retrospective cohort study.

    PubMed

    De Santis, R J; Poon, I; Lee, J; Karam, I; Enepekides, D J; Higgins, K M

    2016-08-02

    The literature reports various treatment methodologies, such as trans-oral laser microsurgery, radiation therapy, total/partial laryngectomies, and concurrent radiation chemotherapy for patients with early larynx cancer. However, at the forefront of early glottis treatment is trans-oral laser microsurgery and radiation therapy, likely due to better functional and survival outcomes. Here we conduct the largest Canadian head-to-head comparison of consecutive patients treated with either radiation therapy or trans-oral laser microsurgery. Additionally, we compare these two treatments and their 5-year survival rates post treatment to add to the existing literature. Charts of patients who were diagnosed with early glottic cancer between 2006 and 2013 were reviewed. Seventy-five patients were identified, and split into 2 groups based on their primary treatment, trans-oral laser microsurgery and radiation therapy. Kaplan-Meier survival curves, life-tables, and the log-rank statistic were reported to determine if there was a difference between the two treatment groups and their disease-specific survival, disease-free survival, and total laryngectomy-free survival. Additionally, each different survival analysis was stratified by potential confounding variables, to help conclude which treatment is more efficacious in this population. The 5-year disease-specific survival rate is 93.3 % σ = 0.063 and 90.8 % σ = 0.056 for patients treated with trans-oral laser microsurgery and radiation therapy, respectively (χ (2) < 0.001, p = 0.983). The disease free survival rate is 60.0 % (σ =0.121) for patients treated with trans-oral laser microsurgery, and 67.2 % (σ = 0.074) for those who received RT (χ (2) = 0.19, p = 0.663). Additionally, the total laryngectomy-free survival rate is 84.1 % (σ = 0.1) and 79.1 % (σ = 0.072) for patients' early glottic cancer treated by trans-oral laser microsurgery and radiation therapy, respectively (

  14. Association of Low-Dose Aspirin and Survival of Women With Endometrial Cancer.

    PubMed

    Matsuo, Koji; Cahoon, Sigita S; Yoshihara, Kosuke; Shida, Masako; Kakuda, Mamoru; Adachi, Sosuke; Moeini, Aida; Machida, Hiroko; Garcia-Sayre, Jocelyn; Ueda, Yutaka; Enomoto, Takayuki; Mikami, Mikio; Roman, Lynda D; Sood, Anil K

    2016-07-01

    To examine the survival outcomes in women with endometrial cancer who were taking low-dose aspirin (81-100 mg/d). A multicenter retrospective study was conducted examining patients with stage I-IV endometrial cancer who underwent hysterectomy-based surgical staging between January 2000 and December 2013 (N=1,687). Patient demographics, medical comorbidities, medication types, tumor characteristics, and treatment patterns were correlated to survival outcomes. A Cox proportional hazard regression model was used to estimate adjusted hazard ratio for disease-free and disease-specific overall survival. One hundred fifty-eight patients (9.4%, 95% confidence interval [CI] 8.8-11.9) were taking low-dose aspirin. Median follow-up time for the study cohort was 31.5 months. One hundred twenty-seven patients (7.5%) died of endometrial cancer. Low-dose aspirin use was significantly correlated with concurrent obesity, hypertension, diabetes mellitus, and hypercholesterolemia (all P<.001). Low-dose aspirin users were more likely to take other antihypertensive, antiglycemic, and anticholesterol agents (all P<.05). Low-dose aspirin use was not associated with histologic subtype, tumor grade, nodal metastasis, or cancer stage (all P>.05). On multivariable analysis, low-dose aspirin use remained an independent prognostic factor associated with an improved 5-year disease-free survival rate (90.6% compared with 80.9%, adjusted hazard ratio 0.46, 95% CI 0.25-0.86, P=.014) and disease-specific overall survival rate (96.4% compared with 87.3%, adjusted hazard ratio 0.23, 95% CI 0.08-0.64, P=.005). The increased survival effect noted with low-dose aspirin use was greatest in patients whose age was younger than 60 years (5-year disease-free survival rates, 93.9% compared with 84.0%, P=.013), body mass index was 30 or greater (92.2% compared with 81.4%, P=.027), who had type I cancer (96.5% compared with 88.6%, P=.029), and who received postoperative whole pelvic radiotherapy (88.2% compared

  15. Survival of patients treated for end-stage renal disease by dialysis and transplantation.

    PubMed Central

    Higgins, M. R.; Grace, M.; Dossetor, J. B.

    1977-01-01

    The results of treatment in 213 patients with end-stage renal disease who underwent hemodialysis, peritoneal dialysis or transplantation, or a combination, between 1962 and 1975 were analysed. Comparison by censored survival analysis showed significantly better (P less than 0.01) patient survival with the integrated therapy of dialysis and transplantation than with either form of dialysis alone. There was no significant difference in survival of males and females but survival at the extremes of age was poorer. Analysis of survival by major cause of renal failure indicated best survival in patients with congenital renal disease. Graft and patient survival rates at 1 year after the first transplantation were 42% and 69%. The major cause of death in this series was vascular disease but infection was responsible for 50% of deaths after transplantation. While integration of dialysis with transplantation produces best patient survival, this course is possible only when sufficient cadaver kidneys are available. PMID:334354

  16. 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...

  17. Hurthle cell carcinoma: an update on survival over the last 35 years.

    PubMed

    Nagar, Sapna; Aschebrook-Kilfoy, Briseis; Kaplan, Edwin L; Angelos, Peter; Grogan, Raymon H

    2013-12-01

    Hurthle cell carcinoma (HCC) of the thyroid is a variant of follicular cell carcinoma (FCC). A low incidence and lack of long-term follow-up data have caused controversy regarding the survival characteristics of HCC. We aimed to clarify this controversy by analyzing HCC survival over a 35-year period using the Surveillance, Epidemiology, and End Results (SEER) database. Cases of HCC and FCC were extracted from the SEER-9 database (1975-2009). Five- and 10-year survival rates were calculated. We compared changes in survival over time by grouping cases into 5-year intervals. We identified 1,416 cases of HCC and 4,973 cases of FCC. For cases diagnosed from 1975 to 1979, HCC showed a worse survival compared with FCC (5 years, 75%; 95% confidence interval [CI], 60.2-85) versus 88.7% (95% CI, 86-90.8; 10 years, 66.7% [95% CI, 51.5-78.1] vs. 79.7% [95% CI, 76.5-82.6]). For cases diagnosed from 2000 to 2004 we found no difference in 5-year survival between HCC and FCC (91.1% [95% CI, 87.6-93.7] vs. 89.1% [95% CI, 86.5-91.2]). For cases diagnosed from 1995 to 1999, there was no difference in 10-year survival between HCC and FCC (80.9% [95% CI, 75.6-85.2] vs. 83.9% [95% CI, 80.8-86.6]). HCC survival improved over the study period while FCC survival rates remained stable (increase in survival at 5 years, 21.7% vs. 0.4%; at 10 years, 21.3% vs. 5.2%). Improvement in HCC survival was observed for both genders, in age ≥45 years, in local and regional disease, for tumors >4 cm, and with white race. HCC survival has improved dramatically over time such that HCC and FCC survival rates are now the same. These findings explain how studies over the last 4 decades have shown conflicting results regarding HCC survival; however, our data do not explain why HCC survival has improved. Copyright © 2013 Mosby, Inc. All rights reserved.

  18. 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

  19. Impact of disease on the survival of three commercially fished species.

    PubMed

    Hoenig, John M; Groner, Maya L; Smith, Matthew W; Vogelbein, Wolfgang K; Taylor, David M; Landers, Donald F; Swenarton, John T; Gauthier, David T; Sadler, Philip; Matsche, Mark A; Haines, Ashley N; Small, Hamish J; Pradel, Roger; Choquet, Rémi; Shields, Jeffrey D

    2017-10-01

    Recent increases in emergent infectious diseases have raised concerns about the sustainability of some marine species. The complexity and expense of studying diseases in marine systems often dictate that conservation and management decisions are made without quantitative data on population-level impacts of disease. Mark-recapture is a powerful, underutilized, tool for calculating impacts of disease on population size and structure, even in the absence of etiological information. We applied logistic regression models to mark-recapture data to obtain estimates of disease-associated mortality rates in three commercially important marine species: snow crab (Chionoecetes opilio) in Newfoundland, Canada, that experience sporadic epizootics of bitter crab disease; striped bass (Morone saxatilis) in the Chesapeake Bay, USA, that experience chronic dermal and visceral mycobacteriosis; and American lobster (Homarus americanus) in the Southern New England stock, that experience chronic epizootic shell disease. All three diseases decreased survival of diseased hosts. Survival of diseased adult male crabs was 1% (0.003-0.022, 95% CI) that of uninfected crabs indicating nearly complete mortality of infected crabs in this life stage. Survival of moderately and severely diseased striped bass (which comprised 15% and 11% of the population, respectively) was 84% (70-100%, 95% CI), and 54% (42-68%, 95% CI) that of healthy striped bass. The disease-adjusted yearly natural mortality rate for striped bass was 0.29, nearly double the previously accepted value, which did not include disease. Survival of moderately and severely diseased lobsters was 30% (15-60%, 95% CI) that of healthy lobsters and survival of mildly diseased lobsters was 45% (27-75%, 95% CI) that of healthy lobsters. High disease mortality in ovigerous females may explain the poor recruitment and rapid declines observed in this population. Stock assessments should account for disease-related mortality when resource

  20. 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

  1. Comparison of survival analysis and palliative care involvement in patients aged over 70 years choosing conservative management or renal replacement therapy in advanced chronic kidney disease.

    PubMed

    Hussain, Jamilla A; Mooney, Andrew; Russon, Lynne

    2013-10-01

    There are limited data on the outcomes of elderly patients with chronic kidney disease undergoing renal replacement therapy or conservative management. We aimed to compare survival, hospital admissions and palliative care access of patients aged over 70 years with chronic kidney disease stage 5 according to whether they chose renal replacement therapy or conservative management. Retrospective observational study. Patients aged over 70 years attending pre-dialysis clinic. In total, 172 patients chose conservative management and 269 chose renal replacement therapy. The renal replacement therapy group survived for longer when survival was taken from the time estimated glomerular filtration rate <20 mL/min (p < 0.0001), <15 mL/min (p < 0.0001) and <12 mL/min (p = 0.002). When factors influencing survival were stratified for both groups independently, renal replacement therapy failed to show a survival advantage over conservative management, in patients older than 80 years or with a World Health Organization performance score of 3 or more. There was also a significant reduction in the effect of renal replacement therapy on survival in patients with high Charlson's Comorbidity Index scores. The relative risk of an acute hospital admission (renal replacement therapy vs conservative management) was 1.6 (p < 0.05; 95% confidence interval = 1.14-2.13). A total of 47% of conservative management patients died in hospital, compared to 69% undergoing renal replacement therapy (Renal Registry data). Seventy-six percent of the conservative management group accessed community palliative care services compared to 0% of renal replacement therapy patients. For patients aged over 80 years, with a poor performance status or high co-morbidity scores, the survival advantage of renal replacement therapy over conservative management was lost at all levels of disease severity. Those accessing a conservative management pathway had greater access to palliative care services and were less

  2. 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.

  3. Timing of Adjuvant Surgical Oophorectomy in the Menstrual Cycle and Disease-Free and Overall Survival in Premenopausal Women With Operable Breast Cancer

    PubMed Central

    Laudico, Adriano V.; Van Dinh, Nguyen; Allred, D. Craig; Uy, Gemma B.; Quang, Le Hong; Salvador, Jonathan Disraeli S.; Siguan, Stephen Sixto S.; Mirasol-Lumague, Maria Rica; Tung, Nguyen Dinh; Benjaafar, Noureddine; Navarro, Narciso S.; Quy, Tran Tu; De La Peña, Arturo S.; Dofitas, Rodney B.; Bisquera, Orlino C.; Linh, Nguyen Dieu; To, Ta Van; Young, Gregory S.; Hade, Erinn M.; Jarjoura, David

    2015-01-01

    Background: For women with hormone receptor–positive, operable breast cancer, surgical oophorectomy plus tamoxifen is an effective adjuvant therapy. We conducted a phase III randomized clinical trial to test the hypothesis that oophorectomy surgery performed during the luteal phase of the menstrual cycle was associated with better outcomes. Methods: Seven hundred forty premenopausal women entered a clinical trial in which those women estimated not to be in the luteal phase of their menstrual cycle for the next one to six days (n = 509) were randomly assigned to receive treatment with surgical oophorectomy either delayed to be during a five-day window in the history-estimated midluteal phase of the menstrual cycles, or in the next one to six days. Women who were estimated to be in the luteal phase of the menstrual cycle for the next one to six days (n = 231) were excluded from random assignment and received immediate surgical treatments. All patients began tamoxifen within 6 days of surgery and continued this for 5 years. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess differences in five-year disease-free survival (DFS) between the groups. All statistical tests were two-sided. Results: The randomized midluteal phase surgery group had a five-year DFS of 64%, compared with 71% for the immediate surgery random assignment group (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 0.91 to 1.68, P = .18). Multivariable Cox regression models, which included important prognostic variables, gave similar results (aHR = 1.28, 95% CI = 0.94 to 1.76, P = .12). For overall survival, the univariate hazard ratio was 1.33 (95% CI = 0.94 to 1.89, P = .11) and the multivariable aHR was 1.43 (95% CI = 1.00 to 2.06, P = .05). Better DFS for follicular phase surgery, which was unanticipated, proved consistent across multiple exploratory analyses. Conclusions: The hypothesized benefit of adjuvant luteal phase oophorectomy was

  4. The Cameroon 2008 Burkitt lymphoma protocol: improved event-free survival with treatment adapted to disease stage and the response to induction therapy.

    PubMed

    Hesseling, P B; Njume, E; Kouya, F; Katayi, T; Wharin, P; Tamannai, M; Achu, P; Kidd, M; McCormick, P

    2012-03-01

    Treatment of endemic Burkitt lymphoma (BL) with cyclophosphamide (CPM) and intrathecal methotrexate (IT MTX) can cure 50% of patients. In this study, induction therapy with CPM and IT MTX was followed by consolidation chemotherapy adapted for stage, clinical response, and abdominal ultrasound findings. One hundred and twenty-nine consecutive patients with BL, 77 male and 52 female with a median age of 7.9 years, were treated in mission hospitals in Cameroon. The diagnosis rested on fine-needle aspirate (79%), biopsy, bone marrow, cerebrospinal fluid, abdominal ultrasound, and clinical examination. Six percent had St Jude stage I, 13% stage II, 72% stage III, and 12% stage IV disease. The abdomen (76%) and face (50%) were mainly involved. Induction chemotherapy was CPM 40 mg/kg and IT MTX 12.5 mg and IT hydrocortisone 12.5 mg on days 1, 8, and 15. Stage I and II patients received CPM 60 mg/kg on day 29, and stage III patients CPM 60 mg/kg on days 29 and 43 if in remission on day 28. Stage IV patients and patients not in remission received CPM 60 mg/kg on days 29, 43, and 57 and 1.0 g/m(2) MTX intravenous (IV) and vincristine 1.5 mg/m(2) IV on day 29. Event-free survival (EFS) at mean 365 days was 61% (n = 79) and 100% in stage I, 85% in stage II, 60% in stage III, and 27% in stage IV patients. Deaths (n = 24) were disease or treatment related and 26 patients relapsed (mean 135 days). Risk-adapted treatment achieved 61% 1-year EFS.

  5. Disparate outcomes in patients with colorectal cancer: effect of race on long-term survival.

    PubMed

    Wudel, L James; Chapman, William C; Shyr, Yu; Davidson, Mark; Jeyakumar, Anita; Rogers, Selwyn O; Allos, Tara; Stain, Steven C

    2002-05-01

    Increasing evidence suggests significant disparity in colorectal cancer outcomes between black and white patients. Contributing factors may include advanced tumor stage at diagnosis, differences in treatment, more aggressive tumor biology, access to care, and patient comorbidity. Disparities in colorectal cancer outcomes exist despite similar objective measures of treatment. Ten-year retrospective review of all patients with colorectal cancer using tumor registries at a city hospital (n = 83) and a university medical center (n = 585) in the same city. We assessed stage at diagnosis; curative surgical resection; use of adjuvant treatment; overall, disease-free, and stage-specific survival; and socioeconomic status. Patients with nonwhite, nonblack ethnicity (4% overall) were excluded. Differences in stage and treatments were compared using the chi(2) test, and median survival rates were compared using log-rank tests. Significantly more black patients were treated at the city hospital (53.0%) vs the university medical center (10.6%) (P<.001). No differences were identified in stage distribution or treatments received between hospitals or between black and white patients. Significantly worse survival was noted among patients treated at the city hospital (2.1 vs 5.3 years; P<.001) and among black patients treated at both institutions (city hospital: 1.4 vs 2.1 years, and university hospital: 3.2 vs 5.7 years; P<.001 for both). Disease-free survival rates showed similar significant reductions for black patients at both institutions. There was no association between survival and socioeconomic status at either institution. The marked reductions in overall and disease-free survival for black patients with colorectal cancer do not seem to be related to variation in treatment but may be due to biologic factors or non-cancer-related health conditions.

  6. Epidemiology, management and survival outcomes of primary cutaneous melanoma: a ten-year overview.

    PubMed

    Aubuchon, M M F; Bolt, L J J; Janssen-Heijnen, M L G; Verleisdonk-Bolhaar, S T H P; van Marion, A; van Berlo, C L H

    2017-02-01

    Malignant melanoma (MM) is the most aggressive type of skin cancer, accounting for 90% of all the skin cancer mortality. The objective of this study was providing an overview of current patient- and tumour characteristics, treatment strategies, complications and survival in patients with MM over the past ten years. Hereby, an up-to-date view of every day clinical practice is obtained. Files of patients treated for primary cutaneous melanoma (n = 686) in the VieCuri Medical Centre in the Netherlands between January 2002 and December 2013 were retrospectively reviewed. Relevant patient features, tumour characteristics, and (surgical) outcomes were evaluated. The majority of all the patients presented thin tumours (59.1% stage 1A/in situ melanoma). Men showed more ulceration (17.7% vs. 8.4%, p < .01) and a significantly higher Breslow thickness than women (1.2 mm vs. 0.9 mm, p < .01). 14.6% (40/273) underwent sentinel lymph node biopsy (SLNB); 10/40 (25%) showed nodal metastasis, 50 patients (7.3%) developed distant metastases (M: 10.6%, F: 5%, p < .01). One-, 5- and 10- year disease specific survival rates were 96%, 86% and 84%, respectively. Median survival for stage 4 MM was 3 months. Extensive surgery was uncommon (n = 3). Patients generally presented with thin melanomas. Lymph node disease and distant metastases remained infrequently observed during following years, and general 1- and 5-year overall disease-specific survival rates exceeded 85%. Small numbers of rescue surgery and palliative medical treatment warrant further centralisation and investigation.

  7. Disease Management Project Breast Cancer in Hesse - 5-Year Survival Data: Successful Model of Intersectoral Communication for Quality Assurance.

    PubMed

    Jackisch, C; Funk, A; König, K; Lubbe, D; Misselwitz, B; Wagner, U

    2014-03-01

    Introduction: The Disease Management Project Breast Cancer (DMP Breast Cancer) was first launched in Hesse in 2004. The project is supported by the health insurance companies in Hesse and the Professional Association of Gynaecologists in Hesse. The aim is to offer structured treatment programmes to all women diagnosed with breast cancer in Hesse by creating intersectoral cooperations between coordinating clinics, associated hospitals and gynaecologists in private practice who registered in the DMP programme. Method: Between 1 January 2005 and 30 June 2011, 13 973 women were enrolled in the DMP programme. Results: After data cleansing, survival rates were calculated for a total of 11 214 women. The 5-year overall survival (OS) rate was 86.3 %; survival rates according to tumour stage on presentation were 92.2 % (pT1) and 82.3 % (pT2), respectively. The impact of steroid hormone receptor status on survival (87.8 % for receptor-positive cancers vs. 78.9 % for receptor-negative cancers) and of age at first diagnosis on survival (≤ 35 years = 91 %) were calculated. Conclusion: The project showed that intersectoral cooperation led to significant improvements in the quality of treatment over time, as measured by quality indicators and outcomes after treatment.

  8. Survival Outcomes After Intracranial Hemorrhage in Liver Disease.

    PubMed

    Lagman, Carlito; Nagasawa, Daniel T; Azzam, Daniel; Sheppard, John P; Chen, Cheng Hao Jacky; Ong, Vera; Nguyen, Thien; Prashant, Giyarpuram N; Niu, Tianyi; Tucker, Alexander M; Kim, Won; Kaldas, Fady M; Pouratian, Nader; Busuttil, Ronald W; Yang, Isaac

    2018-05-15

    Survival outcomes for patients with liver disease who suffer an intracranial hemorrhage (ICH) have not been thoroughly investigated. To understand survival outcomes for 3 groups: (1) patients with an admission diagnosis of liver disease (end-stage liver disease [ESLD] or non-ESLD) who developed an ICH in the hospital, (2) patients with ESLD who undergo either operative vs nonoperative management, and (3) patients with ESLD on the liver transplant waitlist who developed an ICH in the hospital. We retrospectively reviewed hospital charts from March 2006 through February 2017 of patients with liver disease and an ICH evaluated by the neurosurgery service at a single academic medical center. The primary outcome was survival. We included a total of 53 patients in this study. The overall survival for patients with an admission diagnosis of liver disease who developed an ICH (n = 29, 55%) in the hospital was 22%. Of those patients with an admission diagnosis of liver disease, 27 patients also had ESLD. Kaplan-Meier analysis found no significant difference in survival for ESLD patients (n = 33, 62%) according to operative status. There were 11 ESLD patients on the liver transplant waitlist. The overall survival for patients with ESLD on the liver transplant waitlist who suffered an in-hospital ICH (n = 7, 13%) was 14%. ICH in the setting of liver disease carries a grave prognosis. Also, a survival advantage for surgical hematoma evacuation in ESLD patients is not clear.

  9. ADD-ASPIRIN: A phase III, double-blind, placebo controlled, randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common non-metastatic solid tumours.

    PubMed

    Coyle, Christopher; Cafferty, Fay H; Rowley, Samuel; MacKenzie, Mairead; Berkman, Lindy; Gupta, Sudeep; Pramesh, C S; Gilbert, Duncan; Kynaston, Howard; Cameron, David; Wilson, Richard H; Ring, Alistair; Langley, Ruth E

    2016-11-01

    There is a considerable body of pre-clinical, epidemiological and randomised data to support the hypothesis that aspirin has the potential to be an effective adjuvant cancer therapy. Add-Aspirin is a phase III, multi-centre, double-blind, placebo-controlled randomised trial with four parallel cohorts. Patients who have undergone potentially curative treatment for breast (n=3100), colorectal (n=2600), gastro-oesophageal (n=2100) or prostate cancer (n=2120) are registered into four tumour specific cohorts. All cohorts recruit in the United Kingdom, with the breast and gastro-oesophageal cohort also recruiting in India. Eligible participants first undertake an active run-in period where 100mg aspirin is taken daily for approximately eight weeks. Participants who are able to adhere and tolerate aspirin then undergo a double-blind randomisation and are allocated in a 1:1:1 ratio to either 100mg aspirin, 300mg aspirin or a matched placebo to be taken daily for at least five years. Those participants ≥75years old are only randomised to 100mg aspirin or placebo due to increased toxicity risk. The primary outcome measures are invasive disease-free survival for the breast cohort, disease-free survival for the colorectal cohort, overall survival for the gastro-oesophageal cohort, and biochemical recurrence-free survival for the prostate cohort, with a co-primary outcome of overall survival across all cohorts. Secondary outcomes include adherence, toxicity including serious haemorrhage, cardiovascular events and some cohort specific measures. The Add-Aspirin trial investigates whether regular aspirin use after standard therapy prevents recurrence and prolongs survival in participants with four non-metastatic common solid tumours. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Organ Preservation in Rectal Adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management.

    PubMed

    Smith, J Joshua; Chow, Oliver S; Gollub, Marc J; Nash, Garrett M; Temple, Larissa K; Weiser, Martin R; Guillem, José G; Paty, Philip B; Avila, Karin; Garcia-Aguilar, Julio

    2015-10-23

    Treatment of patients with non-metastatic, locally advanced rectal cancer (LARC) includes pre-operative chemoradiation, total mesorectal excision (TME) and post-operative adjuvant chemotherapy. This trimodality treatment provides local tumor control in most patients; but almost one-third ultimately die from distant metastasis. Most survivors experience significant impairment in quality of life (QoL), due primarily to removal of the rectum. A current challenge lies in identifying patients who could safely undergo rectal preservation without sacrificing survival benefit and QoL. This multi-institutional, phase II study investigates the efficacy of total neoadjuvant therapy (TNT) and selective non-operative management (NOM) in LARC. Patients with MRI-staged Stage II or III rectal cancer amenable to TME will be randomized to receive FOLFOX/CAPEOX: a) before induction neoadjuvant chemotherapy (INCT); or b) after consolidation neoadjuvant chemotherapy (CNCT), with 5-FU or capecitabine-based chemoradiation. Patients in both arms will be re-staged after completing all neoadjuvant therapy. Those with residual tumor at the primary site will undergo TME. Patients with clinical complete response (cCR) will receive non-operative management (NOM). NOM patients will be followed every 3 months for 2 years, and every 6 months thereafter. TME patients will be followed according to NCCN guidelines. All will be followed for at least 5 years from the date of surgery or--in patients treated with NOM--the last day of treatment. The studies published thus far on the safety of NOM in LARC have compared survival between select groups of patients with a cCR after NOM, to patients with a pathologic complete response (pCR) after TME. The current study compares 3-year disease-free survival (DFS) in an entire population of patients with LARC, including those with cCR and those with pCR. We will compare the two arms of the study with respect to organ preservation at 3 years, treatment compliance

  11. Patient and implant survival following joint replacement because of metastatic bone disease

    PubMed Central

    2013-01-01

    Background Patients suffering from a pathological fracture or painful bony lesion because of metastatic bone disease often benefit from a total joint replacement. However, these are large operations in patients who are often weak. We examined the patient survival and complication rates after total joint replacement as the treatment for bone metastasis or hematological diseases of the extremities. Patients and methods 130 patients (mean age 64 (30–85) years, 76 females) received 140 joint replacements due to skeletal metastases (n = 114) or hematological disease (n = 16) during the period 2003–2008. 21 replaced joints were located in the upper extremities and 119 in the lower extremities. Clinical and survival data were extracted from patient files and various registers. Results The probability of patient survival was 51% (95% CI: 42–59) after 6 months, 39% (CI: 31–48) after 12 months, and 29% (CI: 21–37) after 24 months. The following surgical complications were seen (8 of which led to additional surgery): 2–5 hip dislocations (n = 8), deep infection (n = 3), peroneal palsy (n = 2), a shoulder prosthesis penetrating the skin (n = 1), and disassembly of an elbow prosthesis (n = 1). The probability of avoiding all kinds of surgery related to the implanted prosthesis was 94% (CI: 89–99) after 1 year and 92% (CI: 85–98) after 2 years. Conclusion Joint replacement operations because of metastatic bone disease do not appear to have given a poorer rate of patient survival than other types of surgical treatment, and the reoperation rate was low. PMID:23530874

  12. Social determinants of health and 5-year survival of colorectal cancer.

    PubMed

    Heidarnia, Mohammad Ali; Monfared, Esmat Davoudi; Akbari, Mohammad Esmail; Yavari, Parvin; Amanpour, Farzaneh; Mohseni, Maryam

    2013-01-01

    Early in the 21st century, cancers are the second cause of death worldwide. Colon cancer is third most common cancer and one of the few amenable to early diagnosis and treatment. Evaluation of factors affecting this cancer is important to increase survival time. Some of these factors affecting all diseases including cancer are social determinants of health. According to the importance of this disease and relation with these factors, this study was conducted to assess the relationship between social determinants of health and colon cancer survival. This was a cross-sectional, descriptive study for patients with colon cancer registered in the Cancer Research Center of Shahid Beheshti University of Medical Science, from April 2005 to November 2006, performed using questionnaires filled by telephone interview with patients (if patients had died, with family members). Data was analyzed with SPSS software (version 19) for descriptive analysis and STATA software for survival analysis including log rank test and three step Cox Proportional Hazard regression. Five hundred fifty nine patients with ages ranging from 23 to 88 years with mean ± standard deviation of 63 ± 11.8 years were included in the study. The five year survival was 68.3%( 387 patients were alive and 172 patients were dead by the end of the study). The Cox proportional hazard regression showed 5-year survival was related to age (HR=0.53, p=0.042 for>50 years versus<50 years old) in first step, gender (HR=0.60, p=0.006 for female versus male) in second step, job (HR=1.7, p=0.001 for manual versus non manual jobs), region of residency (HR=3.49, p=0.018 for west versus south regions), parents in childhood (HR=2.87, p=0.012 for having both parents versus not having), anatomical cancer location (HR=2.16, p<0.033 for colon versus rectal cancer) and complete treatment (HR=5.96, p<0.001 for incomplete versus complete treatment). Social determinants of health such as job, city region residency and having parents

  13. Sequential versus simultaneous use of chemotherapy and gonadotropin-releasing hormone agonist (GnRHa) among estrogen receptor (ER)-positive premenopausal breast cancer patients: effects on ovarian function, disease-free survival, and overall survival.

    PubMed

    Zhang, Ying; Ji, Yajie; Li, Jianwei; Lei, Li; Wu, Siyu; Zuo, Wenjia; Jia, Xiaoqing; Wang, Yujie; Mo, Miao; Zhang, Na; Shen, Zhenzhou; Wu, Jiong; Shao, Zhimin; Liu, Guangyu

    2018-04-01

    To investigate ovarian function and therapeutic efficacy among estrogen receptor (ER)-positive, premenopausal breast cancer patients treated with gonadotropin-releasing hormone agonist (GnRHa) and chemotherapy simultaneously or sequentially. This study was a phase 3, open-label, parallel, randomized controlled trial (NCT01712893). Two hundred sixteen premenopausal patients (under 45 years) diagnosed with invasive ER-positive breast cancer were enrolled from July 2009 to May 2013 and randomized at a 1:1 ratio to receive (neo)adjuvant chemotherapy combined with sequential or simultaneous GnRHa treatment. All patients were advised to receive GnRHa for at least 2 years. The primary outcome was the incidence of early menopause, defined as amenorrhea lasting longer than 12 months after the last chemotherapy or GnRHa dose, with postmenopausal or unknown follicle-stimulating hormone and estradiol levels. The menstrual resumption period and survivals were the secondary endpoints. The median follow-up time was 56.9 months (IQR 49.5-72.4 months). One hundred and eight patients were enrolled in each group. Among them, 92 and 78 patients had complete primary endpoint data in the sequential and simultaneous groups, respectively. The rates of early menopause were 22.8% (21/92) in the sequential group and 23.1% (18/78) in the simultaneous group [simultaneous vs. sequential: OR 1.01 (95% CI 0.50-2.08); p = 0.969; age-adjusted OR 1.13; (95% CI 0.54-2.37); p = 0.737]. The median menstruation resumption period was 12.0 (95% CI 9.3-14.7) months and 10.3 (95% CI 8.2-12.4) months for the sequential and simultaneous groups, respectively [HR 0.83 (95% CI 0.59-1.16); p = 0.274; age-adjusted HR 0.90 (95%CI 0.64-1.27); p = 0.567]. No significant differences were evident for disease-free survival (p = 0.290) or overall survival (p = 0.514) between the two groups. For ER-positive premenopausal patients, the sequential use of GnRHa and chemotherapy showed ovarian preservation

  14. 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.

  15. Beneficial Role of Low-Dose Antithymocyte Globulin in Unrelated Stem Cell Transplantation for Adult Patients with Acquired Severe Aplastic Anemia: Reduction of Graft-versus-Host Disease and Improvement of Graft-versus-Host Disease-Free, Failure-Free Survival Rate.

    PubMed

    Park, Sung-Soo; Kwak, Dae Hun; Jeon, Young-Woo; Yoon, Jae-Ho; Lee, Sung-Eun; Cho, Byung-Sik; Eom, Ki-Seong; Kim, Yoo-Jin; Kim, Hee-Je; Lee, Seok; Min, Chang-Ki; Cho, Seok-Goo; Kim, Dong-Wook; Min, Woo-Sung; Lee, Jong Wook

    2017-09-01

    Stem cell transplantation (SCT) from an unrelated donor (URD) is often considered in patients with severe aplastic anemia (SAA) whom immunosuppressive therapy failed and matched sibling donor is not available. To reduce the incidence of graft-versus-host disease (GVHD) in URD SCT, introducting antithymocyte globulin (ATG) into the conditioning regimen has been proposed. Although ATG was shown to play a role in reducing GVHD in a cohort with diverse hematologic diseases, its role in SAA remains uncertain. The aim of this study was to determine the efficacy and toxicity of ATG in URD SCT for adult patients with SAA. We investigated 83 adult patients with SAA who underwent URD SCT between 2003 and 2014. The transplantation strategy consisted of total body irradiation (total 800 cGy) and cyclophosphamide (total 100 mg/kg to 120 mg/kg), followed by tacrolimus and a short-term methotrexate. We divided patients into 2 groups: group 1 (n = 25), which received HLA-matched (8/8) bone marrow (BM) without ATG, and group 2 (n = 58), which received SCT from either an HLA-mismatched donor or peripheral blood (PB). Thereafter, group 2 was subdivided according to ATG use into group 2A (without ATG, n = 26), which served as a historical cohort, and group 2B (with ATG, n = 32). Rabbit ATG (Thymoglobulin; Genzyme-Sanofi, Lyon, France) was used in group 2B at a dose of 2.5 mg/kg. The median age of all patients was 30 years (range, 17 to 59 years). The incidence of GVHD was significantly lower in group 2B than group 2A, as demonstrated by the rate of grade II to IV acute GVHD at day 100 (31.2% versus 61.5%, P = .003) and the rate of chronic GVHD at 3 years (21.9% versus 65.4%, P = .002). The overall survival rates of the 3 groups were similar. However, GVHD-free, failure-free survival (GFFS) was significantly higher in group 2B than group 2A (P = .034). A multivariable model identified use of ATG as an independent factor affecting grades II to IV acute

  16. Male breast cancer: 20-year survival data for post-mastectomy radiotherapy.

    PubMed

    Eggemann, Holm; Ignatov, Atanas; Stabenow, Roland; von Minckwitz, Gunter; Röhl, Friedrich Wilhelm; Hass, Peter; Costa, Serban-Dan

    2013-08-01

    The goal of this population-based study was to determine the impact of post-mastectomy radiation therapy on long-term overall survival (OS) of male patients with breast cancer. We investigated 20-year OS rates of 664 patients diagnosed with primary stage I-III breast cancer in former East Germany between 1970 and 1989. Patients had a radical mastectomy with axillary lymph node dissection without systemic adjuvant therapy. Median follow-up time was 26.2 years (range 19-38 years). 52.4% of the patients had post-mastectomy radiotherapy. Radiotherapy showed different effects in each stage group after 20 years. Whereas there was an OS trend for radiotherapy to harm patients with stage I disease (hazard ratio (HR) 1.45; 95% confidence interval (CI) 0.98-2.15; p = 0.065), radiotherapy showed no benefit in patients with stage II disease (HR 0.82; 95% CI 0.62-1.1; p = 0.15). There was a significant survival benefit for patients with stage III disease receiving radiotherapy (HR 0.60; 95% CI 0.41-0.88; p = 0.008). Post-mastectomy radiotherapy is associated with longer OS in male patients with stage III breast cancer. Male breast cancer patients at stages I and II do not seem to benefit from radiotherapy, but obsolete irradiation techniques might explain adverse long-term effects in earlier stages.

  17. 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.

  18. Genetic variants in the vitamin D pathway and breast cancer disease-free survival

    PubMed Central

    Brewster, Abenaa M.

    2013-01-01

    Epidemiological studies have investigated the association between vitamin D pathway genes and breast cancer risk; however, little is known about the association between vitamin D pathway genes and breast cancer prognosis. In a retrospective cohort of 1029 patients with early-stage breast cancer, we analyzed the association between 106 tagging single nucleotide polymorphisms (SNPs) in eight vitamin D pathway genes and breast cancer disease-free survival (DFS) using Cox regression analysis adjusted for known prognostic variables. Using a false discovery rate of 10%, six intronic SNPs were significantly associated with poorer DFS: retinoid-X receptor alpha (RXRA) SNPs (rs881658, rs11185659, rs10881583, rs881657 and rs7864987) and plasminogen activator and urokinase receptor (PLAUR) SNP (rs4251864). Treatment received (no systemic therapy, hormone therapy alone or chemotherapy) was an effect modifier of the RXRA SNPs association with DFS (P < 0.05); therefore, we stratified further analysis by treatment group. Among patients who did not receive systemic therapy, RXRA SNP [rs10881583 (P = 0.02)] was associated with poorer DFS, and among patients who received chemotherapy, RXRA SNPs (rs881658, rs11185659, rs10881583, rs881657 and rs7864987) were associated with poorer DFS (P < 0.001 for all SNPs). However, RXRA SNPs: rs10881583 (P < 0.001) and rs881657 (P = 0.02) were associated with improved DFS in patients treated with hormone therapy alone. Our results suggest that SNPs in the RXRA and PLAUR genes in the vitamin D pathway may contribute to breast cancer DFS. In particular, SNPs in RXRA may predict for poorer or improved DFS in patients, according to type of systemic treatment received. If validated, these markers could be used for risk stratification of breast cancer patients. PMID:23180655

  19. Ten-Year Survival in Patients with Idiopathic Pulmonary Fibrosis After Lung Transplantation.

    PubMed

    ten Klooster, Liesbeth; Nossent, George D; Kwakkel-van Erp, Johanna M; van Kessel, Diana A; Oudijk, Erik J; van de Graaf, Ed A; Luijk, Bart; Hoek, Rogier A; van den Blink, Bernt; van Hal, Peter Th; Verschuuren, Erik A; van der Bij, Wim; van Moorsel, Coline H; Grutters, Jan C

    2015-12-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal fibrosing lung disease with a median survival of approximately 3 years after diagnosis. The only medical option to improve survival in IPF is lung transplantation (LTX). The purpose of this study was to evaluate trajectory data of IPF patients listed for LTX and to investigate the survival after LTX. Data were retrospectively collected from September 1989 until July 2011 of all IPF patients registered for LTX in the Netherlands. Patients were included after revision of the diagnosis based on the criteria set by the ATS/ERS/JRS/ALAT. Trajectory data, clinical data at time of screening, and donor data were collected. In total, 98 IPF patients were listed for LTX. During the waiting list period, 30 % of the patients died. Mean pulmonary artery pressure, 6-min walking distance, and the use of supplemental oxygen were significant predictors of mortality on the waiting list. Fifty-two patients received LTX with a median overall survival after transplantation of 10 years. This study demonstrated a 10-year survival time after LTX in IPF. Furthermore, our study demonstrated a significantly better survival after bilateral LTX in IPF compared to single LTX although bilateral LTX patients were significantly younger.

  20. The natural history of prevalent ischaemic heart disease in middle-aged men.

    PubMed

    Lampe, F C; Whincup, P H; Wannamethee, S G; Shaper, A G; Walker, M; Ebrahim, S

    2000-07-01

    To describe the long-term outcome of different forms of symptomatic and asymptomatic ischaemic heart disease in middle-aged men. 7735 men aged 40-59, randomly selected from 24 general practices in Britain were classified into one of seven ischaemic heart disease groups according to a questionnaire and electrocardiogram (ECG): I=diagnosed myocardial infarction; II=unrecognized myocardial infarction; III= diagnosed angina; IV=angina symptoms; V=possible myocardial infarction symptoms; VI=ECG ischaemia or possible myocardial infarction; VII=no evidence of ischaemic heart disease. The association of disease group with a range of fatal and non-fatal outcomes during 15 years of follow-up was assessed. At baseline 25% of men had evidence of ischaemic heart disease (groups I-VI). Risks of major ischaemic heart disease events, total and cardiovascular mortality, stroke, and major cardiovascular events tended to increase strongly from group VII to I. Diagnosed myocardial infarction was associated with a much poorer prognosis than all other groups (including unrecognized infarction) for all cardiovascular outcomes other than stroke. The relative risk associated with ischaemic heart disease at baseline declined dramatically over time. However, men with myocardial infarction who survived event-free for 10 years continued to experience a high excess risk in the subsequent 5 years, in contrast to event-free survivors of angina and other ischaemic heart disease. Adjusted to an average age of 50, the percentage of men surviving for 15 years free of a new major cardiovascular event was 44 for diagnosed myocardial infarction, 52 for unrecognized myocardial infarction, 66 for diagnosed angina, 68 for angina symptoms, 73 for possible myocardial infarction symptoms, 73 for ECG ischaemia, and 79 for no ischaemic heart disease. Comparison of outcome between prevalent and incident myocardial infarction illustrated the improved prognosis of men surviving the initial years after their event

  1. Radiation-Induced Differentiated Thyroid Cancer Is Associated with Improved Overall Survival but Not Thyroid Cancer-Specific Mortality or Disease-Free Survival.

    PubMed

    White, Michael G; Cipriani, Nicole A; Abdulrasool, Layth; Kaplan, Sharone; Aschebrook-Kilfoy, Briseis; Angelos, Peter; Kaplan, Edwin L; Grogan, Raymon H; Onel, Kenan

    2016-08-01

    Radiation is a well-described risk factor for differentiated thyroid carcinoma (DTC). Although the natural history of DTC following nuclear disasters and in healthcare workers with chronic radiation exposure (RE) has been described, little is known about DTC following short-term exposure to therapeutic medical radiation for benign disease. This study compares DTC morphology and outcomes in patients with and without a prior history of therapeutic external RE. A retrospective review was performed of patients with DTC treated at The University of Chicago between 1951 and 1987, with a median follow-up of 27 years (range 0.3-60 years). Patients were classified as either having (RE+) or not having (RE-) a history of therapeutic RE. Variables examined included sex, age at RE, dose of RE, indication for RE, DTC histology, and outcome. Morphology was determined by blinded retrospective review of all available histologic slides. Outcomes were assessed using Cox proportional hazards model and Kaplan-Meier curves. Of 257 DTC patients, 165 (64%) were RE- and 92 (36%) were RE+, with males comprising a greater proportion of the RE+ group (43.5% vs. 27.3%; p = 0.01). A total of 94.2% of DTC cases were classic papillary cancers; histology did not differ between RE+ and RE- cohorts (p = 0.73). RE was associated with an increased median overall survival (OS; 43 years vs. 38 years; hazard ratio [HR] = 0.55 [confidence interval (CI) 0.34-0.89]; p = 0.01). Survival for males in the RE- group was significantly worse than it was for RE- females (HR = 1.78 [CI 1.05-3.03]; p = 0.03) or RE+ males (HR = 2.98 [CI 1.39-6.38]; p = 0.01). Recurrence did not differ between the RE+ and RE- groups (HR = 0.85 [CI 0.52-1.41]; p = 0.54), nor did DTC-specific mortality (HR = 0.54 [CI 0.21-1.37]; p = 0.20). While DTC following RE has historically been considered a more aggressive variant than DTC in the absence of RE, the present data indicate that RE+ DTC

  2. 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.

  3. Disease-specific survival following the brachytherapy management of prostate cancer.

    PubMed

    Stock, Richard G; Cesaretti, Jamie A; Stone, Nelson N

    2006-03-01

    To determine disease-specific survival (DSS) and associated predictive factors after prostate brachytherapy. A total of 1561 patients underwent brachytherapy for prostate cancer from 1990 to 2004 (median follow-up, 3.8 years). Treatment included brachytherapy alone (n = 634), brachytherapy and hormonal therapy (n = 420), and implant and external beam therapy (n = 507). The DSS and overall survival rates at 10 years were 96% and 74%, respectively. Gleason score significantly impacted DSS, with 10-year rates of 98%, 91%, and 92% for scores of < or = 6, 7, and > or = 8, respectively (p < 0.0001). Multivariate analysis revealed that PSA status after treatment had the most significant effect on DSS. Ten-year DSS rates were 100%, 52%, and 98%, respectively for patients without PSA failure (n = 1430), failure with a doubling time (DT) < or = 10 months (n = 64), and failure with a DT > 10 months (n = 67), respectively (p < 0.0001). In patients with PSA failure, DSS rates were 30%, 67%, and 98%, for those with DT < or = 6 months, > 6-10 months, and > 10 months, respectively (p < 0.0001). The 10-year DSS rate supports the efficacy of brachytherapy. Patients dying with disease within 10 years after treatment harbor inherently aggressive cancer with high Gleason scores and short DT.

  4. 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

  5. Survival Pattern of Hodgkin Lymphoma Patients in the Last 25 Years in Lebanon.

    PubMed

    Massoud, Marcel; Kerbage, Fouad; Nehme, Joseph; Sakr, Riwa; Rached, Layale; Zeghondy, Jean; Nasr, Fady; Chahine, Georges

    2017-07-01

    After the emergence of combination chemotherapy in 1960s, survival of patients with Hodgkin lymphoma (HL) has dramatically improved worldwide. We lack studies that document the favorable evolution of survival regarding this disease in Lebanon. To compare the overall survival in HL over 3 different decades in Lebanon. We retrospectively reviewed the charts of 196 patients diagnosed with HL, treated and followed from 1990 to 2015 in our center. Patients were divided into 3 groups according to period of analysis: group A (1990-1999), group B (2000-2009), and group C (2010-2015). We studied the characteristics and survival patterns of patients in each group. The male-to-female sex ratio was 1.06. The median age at diagnosis was 33 years in group A, 30.4 in group B, and 33.12 in group C (P = .6). Results showed variations in the subtypes of the disease according to the following: nodular-sclerosis HL 59.5% in group A, 76.2% in group B, and 85.4% in group C. Mixed cellularity HL 21.6% in group A, 2.4% in group B, and 73.7% in group C (P = .0001). Patients presented with localized disease in 58.6%, 73.7%, and 56.4% in groups A, B, and C, respectively (P = .173). Complete remission was achieved in 76.5% in group A, 85.3% in group B, and 69.5% in group C (P = .007). The survival rate at 5 years in group A was 91%, 94% in group B, and 100% in group C. The survival of patients with HL has dramatically improved over the past 25 years in Lebanon. These results resemble those achieved in Western countries due to the fast adoption of new molecular imaging technologies at diagnosis and follow-up and the rapid approval of new drugs for relapse in the Lebanese market. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed

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

    1999-10-01

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

  7. Long-term survival of patients with CLL after allogeneic transplantation: a report from the European Society for Blood and Marrow Transplantation.

    PubMed

    van Gelder, M; de Wreede, L C; Bornhäuser, M; Niederwieser, D; Karas, M; Anderson, N S; Gramatzki, M; Dreger, P; Michallet, M; Petersen, E; Bunjes, D; Potter, M; Beelen, D; Cornelissen, J J; Yakoub-Agha, I; Russell, N H; Finke, J; Schoemans, H; Vitek, A; Urbano-Ispízua, Á; Blaise, D; Volin, L; Chevallier, P; Caballero, D; Putter, H; van Biezen, A; Henseler, A; Schönland, S; Kröger, N; Schetelig, J

    2017-03-01

    Even with the availability of targeted drugs, allogeneic hematopoietic cell transplantation (allo-HCT) is the only therapy with curative potential for patients with CLL. Cure can be assessed by comparing long-term survival of patients to the matched general population. Using data from 2589 patients who received allo-HCT between 2000 and 2010, we used landmark analyses and methods from relative survival analysis to calculate excess mortality compared with an age-, sex- and calendar year-matched general population. Estimated event-free survival, overall survival and non-relapse mortality (NRM) 10 years after allo-HCT were 28% (95% confidence interval (CI), 25-31), 35% (95% CI, 32-38) and 40% (95% CI, 37-42), respectively. Patients who passed the 5-year landmark event-free survival (N=394) had a 79% probability (95% CI, 73-85) of surviving the subsequent 5 years without an event. Relapse and NRM contributed equally to treatment failure. Five-year mortality for 45- and 65-year-old reference patients who were event-free at the 5-year landmark was 8% and 47% compared with 3% and 14% in the matched general population, respectively. The prospect of long-term disease-free survival remains an argument to consider allo-HCT for young patients with high-risk CLL, and programs to understand and prevent late causes of failure for long-term survivors are warranted, especially for older patients.

  8. Effect of PCI on Long-Term Survival in Patients with Stable Ischemic Heart Disease.

    PubMed

    Sedlis, Steven P; Hartigan, Pamela M; Teo, Koon K; Maron, David J; Spertus, John A; Mancini, G B John; Kostuk, William; Chaitman, Bernard R; Berman, Daniel; Lorin, Jeffrey D; Dada, Marcin; Weintraub, William S; Boden, William E

    2015-11-12

    Percutaneous coronary intervention (PCI) relieves angina in patients with stable ischemic heart disease, but clinical trials have not shown that it improves survival. Between June 1999 and January 2004, we randomly assigned 2287 patients with stable ischemic heart disease to an initial management strategy of optimal medical therapy alone (medical-therapy group) or optimal medical therapy plus PCI (PCI group) and did not find a significant difference in the rate of survival during a median follow-up of 4.6 years. We now report the rate of survival among the patients who were followed for up to 15 years. We obtained permission from the patients at the Department of Veterans Affairs (VA) sites and some non-VA sites in the United States to use their Social Security numbers to track their survival after the original trial period ended. We searched the VA national Corporate Data Warehouse and the National Death Index for survival information and the dates of death from any cause. We calculated survival according to the Kaplan-Meier method and used a Cox proportional-hazards model to adjust for significant between-group differences in baseline characteristics. Extended survival information was available for 1211 patients (53% of the original population). The median duration of follow-up for all patients was 6.2 years (range, 0 to 15); the median duration of follow-up for patients at the sites that permitted survival tracking was 11.9 years (range, 0 to 15). A total of 561 deaths (180 during the follow-up period in the original trial and 381 during the extended follow-up period) occurred: 284 deaths (25%) in the PCI group and 277 (24%) in the medical-therapy group (adjusted hazard ratio, 1.03; 95% confidence interval, 0.83 to 1.21; P=0.76). During an extended-follow-up of up to 15 years, we did not find a difference in survival between an initial strategy of PCI plus medical therapy and medical therapy alone in patients with stable ischemic heart disease. (Funded by the VA

  9. Sentinel lymph node biopsy does not change melanoma-specific survival among patients with Breslow thickness greater than four millimeters.

    PubMed

    Caracò, Corrado; Celentano, Egidio; Lastoria, Secondo; Botti, Gerardo; Ascierto, Paolo Antonio; Mozzillo, Nicola

    2004-03-01

    Management of patients with cutaneous melanoma in the absence of lymph node metastases is still controversial. The experience at the National Cancer Institute in Naples was analyzed to evaluate 3-year disease-free survival and overall survival for all patients who underwent sentinel lymph node biopsy (SLB) with Breslow thickness greater than 4 mm. Data from 359 sentinel biopsies performed in the past 5 years were reviewed to determine the effect of the treatment on disease-free survival and overall survival after stratifying patients for node status, tumor ulceration, and Breslow thickness. Statistical analysis showed a better 3-year survival for sentinel node-negative patients than for sentinel node-positive cases (88.4% and 72.9%, respectively; P <.05). Tumor ulceration retained its prognostic significance despite lymph node status, indicating a higher risk for development of distant metastases. Survival curves associated with thicker melanomas did not show significant differences between negative- and positive-SLB patients. SLB provides accurate staging of nodal status in melanoma patients who have no clinical evidence of metastases. Longer follow-up and final results from ongoing trials are necessary to definitively clarify the role of this procedure.

  10. Increased survival and decreased recurrence in colorectal cancer patients diagnosed in a screening programme.

    PubMed

    Mengual-Ballester, Mónica; Pellicer-Franco, Enrique; Valero-Navarro, Graciela; Soria-Aledo, Victoriano; García-Marín, José Andrés; Aguayo-Albasini, José Luis

    2016-08-01

    Population-based screening programmes for colorectal cancer (CRC) allow an early diagnosis, even before the onset of symptoms, but there are few studies and none in Spain on the influence they have on patient survival. The aim of the present study is to show that patients receiving surgery for CRC following diagnosis via a screening programme have a higher survival and disease-free survival rate than those diagnosed in the symptomatic stage. Prospective study of all the patients undergoing programmed surgery for CRC at the JM Morales Meseguer Hospital in Murcia (Spain) between 2004 and 2010. The patients were divided into two groups: (a) those diagnosed through screening (125 cases); and (b) those diagnosed in the symptomatic stage (565 cases). Survival and disease-free survival were analysed and compared for both groups using the Mantel method. The screen-detected CRC patients show a higher rate of survival (86.3% versus 72.1% at 5 years, p<0.05) and a lower rate of tumour recurrence (73.4% versus 88.3% at 5 years, p<0.05). Population-based screening for CRC is an effective strategic measure for reducing mortality specific to this neoplasia. Copyright © 2016. Published by Elsevier Ltd.

  11. Impact of Nurse-Led, Multidisciplinary Home-Based Intervention on Event-Free Survival Across the Spectrum of Chronic Heart Disease

    PubMed Central

    Wiley, Joshua F.; Ball, Jocasta; Chan, Yih-Kai; Ahamed, Yasmin; Thompson, David R.; Carrington, Melinda J.

    2016-01-01

    Background— We sought to determine the overall impact of a nurse-led, multidisciplinary home-based intervention (HBI) adapted to hospitalized patients with chronic forms of heart disease of varying types. Methods and Results— Prospectively planned, combined, secondary analysis of 3 randomized trials (1226 patients) of HBI were compared with standard management. Hospitalized patients presenting with heart disease but not heart failure, atrial fibrillation but not heart failure, and heart failure, as well, were recruited. Overall, 612 and 614 patients, respectively, were allocated to a home visit 7 to 14 days postdischarge by a cardiac nurse with follow-up and multidisciplinary support according to clinical need or standard management. The primary outcome of days-alive and out-of-hospital was examined on an intention-to-treat basis. During 1371 days (interquartile range, 1112–1605) of follow-up, 218 patients died and 17 917 days of hospital stay were recorded. In comparison with standard management, HBI patients achieved significantly prolonged event-free survival (90.1% [95% confidence interval, 88.2–92.0] versus 87.2% [95% confidence interval, 85.1–89.3] days-alive and out-of-hospital; P=0.020). This reflected less all-cause mortality (adjusted hazard ratio, 0.67; 95% confidence interval, 0.50–0.88; P=0.005) and unplanned hospital stay (median, 0.22 [interquartile range, 0–1.3] versus 0.36 [0–2.1] days/100 days follow-up; P=0.011). Analyses of the differential impact of HBI on all-cause mortality showed significant interactions (characterized by U-shaped relationships) with age (P=0.005) and comorbidity (P=0.041); HBI was most effective for those aged 60 to 82 years (59%–65% of individual trial cohorts) and with a Charlson Comorbidity Index Score of 5 to 8 (36%–61%). Conclusions— These data provide further support for the application of postdischarge HBI across the full spectrum of patients being hospitalized for chronic forms of heart

  12. 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

  13. 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.

  14. 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.

  15. Socioeconomic and Other Demographic Disparities Predicting Survival among Head and Neck Cancer Patients

    PubMed Central

    Choi, Seung Hee; Terrell, Jeffrey E.; Fowler, Karen E.; McLean, Scott A.; Ghanem, Tamer; Wolf, Gregory T.; Bradford, Carol R.; Taylor, Jeremy; Duffy, Sonia A.

    2016-01-01

    Background The Institute of Medicine (IOM) report, “Unequal Treatment,” which defines disparities as racially based, indicates that disparities in cancer diagnosis and treatment are less clear. While a number of studies have acknowledged cancer disparities, they have limitations of retrospective nature, small sample sizes, inability to control for covariates, and measurement errors. Objective The purpose of this study was to examine disparities as predictors of survival among newly diagnosed head and neck cancer patients recruited from 3 hospitals in Michigan, USA, while controlling for a number of covariates (health behaviors, medical comorbidities, and treatment modality). Methods Longitudinal data were collected from newly diagnosed head and neck cancer patients (N = 634). The independent variables were median household income, education, race, age, sex, and marital status. The outcome variables were overall, cancer-specific, and disease-free survival censored at 5 years. Kaplan-Meier curves and univariate and multivariate Cox proportional hazards models were performed to examine demographic disparities in relation to survival. Results Five-year overall, cancer-specific, and disease-free survival were 65.4% (407/622), 76.4% (487/622), and 67.0% (427/622), respectively. Lower income (HR, 1.5; 95% CI, 1.1–2.0 for overall survival; HR, 1.4; 95% CI, 1.0–1.9 for cancer-specific survival), high school education or less (HR, 1.4; 95% CI, 1.1–1.9 for overall survival; HR, 1.4; 95% CI, 1.1–1.9 for cancer-specific survival), and older age in decades (HR, 1.4; 95% CI, 1.2–1.7 for overall survival; HR, 1.2; 95% CI, 1.1–1.4 for cancer-specific survival) decreased both overall and disease-free survival rates. A high school education or less (HR, 1.4; 95% CI, 1.0–2.1) and advanced age (HR, 1.3; 95% CI, 1.1–1.6) were significant independent predictors of poor cancer-specific survival. Conclusion Low income, low education, and advanced age predicted poor

  16. Socioeconomic and Other Demographic Disparities Predicting Survival among Head and Neck Cancer Patients.

    PubMed

    Choi, Seung Hee; Terrell, Jeffrey E; Fowler, Karen E; McLean, Scott A; Ghanem, Tamer; Wolf, Gregory T; Bradford, Carol R; Taylor, Jeremy; Duffy, Sonia A

    2016-01-01

    The Institute of Medicine (IOM) report, "Unequal Treatment," which defines disparities as racially based, indicates that disparities in cancer diagnosis and treatment are less clear. While a number of studies have acknowledged cancer disparities, they have limitations of retrospective nature, small sample sizes, inability to control for covariates, and measurement errors. The purpose of this study was to examine disparities as predictors of survival among newly diagnosed head and neck cancer patients recruited from 3 hospitals in Michigan, USA, while controlling for a number of covariates (health behaviors, medical comorbidities, and treatment modality). Longitudinal data were collected from newly diagnosed head and neck cancer patients (N = 634). The independent variables were median household income, education, race, age, sex, and marital status. The outcome variables were overall, cancer-specific, and disease-free survival censored at 5 years. Kaplan-Meier curves and univariate and multivariate Cox proportional hazards models were performed to examine demographic disparities in relation to survival. Five-year overall, cancer-specific, and disease-free survival were 65.4% (407/622), 76.4% (487/622), and 67.0% (427/622), respectively. Lower income (HR, 1.5; 95% CI, 1.1-2.0 for overall survival; HR, 1.4; 95% CI, 1.0-1.9 for cancer-specific survival), high school education or less (HR, 1.4; 95% CI, 1.1-1.9 for overall survival; HR, 1.4; 95% CI, 1.1-1.9 for cancer-specific survival), and older age in decades (HR, 1.4; 95% CI, 1.2-1.7 for overall survival; HR, 1.2; 95% CI, 1.1-1.4 for cancer-specific survival) decreased both overall and disease-free survival rates. A high school education or less (HR, 1.4; 95% CI, 1.0-2.1) and advanced age (HR, 1.3; 95% CI, 1.1-1.6) were significant independent predictors of poor cancer-specific survival. Low income, low education, and advanced age predicted poor survival while controlling for a number of covariates (health behaviors

  17. Survival after resection for lung cancer is the outcome that matters.

    PubMed

    Reed, Michael F; Molloy, Mark; Dalton, Erica L; Howington, John A

    2004-11-01

    Lung cancer is the leading cause of cancer mortality in the United States. Stage-specific survival is well documented in national data sets; however, there remains limited recording of longitudinal survival in individual centers. The VistA Surgery Package was employed to list operations performed by the thoracic surgery service at one Veterans Administration (VA) Medical Center. During a period of 107 months, 416 thoracic operations were performed, 211 of them for lung cancer. Stage distribution was 66% stage I, 18% stage II, 12% stage III, and 4% stage IV. During follow-up, 102 patients died, 57 of them from disease-specific causes. Median survival was 39 months for stage I. Disease-specific median survival was 83 months for stage I, and 5-year survival was 52% (72% for stage IA and 32% for stage IB). Pulmonary resection offers high disease-free survival for early-stage lung cancer. Decentralized hospital computer programming (DHCP) allows individual oncology programs to reliably measure survival. Use of this important outcome measure in quality improvement programs facilitates realistic counseling of patients and meaningful assessments of practice effectiveness.

  18. 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

  19. 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

  20. One-millimeter cancer-free margin is curative for colorectal liver metastases: a propensity score case-match approach.

    PubMed

    Hamady, Zaed Z R; Lodge, J Peter A; Welsh, Fenella K; Toogood, Giles J; White, Alan; John, Timothy; Rees, Myrddin

    2014-03-01

    To investigate the influence of clear surgical resection margin width on disease recurrence rate after intentionally curative resection of colorectal liver metastases. There is consensus that a histological positive resection margin is a predictor of disease recurrence after resection of colorectal liver metastases. The dispute, however, over the width of cancer-free resection margin required is ongoing. Analysis of observational prospectively collected data for 2715 patients who underwent primary resection of colorectal liver metastases from 2 major hepatobiliary units in the United Kingdom. Histological cancer-free resection margin was classified as positive (if cancer cells present at less than 1 mm from the resection margin) or negative (if the distance between the cancer and the margin is 1 mm or more). The negative margin was further classified according to the distance from the tumor in millimeters. Predictors of disease-free survival were analyzed in univariate and multivariate analyses. A case-match analysis by a propensity score method was undertaken to reduce bias. A 1-mm cancer-free resection margin was sufficient to achieve 33% 5-year overall disease-free survival. Extra margin width did not add disease-free survival advantage (P > 0.05). After the propensity case-match analysis, there is no statistical difference in disease-free survival between patients with negative narrow and wider margin clearance [hazard ratio (HR) 1.0; 95% (confidence interval) CI: 0.9-1.2; P = 0.579 at 5-mm cutoff and HR 1.1; 95% CI: 0.96-1.3; P = 0.149 at 10-mm cutoff]. Patients with extrahepatic disease and positive lymph node primary tumor did not have disease-free survival advantage despite surgical margin clearance (9 months for <1-mm vs 12 months for ≥1-mm margin clearance; P = 0.062). One-mm cancer-free resection margin achieved in patients with colorectal liver metastases should now be considered the standard of care.

  1. 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

    Reduction of cyclin-dependent kinase inhibitor 2A (CDKN2A) (p16 and p14) expression through DNA methylation has been reported in prostate cancer (PCa). This meta-analysis was conducted to assess the difference of p16 and p14 methylation between PCa and different histological types of nonmalignant controls and the correlation of p16 or p14 methylation with clinicopathological features of PCa. According to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement criteria, articles were searched in PubMed, Embase, EBSCO, Wanfang, and CNKI databases. The strength of correlation was calculated by the pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). Trial sequential analysis (TSA) was used to estimate the required population information for significant results. A total of 20 studies published from 1997 to 2017 were identified in this meta-analysis, including 1140 PCa patients and 530 cases without cancer. Only p16 methylation in PCa was significantly higher than in benign prostatic lesions (OR = 4.72, P = .011), but had a similar level in PCa and adjacent tissues or high-grade prostatic intraepithelial neoplasias (HGPIN). TSA revealed that this analysis on p16 methylation is a false positive result in cancer versus benign prostatic lesions (the estimated required information size of 5116 participants). p16 methylation was not correlated with PCa in the urine and blood. Besides, p16 methylation was not linked to clinical stage, prostate-specific antigen (PSA) level, and Gleason score (GS) of patients with PCa. p14 methylation was not correlated with PCa in tissue and urine samples. No correlation was observed between p14 methylation and clinical stage or GS. CDKN2A mutation and copy number alteration were not associated with prognosis of PCa in overall survival and disease-free survival. CDKN2A expression was not correlated with the prognosis of PCa in overall survival (492 cases) (P > .1

  2. Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial.

    PubMed

    Giuliano, Armando E; Ballman, Karla V; McCall, Linda; Beitsch, Peter D; Brennan, Meghan B; Kelemen, Pond R; Ollila, David W; Hansen, Nora M; Whitworth, Pat W; Blumencranz, Peter W; Leitch, A Marilyn; Saha, Sukamal; Hunt, Kelly K; Morrow, Monica

    2017-09-12

    The results of the American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) trial were first reported in 2005 with a median follow-up of 6.3 years. Longer follow-up was necessary because the majority of the patients had estrogen receptor-positive tumors that may recur later in the disease course (the ACOSOG is now part of the Alliance for Clinical Trials in Oncology). To determine whether the 10-year overall survival of patients with sentinel lymph node metastases treated with breast-conserving therapy and sentinel lymph node dissection (SLND) alone without axillary lymph node dissection (ALND) is noninferior to that of women treated with axillary dissection. The ACOSOG Z0011 phase 3 randomized clinical trial enrolled patients from May 1999 to December 2004 at 115 sites (both academic and community medical centers). The last date of follow-up was September 29, 2015, in the ACOSOG Z0011 (Alliance) trial. Eligible patients were women with clinical T1 or T2 invasive breast cancer, no palpable axillary adenopathy, and 1 or 2 sentinel lymph nodes containing metastases. All patients had planned lumpectomy, planned tangential whole-breast irradiation, and adjuvant systemic therapy. Third-field radiation was prohibited. The primary outcome was overall survival with a noninferiority hazard ratio (HR) margin of 1.3. The secondary outcome was disease-free survival. Among 891 women who were randomized (median age, 55 years), 856 (96%) completed the trial (446 in the SLND alone group and 445 in the ALND group). At a median follow-up of 9.3 years (interquartile range, 6.93-10.34 years), the 10-year overall survival was 86.3% in the SLND alone group and 83.6% in the ALND group (HR, 0.85 [1-sided 95% CI, 0-1.16]; noninferiority P = .02). The 10-year disease-free survival was 80.2% in the SLND alone group and 78.2% in the ALND group (HR, 0.85 [95% CI, 0.62-1.17]; P = .32). Between year 5 and year 10, 1 regional recurrence was seen in the SLND alone group vs none in

  3. 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.

  4. Nine-year prostate cancer survival differences between aggressive versus conservative therapy in men with advanced and metastatic prostate cancer.

    PubMed

    Dall'Era, Marc A; Lo, Mary J; Chen, Jaclyn; Cress, Rosemary; Hamilton, Ann S

    2018-05-01

    To the authors' knowledge, the survival benefit of local therapy in the setting of advanced prostate cancer remains unknown. The authors investigated whether prostate-directed treatment with either surgery or radiotherapy versus conservative treatment in the setting of locally advanced or metastatic disease was associated with improved survival within a cohort of men from the Centers for Disease Control and Prevention's (CDC) Breast and Prostate Cancer Data Quality and Patterns of Care Study (CDC POC-BP). Men diagnosed with locally advanced (cT3-T4 or N+ and M0) or metastatic prostate cancer were identified. The authors compared survival by treatment type, categorized as conservative (androgen deprivation therapy only) versus aggressive (radical prostatectomy or any type of radiotherapy). Nine-year overall survival and prostate cancer-specific survival were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used to determine factors independently associated with 9-year prostate cancer-specific survival. For men with advanced, nonmetastatic prostate cancer, conservative treatment alone was associated with a 4 times higher likelihood of prostate cancer mortality compared with men treated with surgery (hazard ratio, 4.18; 95% confidence interval, 1.44-12.14). In contrast, no difference was found between conservative versus aggressive treatment after adjusting for covariates for men with metastatic disease. The 9-year prostate cancer-specific survival rate was 27% for those receiving aggressive treatment versus 24% for men undergoing conservative treatment. The authors did not observe a survival advantage with local therapy in addition to standard androgen deprivation therapy for men with metastatic prostate cancer. However, the results of the current study did affirm advantages in the setting of locally advanced disease. Aggressive local therapy in the setting of metastatic disease needs to be studied carefully before clinical adoption

  5. External validation of a 5-year survival prediction model after elective abdominal aortic aneurysm repair.

    PubMed

    DeMartino, Randall R; Huang, Ying; Mandrekar, Jay; Goodney, Philip P; Oderich, Gustavo S; Kalra, Manju; Bower, Thomas C; Cronenwett, Jack L; Gloviczki, Peter

    2018-01-01

    The benefit of prophylactic repair of abdominal aortic aneurysms (AAAs) is based on the risk of rupture exceeding the risk of death from other comorbidities. The purpose of this study was to validate a 5-year survival prediction model for patients undergoing elective repair of asymptomatic AAA <6.5 cm to assist in optimal selection of patients. All patients undergoing elective repair for asymptomatic AAA <6.5 cm (open or endovascular) from 2002 to 2011 were identified from a single institutional database (validation group). We assessed the ability of a prior published Vascular Study Group of New England (VSGNE) model (derivation group) to predict survival in our cohort. The model was assessed for discrimination (concordance index), calibration (calibration slope and calibration in the large), and goodness of fit (score test). The VSGNE derivation group consisted of 2367 patients (70% endovascular). Major factors associated with survival in the derivation group were age, coronary disease, chronic obstructive pulmonary disease, renal function, and antiplatelet and statin medication use. Our validation group consisted of 1038 patients (59% endovascular). The validation group was slightly older (74 vs 72 years; P < .01) and had a higher proportion of men (76% vs 68%; P < .01). In addition, the derivation group had higher rates of advanced cardiac disease, chronic obstructive pulmonary disease, and baseline creatinine concentration (1.2 vs 1.1 mg/dL; P < .01). Despite slight differences in preoperative patient factors, 5-year survival was similar between validation and derivation groups (75% vs 77%; P = .33). The concordance index of the validation group was identical between derivation and validation groups at 0.659 (95% confidence interval, 0.63-0.69). Our validation calibration in the large value was 1.02 (P = .62, closer to 1 indicating better calibration), calibration slope of 0.84 (95% confidence interval, 0.71-0.97), and score test of P = .57 (>.05

  6. Free-Text Disease Classification

    DTIC Science & Technology

    2011-09-01

    NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS FREE-TEXT DISEASE CLASSIFICATION by Craig Maxey September 2011 Thesis Advisor: Lyn R. Whitaker...2104-10-31 Free-Text Disease Classification Craig Maxey Naval Postgraduate School Monterey, CA 93943 Department of the Navy Approved for public...POSTGRADUATE SCHOOL September 2011 Author: Craig Maxey Approved by: Lyn R. Whitaker Thesis Advisor Samuel E. Buttrey Second Reader Robert F. Dell Chair

  7. 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.

  8. Pressure-Flow During Exercise Catheterization Predicts Survival in Pulmonary Hypertension.

    PubMed

    Hasler, Elisabeth D; Müller-Mottet, Séverine; Furian, Michael; Saxer, Stéphanie; Huber, Lars C; Maggiorini, Marco; Speich, Rudolf; Bloch, Konrad E; Ulrich, Silvia

    2016-07-01

    Pulmonary hypertension manifests with impaired exercise capacity. Our aim was to investigate whether the mean pulmonary arterial pressure to cardiac output relationship (mPAP/CO) predicts transplant-free survival in patients with pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Hemodynamic data according to right heart catheterization in patients with PAH and CTEPH at rest and during supine incremental cycle exercise were analyzed. Transplant-free survival and predictive value of hemodynamics were assessed by using Kaplan-Meier and Cox regression analyses. Seventy patients (43 female; 54 with PAH, 16 with CTEPH; median (quartiles) age, 65 [50; 73] years; mPAP, 34 [29; 44] mm Hg; cardiac index, 2.8 [2.3; 3.5] [L/min]/m(2)) were followed up for 610 (251; 1256) days. Survival at 1, 3, 5, and 7 years was 89%, 81%, 71%, and 59%. Age, World Health Organization-functional class, 6-min walk test, and mixed-venous oxygen saturation (but not resting hemodynamics) predicted transplant-free survival. Maximal workload (hazard ratio [HR], 0.94 [95% CI, 0.89-0.99]; P = .027), peak cardiac index (HR, 0.51 [95% CI, 0.27-0.95]; P = .034), change in cardiac index, 0.25 [95% CI, 0.06-0.94]; P = .040), and mPAP/CO (HR, 1.02 [95% CI, 1.01-1.03]; P = .003) during exercise predicted survival. Values for mPAP/CO predicted 3-year transplant-free survival with an area under the curve of 0.802 (95% CI, 0.66-0.95; P = .004). In this collective of patients with PAH or CTEPH, the pressure-flow relationship during exercise predicted transplant-free survival and correlated with established markers of disease severity and outcome. Right heart catheterization during exercise may provide important complementary prognostic information in the management of pulmonary hypertension. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  9. Neutrophil-to-lymphocyte ratio as an independent predictor for survival in patients with localized clear cell renal cell carcinoma after radiofrequency ablation: a propensity score matching analysis.

    PubMed

    Chang, Xiaofeng; Zhang, Fan; Liu, Tieshi; Wang, Wei; Guo, Hongqian

    2017-06-01

    To investigate the role of neutrophil-to-lymphocyte ratio as a prognostic indicator in patients with localized clear cell renal cell carcinoma treated with radiofrequency ablation. We retrospectively analyzed data from patients with renal cell carcinoma who underwent radiofrequency ablation from 2006 to 2013. The Kaplan-Meier method was used to generate the survival curves according to different categories of neutrophil-to-lymphocyte ratio. Relationships between preoperative neutrophil-to-lymphocyte ratio or the change of neutrophil-to-lymphocyte ratio and survival were evaluated with multivariable Cox proportional hazards regression analysis. A propensity score matching analysis was carried out to avoid confounding bias. A total of 185 patients were included in present study. When stratified by preoperative neutrophil-to-lymphocyte ratio cutoff value of 2.79, 5-year recurrence-free survival, 5-year disease-free survival, and 5-year overall survival rates of neutrophil-to-lymphocyte ratio <2.79 versus ≥2.79 were 100, 98.5, and 99.2% versus 80.5, 72.6, and 90.6%, respectively (P < 0.001, P < 0.001, P = 0.003). In terms of propensity score matching analysis, 5-year recurrence-free survival, 5-year disease-free survival, and 5-year overall survival rates of neutrophil-to-lymphocyte ratio <2.79 versus ≥2.79 were 100, 97.9, and 100% versus 82.3, 73.4, and 89.4%, respectively (P = 0.003, P = 0.001, P = 0.022). When combining preoperative neutrophil-to-lymphocyte ratio with the change of neutrophil-to-lymphocyte ratio, patients with both preoperative neutrophil-to-lymphocyte ratio ≥2.79 and the change of neutrophil-to-lymphocyte ratio ≥0.40 had the worst disease-free survival. Results of multivariable analysis showed that preoperative neutrophil-to-lymphocyte ratio and the change of neutrophil-to-lymphocyte ratio correlated with cancer relapse remarkably. High preoperative neutrophil-to-lymphocyte ratio and elevated postoperative neutrophil

  10. Survival Analysis of Patients with End Stage Renal Disease

    NASA Astrophysics Data System (ADS)

    Urrutia, J. D.; Gayo, W. S.; Bautista, L. A.; Baccay, E. B.

    2015-06-01

    This paper provides a survival analysis of End Stage Renal Disease (ESRD) under Kaplan-Meier Estimates and Weibull Distribution. The data were obtained from the records of V. L. MakabaliMemorial Hospital with respect to time t (patient's age), covariates such as developed secondary disease (Pulmonary Congestion and Cardiovascular Disease), gender, and the event of interest: the death of ESRD patients. Survival and hazard rates were estimated using NCSS for Weibull Distribution and SPSS for Kaplan-Meier Estimates. These lead to the same conclusion that hazard rate increases and survival rate decreases of ESRD patient diagnosed with Pulmonary Congestion, Cardiovascular Disease and both diseases with respect to time. It also shows that female patients have a greater risk of death compared to males. The probability risk was given the equation R = 1 — e-H(t) where e-H(t) is the survival function, H(t) the cumulative hazard function which was created using Cox-Regression.

  11. 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.

  12. Survival from colorectal cancer in Victoria: 10-year follow up of the 1987 management survey.

    PubMed

    McLeish, John A; Thursfield, Vicky J; Giles, Graham G

    2002-05-01

    In 1987, the Victorian Cancer Registry identified a population-based sample of patients who underwent surgery for colorectal cancer for an audit of management following resection. Over 10 years have passed since this survey, and data on the survival of these patients (incorporating various prognostic indicators collected at the time of the survey) are now discussed in the present report. Relative survival analysis was conducted for each prognostic indicator separately and then combined in a multivariate model. Relative survival at 5 years for patients undergoing curative resections was 76% compared with 7% for those whose treatment was considered palliative. Survival at 10 years was little changed (73% and 7% respectively). Survival did not differ significantly by sex or age irrespective of treatment intention. In the curative group, only stage was a significant predictor of survival. Multivariate analysis was performed only for the curative group. Adjusting for all variables simultaneously,stage was the only -significant predictor of survival. Patients with Dukes' stage C disease were at a significantly greater risk (OR 5.5 (1.7-17.6)) than those with Dukes' A. Neither tumour site, sex, age, surgeon activity level nor adjuvant therapies made a significant contribution to the model.

  13. Addition of Androgens Improves Survival in Elderly Patients With Acute Myeloid Leukemia: A GOELAMS Study.

    PubMed

    Pigneux, Arnaud; Béné, Marie C; Guardiola, Philippe; Recher, Christian; Hamel, Jean-Francois; Sauvezie, Mathieu; Harousseau, Jean-Luc; Tournilhac, Olivier; Witz, Francis; Berthou, Christian; Escoffre-Barbe, Martine; Guyotat, Denis; Fegueux, Nathalie; Himberlin, Chantal; Hunault, Mathilde; Delain, Martine; Lioure, Bruno; Jourdan, Eric; Bauduer, Frederic; Dreyfus, Francois; Cahn, Jean-Yves; Sotto, Jean-Jacques; Ifrah, Norbert

    2017-02-01

    Purpose Elderly patients with acute myeloid leukemia (AML) have a poor prognosis, and innovative maintenance therapy could improve their outcomes. Androgens, used in the treatment of aplastic anemia, have been reported to block proliferation of and initiate differentiation in AML cells. We report the results of a multicenter, phase III, randomized open-label trial exploring the benefit of adding androgens to maintenance therapy in patients 60 years of age or older. Patients and Methods A total of 330 patients with AML de novo or secondary to chemotherapy or radiotherapy were enrolled in the study. Induction therapy included idarubicin 8 mg/m 2 on days 1 to 5, cytarabine 100 mg/m 2 on days 1 to 7, and lomustine 200 mg/m 2 on day 1. Patients in complete remission or partial remission received six reinduction courses, alternating idarubicin 8 mg/m 2 on day 1, cytarabine 100 mg/m 2 on days 1 to 5, and a regimen of methotrexate and mercaptopurine. Patients were randomly assigned to receive norethandrolone 10 or 20 mg/day, according to body weight, or no norethandrolone for a 2-year maintenance therapy regimen. The primary end point was disease-free survival by intention to treat. Secondary end points were event-free survival, overall survival, and safety. This trial was registered at www.ClinicalTrials.gov identifier NCT00700544. Results Random assignment allotted 165 patients to each arm; arm A received norethandrolone, and arm B did not receive norethandrolone. Complete remission or partial remission was achieved in 247 patients (76%). The Schoenfeld time-dependent model showed that norethandrolone significantly improved survival for patients still in remission at 1 year after induction. In arms A and B, respectively, 5-year disease-free survival was 31.2% and 16.2%, event-free survival was 21.5% and 12.9%, and overall survival was 26.3% and 17.2%. Norethandrolone improved outcomes irrelevant to all prognosis factors. Only patients with baseline leukocytes > 30 × 10

  14. 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.

  15. Trends in survival of multiple myeloma: a thirty-year population-based study in a single institution.

    PubMed

    Ríos-Tamayo, Rafael; Sánchez, María José; Puerta, José Manuel; Sáinz, Juan; Chang, Daysi-Yoe-Ling; Rodríguez, Teresa; López, Pilar; de Pablos, José María; Navarro, Pilar; de Veas, José Luís García; Romero, Antonio; Garrido, Pilar; Moratalla, Lucía; Alarcón-Payer, Carolina; López-Fernández, Elisa; González, Pedro Antonio; Jiménez-Moleón, José Juan; Calleja-Hernández, Miguel Ángel; Jurado, Manuel

    2015-10-01

    Despite the progress made in recent years, multiple myeloma is still considered an incurable disease. Most survival data come from clinical trials. Little is known about the outcome in unselected real-life patients. Overall survival was analyzed in a cohort of newly diagnosed symptomatic multiple myeloma patients, over the last three decades, in a single institution population-based study. 582 consecutive myeloma patients were included in the study. Survival increased over time in patients younger than 65 years but did not reach statistical significance in patients with 65 years or older. The prognostic factors associated with overall survival were the International Staging System, the serum lactate dehydrogenase level, the renal impairment, the realization of autologous stem cell transplantation, and the presence of concomitant amyloidosis. Overall survival shows a steady improvement over time. The survival of myeloma is improving progressively in real-life patients, particularly after the widespread use of the novel agents. A comprehensive assessment of comorbidity can help to explain the huge heterogeneity of myeloma outcome. The optimization of current therapeutic resources as well as the incorporation of new drugs will allow further improvement of survival in the coming years. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Determinants of 1-year survival in critically ill acute leukemia patients: a GRRR-OH study.

    PubMed

    Tavares, Márcio; Lemiale, Virginie; Mokart, Djamel; Pène, Frédéric; Lengliné, Etienne; Kouatchet, Achille; Mayaux, Julien; Vincent, François; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Lebert, Christine; Perez, Pierre; Meert, Anne-Pascale; Benoit, Dominique; Darmon, Michael; Azoulay, Elie

    2018-06-01

    Acute leukemia (AL) is the most common hematological malignancy requiring intensive care unit (ICU) management. Data on long-term survival are limited. This is a post hoc analysis of the prospective multicenter data from France and Belgium: A Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique [A Research Group on Acute Respiratory Failure in Onco-Hematological Patients (French)] Study, to identify determinants of 1-year survival in critically ill AL patients. A total of 278 patients were admitted in the 17 participating ICUs. Median age was 58 years and 70% had newly diagnosed leukemia. ICU mortality rate was 28.6 and 39.6% of the patients alive at 1 year. Admission for intensive monitoring was independently associated with better 1-year survival by multivariate analysis. Conversely, relapsed/refractory disease, secondary leukemia, mechanical ventilation and renal replacement therapy were independently associated with 1-year mortality. This study confirms the impact of organ dysfunction on long-term survival in ICU patients with AL. Follow-up studies to assess respiratory and renal recovery are warranted.

  17. Survival of foot-and-mouth disease virus in cheese.

    PubMed

    Blackwell, J H

    1976-09-01

    Persistence of foot-and-mouth disease virus during the manufacture of Cheddar, Mozzarella, Camembert cheese prepared from milk of cows experimentally infected with the virus was studied. Cheese samples were made on a laboratory scale with commercial lactic acid starter cultures and the microbial protease MARZYME as a coagulant. Milk was heated at different temperatures for different intervals before it was made into cheese. Food-and-mouth disease virus survived the acidic conditions of Cheddar and Camembert cheese processing but not that of Mozzarella. Foot-and-mouth disease virus survived processing but not curing for 30 days in Cheddar cheese preparaed from heated milk. However, the virus survived curing for 60 days but not for 120 days in cheese (pH 5) prepared from unheated milk. Foot-and-mouth disease virus survived in Camembert cheese (pH 5) for 21 days at 2 C but not for 35 days.

  18. Use of Cox's Cure Model to Establish Clinical Determinants of Long-Term Disease-Free Survival in Neoadjuvant-Chemotherapy-Treated Breast Cancer Patients without Pathologic Complete Response.

    PubMed

    Asano, Junichi; Hirakawa, Akihiro; Hamada, Chikuma; Yonemori, Kan; Hirata, Taizo; Shimizu, Chikako; Tamura, Kenji; Fujiwara, Yasuhiro

    2013-01-01

    In prognostic studies for breast cancer patients treated with neoadjuvant chemotherapy (NAC), the ordinary Cox proportional-hazards (PH) model has been often used to identify prognostic factors for disease-free survival (DFS). This model assumes that all patients eventually experience relapse or death. However, a subset of NAC-treated breast cancer patients never experience these events during long-term follow-up (>10 years) and may be considered clinically "cured." Clinical factors associated with cure have not been studied adequately. Because the ordinary Cox PH model cannot be used to identify such clinical factors, we used the Cox PH cure model, a recently developed statistical method. This model includes both a logistic regression component for the cure rate and a Cox regression component for the hazard for uncured patients. The purpose of this study was to identify the clinical factors associated with cure and the variables associated with the time to recurrence or death in NAC-treated breast cancer patients without a pathologic complete response, by using the Cox PH cure model. We found that hormone receptor status, clinical response, human epidermal growth factor receptor 2 status, histological grade, and the number of lymph node metastases were associated with cure.

  19. Cardiovascular Risk Reduction is Important for Improving Patient and Graft Survival After Ligation and Bypass Surgery for Popliteal Artery Aneurysm.

    PubMed

    Dattani, N; Ali, M; Aber, A; Kannan, R Yap; Choke, E C; Bown, M J; Sayers, R D; Davies, R S

    2017-07-01

    To report outcomes following ligation and bypass (LGB) surgery for popliteal artery aneurysm (PAA) and study factors influencing patient and graft survival. A retrospective review of patients undergoing LGB surgery for PAA between September 1999 and August 2012 at a tertiary referral vascular unit was performed. Primary graft patency (PGP), primary-assisted graft patency (PAGP), and secondary graft patency (SGP) rates were calculated using survival analyses. Patient, graft aneurysm-free survival (GAFS), aneurysm reperfusion-free survival (ARFS), and amputation-free survival (AFS) rates were also calculated. Log-rank testing and Cox proportional hazards modeling were used to perform univariate and multivariate analysis of influencing factors, respectively. Eighty-four LGB repairs in 69 patients (mean age 71.3 years, 68 males) were available for study. The 5-year PGP, PAGP, SGP, and patient survival rates were 58.1%, 84.4%, 85.2%, and 81.1%, respectively. On multivariate analysis, the principal determinants of PGP were urgency of operation ( P = .009) and smoking status ( P = .019). The principal determinants of PAGP were hyperlipidemia status ( P = .048) and of SGP were hyperlipidemia ( P = .042) and cerebrovascular disease (CVD) status ( P = .045). The principal determinants of patient survival were previous myocardial infarction ( P = .004) and CVD ( P = .001). The 5-year GAFS, ARFS, and AFS rates were 87.9%, 91.6%, and 96.1%, respectively. This study has shown that traditional cardiovascular risk factors, such as a smoking and ischemic heart disease, are the most important predictors of early graft failure and patient death following LGB surgery for PAA.

  20. Survival Rate of Dental Implants in Patients with History of Periodontal Disease: A Retrospective Cohort Study.

    PubMed

    Correia, Francisco; Gouveia, Sónia; Felino, António Campos; Costa, Ana Lemos; Almeida, Ricardo Faria

    To evaluate the differences between the survival rates of implants placed in patients with no history of periodontal disease (NP) and in patients with a history of chronic periodontal disease (CP). A retrospective cohort study was conducted in which all consenting patients treated with dental implants in a private clinic in Oporto, Portugal, from November 2, 2002 through February 11, 2011 were included. All patients were treated consecutively by the same experimental operator. This study aimed to analyze how the primary outcomes (presence of disease, time of placement, and time of loading) and the secondary outcomes (severity-generalized periodontitis, brand, implant length, prosthesis type, prosthesis metal-ceramic extension) influence the survival rate of dental implants. The survival analysis was performed through the Kaplan-Meier method, and the equality of survival distributions for all groups was tested with the log-rank test with a significance level of .05 for all comparisons. The sample consisted of 202 patients (47% NP and 53% CP) and 689 implants (31% NP and 69% CP). The survival rate in the NP and CP groups showed no statistically significant differences (95.8% versus 93.1%; P ≥ .05). Implants were lost before loading in 54.9% of the cases. The majority of the implants were lost in the first year and stabilized after the second year. Survival rates in the NP and CP patients showed no statistically significant differences when comparing the following factors: subclassification of the disease, implant brands, implant length (short/standard), type of prosthesis, extension of the prosthesis metal-ceramic, and time of placement and loading (P ≥ .05). This work disclosed no statistically significant differences in terms of survival rates when compared with the control group. Placing implants in patients with a history of periodontal disease appears to be viable and safe.

  1. High survival rates and associated factors among ebola virus disease patients hospitalized at donka national hospital, conakry, Guinea.

    PubMed

    Qureshi, Adnan I; Chughtai, Morad; Bah, Elhadj Ibrahima; Barry, Moumié; Béavogui, Kézély; Loua, Tokpagnan Oscar; Malik, Ahmed A

    2015-02-01

    Anecdotal reports suggesting that survival rates among hospitalized patients with Ebola virus disease in Guinea are higher than the 29.2% rate observed in the current epidemic in West Africa. Survival after symptom onset was determined using Kaplan Meier survival methods among patients with confirmed Ebola virus disease treated in Conakry, Guinea from March 25, 2014, to August 5, 2014. We analyzed the relationship between survival and patient factors, including demographics and clinical features. Of the 70 patients analyzed [mean age ± standard deviation (SD), 34 ± 14.1; 44 were men], 42 were discharged alive with a survival rate among hospitalized patients of 60% (95% confidence interval, 41.5-78.5%). The survival rate was 28 (71.8%) among 39 patients under 34 years of age, and 14 (46.7%) among 30 patients aged 35 years or greater (p = 0.034). The rates of myalgia (3 of 42 versus 7 of 28, p = 0.036) and hiccups (1 of 42 versus 5 of 28, p = 0.023) were significantly lower among patients who survived. Our results provide insights into a cohort of hospitalized patients with Ebola virus disease in whom survival is prominently higher than seen in other cohorts of hospitalized patients.

  2. High Survival Rates and Associated Factors Among Ebola Virus Disease Patients Hospitalized at Donka National Hospital, Conakry, Guinea

    PubMed Central

    Qureshi, Adnan I.; Chughtai, Morad; Bah, Elhadj Ibrahima; Barry, Moumié; Béavogui, Kézély; Loua, Tokpagnan Oscar; Malik, Ahmed A.

    2015-01-01

    Background Anecdotal reports suggesting that survival rates among hospitalized patients with Ebola virus disease in Guinea are higher than the 29.2% rate observed in the current epidemic in West Africa. Methods Survival after symptom onset was determined using Kaplan Meier survival methods among patients with confirmed Ebola virus disease treated in Conakry, Guinea from March 25, 2014, to August 5, 2014. We analyzed the relationship between survival and patient factors, including demographics and clinical features. Results Of the 70 patients analyzed [mean age ± standard deviation (SD), 34 ± 14.1; 44 were men], 42 were discharged alive with a survival rate among hospitalized patients of 60% (95% confidence interval, 41.5–78.5%). The survival rate was 28 (71.8%) among 39 patients under 34 years of age, and 14 (46.7%) among 30 patients aged 35 years or greater (p = 0.034). The rates of myalgia (3 of 42 versus 7 of 28, p = 0.036) and hiccups (1 of 42 versus 5 of 28, p = 0.023) were significantly lower among patients who survived. Conclusions Our results provide insights into a cohort of hospitalized patients with Ebola virus disease in whom survival is prominently higher than seen in other cohorts of hospitalized patients. PMID:25992182

  3. 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.

  4. 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.

  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. Ten-year outcomes of a randomised trial of laparoscopic versus open surgery for colon cancer.

    PubMed

    Deijen, Charlotte L; Vasmel, Jeanine E; de Lange-de Klerk, Elly S M; Cuesta, Miguel A; Coene, Peter-Paul L O; Lange, Johan F; Meijerink, W J H Jeroen; Jakimowicz, Jack J; Jeekel, Johannes; Kazemier, Geert; Janssen, Ignace M C; Påhlman, Lars; Haglind, Eva; Bonjer, H Jaap

    2017-06-01

    Laparoscopic surgery for colon cancer is associated with improved recovery and similar cancer outcomes at 3 and 5 years in comparison with open surgery. However, long-term survival rates have rarely been reported. Here, we present survival and recurrence rates of the Dutch patients included in the COlon cancer Laparoscopic or Open Resection (COLOR) trial at 10-year follow-up. Between March 1997 and March 2003, patients with non-metastatic colon cancer were recruited by 29 hospitals in eight countries and randomised to either laparoscopic or open surgery. Main inclusion criterion for the COLOR trial was solitary adenocarcinoma of the left or right colon. The primary outcome was disease-free survival at 3 years, and secondary outcomes included overall survival and recurrence. The 10-year follow-up data of all Dutch patients were collected. Analysis was by intention-to-treat. The trial was registered at ClinicalTrials.gov (NCT00387842). In total, 1248 patients were randomised, of which 329 were Dutch. Fifty-eight Dutch patients were excluded and 15 were lost to follow-up, leaving 256 patients for 10-year analysis. Median follow-up was 112 months. Disease-free survival rates were 45.2 % in the laparoscopic group and 43.2 % in the open group (difference 2.0 %; 95 % confidence interval (CI) -10.3 to 14.3; p = 0.96). Overall survival rates were 48.4 and 46.7 %, respectively (difference 1.7 %; 95 % CI -10.6 to 14.0; p = 0.83). Stage-specific analysis revealed similar survival rates for both groups. Sixty-two patients were diagnosed with recurrent disease, accounting for 29.4 % in the laparoscopic group and 28.2 % in the open group (difference 1.2 %; 95 % CI -11.1 to 13.5; p = 0.73). Seven patients had port- or wound-site recurrences (laparoscopic n = 3 vs. open n = 4). Laparoscopic surgery for non-metastatic colon cancer is associated with similar rates of disease-free survival, overall survival and recurrences as open surgery at 10-year follow-up.

  7. Time Interval From Breast-Conserving Surgery to Breast Irradiation in Early Stage Node-Negative Breast Cancer: 17-Year Follow-Up Results and Patterns of Recurrence

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

    Vujovic, Olga, E-mail: olga.vujovic@lhsc.on.ca; Yu, Edward; Cherian, Anil

    Purpose: A retrospectivechart review was conducted to determine whether the time interval from breast-conserving surgery to breast irradiation (surgery-radiation therapy interval) in early stage node-negative breast cancer had any detrimental effects on recurrence rates. Methods and Materials: There were 566 patients with T1 to T3, N0 breast cancer treated with breast-conserving surgery and breast irradiation and without adjuvant systemic treatment between 1985 and 1992. The surgery-to-radiation therapy intervals used for analysis were 0 to 8 weeks (201 patients), >8 to 12 weeks (233 patients), >12 to 16 weeks (91 patients), and >16 weeks (41 patients). Kaplan-Meier estimates of time to local recurrence, disease-free survival, distantmore » disease-free survival, cause-specific survival, and overall survival rates were calculated. Results: Median follow-up was 17.4 years. Patients in all 4 time intervals were similar in terms of characteristics and pathologic features. There were no statistically significant differences among the 4 time groups in local recurrence (P=.67) or disease-free survival (P=.82). The local recurrence rates at 5, 10, and 15 years were 4.9%, 11.5%, and 15.0%, respectively. The distant disease relapse rates at 5, 10, and 15 years were 10.6%, 15.4%, and 18.5%, respectively. The disease-free failure rates at 5, 10, and 15 years were 20%, 32.3%, and 39.8%, respectively. Cause-specific survival rates at 5, 10, and 15 years were 92%, 84.6%, and 79.8%, respectively. The overall survival rates at 5, 10, and 15 years were 89.3%, 79.2%, and 66.9%, respectively. Conclusions: Surgery-radiation therapy intervals up to 16 weeks from breast-conserving surgery are not associated with any increased risk of recurrence in early stage node-negative breast cancer. There is a steady local recurrence rate of 1% per year with adjuvant radiation alone.« less

  8. 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

  9. Cardiovascular Complications Over 5 Years and Their Association With Survival in the GERODIAB Cohort of Elderly French Patients With Type 2 Diabetes.

    PubMed

    Bauduceau, Bernard; Le Floch, Jean-Pierre; Halimi, Serge; Verny, Christiane; Doucet, Jean

    2018-01-01

    The GERODIAB study is a multicenter prospective observational study performed over 5 years in French patients aged 70 years or above with type 2 diabetes. This report deals with their cardiovascular complications and their relationship with survival. Consecutive patients ( n = 987, median age = 77 years) were included from 56 diabetes centers over 1 year. Individual characteristics, history and complications of diabetes, geriatric factors, and clinical and biological parameters were recorded. Survival was analyzed using the Kaplan-Meier method and proportional hazards regression models. The frequency of cardiovascular complications increased from 47% at inclusion to 67% at 5 years. The most frequent complications were coronary heart disease (increasing from 30% to 41%) and vascular disease of the lower limbs (25% to 35%) and of the cerebral vessels (15% to 26%). Heart failure was less common, but its frequency doubled during the follow-up (9% to 20%). It was strongly associated with poor survival ( P < 0.0001), as was vascular disease of the lower limbs ( P = 0.0004), whereas coronary heart disease ( P = 0.0056) and vascular disease of cerebral vessels ( P = 0.026) had mild associations. Amputation ( P < 0.0001) and foot wounds ( P < 0.0001) were strongly associated with survival. In multivariate models, heart failure was the strongest predictor of poor survival (hazard ratio [HR] 1.96 [95% CI 1.45-2.64]; P < 0.0001). It remained significant when other factors were considered simultaneously (HR 1.92 [95% CI 1.43-2.58]; P < 0.0001). Cardiovascular complications are associated with poor survival in elderly patients with type 2 diabetes, especially heart failure. © 2017 by the American Diabetes Association.

  10. Survival of Persons with Alzheimer's Disease: Caregiver Coping Matters

    ERIC Educational Resources Information Center

    McClendon, McKee J.; Smyth, Kathleen A.; Neundorfer, Marcia M.

    2004-01-01

    Purpose: Although persons with Alzheimer's disease (AD) require increasingly more assistance with activities of daily living as their disease progresses, the caregiving environment has received little attention as a source of predictors of their survival time. We report here on a study to determine whether variation in survival time of persons…

  11. 11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial.

    PubMed

    Cameron, David; Piccart-Gebhart, Martine J; Gelber, Richard D; Procter, Marion; Goldhirsch, Aron; de Azambuja, Evandro; Castro, Gilberto; Untch, Michael; Smith, Ian; Gianni, Luca; Baselga, Jose; Al-Sakaff, Nedal; Lauer, Sabine; McFadden, Eleanor; Leyland-Jones, Brian; Bell, Richard; Dowsett, Mitch; Jackisch, Christian

    2017-03-25

    Clinical trials have shown that trastuzumab, a recombinant monoclonal antibody against HER2 receptor, significantly improves overall survival and disease-free survival in women with HER2-positive early breast cancer, but long-term follow-up data are needed. We report the results of comparing observation with two durations of trastuzumab treatment at a median follow-up of 11 years, for patients enrolled in the HERA (HERceptin Adjuvant) trial. HERA (BIG 1-01) is an international, multicentre, open-label, phase 3 randomised trial of 5102 women with HER2-positive early breast cancer, who were enrolled from hospitals in 39 countries between Dec 7, 2001, and June 20, 2005. After completion of all primary therapy (including, surgery, chemotherapy, and radiotherapy as indicated), patients were randomly assigned (1:1:1) to receive trastuzumab for 1 year (once at 8 mg/kg of bodyweight intravenously, then 6 mg/kg once every 3 weeks) or for 2 years (with the same dose schedule), or to the observation group. Primary endpoint is disease-free survival, and analyses are in the intention-to-treat population. Hazard ratios (HRs) were estimated from Cox models, and survival curves were estimated by the Kaplan-Meier method. Comparison of 2 years versus 1 year of trastuzumab is based on 366-day landmark analyses. This study is registered with ClinicalTrials.gov (NCT00045032). Of the 5102 women randomly assigned in the HERA trial, three patients had no evidence of having provided written informed consent to participate. We followed up the intention-to-treat population of 5099 patients (1697 in observation, 1702 in 1-year trastuzumab, and 1700 in 2-years trastuzumab groups). After a median follow-up of 11 years (IQR 10·09-11·53), random assignment to 1 year of trastuzumab significantly reduced the risk of a disease-free survival event (HR 0·76, 95% CI 0·68-0·86) and death (0·74, 0·64-0·86) compared with observation. 2 years of adjuvant trastuzumab did not improve disease free-survival

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

    PubMed

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

    2017-05-01

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

  13. p27Kip1 and Cyclin E Expression and Breast Cancer Survival After Treatment With Adjuvant Chemotherapy

    PubMed Central

    Barlow, WE; Yeh, I-T; Lin, M-G; Yuan, X; Donato, E; Sledge, GW; Shapiro, CL; Ingle, JN; Haskell, CM; Albain, KS; Roberts, JM; Livingston, RB; Hayes, DF

    2009-01-01

    Background Abnormal expression of the cell cycle regulatory proteins p27Kip1 and cyclin E may be associated with breast cancer survival and relapse. We studied these markers in a clinical trial setting with patients with breast cancer treated by a uniform drug regimen so that treatment was not associated with variability in outcome. Methods We used tissue microarrays to evaluate the expression of p27Kip1 and cyclin E protein by immunohistochemistry in tumor tissue from 2123 (68%) of 3122 patients with moderate-risk primary breast cancer who were enrolled in Southwest Oncology Group/Intergroup Trial S9313, in which patients were assigned to receive doxorubicin and cyclophosphamide administered concurrently (n = 1595) or sequentially (n = 1527). Disease-free and overall survival were equivalent in the two arms. Expression of the proteins was rated on a scale of 1-7, and the median value was used as the cutpoint. Log-rank tests and Cox regression analyses were used to assess associations with survival. Overall survival was defined as time to death from all causes; disease-free survival was defined as time to recurrence or death. All P values were from two-sided statistical tests. Results Lower p27Kip1 expression was associated with worse overall survival (unadjusted hazard ratio [HR] =1.50, 95% confidence interval [CI] = 1.21 to1.86) and disease-free survival (unadjusted HR = 1.31, 95% CI = 1.10 to 1.57) than higher p27Kip1 expression. Among hormone receptor-positive patients, lower p27Kip1 expression was associated with worse overall survival (HR = 1.42, 95% CI = 1.05 to 1.94) and worse disease-free survival (HR = 1.27, 95% CI = 0.99 to 1.63) than higher p27Kip1 expression after adjustment for treatment, menopausal status, tumor size, and number of positive lymph nodes. . Among these patients, five year overall survival for higher p27 was 0.91 (95% CI 0.89-0.93) compared to 0.85 (95% CI 0.82-0.87) for lower p27. No association between p27Kip1 expression and survival

  14. 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

  15. 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.

  16. Supraclavicular node disease is not an independent prognostic factor for survival of esophageal cancer patients treated with definitive chemoradiation.

    PubMed

    Jeene, Paul M; Versteijne, Eva; van Berge Henegouwen, Mark I; Bergmann, Jacques J G H M; Geijsen, Elisabeth D; van Laarhoven, Hanneke W M; Hulshof, Maarten C C M

    2017-01-01

    The prognostic value of supraclavicular lymph node (SCN) metastases in esophageal cancer is not well established. We analyzed the prognostic value of SCN disease in patients after definitive chemoradiation (dCRT) for esophageal cancer. We retrospectively analyzed 207 patients treated between 2003 and 2013 to identify the prognostic value of metastasis in the SCN on treatment failure and survival. All patients were treated with external beam radiotherapy (50.4 Gy in 28 fractions) combined with weekly concurrent paclitaxel 50 mg/m 2 and carboplatin AUC2. Median follow-up for patients alive was 43.3 months. The median overall survival (OS) for all patients was 17.5 months. OS at one, three and five years was 67%, 36% and 21%, respectively. For patients with metastasis in a SCN, OS was 23.6 months compared to 17.1 months for patients without metastasis in the SCN (p = .51). In multivariate analyses, higher cT status, cN status and adenocarcinoma were found to be prognostically unfavorable, but a positive SCN was not (p = .67). Median OS and median disease-free survival for tumors with SCN involvement and N0/1 disease was 49.0 months and 51.6 months, respectively, compared to 14.2 months and 8.2 months, respectively, in patients with N2/3 disease. In esophageal cancer treated with dCRT, the number of affected lymph nodes is an important independent prognostic factor, whereas involvement of a SCN is not. Supraclavicular lymph nodes should be considered as regional lymph nodes and treated with curative intent if the total number of involved lymph nodes is limited.

  17. Ten-Year Survival of End-Stage Renal Disease Patients Treated with High-Efficiency Online Hemodiafiltration: A Cohort Study of a Center in South East Asia.

    PubMed

    Tiranathanagul, Khajohn; Susantitaphong, Paweena; Srisawat, Nattachai; Mahatanan, Nanta; Tungsanga, Kriang; Praditpornsilpa, Kearkiat; Eiam-Ong, Somchai

    2018-03-07

    Recently, in the first hemodiafiltration (HDF) experience report from South East Asia (SEA), we reported a 3-year prospective study demonstrating the various short-term benefits of high-efficiency online HDF (OL-HDF) over high-flux hemodialysis (HD). Very few long-term survival reports of high-efficiency OL-HDF are available and the data are heterogeneous and incomplete. The present historical cohort study was conducted to determine the long-term survival and outcome of high-efficiency OL-HDF-treated patients. Sixty-six high-efficiency OL-HDF treated patients at a center in SEA were included in the study. The prescription included blood and dialysis fluid flow rates of 400 and 800 mL/min, respectively. The post- or pre-dilution substitution fluid of 100 or 200 mL/min, respectively, was prescribed. Of 66 HDF patients, whose age was 57.4 ± 14.0 years, there were 38 (58%) females. The majority of comorbidity was diabetes (36%). There were 33 (50%) incident HDF cases that were prescribed OL-HDF at the dialysis initiation and 33 (50%) prevalent HDF cases that were switched from HD to OL-HDF. The 1-, 3-, 5-, and 10-year survival rate were 95.1, 83.4, 77.7, and 61.8% respectively. The mean survival time was 8.99 ± 0.64 years. There were 15 transplantations and 15 deaths during this study periods. The 2 major causes of death were cardiovascular (33.3%) and infectious diseases (20%). Serum ferritin was the only parameter that correlated with mortality (HR 1.004, p = 0.005). There was comparable survival between incident and prevalent HDF cases. The survival after transplantation of a sub-group of patients who received kidney transplantation (KT) was not different from that of the overall HDF patients (p = 0.93). High-efficiency OL-HDF could provide an excellent long-term survival nearly comparable to the KT sub-group. © 2018 S. Karger AG, Basel.

  18. Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor epidermal growth factor receptor (EGFR) mutations

    PubMed Central

    Janjigian, Yelena Y.; Park, Bernard J.; Zakowski, Maureen F.; Ladanyi, Marc; Pao, William; D’Angelo, Sandra P.; Kris, Mark G.; Shen, Ronglai; Zheng, Junting; Azzoli, Christopher G.

    2013-01-01

    Background Patients with stage IV lung adenocarcinoma and EGFR mutation derive clinical benefit from treatment with EGFR tyrosine kinase inhibitors (TKI). Whether treatment with TKI improves outcomes in patients with resected lung adenocarcinoma and EGFR mutation is unknown. Methods Data were analyzed from a surgical database of patients with resected lung adenocarcinoma harboring EGFR exon 19 or 21 mutations. In a multivariate analysis, we evaluated the impact of treatment with adjuvant TKI. Results The cohort consists of 167 patients with completely resected stage I–III lung adenocarcinoma. 93 patients (56%) had exon 19 del, 74 patients (44%) had exon 21 mutations, 56 patients (33%) received perioperative TKI. In a multivariate analysis controlling for sex, stage, type of surgery and adjuvant platinum chemotherapy, the 2-year DFS was 89% for patients treated with adjuvant TKI compared with 72% in control group (hazard ratio [HR] = 0.53; 95% confidence interval [CI] 0.28 to 1.03; p = 0.06). The 2-year OS was 96% with adjuvant EGFR TKI and 90% in the group that did not receive TKI (HR 0.62; 95% CI 0.26 to 1.51; p = 0.296). Conclusions Compared to patients who did not receive adjuvant TKI, we observed a trend toward improvement in disease free survival among individuals with resected stages I–III lung adenocarcinomas harboring mutations in EGFR exons 19 or 21 who received these agents as adjuvant therapy. Based on these data, 320 patients are needed for a randomized trial to prospectively validate this DFS benefit. PMID:21150674

  19. 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.

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

    PubMed Central

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

    2017-01-01

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

  1. 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 .).

  2. Selection of Ideal Candidates for Surgical Salvage of Head and Neck Squamous Cell Carcinoma: Effect of the Charlson-Age Comorbidity Index and Oncologic Characteristics on 1-Year Survival and Hospital Course.

    PubMed

    Kim, JeeHong; Kim, Seungwon; Albergotti, William G; Choi, Phillip A; Kaplan, Daniel James; Abberbock, Shira; Johnson, Jonas T; Gildener-Leapman, Neil

    2015-12-01

    Salvage surgery for recurrent head and neck squamous cell carcinoma (HNSCC) carries substantial risks of morbidity and mortality. Risk factors for death within 1 year should be better defined. To report preoperative oncologic prognostic factors predictive of short-term (<1 year) survival after salvage surgery in patients with HNSCC, to assess whether preoperative age and comorbidity predicts 1-year mortality, and to report hospital courses after salvage surgery within 1 year. A retrospective medical record review of 191 patients with recurrent HNSCC treated with salvage surgery from January 1, 2003, through December 31, 2013, at a tertiary academic center. Surgical salvage of HNSCC (larynx, oral cavity, oropharynx, or hypopharynx) with curative intent. Primary outcome was survival 1 year after salvage surgery. Secondary outcomes were length of inpatient hospital stay, days of admissions, and skilled nursing facility disposition within 1 year stratified by survival status. Presalvage Charlson-Age Comorbidity Index (CACI) was calculated. Associations among CACI, oncologic risk factors, and risk of death within 1 year after salvage surgery are investigated using multivariable analysis. Of 191 patients studied, 53 (27.7%) died within 1 year after salvage surgery. Patients who died within 1 year had more total inpatient admissions (P < .001), longer total length of stay (P < .001), and higher risk of discharge to a skilled nursing facility (P < .001) and spent 17.3% (interquartile range, 5.2-36.3) of their remaining days in the hospital. Independent risk factors for death within 1 year are CACI (relative risk [RR], 1.43; 95% CI, 1.16-1.76), primary T3 or T4 stage (RR, 2.34; 95% CI, 1.27-4.31), and disease-free interval of less than 6 months (RR, 5.61; 95% CI, 1.78-16.7). Medical comorbidity and age as measured by the CACI, primary T3 or T4 stage, and short disease-free interval must be considered in selecting patients ideal for surgical salvage surgery for

  3. A gluten-free diet effectively reduces symptoms and health care consumption in a Swedish celiac disease population.

    PubMed

    Norström, Fredrik; Sandström, Olof; Lindholm, Lars; Ivarsson, Anneli

    2012-09-17

    A gluten-free diet is the only available treatment for celiac disease. Our aim was to investigate the effect of a gluten-free diet on celiac disease related symptoms, health care consumption, and the risk of developing associated immune-mediated diseases. A questionnaire was sent to 1,560 randomly selected members of the Swedish Society for Coeliacs, divided into equal-sized age- and sex strata; 1,031 (66%) responded. Self-reported symptoms, health care consumption (measured by health care visits and hospitalization days), and missed working days were reported both for the year prior to diagnosis (normal diet) and the year prior to receiving the questionnaire while undergoing treatment with a gluten-free diet. Associated immune-mediated diseases (diabetes mellitus type 1, rheumatic disease, thyroid disease, vitiligo, alopecia areata and inflammatory bowel disease) were self-reported including the year of diagnosis. All investigated symptoms except joint pain improved after diagnosis and initiated gluten-free diet. Both health care consumption and missed working days decreased. Associated immune-mediated diseases were diagnosed equally often before and after celiac disease diagnosis. Initiated treatment with a gluten-free diet improves the situation for celiac disease patients in terms of reduced symptoms and health care consumption. An earlier celiac disease diagnosis is therefore of great importance.

  4. Survival and contralateral breast cancer in CHEK2 1100delC breast cancer patients: impact of adjuvant chemotherapy.

    PubMed

    Kriege, M; Hollestelle, A; Jager, A; Huijts, P E A; Berns, E M; Sieuwerts, A M; Meijer-van Gelder, M E; Collée, J M; Devilee, P; Hooning, M J; Martens, J W M; Seynaeve, C

    2014-08-26

    We assessed the sensitivity to adjuvant chemotherapy in cell cycle checkpoint kinase 2 (CHEK2) vs non-CHEK2 breast cancer patients by comparing the contralateral breast cancer incidence and distant disease-free and breast cancer-specific survival between both groups, stratified for adjuvant chemotherapy. One Dutch hereditary non-BRCA1/2 breast cancer patient cohort (n=1220) and two Dutch cohorts unselected for family history (n=1014 and n=2488, respectively) were genotyped for CHEK2 1100delC. Hazard ratios for contralateral breast cancer, distant disease-free and breast cancer-specific death for mutation carriers vs noncarriers were calculated using the Cox proportional hazard method, stratified for adjuvant chemotherapy. The CHEK2 mutation carriers (n=193) had an increased incidence of contralateral breast cancer (multivariate hazard ratio 3.97, 95% confidence interval 2.59-6.07). Distant disease-free and breast cancer-specific survival were similar in the first 6 years in mutation carriers compared with noncarriers, but diverted as of 6 years after breast cancer diagnosis (multivariate hazard ratios and 95% confidence intervals 2.65 (1.79-3.93) and 2.05 (1.41-2.99), respectively). No significant interaction between CHEK2 and adjuvant chemotherapy was observed. The CHEK2 1100delC-associated breast cancer is associated with a higher contralateral breast cancer rate as well as worse survival measures beyond 6 years after diagnosis. No differential sensitivity to adjuvant chemotherapy was observed in CHEK2 patients.

  5. [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.

  6. Myositis-associated usual interstitial pneumonia has a better survival than idiopathic pulmonary fibrosis.

    PubMed

    Aggarwal, Rohit; McBurney, Christine; Schneider, Frank; Yousem, Samuel A; Gibson, Kevin F; Lindell, Kathleen; Fuhrman, Carl R; Oddis, Chester V

    2017-03-01

    To compare the survival outcomes between myositis-associated usual interstitial pneumonia (MA-UIP) and idiopathic pulmonary fibrosis (IPF-UIP). Adult MA-UIP and IPF-UIP patients were identified using CTD and IPF registries. The MA-UIP cohort included myositis or anti-synthetase syndrome patients with interstitial lung disease while manifesting UIP on high-resolution CT chest and/or a lung biopsy revealing UIP histology. IPF subjects met American Thoracic Society criteria and similarly had UIP histopathology. Kaplan-Meier survival curves compared cumulative and pulmonary event-free survival (event = transplant or death) between (i) all MA-UIP and IPF-UIP subjects, (ii) MA-UIP with biopsy proven UIP (n = 25) vs IPF-UIP subjects matched for age, gender and baseline forced vital capacity (±10%). Cox proportional hazards ratios compared the survival controlling for co-variates. Eighty-one IPF-UIP and 43 MA-UIP subjects were identified. The median cumulative and event-free survival time in IPF vs MA-UIP was 5.25/1.8 years vs 16.2/10.8 years, respectively. Cumulative and event-free survival was significantly worse in IPF-UIP vs MA-UIP [hazards ratio of IPF-UIP was 2.9 (95% CI: 1.5, 5.6) and 5.0 (95% CI: 2.8, 8.7) (P < 0.001), respectively]. IPF-UIP event-free survival (but not cumulative) remained significantly worse than MA-UIP with a hazards ratio of 6.4 (95% CI: 3.0, 13.8) after controlling for age at interstitial lung disease diagnosis, gender, ethnicity and baseline forced vital capacity%. Respiratory failure was the most common cause of death in both groups. A sub-analysis of 25 biopsy-proven MA-UIP subjects showed similar results. MA-UIP patients demonstrated a significant survival advantage over a matched IPF cohort, suggesting that despite similar histological and radiographic findings at presentation, the prognosis of MA-UIP is superior to that of IPF-UIP. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology

  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. Compensatory effects of recruitment and survival when amphibian populations are perturbed by disease

    USGS Publications Warehouse

    Muths, E.; Scherer, R. D.; Pilliod, D.S.

    2011-01-01

    The need to increase our understanding of factors that regulate animal population dynamics has been catalysed by recent, observed declines in wildlife populations worldwide. Reliable estimates of demographic parameters are critical for addressing basic and applied ecological questions and understanding the response of parameters to perturbations (e.g. disease, habitat loss, climate change). However, to fully assess the impact of perturbation on population dynamics, all parameters contributing to the response of the target population must be estimated. We applied the reverse-time model of Pradel in Program mark to 6years of capture-recapture data from two populations of Anaxyrus boreas (boreal toad) populations, one with disease and one without. We then assessed a priori hypotheses about differences in survival and recruitment relative to local environmental conditions and the presence of disease. We further explored the relative contribution of survival probability and recruitment rate to population growth and investigated how shifts in these parameters can alter population dynamics when a population is perturbed. High recruitment rates (0??41) are probably compensating for low survival probability (range 0??51-0??54) in the population challenged by an emerging pathogen, resulting in a relatively slow rate of decline. In contrast, the population with no evidence of disease had high survival probability (range 0??75-0??78) but lower recruitment rates (0??25). Synthesis and applications.We suggest that the relationship between survival and recruitment may be compensatory, providing evidence that populations challenged with disease are not necessarily doomed to extinction. A better understanding of these interactions may help to explain, and be used to predict, population regulation and persistence for wildlife threatened with disease. Further, reliable estimates of population parameters such as recruitment and survival can guide the formulation and implementation of

  9. 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.

  10. 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.

  11. Cerebral metastases in metastatic breast cancer: disease-specific risk factors and survival.

    PubMed

    Heitz, F; Rochon, J; Harter, P; Lueck, H-J; Fisseler-Eckhoff, A; Barinoff, J; Traut, A; Lorenz-Salehi, F; du Bois, A

    2011-07-01

    Survival of patients suffering from cerebral metastases (CM) is limited. Identification of patients with a high risk for CM is warranted to adjust follow-up care and to evaluate preventive strategies. Exploratory analysis of disease-specific parameter in patients with metastatic breast cancer (MBC) treated between 1998 and 2008 using cumulative incidences and Fine and Grays' multivariable regression analyses. After a median follow-up of 4.0 years, 66 patients (10.5%) developed CM. The estimated probability for CM was 5%, 12% and 15% at 1, 5 and 10 years; in contrast, the probability of death without CM was 21%, 61% and 76%, respectively. A small tumor size, ER status, ductal histology, lung and lymph node metastases, human epidermal growth factor receptor 2 positive (HER2+) tumors, younger age and M0 were associated with CM in univariate analyses, the latter three being risk factors in the multivariable model. Survival was shortened in patient developing CM (24.0 months) compared with patients with no CM (33.6 months) in the course of MBC. Young patients, primary with non-metastatic disease and HER2+ tumors, have a high risk to develop CM in MBC. Survival of patients developing CM in the course of MBC is impaired compared with patients without CM.

  12. Respiratory disease, behavior, and survival of mountain goat kids

    USGS Publications Warehouse

    Blanchong, Julie A.; Anderson, Christopher A.; Clark, Nicholas J.; Klaver, Robert W.; Plummer, Paul J.; Cox, Mike; Mcadoo, Caleb; Wolff, Peregrine L.

    2018-01-01

    Bacterial pneumonia is a threat to bighorn sheep (Ovis canadensis) populations. Bighorn sheep in the East Humboldt Mountain Range (EHR), Nevada, USA, experienced a pneumonia epizootic in 2009–2010. Testing of mountain goats (Oreamnos americanus) that were captured or found dead on this range during and after the epizootic detected bacteria commonly associated with bighorn sheep pneumonia die‐offs. Additionally, in years subsequent to the bighorn sheep epizootic, the mountain goat population had low kid:adult ratios, a common outcome for bighorn sheep populations that have experienced a pneumonia epizootic. We hypothesized that pneumonia was present and negatively affecting mountain goat kids in the EHR. From June–August 2013–2015, we attempted to observe mountain goat kids with marked adult females in the EHR at least once per week to document signs of respiratory disease; identify associations between respiratory disease, activity levels, and subsequent disappearance (i.e., death); and estimate weekly survival. Each time we observed a kid with a marked adult female, we recorded any signs of respiratory disease and collected behavior data that we fit to a 3‐state discrete hidden Markov model (HMM) to predict a kid's state (active vs. sedentary) and its probability of disappearing. We first observed clinical signs of respiratory disease in kids in late July–early August each summer. We observed 8 of 31 kids with marked adult females with signs of respiratory disease on 13 occasions. On 11 of these occasions, the HMM predicted that kids were in the sedentary state, which was associated with increased probability of subsequent death. We estimated overall probability of kid survival from June–August to be 0.19 (95% CI = 0.08–0.38), which was lower than has been reported in other mountain goat populations. We concluded that respiratory disease was present in the mountain goat kids in the EHR and negatively affected their activity levels and survival

  13. Chronic kidney disease in dogs in UK veterinary practices: prevalence, risk factors, and survival.

    PubMed

    O'Neill, D G; Elliott, J; Church, D B; McGreevy, P D; Thomson, P C; Brodbelt, D C

    2013-01-01

    The prevalence for chronic kidney disease (CKD) in dogs varies widely (0.05-3.74%). Identified risk factors include advancing age, specific breeds, small body size, and periodontal disease. To estimate the prevalence and identify risk factors associated with CKD diagnosis and survival in dogs. Purebred dogs were hypothesized to have higher CKD risk and poorer survival characteristics than crossbred dogs. A merged clinical database of 107,214 dogs attending 89 UK veterinary practices over a 2-year period (January 2010-December 2011). A longitudinal study design estimated the apparent prevalence (AP) whereas the true prevalence (TP) was estimated using Bayesian analysis. A nested case-control study design evaluated risk factors. Survival analysis used the Kaplan-Meier survival curve method and multivariable Cox proportional hazards regression modeling. The CKD AP was 0.21% (95% CI: 0.19-0.24%) and TP was 0.37% (95% posterior credibility interval 0.02-1.44%). Significant risk factors included increasing age, being insured, and certain breeds (Cocker Spaniel, Cavalier King Charles Spaniel). Cardiac disease was a significant comorbid disorder. Significant clinical signs included halitosis, weight loss, polyuria/polydipsia, urinary incontinence, vomiting, decreased appetite, lethargy, and diarrhea. The median survival time from diagnosis was 226 days (95% CI 112-326 days). International Renal Interest Society stage and blood urea nitrogen concentration at diagnosis were significantly associated with hazard of death due to CKD. Chronic kidney disease compromises dog welfare. Increased awareness of CKD risk factors and association of blood biochemistry results with survival time should facilitate diagnosis and optimize case management to improve animal survival and welfare. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  14. The Norwegian dietary guidelines and colorectal cancer survival (CRC-NORDIET) study: a food-based multicentre randomized controlled trial.

    PubMed

    Henriksen, Hege Berg; Ræder, Hanna; Bøhn, Siv Kjølsrud; Paur, Ingvild; Kværner, Ane Sørlie; Billington, Siv Åshild; Eriksen, Morten Tandberg; Wiedsvang, Gro; Erlund, Iris; Færden, Arne; Veierød, Marit Bragelien; Zucknick, Manuela; Smeland, Sigbjørn; Blomhoff, Rune

    2017-01-30

    Colorectal cancer survivors are not only at risk for recurrent disease but also at increased risk of comorbidities such as other cancers, cardiovascular disease, diabetes, hypertension and functional decline. In this trial, we aim at investigating whether a diet in accordance with the Norwegian food-based dietary guidelines and focusing at dampening inflammation and oxidative stress will improve long-term disease outcomes and survival in colorectal cancer patients. This paper presents the study protocol of the Norwegian Dietary Guidelines and Colorectal Cancer Survival study. Men and women aged 50-80 years diagnosed with primary invasive colorectal cancer (Stage I-III) are invited to this randomized controlled, parallel two-arm trial 2-9 months after curative surgery. The intervention group (n = 250) receives an intensive dietary intervention lasting for 12 months and a subsequent maintenance intervention for 14 years. The control group (n = 250) receives no dietary intervention other than standard clinical care. Both groups are offered equal general advice of physical activity. Patients are followed-up at 6 months and 1, 3, 5, 7, 10 and 15 years after baseline. The study center is located at the Department of Nutrition, University of Oslo, and patients are recruited from two hospitals within the South-Eastern Norway Regional Health Authority. Primary outcomes are disease-free survival and overall survival. Secondary outcomes are time to recurrence, cardiovascular disease-free survival, compliance to the dietary recommendations and the effects of the intervention on new comorbidities, intermediate biomarkers, nutrition status, physical activity, physical function and quality of life. The current study is designed to gain a better understanding of the role of a healthy diet aimed at dampening inflammation and oxidative stress on long-term disease outcomes and survival in colorectal cancer patients. Since previous research on the role of diet for

  15. Longitudinal Associations of Smoke-Free Policies and Incident Cardiovascular Disease: CARDIA Study.

    PubMed

    Mayne, Stephanie L; Widome, Rachel; Carroll, Allison J; Schreiner, Pamela J; Gordon-Larsen, Penny; Jacobs, David R; Kershaw, Kiarri N

    2018-05-07

    Background -Smoke-free legislation has been associated with lower rates of cardiovascular disease hospital admissions in ecological studies. However, prior studies lacked detailed information on individual-level factors (eg, sociodemographic and clinical characteristics) that could potentially confound associations. Our objective was to estimate associations of smoke-free policies with incident cardiovascular disease in a longitudinal cohort after controlling for sociodemographics, cardiovascular disease risk factors, and policy covariates. Methods -Longitudinal data from 3783 black and white adults in the CARDIA study (Coronary Artery Risk Development in Young Adults; 1995-2015) were linked to state, county, and local 100% smoke-free policies in bars, restaurants, and nonhospitality workplaces by Census tract. Extended Cox regression estimated hazard ratios (HRs) of incident cardiovascular disease associated with time-dependent smoke-free policy exposures. Models were adjusted for sociodemographic characteristics, cardiovascular disease risk factors, state cigarette tax, participant-reported presence of a smoking ban at their workplace, field center, and metropolitan statistical area poverty. Results -During a median follow-up of 20 years (68 332 total personyears), 172 participants had an incident cardiovascular disease event (2.5 per 1000 person-years). Over the follow-up period, 80% of participants lived in areas with smoke-free policies in restaurants, 67% in bars, and 65% in nonhospitality workplaces. In fully adjusted models, participants living in an area with a restaurant, bar, or workplace smoke-free policy had a lower risk of incident cardiovascular disease compared with those in areas without smoke-free policies (HR, 0.75, 95% confidence interval, 0.49-1.15; HR, 0.76, 95% confidence interval, 0.47-1.24; HR, 0.54, 95% confidence interval, 0.34-0.86, respectively; HR, 0.58, 95% confidence interval, 0.33-1.00 for living in an area with all 3 types of

  16. Supradiaphragmatic Hodgkin's disease: significance of large mediastinal masses

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

    Prosnitz, L.R.; Curtis, A.M.; Knowlton, A.H.

    In order to assess the significance of large mediastinal masses in patients with Hodgkin's disease, we analyzed all patients with pathological stage (PS) IA or IIA disease evaluated and treated at Yale between 1969 and 1978. There were 131 such patients treated initially with radical radiotherapy only, combination chemotherapy being reserved for those who failed radiation. Actuarial 5 and 10 year survivals were 95%. The presence of a mediastinal mass regardless of size did not affect survival. Relapse-free survival was 77% at 5 years, 74% at 10 years in the entire group. Patients with any mediastinal involvement had a 65%more » relapse-free survival, 72% if the mass was < 33% of transverse chest diameter, 55% if the mass was > 33%. These differences are suggestive of a greater tendency of such patients to fail radiotherapy but the differences were not statistically significant. Patients who did fail radiotherapy were for the most part successfully retreated with combined modality therapy (chemotherapy and radiation), accounting for the most part successfully retreated with combined modality therapy (chemotherapy and radiation), accounting for the overall survival of 95%. Only 6 patients died of causes related to Hodgkin's disease and 2 of these deaths were related to combined modality therapy complications. Because of the serious potential long term consequences of combined modality treatment, it should be used with great caution and on an individual basis only in PSIA and IIA patients.« less

  17. Evaluating first-year pine seedling survival plateau in Louisiana

    Treesearch

    Puskar N. Khana; Thomas J. Dean; Scott D. Roberts; Donald L. Grebner

    2016-01-01

    First-year seeding survival has been a continuing problem since the start of commercial pine plantation forestry in the 1950s. First-year survival of bare-root loblolly pine seedlings on intensively prepared sites in Louisiana has maintained a survival plateau between 79 to 89 percent with an average of about 82 percent. The specific objectives of this study were to...

  18. Determinants of survival after liver resection for metastatic colorectal carcinoma.

    PubMed

    Parau, Angela; Todor, Nicolae; Vlad, Liviu

    2015-01-01

    Prognostic factors for survival after liver resection for metastatic colorectal cancer identified up to date are quite inconsistent with a great inter-study variability. In this study we aimed to identify predictors of outcome in our patient population. A series of 70 consecutive patients from the oncological hepatobiliary database, who had undergone curative hepatic surgical resection for hepatic metastases of colorectal origin, operated between 2006 and 2011, were identified. At 44.6 months (range 13.7-73), 30 of 70 patients (42.85%) were alive. Patient demographics, primary tumor and liver tumor factors, operative factors, pathologic findings, recurrence patterns, disease-free survival (DFS), overall survival (OS) and cancer-specific survival (CSS) were analyzed. Clinicopathologic variables were tested using univariate and multivariate analyses. The 3-year CSS after first hepatic resection was 54%. Median CSS survival after first hepatic resection was 40.2 months. Median CSS after second hepatic resection was 24.2 months. The 3-year DFS after first hepatic resection was 14%. Median disease free survival after first hepatic resection was 18 months. The 3-year DFS after second hepatic resection was 27% and median DFS after second hepatic resection 12 months. The 30-day mortality and morbidity rate after first hepatic resection was 5.71% and 12.78%, respectively. In univariate analysis CSS was significantly reduced for the following factors: age >53 years, advanced T stage of primary tumor, moderately- poorly differentiated tumor, positive and narrow resection margin, preoperative CEA level >30 ng/ml, DFS <18 months. Perioperative chemotherapy related to metastasectomy showed a trend in improving CSS (p=0.07). Perioperative chemotherapy improved DFS in a statistically significant way (p=0.03). Perioperative chemotherapy and achievement of resection margins beyond 1 mm were the major determinants of both CSS and DFS after first liver resection in multivariate

  19. Prostate cancer in young adults-Seventeen-year clinical experience of a single center.

    PubMed

    Huang, Tzu-Hao; Kuo, Junne-Yih; Huang, Yi-Hsiu; Chung, Hsiao-Jen; Huang, William J S; Wu, Howard H H; Chang, Yen-Hwa; Lin, Alex T L; Chen, Kuang-Kuo

    2017-01-01

    In the general population, prostate adenocarcinoma affects predominately older men. If fact, most current guidelines suggest that males over the age of 50 years should undergo prostate cancer screening. However, the clinical behavior and prognosis of prostate cancer in young adults is not well defined. The aim of this study was to evaluate the clinical behavior, pathological characteristics, and prognosis of prostate cancer in young adults. We retrospectively reviewed the records of young patients (age, ≤50 years) in our hospital with prostate adenocarcinoma between 1997 and 2013. We compared data including initial presentation, cancer cell type, Gleason score, disease stage, prostate-specific antigen (PSA) level, prostate volume, treatment, and survival between patients both younger and older than 50 years. Data were analyzed using the Kaplan-Meier method to assess survival. Twenty-six patients were enrolled in our study, accounting for 0.55% of all patients with a diagnosis of prostate cancer at our facility. All 26 patients had a pathology diagnosis of adenocarcinoma, with a mean age on diagnosis of 46.8±2.8 years (range, 39-50 years). On initial presentation, patients older than 50 years more frequently displayed lower urinary tract symptoms (LUTS) than younger patients (62.3% vs. 30.4%, p=0.008). There was no statistical difference in histological grade, disease stage, PSA level, overall survival, and biochemical-free survival between the two groups. The result of our investigation indicated that prostate adenocarcinoma patients younger than 50 years had similar histological grade, disease stage, PSA level, overall survival, and biochemical-free survival as the older population. However, patients younger than 50 years with prostate cancer less frequently showed initial symptoms of LUTS. Copyright © 2016. Published by Elsevier Taiwan LLC.

  20. Timing of intra-aortic balloon pump support and 1-year survival.

    PubMed

    Ramnarine, Ian R; Grayson, Antony D; Dihmis, Walid C; Mediratta, Neeraj K; Fabri, Brian M; Chalmers, John A C

    2005-05-01

    The relationship between the timing of intra-aortic balloon pump (IABP) support and surgical outcome remains a subject of debate. Peri-operative mechanical circulatory support is commenced either prophylactically or after increasing inotropic support has proved inadequate. This study evaluates the effect timing of IABP support on the 1-year survival of patients undergoing cardiac surgery. From April 1997 to September 2002, 7698 consecutive cardiac surgical procedures were performed. This included 5678 isolated coronary artery bypasses (CABGs), 1245 isolated valve procedures and 775 simultaneous CABG and valve procedures. IABP support was required in 237 patients (3.1%). Twenty-seven patients (0.35%) were classed as high-risk and received preoperative IABP support, 25 patients (0.32%) were haemodynamically compromised and required preoperative IABP support, 120 patients (1.56%) required intra-operative IABP support, and 65 patients (0.84%) required post-operative IABP support. Multiple variables were offered to a Cox proportional hazards model and significant predictors of 1-year survival were identified. These were used to risk adjust Kaplan-Meier survival curves. 1-year follow-up was complete and 450 deaths (5.8%) were recorded. The significant independent predictors of increased mortality at 1-year (P<0.05, HR=hazard ratio) were post-operative renal failure (HR=3.5), increasing EuroSCORE (HR=1.2), post-operative myocardial infarction (HR=3.7), post-operative IABP (HR=4.1) intra-operative IABP (HR=2.8), post-operative stroke (HR=2.5), increasing number of valves (HR=1.6), ejection fraction <30% (HR=1.3) and triple-vessel disease (HR=1.3). After risk-adjustment, 1-year survival for patients who required intra-operative IABP support was significantly greater than for those patients who required IABP support in the post-operative period. Patients who warrant IABP support in the post-operative setting have a significantly increased mortality at 1-year when compared to

  1. 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

  2. Ten-year survival and complication rates of lithium-disilicate (Empress 2) tooth-supported crowns, implant-supported crowns, and fixed dental prostheses.

    PubMed

    Teichmann, Maren; Göckler, Fabian; Weber, Volker; Yildirim, Murat; Wolfart, Stefan; Edelhoff, Daniel

    2017-01-01

    To prospectively evaluate the clinical long-term outcome of tooth-supported crowns (SCs), implant-supported crowns (ISCs), and fixed dental prostheses (FDPs) made of a lithium-disilicate glass-ceramic framework material (IPS Empress 2). Between 1997 and 1999, a total of 184 restorations (106 SCs, 32 ISCs, 33 FDPs, and 13 diverse restorations) were placed in 73 patients. Kaplan-Meier estimation was applied for survival and chipping-free rates. Inter-group comparison of both rates was realized by a log rank test and a 2×2 contingency table. Also, SCs and FDPs were compared regarding adhesive vs. conventional cementation, and anterior vs. posterior positioning, for impact on survival. Due to 14 dropouts (34 restorations) and reasonable exclusion of 19 other restorations, the final dataset included: i) 87 SCs [37 patients, mean observation time 11.4 (±3.8)years]; ii) 17 ISCs [12 patients, mean observation time 13.3 (±2.3)years; and iii) 27 FDPs [19 patients, mean observation time 8.9 (±5.4)years]. The 10-year survival rate/chipping-free rate for SCs were 86.1%/83.4%, for ISCs 93.8%/94.1%, and for FDPs were 51.9%/90.8%. Both ISCs and SCs had a significantly higher survival than FDPs (ISCs vs. FDPs: both tests p=0.001; SCs vs. FDPs: p=0.001 and p=0.005). Differences in the chipping-free rates did not reach significance. Also, neither the cementation mode nor positioning of the restoration had an impact on survival. SCs had a slightly lower outcome than can generally be expected from single crowns. In contrast, ICSs had a favorable outcome and the FDPs predominantly failed. The practitioner's choice of dental materials is based (at best) on long-term experience. The present 10-year results are based on comprehensive data analyses and show the high potential of lithium-disilicate as a reliable material, especially for single-unit restoration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Association of Adjuvant Chemotherapy With Survival in Patients With Stage II or III Gastric Cancer

    PubMed Central

    Jiang, Yuming; Li, Tuanjie; Liang, Xiaoling; Hu, Yanfeng; Huang, Lei; Liao, Zhenchen; Zhao, Liying; Han, Zhen; Zhu, Shuguang; Wang, Menglan; Xu, Yangwei; Qi, Xiaolong; Liu, Hao; Yang, Yang; Yu, Jiang; Liu, Wei; Cai, Shirong

    2017-01-01

    Importance The current staging system of gastric cancer is not adequate for defining a prognosis and predicting the patients most likely to benefit from chemotherapy. Objective To construct a survival prediction model based on specific tumor and patient characteristics that enables individualized predictions of the net survival benefit of adjuvant chemotherapy for patients with stage II or stage III gastric cancer. Design, Setting, and Participants In this multicenter retrospective analysis, a survival prediction model was constructed using data from a training cohort of 746 patients with stage II or stage III gastric cancer who satisfied the study’s inclusion criteria and underwent surgery between January 1, 2004, and December 31, 2012, at Nanfang Hospital in Guangzhou, China. Patient and tumor characteristics were included as covariates, and their association with overall survival and disease-free survival with and without adjuvant chemotherapy was assessed. The model was internally validated for discrimination and calibration using bootstrap resampling. To externally validate the model, data were included from a validation cohort of 973 patients with stage II or stage III gastric cancer who met the inclusion criteria and underwent surgery at First Affiliated Hospital in Guangzhou, China, and at West China Hospital of Sichuan Hospital in Chendu, China, between January 1, 2000, and June 30, 2009. Data were analyzed from July 10, 2016, to September 1, 2016. Main Outcomes and Measures Concordance index and decision curve analysis for each measure associated with postoperative overall survival and disease-free survival. Results Of the 1719 patients analyzed, 1183 (68.8%) were men and 536 (31.2%) were women and the median (interquartile range) age was 57 (49-66) years. Age, location, differentiation, carcinoembryonic antigen, cancer antigen 19-9, depth of invasion, lymph node metastasis, and adjuvant chemotherapy were significantly associated with overall survival

  4. 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.

  5. Differentiating Graves' disease from subacute thyroiditis using ratio of serum free triiodothyronine to free thyroxine.

    PubMed

    Sriphrapradang, Chutintorn; Bhasipol, Adikan

    2016-09-01

    The measurement of free thyroid hormone, instead of the total form, is more commonly used in current practice. We aimed to evaluate the usefulness of the ratio of serum free triiodothyronine (FT3, pg/mL) to free thyroxine (FT4, ng/dL) for differentiating Graves' disease from subacute thyroiditis. Medical records of thyrotoxic patients aged >15 years who had measurement of FT3, FT4 and thyrotropin on the first diagnosis of thyrotoxicosis before initiating treatment were retrospectively reviewed. Data were collected from all clinics, and were not limited to the endocrine clinic. Pregnant women were excluded. A total of 548 patients (468 with Graves' disease, 40 with subacute thyroiditis and 40 with toxic adenoma/multinodular goiter) were recruited. Mean age was 43.9 ± 15.4 years. Most were female 434 (79.2%), and goiter was present in 55.3%. Prevalence of T3-toxicosis and T4-toxicosis were 5.6% and 6.6%, respectively. Mean FT3/FT4 ratios were 4.62 ± 2 (10(-2) pg/ng) in patients with Graves' disease and 2.73 ± 0.5 in subacute thyroiditis. The area under the ROC curve of the FT3/FT4 ratio for diagnosis of Graves' disease was 0.83 (95%CI, 0.76-0.91). Cutoff level of this ratio >4.4 offered sensitivity of 47.2% and specificity of 92.8%. FT3/FT4 ratio of >4.4 (10(-2) pg/ng) may help in differentiating the cause of thyrotoxicosis.

  6. 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

  7. 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.

  8. The modified Glasgow prognosis score predicts for overall and disease-free survival following cytoreductive surgery and HIPEC in patients with pseudomyxoma peritonei of appendiceal origin.

    PubMed

    Tan, G H C; Novo, C A; Dayal, S; Chandrakumaran, K; Mohamed, F; Cecil, T; Moran, B J

    2017-02-01

    The modified Glasgow prognostic score (incorporating C-reactive protein and albumin) predicts survival in patients with gastro-intestinal tract cancer but has not been evaluated in patients with peritoneal malignancy. The aim was to evaluate the modified Glasgow score preoperatively in patients undergoing complete cytoreductive surgery (CCRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP) of appendiceal origin. Prospectively collected data from patients with PMP of appendiceal origin following CCRS and HIPEC between January 2007 and December 2011 were analysed. The mGPS was calculated from preoperative C-reactive protein and albumin. Predicted overall survival (OS) and disease-free survival (DFS) for each mGPS score were calculated using the Kaplan-Meier model. In a separate analysis, a comparison was made between mGPS and Tumour Markers (TM). 260 patients were included in the study. The mGPS of 0, 1, and 2 were found in 111, 130, and 19 patients respectively. The median follow-up was 48 months. For mGPS-0, -1, and -2, the predicted OS was 82.2, 73.7, and 69.2 months and the DFS was 73.5, 62.9, and 54.4 months respectively. As mGPS increases, there is a reduction in long-term survival. There was no difference between mGPS and TM. Preoperative mGPS may be a cost effective prognostic tool for predicting OS and DFS in patients following complete CRS-HIPEC, and performs well compared to TM for predicting patients at high risk of recurrence. Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  9. Gastrointestinal stromal tumors: Thirty years experience of an Institution

    PubMed Central

    Arolfo, Simone; Teggia, Paolo Mello; Nano, Mario

    2011-01-01

    AIM: To report our experience of gastrointestinal stromal tumors (GISTs) during the last 29 years. METHODS: Thirty two cases of GIST referred to our Institution from the 1st January 1981 to the 10th June 2010 were reviewed. Metastases, recurrence and survival data were collected in relation to age, history, clinical presentation, location, size, resection margins and cellular features. RESULTS: Mean age was 63.7 years (range, 40-90) and incidence was slightly higher in males (56%). R0 resection was performed in 90.7% of cases, R1 in 6.2% (2 cases) and R2 in 3.1% (one case). Using Fletcher’s classification 8/32 (25%) had high risk, 9/32 (28%) intermediate and 15/32 (47%) low risk tumors. Follow-up varied from 1 mo to 29 years, with a median of 8 years; overall survival was 75% (24/32), disease-free survival was 72% and tumor-related mortality was 9.3%. Three patients with high risk GIST were treated with imatinib mesylate: one developed a recurrence after 36 mo, and 2 are free from disease at 41 mo. CONCLUSION: Surgical treatment remains the gold standard therapy for resectable GISTs. Pathological and biological features of the neoplasm represent the most important factors predicting the prognosis. PMID:21528056

  10. A single institution analysis of low-dose-rate brachytherapy: 5-year reported survival and late toxicity outcomes

    PubMed Central

    Spencer, Sandra; Guerrieri, Mario; Ding, Wei; Goharian, Mehran; Ho, Huong; Ng, Michael; Healey, Danielle; Tan, Alwin; Cham, Chee; Joon, Daryl Lim; Lawrentschuk, Nathan; Travis, Douglas; Sengupta, Shomik; Chan, Yee; Troy, Andrew; Pham, Trung; Clarke, David; Liodakis, Peter; Bolton, Damien

    2018-01-01

    Purpose To report the 5-year biochemical relapse-free survival (BRFS), overall survival (OS), and long-term toxicity outcomes of patients treated with low-dose-rate (LDR) brachytherapy as monotherapy for low- to intermediate-risk prostate cancer. Material and methods Between 2004 and 2011, 371 patients were treated with LDR brachytherapy as monotherapy. Of these, 102 patients (27%) underwent transurethral resection of the prostate (TURP) prior to implantation. Follow-up was performed every 3 months for 12 months, then every 6 months over 4 years and included prostate specific antigen evaluation. The biochemical relapse-free survival (BRFS) was defined according to the Phoenix criteria. Acute and late toxicities were documented using the Common Terminology Criteria for Adverse Events version 4.0. The BRFS and OS estimates were calculated using Kaplan-Meier plots. Univariate and multivariate analyses were performed to evaluate outcomes by pre-treatment clinical prognostic factors and radiation dosimetry. Results The median follow-up of all patients was 5.45 years. The 5-year BRFS and OS rates were 95% and 96%, respectively. The BRFS rates for patients with Gleason score (GS) > 7 and GS ≤ 6 were 96% and 91% respectively (p = 0.06). On univariate analysis, T1 and T2 staging, risk-group classification, and prostate volumes had no impact on survival at 5 years (p > 0.1). Late grade 2 and 3 genitourinary (GU) toxicities were observed in 10% and 5% of patients respectively. Additionally, patients with prior TURP had a greater incidence of late grade 2 or 3 urinary retention (p = 0.001). There were 14 deaths in total; however, none were attributed to prostate cancer. Conclusions LDR brachytherapy is an effective treatment option in low- to intermediate-risk prostate cancer patients. We observed low biochemical relapse rates and minimal GU toxicities several years after treatment in patients with or without TURP. However, a small risk of urinary retention was observed in

  11. Stratified aspartate aminotransferase-to-platelet ratio index accurately predicts survival in hepatocellular carcinoma patients undergoing curative liver resection.

    PubMed

    Yang, Hao-Jie; Jiang, Jing-Hang; Yang, Yu-Ting; Guo, Zhe; Li, Ji-Jia; Liu, Xuan-Han; Lu, Fei; Zeng, Feng-Hua; Ye, Jin-Song; Zhang, Ke-Lan; Chen, Neng-Zhi; Xiang, Bang-De; Li, Le-Qun

    2017-03-01

    The aspartate aminotransferase-to-platelet ratio index has been reported to predict prognosis of patients with hepatocellular carcinoma. This study examined the prognostic potential of stratified aspartate aminotransferase-to-platelet ratio index for hepatocellular carcinoma patients undergoing curative liver resection. A total of 661 hepatocellular carcinoma patients were retrieved and the associations between aspartate aminotransferase-to-platelet ratio index and clinicopathological variables and survivals (overall survival and disease-free survival) were analyzed. Higher aspartate aminotransferase-to-platelet ratio index quartiles were significantly associated with poorer overall survival (p = 0.002) and disease-free survival (p = 0.001). Multivariate analysis showed aspartate aminotransferase-to-platelet ratio index to be an independent risk factor for overall survival (p = 0.018) and disease-free survival (p = 0.01). Patients in the highest aspartate aminotransferase-to-platelet ratio index quartile were at 44% greater risk of death than patients in the first quartile (hazard ratio = 1.445, 95% confidence interval = 1.081 - 1.931, p = 0.013), as well as 49% greater risk of recurrence (hazard ratio = 1.49, 95% confidence interval = 1.112-1.998, p = 0.008). Subgroup analysis also showed aspartate aminotransferase-to-platelet ratio index to be an independent predictor of poor overall survival and disease-free survival in patients positive for hepatitis B surface antigen or with cirrhosis (both p < 0.05). Similar results were obtained when aspartate aminotransferase-to-platelet ratio index was analyzed as a dichotomous variable with cutoff values of 0.25 and 0.62. Elevated preoperative aspartate aminotransferase-to-platelet ratio index may be independently associated with poor overall survival and disease-free survival in hepatocellular carcinoma patients following curative resection.

  12. 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...

  13. 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

  14. Effect of a Shortened Duration of FOLFOX Chemotherapy on the Survival Rate of Patients with Stage II and III Colon Cancer.

    PubMed

    Ji, Woong Bae; Hong, Kwang Dae; Kim, Jung-Sik; Joung, Sung-Yup; Um, Jun Won; Min, Byung-Wook

    2018-01-01

    FOLFOX chemotherapy is widely used as an adjuvant treatment for advanced colon cancer. The duration of adjuvant chemotherapy is usually set to 6 months, which is based on a former study of 5-fluorouracil/leucovorin chemotherapy. However, the FOLFOX regimen is known to have complications, such as peripheral neuropathy. The aim of this study was to compare the survival rates and complications experienced by patients receiving either 4 or 6 months of FOLFOX chemotherapy. Retrospective data analysis was performed for stage II and III patients who underwent radical resection of colon cancer. We compared the 5-year survival rates and the occurrence of complications in patients who completed only 8 cycles of FOLFOX chemotherapy with patients who completed 12 cycles of chemotherapy. Among 188 patients who underwent adjuvant FOLFOX chemotherapy for stage II or III colon cancer, 83 (44.1%) completed 6 months of FOLFOX chemotherapy and 64 (34.0%) patients discontinued after 4 months of chemotherapy. The 5-year overall survival and disease-free survival rates did not show a significant difference. Patients in the 6-month group had peripheral neuropathy more frequently (p = 0.028). Five-year overall and disease-free survival were not significantly different between the 2 groups. Large-scale prospective studies are necessary for the analysis of complications and survival rates. © 2017 S. Karger AG, Basel.

  15. 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.

  16. 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

  17. Survival benefit of lung transplantation for chronic obstructive pulmonary disease in Sweden.

    PubMed

    Tanash, Hanan A; Riise, Gerdt C; Ekström, Magnus P; Hansson, Lennart; Piitulainen, Eeva

    2014-12-01

    Lung transplantation (LTx) is a therapeutic option for patients with life-threatening chronic obstructive pulmonary disease (COPD) that is refractory to conventional therapies. The survival benefit of LTx for COPD is difficult to assess. The aim of this study was to evaluate the Swedish series of LTx performed to treat COPD and to identify differences in outcome between COPD related to severe alpha-1-antitrypsin deficiency (AATD) and COPD with normal alpha-1-antitrypsin (AAT) levels. We retrospectively reviewed the data of 342 patients (128 AATD and 214 non-AATD) receiving lung transplants for end stage COPD from 1990 through 2012. The majority (71%) of patients received a single lung transplant. The median survival time after LTx for all COPD patients was 9 years (95% confidence interval [CI]: 8 to 10). Non-AATD recipients had a shorter survival time than AATD recipients, 6 years (95% CI: 5.0 to 8.8) versus 12 years (95% CI: 9.6 to 13.5, p = 0.000). Mortality was higher among non-AATD recipients after adjusting for age, pack-years of smoking, body mass index, oxygen therapy use, exercise capacity, donor age, cytomegalovirus mismatch, and transplant type (hazard ratio 1.70, 95% CI: 1.02 to 2.82). The 5-year and 10-year survival rates for the AATD recipients were 75% and 59%, respectively, compared with 60% and 31% for the non-AATD recipients. Early deaths were mainly due to cardio/cerebrovascular accidents and sepsis, and late deaths to bronchiolitis obliterans syndrome and pulmonary infections. Survival after LTx is significantly better for patients with severe AATD and end stage COPD than for the patients with COPD related to cigarette smoking. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  18. Long-term survival after resection of a primary leiomyosarcoma of the innominate vein Report of a case.

    PubMed

    Illuminati, Giulio; Miraldi, Fabio; A Pacilè, Maria; Palumbo, Piero; Vietri, Francesco

    2012-10-29

    Leiomyosarcoma of the innominate vein is a rare but usually lethal disease. We report the case of a 50-year-old woman, undergoing a curative resection of the tumor. She is alive and free of disease at 88-month follow-up. Surgical excision remains the current optimal treatment able to provide a chance of cure. KEY WORDS: Late survival, Venous leiomyosarcoma.

  19. 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

  20. Increased Mycoplasma hyopneumoniae Disease Prevalence in Domestic Hybrids Among Free-Living Wild Boar.

    PubMed

    Goedbloed, Daniel J; van Hooft, Pim; Lutz, Walburga; Megens, Hendrik-Jan; van Wieren, Sip E; Ydenberg, Ron C; Prins, Herbert H T

    2015-12-01

    Wildlife immune genes are subject to natural selection exerted by pathogens. In contrast, domestic immune genes are largely protected from pathogen selection by veterinary care. Introgression of domestic alleles into the wild could lead to increased disease susceptibility, but observations are scarce due to low introgression rates, low disease prevalence and reduced survival of domestic hybrids. Here we report the first observation of a deleterious effect of domestic introgression on disease prevalence in a free-living large mammal. A fraction of 462 randomly sampled free-living European wild boar (Sus scrofa) was genetically identified as recent wild boar-domestic pig hybrids based on 351 SNP data. Analysis of antibody prevalence against the bacterial pathogen Mycoplasma hyopneumoniae (Mhyo) showed an increased Mhyo prevalence in wild-domestic hybrids. We argue that the most likely mechanism explaining the observed association between domestic hybrid status and Mhyo antibody prevalence would be introgression of deleterious domestic alleles. We hypothesise that large-scale use of antibiotics in the swine breeding sector may have played a role in shaping the relatively deleterious properties of domestic swine immune genes and that domestic introgression may also lead to increased wildlife disease susceptibility in the case of other species.

  1. MMP-7 expression may influence the rate of distant recurrences and disease-specific survival in HPV-positive oropharyngeal squamous cell carcinoma.

    PubMed

    Vento, Seija I; Jouhi, Lauri; Mohamed, Hesham; Haglund, Caj; Mäkitie, Antti A; Atula, Timo; Hagström, Jaana; Mäkinen, Laura K

    2018-05-02

    The objective of this study was to determine if matrix metalloproteinase-7 (MMP-7) expression is related to human papilloma virus (HPV) status, clinical parameters, and outcome in oropharyngeal squamous cell carcinoma (OPSCC). Tumor tissue specimens from 201 OPSCC patients treated with curative intent were available for immunohistochemistry, and the samples were stained with monoclonal MMP-7 antibody. All the patients were followed up at least 3 years or until death. MMP-7 expression did not differ between HPV-positive and HPV-negative patients. MMP-7 was not prognostic among patients with HPV-negative OPSCC. In the HPV-positive subgroup, patients with moderate, high, or very high MMP-7 expression had significantly worse 5-year disease-specific survival (DSS) (56.6%) than patients with absent, or low MMP-7 expression (77.2%), and MMP-7 expression appeared as a prognostic factor in the multivariate analysis. In addition, among HPV-positive OPSCC with moderate, high, or very high MMP-7 expression, the 5-year distant recurrence-free survival was significantly lower (69.6%) than in those who had low or absent MMP-7 expression (97.5%). Our results suggest that among HPV-positive OPSCC patients, high MMP-7 expression is related to worse 5-year DSS and increased rate of distant recurrences.

  2. Trisomy 13 (Patau syndrome) with an 11-year survival.

    PubMed

    Zoll, B; Wolf, J; Lensing-Hebben, D; Pruggmayer, M; Thorpe, B

    1993-01-01

    Trisomy 13 is very rare in live-born children. Only a small number of these children survive the first year and very few cases are reported to live longer. Survival time depends partly on the cytogenetic findings--full trisomy 13 or trisomy 13 mosaicism--and partly on the existence of serious somatic malformations. We report on a 11-year-old girl with full trisomy 13. In this case, missing cerebral and cardiovascular malformations probably allowed the long survival.

  3. Treatment Adherence and Its Impact on Disease-Free Survival in the Breast International Group 1-98 Trial of Tamoxifen and Letrozole, Alone and in Sequence.

    PubMed

    Chirgwin, Jacquie H; Giobbie-Hurder, Anita; Coates, Alan S; Price, Karen N; Ejlertsen, Bent; Debled, Marc; Gelber, Richard D; Goldhirsch, Aron; Smith, Ian; Rabaglio, Manuela; Forbes, John F; Neven, Patrick; Láng, István; Colleoni, Marco; Thürlimann, Beat

    2016-07-20

    To investigate adherence to endocrine treatment and its relationship with disease-free survival (DFS) in the Breast International Group (BIG) 1-98 clinical trial. The BIG 1-98 trial is a double-blind trial that randomly assigned 6,193 postmenopausal women with hormone receptor-positive early breast cancer in the four-arm option to 5 years of tamoxifen (Tam), letrozole (Let), or the agents in sequence (Let-Tam, Tam-Let). This analysis included 6,144 women who received at least one dose of study treatment. Conditional landmark analyses and marginal structural Cox proportional hazards models were used to evaluate the relationship between DFS and treatment adherence (persistence [duration] and compliance with dosage). Competing risks regression was used to assess demographic, disease, and treatment characteristics of the women who stopped treatment early because of adverse events. Both aspects of low adherence (early cessation of letrozole and a compliance score of < 90%) were associated with reduced DFS (multivariable model hazard ratio, 1.45; 95% CI, 1.09 to 1.93; P = .01; and multivariable model hazard ratio, 1.61; 95% CI, 1.08 to 2.38; P = .02, respectively). Sequential treatments were associated with higher rates of nonpersistence (Tam-Let, 20.8%; Let-Tam, 20.3%; Tam 16.9%; Let 17.6%). Adverse events were the reason for most trial treatment early discontinuations (82.7%). Apart from sequential treatment assignment, reduced adherence was associated with older age, smoking, node negativity, or prior thromboembolic event. Both persistence and compliance are associated with DFS. Toxicity management and, for sequential treatments, patient and physician awareness, may improve adherence. © 2016 by American Society of Clinical Oncology.

  4. Treatment Adherence and Its Impact on Disease-Free Survival in the Breast International Group 1-98 Trial of Tamoxifen and Letrozole, Alone and in Sequence

    PubMed Central

    Giobbie-Hurder, Anita; Coates, Alan S.; Price, Karen N.; Ejlertsen, Bent; Debled, Marc; Gelber, Richard D.; Goldhirsch, Aron; Smith, Ian; Rabaglio, Manuela; Forbes, John F.; Neven, Patrick; Láng, István; Colleoni, Marco; Thürlimann, Beat

    2016-01-01

    Purpose To investigate adherence to endocrine treatment and its relationship with disease-free survival (DFS) in the Breast International Group (BIG) 1-98 clinical trial. Methods The BIG 1-98 trial is a double-blind trial that randomly assigned 6,193 postmenopausal women with hormone receptor–positive early breast cancer in the four-arm option to 5 years of tamoxifen (Tam), letrozole (Let), or the agents in sequence (Let-Tam, Tam-Let). This analysis included 6,144 women who received at least one dose of study treatment. Conditional landmark analyses and marginal structural Cox proportional hazards models were used to evaluate the relationship between DFS and treatment adherence (persistence [duration] and compliance with dosage). Competing risks regression was used to assess demographic, disease, and treatment characteristics of the women who stopped treatment early because of adverse events. Results Both aspects of low adherence (early cessation of letrozole and a compliance score of < 90%) were associated with reduced DFS (multivariable model hazard ratio, 1.45; 95% CI, 1.09 to 1.93; P = .01; and multivariable model hazard ratio, 1.61; 95% CI, 1.08 to 2.38; P = .02, respectively). Sequential treatments were associated with higher rates of nonpersistence (Tam-Let, 20.8%; Let-Tam, 20.3%; Tam 16.9%; Let 17.6%). Adverse events were the reason for most trial treatment early discontinuations (82.7%). Apart from sequential treatment assignment, reduced adherence was associated with older age, smoking, node negativity, or prior thromboembolic event. Conclusion Both persistence and compliance are associated with DFS. Toxicity management and, for sequential treatments, patient and physician awareness, may improve adherence. PMID:27217455

  5. [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.

  6. Model for End-Stage Liver Disease, Model for Liver Transplantation Survival and Donor Risk Index as predictive models of survival after liver transplantation in 1,006 patients.

    PubMed

    Aranzana, Elisa Maria de Camargo; Coppini, Adriana Zuolo; Ribeiro, Maurício Alves; Massarollo, Paulo Celso Bosco; Szutan, Luiz Arnaldo; Ferreira, Fabio Gonçalves

    2015-06-01

    Liver transplantation has not increased with the number of patients requiring this treatment, increasing deaths among those on the waiting list. Models predicting post-transplantation survival, including the Model for Liver Transplantation Survival and the Donor Risk Index, have been created. Our aim was to compare the performance of the Model for End-Stage Liver Disease, the Model for Liver Transplantation Survival and the Donor Risk Index as prognostic models for survival after liver transplantation. We retrospectively analyzed the data from 1,270 patients who received a liver transplant from a deceased donor in the state of São Paulo, Brazil, between July 2006 and July 2009. All data obtained from the Health Department of the State of São Paulo at the 15 registered transplant centers were analyzed. Patients younger than 13 years of age or with acute liver failure were excluded. The majority of the recipients had Child-Pugh class B or C cirrhosis (63.5%). Among the 1,006 patients included, 274 (27%) died. Univariate survival analysis using a Cox proportional hazards model showed hazard ratios of 1.02 and 1.43 for the Model for End-Stage Liver Disease and the Model for Liver Transplantation Survival, respectively (p<0.001). The areas under the ROC curve for the Donor Risk Index were always less than 0.5, whereas those for the Model for End-Stage Liver Disease and the Model for Liver Transplantation Survival were significantly greater than 0.5 (p<0.001). The cutoff values for the Model for End-Stage Liver Disease (≥29.5; sensitivity: 39.1%; specificity: 75.4%) and the Model for Liver Transplantation Survival (≥1.9; sensitivity 63.9%, specificity 54.5%), which were calculated using data available before liver transplantation, were good predictors of survival after liver transplantation (p<0.001). The Model for Liver Transplantation Survival displayed similar death prediction performance to that of the Model for End-Stage Liver Disease. A simpler model

  7. Survival and contralateral breast cancer in CHEK2 1100delC breast cancer patients: impact of adjuvant chemotherapy

    PubMed Central

    Kriege, M; Hollestelle, A; Jager, A; Huijts, P E A; Berns, E M; Sieuwerts, A M; Meijer-van Gelder, M E; Collée, J M; Devilee, P; Hooning, M J; Martens, J W M; Seynaeve, C

    2014-01-01

    Background: We assessed the sensitivity to adjuvant chemotherapy in cell cycle checkpoint kinase 2 (CHEK2) vs non-CHEK2 breast cancer patients by comparing the contralateral breast cancer incidence and distant disease-free and breast cancer-specific survival between both groups, stratified for adjuvant chemotherapy. Methods: One Dutch hereditary non-BRCA1/2 breast cancer patient cohort (n=1220) and two Dutch cohorts unselected for family history (n=1014 and n=2488, respectively) were genotyped for CHEK2 1100delC. Hazard ratios for contralateral breast cancer, distant disease-free and breast cancer-specific death for mutation carriers vs noncarriers were calculated using the Cox proportional hazard method, stratified for adjuvant chemotherapy. Results: The CHEK2 mutation carriers (n=193) had an increased incidence of contralateral breast cancer (multivariate hazard ratio 3.97, 95% confidence interval 2.59–6.07). Distant disease-free and breast cancer-specific survival were similar in the first 6 years in mutation carriers compared with noncarriers, but diverted as of 6 years after breast cancer diagnosis (multivariate hazard ratios and 95% confidence intervals 2.65 (1.79–3.93) and 2.05 (1.41–2.99), respectively). No significant interaction between CHEK2 and adjuvant chemotherapy was observed. Conclusions: The CHEK2 1100delC-associated breast cancer is associated with a higher contralateral breast cancer rate as well as worse survival measures beyond 6 years after diagnosis. No differential sensitivity to adjuvant chemotherapy was observed in CHEK2 patients. PMID:24918820

  8. Survival of Mexican children with acute myeloid leukaemia who received early intensification chemotherapy and an autologous transplant.

    PubMed

    Jiménez-Hernández, Elva; Dueñas-González, María Teresa; Arellano-Galindo, José; Medrano-Ortíz-De-Zárate, María Elena; Bekker-Méndez, Vilma Carolina; Berges-García, Adolfina; Solís-Labastida, Karina; Sánchez-Jara, Berenice; Tiznado-García, Héctor Manuel; Jaimes-Reyes, Ethel Zulie; García-Jiménez, Xochiketzalli; Espinoza-Hernández, Laura; Núñez-Villegas, Nora Nancy; Franco-Ornelas, Sergio; Pérez-Casillas, Ruy Xavier; Villegas, Octavio Martínez; Palomares, Teresa Marin; Mejía-Aranguré, Juan Manuel

    2015-01-01

    In Mexico and other developing countries, few reports of the survival of children with acute leukaemia exist. Objective. We aimed at comparing the disease-free survival of children with acute myeloid leukaemia who, in addition to being treated with the Latin American protocol of chemotherapy and an autologous transplant, either underwent early intensified chemotherapy or did not undergo such treatment. This was a cohort study with a historical control group, forty patients, less than 16 years old. Group A (20 patients), diagnosed in the period 2005-2007, was treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy: high doses of cytarabine and mitoxantrone. Group B (20 patients), diagnosed in the period 1999-2004, was treated as Group A, but without the early intensified chemotherapy. Relapse-free survival for Group A was 90% whereas that for Group B it was 60% (P = 0.041). Overall survival for Group A (18, 90%) was higher than that for Group B (60%). Complete remission continued for two years of follow-up. Relapse-free survival for paediatric patients treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy was higher than that for those who did not receive early intensified chemotherapy.

  9. Clinical Outcomes Among Children With Standard-Risk Medulloblastoma Treated With Proton and Photon Radiation Therapy: A Comparison of Disease Control and Overall Survival

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

    Eaton, Bree R.; Esiashvili, Natia; Kim, Sungjin

    Purpose: The purpose of this study was to compare long-term disease control and overall survival between children treated with proton and photon radiation therapy (RT) for standard-risk medulloblastoma. Methods and Materials: This multi-institution cohort study includes 88 children treated with chemotherapy and proton (n=45) or photon (n=43) RT between 2000 and 2009. Overall survival (OS), recurrence-free survival (RFS), and patterns of failure were compared between the 2 cohorts. Results: Median (range) age was 6 years old at diagnosis (3-21 years) for proton patients versus 8 years (3-19 years) for photon patients (P=.011). Cohorts were similar with respect to sex, histology, extent of surgical resection,more » craniospinal irradiation (CSI) RT dose, total RT dose, whether the RT boost was delivered to the posterior fossa (PF) or tumor bed (TB), time from surgery to RT start, or total duration of RT. RT consisted of a median (range) CSI dose of 23.4 Gy (18-27 Gy) and a boost of 30.6 Gy (27-37.8 Gy). Median follow-up time is 6.2 years (95% confidence interval [CI]: 5.1-6.6 years) for proton patients versus 7.0 years (95% CI: 5.8-8.9 years) for photon patients. There was no significant difference in RFS or OS between patients treated with proton versus photon RT; 6-year RFS was 78.8% versus 76.5% (P=.948) and 6-year OS was 82.0% versus 87.6%, respectively (P=.285). On multivariate analysis, there was a trend for longer RFS with females (P=.058) and higher CSI dose (P=.096) and for longer OS with females (P=.093). Patterns of failure were similar between the 2 cohorts (P=.908). Conclusions: Disease control with proton and photon radiation therapy appears equivalent for standard risk medulloblastoma.« less

  10. Trastuzumab use during pregnancy: long-term survival after locally advanced breast cancer and long-term infant follow-up.

    PubMed

    Andrade, Jurandyr M de; Brito, Luiz G O; Moises, Elaine C D; Amorim, Andréa C; Rapatoni, Liane; Carrara, Hélio H A; Tiezzi, Daniel G

    2016-04-01

    Here, we describe the case of a patient diagnosed with locally advanced breast cancer 8 years ago. Her treatment course was neoadjuvant chemotherapy, followed by mastectomy and then adjuvant radiotherapy and trastuzumab (TTZ). During the use of adjuvant targeted therapy, an incidental pregnancy was diagnosed. Four years later, she developed bone and cerebral metastases, and since then, she has received courses of TTZ, capecitabine, lapatinib, and radiotherapy with intermittent control of the disease. Her 7-year-old son presents a normal physical and long-term neurological developmental curve according to specialized evaluation. This case is unique for several reasons: the patient received the highest dose of TTZ yet described during pregnancy (4400 mg); there has been a long period of disease-free survival after treatment for locally advanced breast cancer and long overall survival despite successive disease progressions during the metastatic phase of the disease (97 months), and there was a monitored pediatric follow-up period (7 years).

  11. No improvement in survival of patients with amyloidosis associated with inflammatory rheumatic diseases -- data from the Finnish national registry for kidney diseases.

    PubMed

    Immonen, Kai; Finne, Patrik; Hakala, Markku; Kautiainen, Hannu; Pettersson, Tom; Grönhagen-Riska, Carola

    2008-07-01

    To assess the incidence and outcome of renal replacement therapy (RRT) among patients with amyloidosis associated with inflammatory rheumatic diseases. Patients with amyloidosis entering RRT from 1987 to 2002 were identified from the Finnish Registry for Kidney Diseases. Five hundred two patients were identified, 80% of whom had amyloidosis associated with an underlying rheumatic disease. They were followed from the time of entering RRT until death or until the end of 2003 using the Finnish national mortality files. During the study period, there was no decline in the number of patients with amyloidosis entering RRT. Mean age of patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) increased significantly from 1987 to 2002 (p < 0.001). Male sex and a diagnosis of JIA indicated an increased risk of mortality. The median survival time after entering RRT was 2.11 years for RA (95% CI 1.93 to 2.69), 2.37 years for ankylosing spondylitis (95% CI 1.11 to 4.31), and 3.05 years for JIA (95% CI 2.19 to 4.23). The 5-year survival rates among patients with the corresponding diagnoses were 18% (95% CI 14% to 23%), 30% (95% CI 14% to 48%), and 27% (95% CI 14% to 41%), respectively. No decline was seen in the number of patients with amyloidosis associated with inflammatory rheumatic diseases accepted for RRT, but over the years, the age of patients with RA or JIA entering RRT was seen to increase. The outcome of patients with amyloidosis and endstage renal disease associated with rheumatic diseases remains poor.

  12. Adenosine triphosphate stress myocardial perfusion imaging for risk stratification of patients aged 70 years and older with suspected coronary artery disease.

    PubMed

    Yao, Zhiming; Zhu, Hui; Li, Wenchan; Chen, Congxia; Wang, Hua; Shi, Lei; Zhang, Wenjie

    2017-04-01

    We investigated the cardiac risk stratification value of adenosine triphosphate stress myocardial perfusion imaging (ATP-MPI) in patients aged 70 years and older with suspected coronary artery disease (CAD). We identified a series of 415 consecutive patients aged 70 years and older with suspected CAD, who had undergone ATP-MPI with 99m Tc-MIBI. The presence of a fixed and/or reversible perfusion defect was considered as an abnormal MPI. Follow-up was available in 399 patients (96.1%) over 3.45 ± 1.71 years after excluding 16 patients who underwent early coronary revascularization <60 days after MPI. The major adverse cardiac events (MACE), including cardiac death, nonfatal infarction, and late coronary revascularization, were recorded. One hundred twenty-five (31.3%) patients had abnormal MPI and the remaining had normal MPI. A multivariable analysis using Cox regression demonstrated that abnormal MPI was independently associated with MACE (hazard ratio 19.50 and 95% confidence interval 5.91-64.31, P value .000). The patients with SSS > 8 had significantly higher cumulative MACE rate than patients with SSS ≤ 8 had (37.8% vs 5.2%, respectively, P < .001). The Kaplan-Meier cumulative MACE-free survival in patients with abnormal MPI (57.0%) was significantly lower than that in patients with normal MPI (89.6%), P < .0001. Among patients with SSS > 8, the Kaplan-Meier cumulative MACE-free survival were 36.9% in patients ≥80 years old and 49.5% in patients 70-79 years old, respectively, P < .05. However, among patients with SSS ≤ 8, there was no difference between the Kaplan-Meier cumulative MACE-free survivals of these two age groups. ATP-MPI data are useful for the prediction of major adverse cardiac events in patients aged 70 years and older with suspected CAD.

  13. Survival and mortality among users and non-users of hydroxyurea with sickle cell disease.

    PubMed

    de Araujo, Olinda Maria Rodrigues; Ivo, Maria Lúcia; Ferreira Júnior, Marcos Antonio; Pontes, Elenir Rose Jardim Cury; Bispo, Ieda Maria Gonçalves Pacce; de Oliveira, Eveny Cristine Luna

    2015-01-01

    to estimate survival, mortality and cause of death among users or not of hydroxyurea with sickle cell disease. cohort study with retrospective data collection, from 1980 to 2010 of patients receiving inpatient treatment in two Brazilian public hospitals. The survival probability was determined using the Kaplan-Meier estimator, survival calculations (SPSS version 10.0), comparison between survival curves, using the log rank method. The level of significance was p=0.05. of 63 patients, 87% had sickle cell anemia, with 39 using hydroxyurea, with a mean time of use of the drug of 20.0±10.0 years and a mean dose of 17.37±5.4 to 20.94±7.2 mg/kg/day, raising the fetal hemoglobin. In the comparison between those using hydroxyurea and those not, the survival curve was greater among the users (p=0.014). A total of 10 deaths occurred, with a mean age of 28.1 years old, and with Acute Respiratory Failure as the main cause. the survival curve is greater among the users of hydroxyurea. The results indicate the importance of the nurse incorporating therapeutic advances of hydroxyurea in her care actions.

  14. Improved survival time: what can survival cure models tell us about population-based survival improvements in late-stage colorectal, ovarian, and testicular cancer?

    PubMed

    Huang, Lan; Cronin, Kathleen A; Johnson, Karen A; Mariotto, Angela B; Feuer, Eric J

    2008-05-15

    The objective of the current study was to investigate the long-term impact of treatment advances on the survival of patients with late-stage ovarian, colorectal (American Joint Committee on Cancer stage III, men), and testicular cancers by estimating the increase in the percentage cured from their disease and the change in survival time of uncured patients. Cause-specific survival data from 1973 to 2000 were obtained from the Surveillance, Epidemiology, and End Results Program. Survival cure models were fit and were used to estimate the gain in life expectancy (GLE) attributed to an increase in the fraction of cured patients and to prolonged survival among noncured patients. Treatment improvement for ovarian cancer resulted in a total GLE of 2 years, and 80% of that GLE was because of an extension of survival time in uncured patients (from 0.9 years to 2.1 years) rather than an increased cure fraction (from 12% to 14%). In contrast, the cure rate rose from 29% to 47% for colorectal cancer, representing 82% of a 2.8-year GLE, and from 23% to 81% for testicular cancer, representing 100% of a 24-year GLE. The current results suggested that treatment benefits for testicular and colorectal cancer in men with late-stage disease primarily are the result of increases in cure fraction, whereas survival gains for ovarian cancer occur despite persisting disease. Cure models, in combination with population-level data, provide insight into how treatment advances are changing survival and ultimately impacting mortality. Survival patterns reflect the underlying biology of response to cancer treatment and suggest promising directions for future research.

  15. 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

  16. Patterns of failure and survival in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy in Saudi Arabia.

    PubMed

    Maklad, Ahmed Marzouk; Bayoumi, Yasser; Senosy Hassan, Mohamed Abdalazez; Elawadi, AbuSaleh A; AlHussain, Hussain; Elyamany, Ashraf; Aldhahri, Saleh F; Al-Qahtani, Khalid Hussain; AlQahtani, Mubarak; Tunio, Mutahir A

    2016-01-01

    We aimed to investigate the patterns of failure (locoregional and distant metastasis), associated factors, and treatment outcomes in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy (IMRT) combined with chemotherapy. From April 2006 to December 2011, 68 nasopharyngeal carcinoma patients were treated with IMRT and chemotherapy at our hospital. Median radiation doses delivered to gross tumor volume and positive neck nodes were 66-70 Gy, 63 Gy to clinical target volume, and 50.4-56 Gy to clinically negative neck. The clinical toxicities, patterns of failures, locoregional control, distant metastasis control, disease-free survival, and overall survival were observed. The median follow-up time was 52.2 months (range: 11-87 months). Epstein-Barr virus infection was positive in 63.2% of patients. Overall disease failure developed in 21 patients, of whom 85.8% belonged to stage III/IV disease. Among these, there were seven locoregional recurrences, three regional recurrences with distant metastases, and eleven distant metastases. The median interval from the date of diagnosis to failure was 26.5 months (range: 16-50 months). Six of ten (60%) locoregional recurrences were treated with reirradiation ± concurrent chemotherapy. The 5-year locoregional control, distant metastasis control, disease-free survival, and overall survival rates of whole cohort were 81.1%, 74.3%, 60.1%, and 73.4%, respectively. Cox regression analyses revealed that neoadjuvant chemotherapy, age, and Epstein-Barr virus were independent predictors for disease-free survival. Neoadjuvant chemotherapy followed by IMRT with or without chemotherapy improves the long-term survival of Saudi patients with nasopharyngeal carcinoma. Distant metastasis was the main pattern of treatment failure. Neoadjuvant chemotherapy, age, and Epstein-Barr virus status before IMRT were important independent prognostic factors.

  17. Patterns of failure and survival in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy in Saudi Arabia

    PubMed Central

    Maklad, Ahmed Marzouk; Bayoumi, Yasser; Senosy Hassan, Mohamed Abdalazez; Elawadi, AbuSaleh A; AlHussain, Hussain; Elyamany, Ashraf; Aldhahri, Saleh F; Al-Qahtani, Khalid Hussain; AlQahtani, Mubarak; Tunio, Mutahir A

    2016-01-01

    Background We aimed to investigate the patterns of failure (locoregional and distant metastasis), associated factors, and treatment outcomes in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy (IMRT) combined with chemotherapy. Patients and methods From April 2006 to December 2011, 68 nasopharyngeal carcinoma patients were treated with IMRT and chemotherapy at our hospital. Median radiation doses delivered to gross tumor volume and positive neck nodes were 66–70 Gy, 63 Gy to clinical target volume, and 50.4–56 Gy to clinically negative neck. The clinical toxicities, patterns of failures, locoregional control, distant metastasis control, disease-free survival, and overall survival were observed. Results The median follow-up time was 52.2 months (range: 11–87 months). Epstein–Barr virus infection was positive in 63.2% of patients. Overall disease failure developed in 21 patients, of whom 85.8% belonged to stage III/IV disease. Among these, there were seven locoregional recurrences, three regional recurrences with distant metastases, and eleven distant metastases. The median interval from the date of diagnosis to failure was 26.5 months (range: 16–50 months). Six of ten (60%) locoregional recurrences were treated with reirradiation ± concurrent chemotherapy. The 5-year locoregional control, distant metastasis control, disease-free survival, and overall survival rates of whole cohort were 81.1%, 74.3%, 60.1%, and 73.4%, respectively. Cox regression analyses revealed that neoadjuvant chemotherapy, age, and Epstein–Barr virus were independent predictors for disease-free survival. Conclusion Neoadjuvant chemotherapy followed by IMRT with or without chemotherapy improves the long-term survival of Saudi patients with nasopharyngeal carcinoma. Distant metastasis was the main pattern of treatment failure. Neoadjuvant chemotherapy, age, and Epstein–Barr virus status before IMRT were important independent prognostic factors

  18. Personalized Prognostic Risk Score for Long-Term Survival for Children with Acute Leukemia after Allogeneic Transplantation.

    PubMed

    Bitan, Menachem; Ahn, Kwang Woo; Millard, Heather R; Pulsipher, Michael A; Abdel-Azim, Hisham; Auletta, Jeffery J; Brown, Valerie; Chan, Ka Wah; Diaz, Miguel Angel; Dietz, Andrew; Vincent, Marta González; Guilcher, Gregory; Hale, Gregory A; Hayashi, Robert J; Keating, Amy; Mehta, Parinda; Myers, Kasiani; Page, Kristin; Prestidge, Tim; Shah, Nirali N; Smith, Angela R; Woolfrey, Ann; Thiel, Elizabeth; Davies, Stella M; Eapen, Mary

    2017-09-01

    We studied leukemia-free (LFS) and overall survival (OS) in children with acute myeloid (AML, n = 790) and acute lymphoblastic leukemia (ALL, n = 1096) who underwent transplantation between 2000 and 2010 and who survived for at least 1 year in remission after related or unrelated donor transplantation. Analysis of patient-, disease-, and transplantation characteristics and acute and chronic graft-versus-host disease (GVHD) was performed to identify factors with adverse effects on LFS and OS. These data were used to develop risk scores for survival. We did not identify any prognostic factors beyond 4 years after transplantation for AML and beyond 3 years for ALL. Risk score for survival for AML includes age, disease status at transplantation, cytogenetic risk group, and chronic GVHD. For ALL, the risk score includes age at transplantation and chronic GVHD. The 10-year probabilities of OS for AML with good (score 0, 1, or 2), intermediate (score 3), and poor risk (score 4, 5, 6, or 7) were 94%, 87%, and 68%, respectively. The 10-year probabilities of OS for ALL were 89% and 80% for good (score 0 or 1) and poor risk (score 2), respectively. Identifying children at risk for late mortality with early intervention may mitigate some excess late mortality. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  19. Living with coeliac disease and a gluten-free diet: a Canadian perspective.

    PubMed

    Zarkadas, M; Dubois, S; MacIsaac, K; Cantin, I; Rashid, M; Roberts, K C; La Vieille, S; Godefroy, S; Pulido, O M

    2013-02-01

    Strict adherence to a gluten-free diet is the only treatment for coeliac disease. The gluten-free diet is complex, costly and impacts on all activities involving food, making it difficult to maintain for a lifetime. The purpose of this cross-sectional study was to evaluate the difficulties experienced, the strategies used and the emotional impact of following a gluten-free diet among Canadians with coeliac disease. A questionnaire was mailed to all members (n = 10 693) of both the Canadian Celiac Association and the Fondation québécoise de la maladie cœliaque in 2008. The overall response rate was 72%. Results are presented for the 5912 respondents (≥18 years) reporting biopsy-confirmed coeliac disease and/or dermatitis herpetiformis. Two-thirds never intentionally consumed gluten. Women reported significantly greater emotional responses to a gluten-free diet but, with time, were more accepting of it than men. Difficulties and negative emotions were experienced less frequently by those on the diet for >5 years, although food labelling and eating away from home remained very problematic. Frustration and isolation because of the diet were the most common negative emotions experienced. The present study quantifies the difficulties experienced, the strategies used and the emotional impact of following a gluten-free diet. It highlights the need to improve the training and education of dietitians, other health providers and the food service industry workers about coeliac disease and a gluten-free diet, with the aim of better helping individuals improve their adherence to a gluten-free diet and their quality of life. © 2012 Canadian Celiac Association and Food Directorate Health Canada Journal of Human Nutrition and Dietetics © 2012 The British Dietetic Association Ltd.

  20. Yonsei nomogram: A predictive model of new-onset chronic kidney disease after on-clamp partial nephrectomy in patients with T1 renal tumors.

    PubMed

    Abdel Raheem, Ali; Shin, Tae Young; Chang, Ki Don; Santok, Glen Denmer R; Alenzi, Mohamed Jayed; Yoon, Young Eun; Ham, Won Sik; Han, Woong Kyu; Choi, Young Deuk; Rha, Koon Ho

    2018-06-19

    To develop a predictive nomogram for chronic kidney disease-free survival probability in the long term after partial nephrectomy. A retrospective analysis was carried out of 698 patients with T1 renal tumors undergoing partial nephrectomy at a tertiary academic institution. A multivariable Cox regression analysis was carried out based on parameters proven to have an impact on postoperative renal function. Patients with incomplete data, <12 months follow up and preoperative chronic kidney disease stage III or greater were excluded. The study end-points were to identify independent risk factors for new-onset chronic kidney disease development, as well as to construct a predictive model for chronic kidney disease-free survival probability after partial nephrectomy. The median age was 52 years, median tumor size was 2.5 cm and mean warm ischemia time was 28 min. A total of 91 patients (13.1%) developed new-onset chronic kidney disease at a median follow up of 60 months. The chronic kidney disease-free survival rates at 1, 3, 5 and 10 year were 97.1%, 94.4%, 85.3% and 70.6%, respectively. On multivariable Cox regression analysis, age (1.041, P = 0.001), male sex (hazard ratio 1.653, P < 0.001), diabetes mellitus (hazard ratio 1.921, P = 0.046), tumor size (hazard ratio 1.331, P < 0.001) and preoperative estimated glomerular filtration rate (hazard ratio 0.937, P < 0.001) were independent predictors for new-onset chronic kidney disease. The C-index for chronic kidney disease-free survival was 0.853 (95% confidence interval 0.815-0.895). We developed a novel nomogram for predicting the 5-year chronic kidney disease-free survival probability after on-clamp partial nephrectomy. This model might have an important role in partial nephrectomy decision-making and follow-up plan after surgery. External validation of our nomogram in a larger cohort of patients should be considered. © 2018 The Japanese Urological Association.

  1. Oncogenic role of SIRT1 associated with tumor invasion, lymph node metastasis, and poor disease-free survival in triple negative breast cancer.

    PubMed

    Chung, Soo Young; Jung, Yoon Yang; Park, In Ae; Kim, Hyojin; Chung, Yul Ri; Kim, Ji Young; Park, Soo Young; Im, Seock-Ah; Lee, Kyung-Hun; Moon, Hyeong-Gon; Noh, Dong-Young; Han, Wonshik; Lee, Chul; Kim, Tae-Yong; Ryu, Han Suk

    2016-02-01

    The aim of this study is to evaluate the biological role and clinical implications of silent mating type information regulation 2 homolog 1 (SIRT1) as a novel candidate for target therapy in triple negative breast cancer (TNBC) for which there is no specific agent. 344 patients who received surgical resection for TNBC from January 2003 to December 2006 at Seoul National University Hospital were enrolled, and the role of SIRT1 protein was evaluated via immunohistochemistry on tissue samples. In vivo experiments to evaluate tumor invasiveness were carried out with three human TNBC cell lines following SIRT1-siRNA transfection. Expression of SIRT1 significantly correlated with lymph node metastasis (p = 0.008). In multivariate analysis, SIRT1 expression (p = 0.011), T stage (p = 0.014), and lymphatic invasion (p < 0.001) were revealed to be independent predictive factors for lymph node metastasis. Combination of these three parameters revealed predictive performance for lymph node metastasis with an area under the curve (AUC) of 0.689 on receiver operating characteristics (ROC) curves analysis. SIRT1 expression correlated with shorter disease-free survival (P = 0.003) but not with overall survival. Inhibition of SIRT1 with small interfering RNA (siRNA) conspicuously suppressed the invasiveness of TNBC cell lines. This study reveals the role of SIRT1 on tumor invasiveness and unfavorable clinical outcomes, and we suggest its potential role as a prognostic indicator as well as a novel therapeutic target in TNBC.

  2. Incidence, Risk Factors, and Analysis of Survival of Unexpected N2 Disease in Stage I Non-Small Cell Lung Cancer.

    PubMed

    Fiorelli, Alfonso; Sagan, Dariusz; Mackiewicz, Lukasz; Cagini, Lucio; Scarnecchia, Elisa; Chiodini, Paolo; Caronia, Francesco Paolo; Puma, Francesco; Santini, Mario; Ragusa, Mark

    2015-10-01

    To evaluate the incidence, predictors, and survival of unexpected pN2 disease in patients with clinical stage I non-small cell lung cancer. This is a retrospective observational multicenter study on all consecutive patients operated for clinical stage I non-small cell lung cancer from January 2006 to December 2012. Medical records were reviewed to investigate the incidence and risk factors for unexpected pN2 disease. Then, the survival of patients with unexpected pN2 disease was statistically compared with that of patients with clinical N2 disease operated after induction therapy in the same period. Our study population counted 901 patients. An incidence of 12% (108/901) unexpected pN2 disease was found. Among 3,389 lymph nodes sampled, 124 distinct metastases were found. Of the 108 patients, 92 (85%) had metastases in single N2 station and 16 (15%) patients had disease in multiple N2 stations; 47 (44%) had pN2 disease without pN1 involvement (skip metastases) and 61/108 (56%) had also pN1 metastases. Factors associated with unexpected pN2 disease were central tumor location (p < 0.003), cT2a (p < 0.0001) and pT2a stage (p < 0.0001), pN1 disease (p = 0.004), and a standard uptake value > 4.0 (0.007). Patients with pN2 disease compared with patients with cN2 disease presented a better median overall survival (56 versus 20 months; p = 0.001) and disease-free survival (46 versus 11 months; p < 0.0001). The preoperative effort to discover unexpected pN2 disease in patients with clinical stage I non-small cell lung cancer is not justified, considering their good survival. Thus, preoperative invasive mediastinal procedures in such cases are not indicated. Georg Thieme Verlag KG Stuttgart · New York.

  3. COX-2 Expression Correlates With Survival in Patients With Osteosarcoma Lung Metastases

    PubMed Central

    Rodriguez, Nidra I.; Hoots, William Keith; Koshkina, Nadezhda V.; Morales-Arias, Jaime A.; Arndt, Carola A.; Inwards, Carrie Y.; Hawkins, Douglas S.; Munsell, Mark F.; Kleinerman, Eugenie S.

    2009-01-01

    Summary The purpose of this study was to determine whether a correlation exists between tumor cyclooxygenase (COX)-2 expression and disease-specific survival in patients with osteosarcoma lung metastases. Thirty-six patients diagnosed with osteosarcoma lung metastases between the years 1990 and 2001 were included in this retrospective study. The majority of the patients (72%) presented newly -diagnosed osteosarcoma lung metastases whereas the remaining patients (28%) presented recurrent disease. Clinicopathologic parameters were obtained from patients’ clinical records. Tissue samples were obtained at the time of resection of the lung metastases and stained for COX-2 using immunohistochemistry. Samples were graded according to the intensity of COX-2 staining (grade 0: negative, grade 1: very weak, grade 2: weak, grade 3: moderate, and grade 4: strong). COX-2 staining was correlated with disease-specific survival and clinicopathologic parameters using the Jonckheere-Terpstra and the Kruskal-Wallis tests. All patients with grade 3 or 4 COX-2 expression died of osteosarcoma lung metastases. Ten percent of patients with grade 2 COX-2 expression and 29% of patients with grade 1 expression were alive and free of disease at the last follow-up. By contrast, 60% of the patients with grade 0 COX-2 expression were alive and free of disease at the last follow-up. No association between COX-2 expression and clinicopathologic parameters was found. However, COX-2 expression correlated inversely with disease-specific survival in patients with osteosarcoma lung metastases. Our data indicate that COX-2 expression in metastatic osteosarcoma may have prognostic significance. PMID:18797196

  4. Impaired intention-to-treat survival after listing for liver transplantation in children with biliary atresia compared to other chronic liver diseases: 20 years' experience from the Nordic countries.

    PubMed

    Malenicka, S; Ericzon, B-G; Jørgensen, M H; Isoniemi, H; Karlsen, T H; Krantz, M; Naeser, V; Olausson, M; Rasmussen, A; Rönnholm, K; Sanengen, T; Scholz, T; Fischler, B; Nemeth, A

    2017-03-01

    Biliary atresia (BA) is the most common indication for LT in children. We investigated whether this diagnosis per se, compared to other chronic liver diseases (OCLD), had an influence on patient survival. Data from 421 Scandinavian children, 194 with BA and 227 with OCLD, listed for LT between 1990 and 2010 were analyzed. The intention-to-treat survival and influencing risk factors were studied. Patients with BA had higher risk of death after listing than patients with OCLD. The youngest (<1 year) and smallest (<10 kg) children with the highest bilirubin (>510 μmol/L), highest INR (>1.6), and highest PELD score (>20) listed during 1990s had the worst outcome. Given the same PELD score, patients with BA had higher risk of death than patients with OCLD. For adolescents, low weight/BMI was the only prognostic marker. Impaired intention-to-treat survival in patients with BA was mainly explained by more advanced liver disease in younger ages and higher proportion of young children in the BA group rather than diagnosis per se. PELD score predicted death, but seemed to underestimate the severity of liver disease in patients with BA. Poor nutritional status and severe cholestasis had negative impact on survival, supporting the "sickest children first" allocation policy and correction of malnutrition before surgery. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Percutaneous radiofrequency ablation for early hepatocellular carcinoma: Risk factors for survival

    PubMed Central

    Kikuchi, Luciana; Menezes, Marcos; Chagas, Aline L; Tani, Claudia M; Alencar, Regiane SSM; Diniz, Marcio A; Alves, Venâncio AF; D’Albuquerque, Luiz Augusto Carneiro; Carrilho, Flair José

    2014-01-01

    AIM: To evaluate outcomes of radiofrequency ablation (RFA) therapy for early hepatocellular carcinoma (HCC) and identify survival- and recurrence-related factors. METHODS: Consecutive patients diagnosed with early HCC by computed tomography (CT) or magnetic resonance imaging (MRI) (single nodule of ≤ 5 cm, or multi- (up to 3) nodules of ≤ 3 cm each) and who underwent RFA treatment with curative intent between January 2010 and August 2011 at the Instituto do Câncer do Estado de São Paulo, Brazil were enrolled in the study. RFA of the liver tumors (with 1.0 cm ablative margin) was carried out under CT-fluoro scan and ultrasonic image guidance of the percutaneous ablation probes. Procedure-related complications were recorded. At 1-mo post-RFA and 3-mo intervals thereafter, CT and MRI were performed to assess outcomes of complete response (absence of enhancing tissue at the tumor site) or incomplete response (enhancing tissue remaining at the tumor site). Overall survival and disease-free survival rates were estimated by the Kaplan-Meier method and compared by the log rank test or simple Cox regression. The effect of risk factors on survival was assessed by the Cox proportional hazard model. RESULTS: A total of 38 RFA sessions were performed during the study period on 34 patients (age in years: mean, 63 and range, 49-84). The mean follow-up time was 22 mo (range, 1-33). The study population showed predominance of male sex (76%), less severe liver disease (Child-Pugh A, n = 26; Child-Pugh B, n = 8), and single tumor (65%). The maximum tumor diameters ranged from 10 to 50 mm (median, 26 mm). The initial (immediately post-procedure) rate of RFA-induced complete tumor necrosis was 90%. The probability of achieving complete response was significantly greater in patients with a single nodule (vs patients with multi-nodules, P = 0.04). Two patients experienced major complications, including acute pulmonary edema (resolved with intervention) and intestinal perforation

  6. 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.

  7. Usefulness of peak exercise oxygen consumption and the heart failure survival score to predict survival in patients >65 years of age with heart failure.

    PubMed

    Parikh, Mona N; Lund, Lars H; Goda, Ayumi; Mancini, Donna

    2009-04-01

    Peak exercise oxygen consumption (Vo(2)) and the Heart Failure (HF) Survival Score (HFSS) were developed in middle-aged patient cohorts referred for heart transplantation with HF. The prognostic value of Vo(2) in patients >65 years has not been well studied. Accordingly, the prognostic value of peak Vo(2) was evaluated in these patients with HF. A retrospective analysis of 396 patients with HF >65 years with cardiopulmonary exercise testing was performed. Peak Vo(2) and components of the HFSS (presence of coronary artery disease, left ventricular ejection fraction, heart rate, mean arterial blood pressure, presence of intraventricular conduction defects, and serum sodium) were collected. Follow-up averaged 1,038 +/- 983 days. Outcome events were defined as death, implantation of a left ventricular assist device, or urgent transplantation. Patients were divided into risk strata for peak Vo(2) and HFSS based on previous cut-off points. Survival curves were derived using Kaplan-Meier analysis and compared using log-rank analysis. Survival differed markedly by Vo(2) stratum (p <0.0001), with significantly better survival rates for the low- (>14 ml/kg/min) versus medium- (10 to 14 ml/kg/min), low- versus high- (<10 ml/kg/min), and medium- versus high-risk strata (all p <0.05). Survival also differed markedly by HFSS stratum (p <0.0001), with significantly better survival rates for the low- (> or =8.10) versus medium- (7.20 to 8.09), low- versus high- (< or =7.19), and medium- versus high-risk strata (all p <0.0001). In conclusion, peak Vo(2) and the HFSS were both excellent parameters to predict survival in patients >65 years with HF.

  8. 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.

  9. A multicenter study on Leigh syndrome: disease course and predictors of survival

    PubMed Central

    2014-01-01

    Background Leigh syndrome is a progressive neurodegenerative disorder, associated with primary or secondary dysfunction of the mitochondrial oxidative phosphorylation. Despite the fact that Leigh syndrome is the most common phenotype of mitochondrial disorders in children, longitudinal natural history data is missing. This study was undertaken to assess the phenotypic and genotypic spectrum of patients with Leigh syndrome, characterise the clinical course and identify predictors of survival in a large cohort of patients. Methods This is a retrospective study of patients with Leigh syndrome that have been followed at eight centers specialising in mitochondrial diseases in Europe; Gothenburg, Rotterdam, Helsinki, Copenhagen, Stockholm, Brussels, Bergen and Oulu. Results A total of 130 patients were included (78 males; 52 females), of whom 77 patients had identified pathogenic mutations. The median age of disease onset was 7 months, with 80.8% of patients presenting by the age of 2 years. The most common clinical features were abnormal motor findings, followed by abnormal ocular findings. Epileptic seizures were reported in 40% of patients. Approximately 44% of patients experienced acute exacerbations requiring hospitalisation during the previous year, mainly due to infections. The presence of pathological signs at birth and a history of epileptic seizures were associated with higher occurrence of acute exacerbations and/or relapses. Increased lactate in the cerebrospinal fluid was significantly correlated to a more severe disease course, characterised by early onset before 6 months of age, acute exacerbations and/or relapses, as well as brainstem involvement. 39% of patients had died by the age of 21 years, at a median age of 2.4 years. Disease onset before 6 months of age, failure to thrive, brainstem lesions on neuroimaging and intensive care treatment were significantly associated with poorer survival. Conclusions This is a multicenter study performed in a

  10. A multicenter study on Leigh syndrome: disease course and predictors of survival.

    PubMed

    Sofou, Kalliopi; De Coo, Irenaeus F M; Isohanni, Pirjo; Ostergaard, Elsebet; Naess, Karin; De Meirleir, Linda; Tzoulis, Charalampos; Uusimaa, Johanna; De Angst, Isabell B; Lönnqvist, Tuula; Pihko, Helena; Mankinen, Katariina; Bindoff, Laurence A; Tulinius, Már; Darin, Niklas

    2014-04-15

    Leigh syndrome is a progressive neurodegenerative disorder, associated with primary or secondary dysfunction of the mitochondrial oxidative phosphorylation. Despite the fact that Leigh syndrome is the most common phenotype of mitochondrial disorders in children, longitudinal natural history data is missing. This study was undertaken to assess the phenotypic and genotypic spectrum of patients with Leigh syndrome, characterise the clinical course and identify predictors of survival in a large cohort of patients. This is a retrospective study of patients with Leigh syndrome that have been followed at eight centers specialising in mitochondrial diseases in Europe; Gothenburg, Rotterdam, Helsinki, Copenhagen, Stockholm, Brussels, Bergen and Oulu. A total of 130 patients were included (78 males; 52 females), of whom 77 patients had identified pathogenic mutations. The median age of disease onset was 7 months, with 80.8% of patients presenting by the age of 2 years. The most common clinical features were abnormal motor findings, followed by abnormal ocular findings. Epileptic seizures were reported in 40% of patients. Approximately 44% of patients experienced acute exacerbations requiring hospitalisation during the previous year, mainly due to infections. The presence of pathological signs at birth and a history of epileptic seizures were associated with higher occurrence of acute exacerbations and/or relapses. Increased lactate in the cerebrospinal fluid was significantly correlated to a more severe disease course, characterised by early onset before 6 months of age, acute exacerbations and/or relapses, as well as brainstem involvement. 39% of patients had died by the age of 21 years, at a median age of 2.4 years. Disease onset before 6 months of age, failure to thrive, brainstem lesions on neuroimaging and intensive care treatment were significantly associated with poorer survival. This is a multicenter study performed in a large cohort of patients with Leigh syndrome

  11. Preliminary study of tumor heterogeneity in imaging predicts two year survival in pancreatic cancer patients.

    PubMed

    Chakraborty, Jayasree; Langdon-Embry, Liana; Cunanan, Kristen M; Escalon, Joanna G; Allen, Peter J; Lowery, Maeve A; O'Reilly, Eileen M; Gönen, Mithat; Do, Richard G; Simpson, Amber L

    2017-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers in the United States with a five-year survival rate of 7.2% for all stages. Although surgical resection is the only curative treatment, currently we are unable to differentiate between resectable patients with occult metastatic disease from those with potentially curable disease. Identification of patients with poor prognosis via early classification would help in initial management including the use of neoadjuvant chemotherapy or radiation, or in the choice of postoperative adjuvant therapy. PDAC ranges in appearance from homogeneously isoattenuating masses to heterogeneously hypovascular tumors on CT images; hence, we hypothesize that heterogeneity reflects underlying differences at the histologic or genetic level and will therefore correlate with patient outcome. We quantify heterogeneity of PDAC with texture analysis to predict 2-year survival. Using fuzzy minimum-redundancy maximum-relevance feature selection and a naive Bayes classifier, the proposed features achieve an area under receiver operating characteristic curve (AUC) of 0.90 and accuracy (Ac) of 82.86% with the leave-one-image-out technique and an AUC of 0.80 and Ac of 75.0% with three-fold cross-validation. We conclude that texture analysis can be used to quantify heterogeneity in CT images to accurately predict 2-year survival in patients with pancreatic cancer. From these data, we infer differences in the biological evolution of pancreatic cancer subtypes measurable in imaging and identify opportunities for optimized patient selection for therapy.

  12. CREATION OF A MODEL TO PREDICT SURVIVAL IN PATIENTS WITH REFRACTORY COELIAC DISEASE USING A MULTINATIONAL REGISTRY

    PubMed Central

    Rubio-Tapia, Alberto; Malamut, Georgia; Verbeek, Wieke H.M.; van Wanrooij, Roy L.J.; Leffler, Daniel A.; Niveloni, Sonia I.; Arguelles-Grande, Carolina; Lahr, Brian D.; Zinsmeister, Alan R.; Murray, Joseph A.; Kelly, Ciaran P.; Bai, Julio C.; Green, Peter H.; Daum, Severin; Mulder, Chris J.J.; Cellier, Christophe

    2016-01-01

    Background Refractory coeliac disease is a severe complication of coeliac disease with heterogeneous outcome. Aim To create a prognostic model to estimate survival of patients with refractory coeliac disease. Methods We evaluated predictors of 5-year mortality using Cox proportional hazards regression on subjects from a multinational registry. Bootstrap re-sampling was used to internally validate the individual factors and overall model performance. The mean of the estimated regression coefficients from 400 bootstrap models was used to derive a risk score for 5-year mortality. Results The multinational cohort was composed of 232 patients diagnosed with refractory coeliac disease across 7 centers (range of 11–63 cases per center). The median age was 53 years and 150 (64%) were women. A total of 51 subjects died during 5-year follow-up (cumulative 5-year all-cause mortality = 30%). From a multiple variable Cox proportional hazards model, the following variables were significantly associated with 5-year mortality: age at refractory coeliac disease diagnosis (per 20 year increase, hazard ratio = 2.21; 95% confidence interval: 1.38, 3.55), abnormal intraepithelial lymphocytes (hazard ratio = 2.85; 95% confidence interval: 1.22, 6.62), and albumin (per 0.5 unit increase, hazard ratio = 0.72; 95% confidence interval: 0.61, 0.85). A simple weighted 3-factor risk score was created to estimate 5-year survival. Conclusions Using data from a multinational registry and previously-reported risk factors, we create a prognostic model to predict 5-year mortality among patients with refractory coeliac disease. This new model may help clinicians to guide treatment and follow-up. PMID:27485029

  13. Creation of a model to predict survival in patients with refractory coeliac disease using a multinational registry.

    PubMed

    Rubio-Tapia, A; Malamut, G; Verbeek, W H M; van Wanrooij, R L J; Leffler, D A; Niveloni, S I; Arguelles-Grande, C; Lahr, B D; Zinsmeister, A R; Murray, J A; Kelly, C P; Bai, J C; Green, P H; Daum, S; Mulder, C J J; Cellier, C

    2016-10-01

    Refractory coeliac disease is a severe complication of coeliac disease with heterogeneous outcome. To create a prognostic model to estimate survival of patients with refractory coeliac disease. We evaluated predictors of 5-year mortality using Cox proportional hazards regression on subjects from a multinational registry. Bootstrap resampling was used to internally validate the individual factors and overall model performance. The mean of the estimated regression coefficients from 400 bootstrap models was used to derive a risk score for 5-year mortality. The multinational cohort was composed of 232 patients diagnosed with refractory coeliac disease across seven centres (range of 11-63 cases per centre). The median age was 53 years and 150 (64%) were women. A total of 51 subjects died during a 5-year follow-up (cumulative 5-year all-cause mortality = 30%). From a multiple variable Cox proportional hazards model, the following variables were significantly associated with 5-year mortality: age at refractory coeliac disease diagnosis (per 20 year increase, hazard ratio = 2.21; 95% confidence interval, CI: 1.38-3.55), abnormal intraepithelial lymphocytes (hazard ratio = 2.85; 95% CI: 1.22-6.62), and albumin (per 0.5 unit increase, hazard ratio = 0.72; 95% CI: 0.61-0.85). A simple weighted three-factor risk score was created to estimate 5-year survival. Using data from a multinational registry and previously reported risk factors, we create a prognostic model to predict 5-year mortality among patients with refractory coeliac disease. This new model may help clinicians to guide treatment and follow-up. © 2016 John Wiley & Sons Ltd.

  14. Factors governing long-term adherence to a gluten-free diet in adult patients with coeliac disease.

    PubMed

    Villafuerte-Galvez, J; Vanga, R R; Dennis, M; Hansen, J; Leffler, D A; Kelly, C P; Mukherjee, R

    2015-09-01

    A strict gluten-free diet is the cornerstone of treatment for coeliac disease. Studies of gluten-free diet adherence have rarely used validated instruments. There is a paucity of data on long-term adherence to the gluten-free diet in the adult population. To determine the long-term adherence to the gluten-free diet and potential associated factors in a large coeliac disease referral centre population. We performed a mailed survey of adults with clinically, serologically and histologically confirmed coeliac disease diagnosed ≥5 years prior to survey. The previously validated Celiac Disease Adherence Test was used to determine adherence. Demographic, socio-economic and potentially associated factors were analysed with adherence as the outcome. The response rate was 50.1% of 709 surveyed, the mean time on a gluten-free diet 9.9 ± 6.4 years. Adequate adherence (celiac disease adherence test score <13) was found in 75.5% of respondents. A higher level of education was associated with adequate adherence (P = 0.002) even after controlling for household income (P = 0.0220). Perceptions of cost, effectiveness of the gluten-free diet, knowledge of the gluten-free diet and self-effectiveness at following the gluten-free diet correlated with adherence scores (P < 0.001). Long-term adherence to a gluten-free diet was adequate in >75% of respondents. Perceived cost remains a barrier to adherence. Perceptions of effectiveness of gluten-free diet as well as its knowledge, are potential areas for intervention. © 2015 John Wiley & Sons Ltd.

  15. Clinical features and symptom recovery on a gluten-free diet in Canadian adults with celiac disease.

    PubMed

    Pulido, Olga; Zarkadas, Marion; Dubois, Sheila; Macisaac, Krista; Cantin, Isabelle; La Vieille, Sebastien; Godefroy, Samuel; Rashid, Mohsin

    2013-08-01

    Celiac disease can present with mild or nongastrointestinal symptoms, and may escape timely recognition. The treatment of celiac disease involves a gluten-free diet, which is complex and challenging. To evaluate clinical features and symptom recovery on a gluten-free diet in a Canadian adult celiac population. All adult members (n=10,693) of the two national celiac support organizations, the Canadian Celiac Association and Fondation québécoise de la maladie coeliaque, were surveyed using a questionnaire. A total of 5912 individuals (≥18 years of age) with biopsy-confirmed celiac disease and⁄or dermatitis herpetiformis completed the survey. The female to male ratio was 3:1, and mean (± SD) age at diagnosis was 45.2 ± 16.4 years. Mean time to diagnosis after onset of symptoms was 12.0 ± 14.4 years. Abdominal pain and bloating (84.9%), extreme weakness⁄tiredness (74.2%), diarrhea (71.7%) and anemia (67.8%) were the most commonly reported symptoms at the time of diagnosis. Many respondents continued to experience symptoms after being on a gluten-free diet for >5 years. Sex differences were reported in clinical features before diagnosis, recovery after being on gluten-free diet and perceived quality of life, with women experiencing more difficulties than men. Delays in diagnosis of celiac disease in Canada remain unacceptably long despite wider availability of serological screening tests. Many patients report continuing symptoms despite adhering to a gluten-free diet for >5 years, with women experiencing more symptoms and a lower recovery rate than men. Awareness of celiac disease needs improvement, and follow-up with a physician and a dietitian is essential for all patients with celiac disease.

  16. Clinical features and symptom recovery on a gluten-free diet in Canadian adults with celiac disease

    PubMed Central

    Pulido, Olga; Zarkadas, Marion; Dubois, Sheila; MacIsaac, Krista; Cantin, Isabelle; La Vieille, Sébastien; Godefroy, Samuel; Rashid, Mohsin

    2013-01-01

    BACKGROUND: Celiac disease can present with mild or nongastrointestinal symptoms, and may escape timely recognition. The treatment of celiac disease involves a gluten-free diet, which is complex and challenging. OBJECTIVE: To evaluate clinical features and symptom recovery on a gluten-free diet in a Canadian adult celiac population. METHODS: All adult members (n=10,693) of the two national celiac support organizations, the Canadian Celiac Association and Fondation québécoise de la maladie coeliaque, were surveyed using a questionnaire. RESULTS: A total of 5912 individuals (≥18 years of age) with biopsy-confirmed celiac disease and/or dermatitis herpetiformis completed the survey. The female to male ratio was 3:1, and mean (± SD) age at diagnosis was 45.2±16.4 years. Mean time to diagnosis after onset of symptoms was 12.0±14.4 years. Abdominal pain and bloating (84.9%), extreme weakness/tiredness (74.2%), diarrhea (71.7%) and anemia (67.8%) were the most commonly reported symptoms at the time of diagnosis. Many respondents continued to experience symptoms after being on a gluten-free diet for >5 years. Sex differences were reported in clinical features before diagnosis, recovery after being on gluten-free diet and perceived quality of life, with women experiencing more difficulties than men. CONCLUSIONS: Delays in diagnosis of celiac disease in Canada remain unacceptably long despite wider availability of serological screening tests. Many patients report continuing symptoms despite adhering to a gluten-free diet for >5 years, with women experiencing more symptoms and a lower recovery rate than men. Awareness of celiac disease needs improvement, and follow-up with a physician and a dietitian is essential for all patients with celiac disease. PMID:23936873

  17. Survival in Response to Multimodal Therapy in Anaplastic Thyroid Cancer.

    PubMed

    Prasongsook, Naiyarat; Kumar, Aditi; Chintakuntlawar, Ashish V; Foote, Robert L; Kasperbauer, Jan; Molina, Julian; Garces, Yolanda; Ma, Daniel; Wittich, Michelle A Neben; Rubin, Joseph; Richardson, Ronald; Morris, John; Hay, Ian; Fatourechi, Vahab; McIver, Bryan; Ryder, Mabel; Thompson, Geoffrey; Grant, Clive; Richards, Melanie; Sebo, Thomas J; Rivera, Michael; Suman, Vera; Jenkins, Sarah M; Smallridge, Robert C; Bible, Keith C

    2017-12-01

    Historical outcomes in anaplastic thyroid cancer (ATC) have been dismal. To determine whether an initial intensive multimodal therapy (MMT) is associated with improved ATC survival. MMT was offered to all patients with newly diagnosed ATC treated at the Mayo Clinic from 2003 through 2015; MMT vs care with palliative intent (PI) was individualized considering clinical status and patient preferences. Outcomes were retrospectively analyzed by American Joint Committee on Cancer stage and treatments compared with patient cohort data from 1949 through 1999. Forty-eight patients (60% male; median age, 62 years); 18 treated with PI, 30 with MMT. Overall survival (OS) and progression-free survival determined by Kaplan-Meier method. Median OS and 1-year survival for the later cohort were 9 months [95% confidence interval (CI), 4 to 22 months] and 42% (95% CI, 28% to 56%) vs 3 months and 10% for the earlier cohort. Median OS was 21 months compared with 3.9 months in the pooled MMT vs PI groups for the later cohort [hazard ratio (HR), 0.32; P = 0.0006]. Among only patients in the later cohort who had stage IVB disease, median OS was 22.4 vs 4 months (HR, 0.12; 95% CI, 0.03 to 0.44; P = 0.0001), with 68% vs 0% alive at 1 year (MMT vs PI). Among patients with stage IVC cancer, OS did not differ by therapy. MMT appears to convey longer survival in ATC among patients with stage IVA/B disease. Copyright © 2017 Endocrine Society

  18. Long-term disease-free survivors with cytogenetically normal acute myeloid leukemia and MLL partial tandem duplication: a Cancer and Leukemia Group B study

    PubMed Central

    Ruppert, Amy S.; Marcucci, Guido; Mrózek, Krzysztof; Paschka, Peter; Langer, Christian; Baldus, Claudia D.; Wen, Jing; Vukosavljevic, Tamara; Powell, Bayard L.; Carroll, Andrew J.; Kolitz, Jonathan E.; Larson, Richard A.; Caligiuri, Michael A.; Bloomfield, Clara D.

    2007-01-01

    The clinical impact of MLL partial tandem duplication (MLL-PTD) was evaluated in 238 adults aged 18 to 59 years with cytogenetically normal (CN) de novo acute myeloid leukemia (AML) who were treated intensively on similar Cancer and Leukemia Group B protocols 9621 and 19808. Twenty-four (10.1%) patients harbored an MLL-PTD. Of those, 92% achieved complete remission (CR) compared with 83% of patients without MLL-PTD (P = .39). Neither overall survival nor disease-free survival significantly differed between the 2 groups (P = .67 and P = .55, respectively). Thirteen MLL-PTD+ patients relapsed within 1.4 years of achieving CR. MLL-PTD+ patients who relapsed more often had other adverse CN-AML–associated molecular markers. In contrast with previously reported studies, 9 (41%) MLL-PTD+ patients continue in long-term first remission (CR1; range, 2.5-7.7 years). Intensive consolidation therapy that included autologous peripheral stem-cell transplantation during CR1 may have contributed to the better outcome of this historically poor-prognosis group of CN-AML patients with MLL-PTD. PMID:17341662

  19. Associations of centrally acting ACE inhibitors with cognitive decline and survival in Alzheimer's disease.

    PubMed

    Fazal, Karim; Perera, Gayan; Khondoker, Mizanur; Howard, Robert; Stewart, Robert

    2017-07-01

    Cognitive improvement has been reported in patients receiving centrally acting angiotensin-converting enzyme inhibitors (C-ACEIs). To compare cognitive decline and survival after diagnosis of Alzheimer's disease between people receiving C-ACEIs, non-centrally acting angiotensin-converting enzyme inhibitors (NC-ACEIs), and neither. Routine Mini-Mental State Examination (MMSE) scores were extracted in 5260 patients receiving acetylcholinesterase inhibitors and analysed against C-/NC-ACEI exposure at the time of Alzheimer's disease diagnosis. In the 9 months after Alzheimer's disease diagnosis, MMSE scores significantly increased by 0.72 and 0.19 points per year in patients on C-ACEIs and neither respectively, but deteriorated by 0.61 points per year in those on NC-ACEIs. There were no significant group differences in score trajectories from 9 to 36 months and no differences in survival. In people with Alzheimer's disease receiving acetylcholinesterase inhibitors, those also taking C-ACEIs had stronger initial improvement in cognitive function, but there was no evidence of longer-lasting influence on dementia progression. R.S. has received research funding from Pfizer, Lundbeck, Roche, Janssen and GlaxoSmithKline. © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

  20. Symptoms of Functional Intestinal Disorders Are Common in Patients with Celiac Disease Following Transition to a Gluten-Free Diet.

    PubMed

    Silvester, Jocelyn A; Graff, Lesley A; Rigaux, Lisa; Bernstein, Charles N; Leffler, Daniel A; Kelly, Ciarán P; Walker, John R; Duerksen, Donald R

    2017-09-01

    Celiac disease and functional intestinal disorders may overlap, yet the natural history of functional symptoms in patients with celiac disease is unknown. To investigate the prevalence of irritable bowel syndrome (IBS), functional dyspepsia (FD), and functional bloating (FB) symptoms among patients with celiac disease at diagnosis and during the first year of a gluten-free diet. Adults with a new diagnosis of celiac disease were surveyed at baseline, 6 months and 1 year using standardized measures for intestinal symptoms [Rome III diagnostic questionnaire and celiac symptom index (CSI)] and gluten-free diet adherence [gluten-free eating assessment tool (GF-EAT) and celiac diet adherence test]. At diagnosis, two-thirds fulfilled Rome III diagnostic questionnaire symptom criteria for IBS (52%), functional dyspepsia (27%), and/or functional bloating (9%). One year post-diagnosis, there was high adherence to a gluten-free diet as 93% reported gluten exposure less than once per month on the GF-EAT and only 8% had ongoing celiac disease symptoms (CSI score >45). The rates of those meeting IBS (22%) and functional dyspepsia (8%) symptom criteria both decreased significantly on a gluten-free diet. The prevalence of functional symptoms (any of IBS, FD or FB) at 1 year was 47%. Long-term follow-up of patients with celiac disease is necessary because many patients with celiac disease who are adherent to a gluten-free diet have persistent gastrointestinal symptoms.

  1. Survival and mortality among users and non-users of hydroxyurea with sickle cell disease

    PubMed Central

    de Araujo, Olinda Maria Rodrigues; Ivo, Maria Lúcia; Ferreira, Marcos Antonio; Pontes, Elenir Rose Jardim Cury; Bispo, Ieda Maria Gonçalves Pacce; de Oliveira, Eveny Cristine Luna

    2015-01-01

    OBJECTIVE: to estimate survival, mortality and cause of death among users or not of hydroxyurea with sickle cell disease. METHOD: cohort study with retrospective data collection, from 1980 to 2010 of patients receiving inpatient treatment in two Brazilian public hospitals. The survival probability was determined using the Kaplan-Meier estimator, survival calculations (SPSS version 10.0), comparison between survival curves, using the log rank method. The level of significance was p=0.05. RESULTS: of 63 patients, 87% had sickle cell anemia, with 39 using hydroxyurea, with a mean time of use of the drug of 20.0±10.0 years and a mean dose of 17.37±5.4 to 20.94±7.2 mg/kg/day, raising the fetal hemoglobin. In the comparison between those using hydroxyurea and those not, the survival curve was greater among the users (p=0.014). A total of 10 deaths occurred, with a mean age of 28.1 years old, and with Acute Respiratory Failure as the main cause. CONCLUSION: the survival curve is greater among the users of hydroxyurea. The results indicate the importance of the nurse incorporating therapeutic advances of hydroxyurea in her care actions. PMID:25806633

  2. Survival of aggressive variants of papillary thyroid carcinoma in patients under 55 years old: a SEER population-based retrospective analysis.

    PubMed

    Feng, Jianhua; Shen, Fei; Cai, Wensong; Gan, Xiaoxiong; Deng, Xingyan; Xu, Bo

    2018-06-16

    Patients younger than 55 years of age with papillary thyroid carcinoma (PTC) have excellent survival. Diffuse sclerosing variant (DSV) and tall cell variant (TCV) of PTC are associated with aggressiveness; the survival of patients <55 years of age with these variants is still unclear. We aim to investigate the clinicopathological features and survival of these variants in the age group <55 years. All adult patients (<55 years old) with DSV, TCV and conventional PTC (CPTC) came from the Surveillance, Epidemiology, and End Results program (1988-2013). Kaplan-Meier method and log-rank test were used to analyze the survival. Prognostic factors associated with survival were analyzed by Cox multivariate regression. There were 280 DSV, 615 TCV, and 56287 CPTC in the age group <55 years. DSV and TCV were associated with multifocality, extrathyroidal extension, lymph node and distant metastasis (all p < 0.05). The 10-year disease-specific survival (DSS) of TCV was worse than CPTC (96.3 vs. 99.4%, p < 0.01), but there was no significant difference between DSV and CPTC (99.5 vs. 99.4%, p > 0.05). Cox multivariate regression showed TCV was the independent predictor of DSS (HR: 5.39, p < 0.01). In the age group <55 years, DSV and TCV are more likely to exhibit aggressive characteristics than CPTC. Patient <55 years of age with DSV have excellent survival likewise, while patients <55 years of age with TCV carry worse survival. Further investigation for the recurrence risk of patients <55 years with these variants would contribute to optimal clinical management making.

  3. Unusual Onset of Celiac Disease and Addison's Disease in a 12-Year-Old Boy.

    PubMed

    Miconi, Francesco; Savarese, Emanuela; Miconi, Giovanni; Cabiati, Gabriele; Rapaccini, Valentina; Principi, Nicola; Esposito, Susanna

    2017-07-29

    Celiac disease (CD) is an autoimmune disorder deriving from an aberrant adaptive immune response against gluten-containing grains in genetically predisposed subjects. In a number of patients, CD is associated with one or more other autoimmune diseases. Primary Addison's disease (AD) and CD may co-exist, although this association is relatively uncommon in children. In addition, it is not precisely defined whether a gluten-free diet influences the course of AD. A case of CD in a 12-year-old boy presenting as acute adrenal insufficiency is described here. A gluten-free diet had a significant therapeutic role in this case, wherein most of the clinical signs and symptoms of AD disappeared in a few days. In addition, the dosage of cortisol acetate, initially administered to treat the AD, was able to be rapidly reduced. This case highlights that CD can be associated with AD in children, and a gluten-free diet seems to positively influence the course of AD.

  4. Human papilloma virus and survival of oropharyngeal cancer patients treated with surgery and adjuvant radiotherapy.

    PubMed

    Broglie, Martina A; Soltermann, Alex; Haile, Sarah R; Huber, Gerhard F; Stoeckli, Sandro J

    2015-07-01

    Impact of p16 protein, a surrogate marker for human papilloma virus induced cancer, p53 and EGFR as well as clinical factors on survival in a patient cohort with oropharyngeal squamous cell carcinoma (OPSCC) treated by surgical resection and adjuvant radiotherapy (RT) ± concomitant chemotherapy (CT). This is a retrospective analysis of patient's charts and tumor tissue. 57 patients were consecutively included and their tumor tissue assembled on a tissue microarray following immunohistochemical analysis. Survival times were estimated by means of Kaplan-Meier analysis. The importance of clinical and immunohistochemical factors for outcome was estimated by cox proportional hazard models. With 88% 5-year overall survival, 91% 5-year disease-specific survival and 91% 5-year disease-free survival, respectively, we found excellent survival rates in this surgically treated patient cohort of mainly advanced OPSCC (93% AJCC stage III or IV). The only factors positively influencing survival were p16 overexpression as well as p53 negativity and even more pronounced the combination of those biomarkers. Survival analysis of patients classified into three risk categories according to an algorithm based on p16, smoking, T- and N-category revealed a low, intermediate and high-risk group with significant survival differences between the low and the high-risk group. Patients with OPSCC can be successfully treated by surgery and adjuvant RT ± CT with a clear survival benefit of p16 positive, p53 negative patients. We recommend considering a combination of immunohistochemical (p16, p53) and clinical factors (smoking, T- and N-category) for risk stratification.

  5. Causal Model of Survival After Pulmonary Metastasectomy of Colorectal Cancer: A Nationwide Prospective Registry.

    PubMed

    Embun, Raul; Rivas de Andrés, Juan J; Call, Sergi; de Olaiz Navarro, Beatriz; Freixinet, Jorge L; Bolufer, Sergio; Jarabo, Jose R; Pajuelo, Nuria; Molins, Laureano

    2016-05-01

    Although numerous existing studies have analyzed the prognostic factors of patients who have had surgical intervention for lung metastases of colorectal carcinoma (CRC), many of the results obtained until now have been contradictory. As a consequence, there is no established consensus about which group of prognostic factors could have a greater value when considered together. This was a multicenter prospective cohort study that included all patients who underwent a first pulmonary metastasectomy of CRC, with radical intent, during a 2-year period (March 2008 to February 2010). The follow-up continued until March 2013, and an analysis of disease-specific survival (DSS), determined from the first pulmonary metastasectomy, was implemented. The selection of the best submodel was taken based on their coefficient of determination (R(2)) and how parsimonious they were depending on the number of variables included. The series, consisting of 522 patients, presented the following survival rates: median, 54.9 months; 3-year DSS, 69.4% (95% confidence interval [CI], 65% to 73.8%); and 5-year DSS, 46.1% (95% CI, 38.5% to 53.7%). The resulting survival model consisted of disease-free interval of 12 months or less (hazard ratio [HR], 1.76; 95% CI, 1.21 to 2.54; p = 0.003), carcinoembryonic antigen level exceeding 5 ng/mL (HR, 1.50; 95% CI, 1.04 to 2.17; p = 0.028), bilateral lung disease (HR, 1.81; 95% CI, 1.20 to 2.75; p = 0.005), and thoracic lymph node involvement (HR, 2.71; 95% CI, 1.44 to 5.12; p = 0.002). According to these results from the Spanish Group of Lung Metastases of Colo-Rectal Cancer, the combination of these four variables-disease-free interval, carcinoembryonic antigen level, laterality, and thoracic lymph node involvement-constitutes the first-choice survival causal model based on the clinical and pathologic factors most frequently referenced in literature. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  6. Incidence, survival and cause-specific mortality in alcoholic liver disease: a population-based cohort study.

    PubMed

    Sahlman, Perttu; Nissinen, Markku; Pukkala, Eero; Färkkilä, Martti

    2016-08-01

    We studied the incidence of severe ALD requiring hospitalization in Finland, and survival and causes of death among the ALD patients. A cohort of 11,873 persons (8796 men and 3077 women) with diagnosis of ALD during the years 1996-2012 was identified from Finnish national Inpatient Register. The annual incidence of alcoholic hepatitis (AH) and alcoholic liver cirrhosis was calculated. The cohort was combined with the data from national Cause of Death Register of Statistics Finland. The incidence of alcoholic liver cirrhosis increased from 8.8/100,000 in year 2001 to 14.6/100,000 in year 2012 among men and from 2.4 to 4.2/100,000 among women. The incidence of AH increased from 3.7 to 6.5/100,000 among men and from 1.3 to 2.7/100,000 among women. The relative 5-year survival ratios of patients with alcoholic liver cirrhosis and AH were 29 and 50% among men and 38 and 52% among women, respectively. Out of 8440 deaths, 65% were due to alcoholic-related causes. The risk of death among ALD patients was increased in malignancies (SMR 6.82; 95% CI: 6.35-7.29), cardiovascular diseases (6.13; 5.74-6.52), respiratory diseases (7.86; 6.70-9.10), dementia (3.31; 2.41-4.44) and accidents and violence (11.12; 10.13-12.15). The incidence of AH and alcoholic liver cirrhosis is increasing. The survival is poor. Most deaths are alcohol-related and other common causes of excess deaths are cancers especially in the upper aerodigestive tract and cardiovascular, digestive and respiratory diseases as well as violence and accidents.

  7. Survival of Mexican Children with Acute Myeloid Leukaemia Who Received Early Intensification Chemotherapy and an Autologous Transplant

    PubMed Central

    Jiménez-Hernández, Elva; Dueñas-González, María Teresa; Arellano-Galindo, José; Medrano-Ortíz-De-Zárate, María Elena; Bekker-Méndez, Vilma Carolina; Berges-García, Adolfina; Solís-Labastida, Karina; Sánchez-Jara, Berenice; Tiznado-García, Héctor Manuel; Jaimes-Reyes, Ethel Zulie; García-Jiménez, Xochiketzalli; Espinoza-Hernández, Laura; Núñez-Villegas, Nora Nancy; Franco-Ornelas, Sergio; Pérez-Casillas, Ruy Xavier; Martínez Villegas, Octavio; Palomares, Teresa Marin; Mejía-Aranguré, Juan Manuel

    2015-01-01

    Background. In Mexico and other developing countries, few reports of the survival of children with acute leukaemia exist. Objective. We aimed at comparing the disease-free survival of children with acute myeloid leukaemia who, in addition to being treated with the Latin American protocol of chemotherapy and an autologous transplant, either underwent early intensified chemotherapy or did not undergo such treatment. Procedure. This was a cohort study with a historical control group, forty patients, less than 16 years old. Group A (20 patients), diagnosed in the period 2005–2007, was treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy: high doses of cytarabine and mitoxantrone. Group B (20 patients), diagnosed in the period 1999–2004, was treated as Group A, but without the early intensified chemotherapy. Results. Relapse-free survival for Group A was 90% whereas that for Group B it was 60% (P = 0.041). Overall survival for Group A (18, 90%) was higher than that for Group B (60%). Complete remission continued for two years of follow-up. Conclusions. Relapse-free survival for paediatric patients treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy was higher than that for those who did not receive early intensified chemotherapy. PMID:25821830

  8. Interferon-Free Therapy in Elderly Patients With Advanced Liver Disease.

    PubMed

    Lens, Sabela; Fernández, Inmaculada; Rodríguez-Tajes, Sergio; Hontangas, Vanessa; Vergara, Mercedes; Forné, Montserrat; Calleja, Jose Luis; Diago, Moisés; Llaneras, Jordi; Llerena, Susana; Torras, Xavier; Sacristán, Begoña; Roget, Merce; Fernández-Rodríguez, Conrado Manuel; Navascués, Mari Carmen; Fuentes, Javier; Sánchez-Ruano, Juan-José; Simón, Miguel-Ángel; Sáez-Royuela, Federico; Baliellas, Carmen; Morillas, Rosa; Forns, Xavier

    2017-09-01

    Interferon-free therapies have an improved safety and efficacy profile. However, data in elderly patients, who have frequently advanced liver disease, associated comorbidities, and use concomitant medications are scarce. The im of this study was to assess the effectiveness and tolerability of all-oral regimens in elderly patients in real-life clinical practice. Retrospective analysis of hepatitis C virus (HCV) patients aged ≥65 years receiving interferon-free regimens within the Spanish National Registry (Hepa-C). Data of 1,252 patients were recorded. Of these, 955 (76%) were aged 65-74 years, 211 (17%) were aged 75-79 years, and 86 (7%) were aged ≥80 years at the start of antiviral therapy. HCV genotype-1b was predominant (88%) and 48% were previous non-responders. A significant proportion of patients had cirrhosis (922; 74%), of whom 11% presented decompensated liver disease. The most used regimens were SOF/LDV (33%), 3D (28%), and SOF/SMV (26%). Ribavirin was added in 49% of patients. Overall, the sustained virological response (SVR12) rate was 94% without differences among the three age categories. Albumin ≤3.5 g/dl was the only independent negative predictor of response (0.25 (0.15-0.41); P<0.01). Regarding tolerability, the rate of severe adverse events increased with age category (8.8, 13, and 14%; P=0.04). In addition, the main predictors of mortality (2.3%) were age ≥75 years (2.59 (1.16-5.83); P =0.02) and albumin ≤3.5 (17 (6.3-47); P <0.01). SVR rates with interferon-free regimens in elderly patients are high and comparable to the general population. Baseline low albumin levels (≤3.5 g/dl) was the only predictor of treatment failure. Importantly, the rate of severe adverse events and death increased with age. Elderly patients (≥75 years) or those with advanced liver disease (albumin ≤3.5) presented higher mortality. Thus a careful selection of patients for antiviral treatment is recommended.

  9. Incidence and Survival in Breast Cancer Patients and Stressful Life Events.

    PubMed

    Fallah, Raheleh; Akbari, Mohammad Esmaeil; Azargashb, Eznollah; Khayamzadeh, E

    2016-01-01

    Due to increasing incidence of breast cancer, recognition of risk factors has become increasingly important. Over the past few decades, among risk factors of this disease, stressful life events have attracted particular attention, but their relationship with breast cancer incidence and survival remains a mystery. This study aimed to examine the relationship between severe stressful life events and incidence and survival of women with breast cancer. In this case-control study, using a structured telephone interview with 355 women with breast cancer and also with 516 women with benign breast diseases who were matched in demographic characteristics, necessary information about the experience of major stressful events in the years before the diagnosis were collected. Data were analyzed using statistical methods of χ2, t, and Kaplan-Meier with a significance level of <0.05. Generally, in the case and control groups, there were no significant association between experience of stressful life events and incidence of breast cancer. Regarding associations between each of the events and incidence of breast cancer only "severe interpersonal problems with spouse" was significant. In the breast cancer group, even after controlling confounding variables, there was no significant association between major stressful events and disease-free survival, or overall 5-and 10-year survival. In this study, only "severe interpersonal problems with spouse" was confirmed as a risk factor. This result can be useful in developing preventive policies. More research regarding the interactive effects of psycho-social factors in the incidence and survival of breast cancer with stressful life events is recommended.

  10. Three-year survival rates for all consecutive heart-only and lung-only transplants performed in Eurotransplant, 1997-1999.

    PubMed

    Smits, Jacqueline M A; Vanhaecke, Johan; Haverich, Axel; de Vries, Erwin; Smith, Mike; Rutgrink, Ellis; Ramsoebhag, Annemarie; Hop, Alinde; Persijn, Guido; Laufer, Gunther

    2003-01-01

    The definition of proper patient selection criteria remains a prominent item in constant need of attention. While the concept of gathering evidence in order to determine practice continues to be hopelessly ambiguous, it can never be emphasized too much that these univariate results are just a first foray into analysing predictors of survival; all following results should be regarded and interpreted in this perspective. HEART TRANSPLANT SURVIVAL: The 3-year survival rate for heart transplant recipients under age 16 was 83% versus 72% for adult recipients. Acutely retransplanted adult heart recipients had a 3-year survival rate of 36% compared with 72% for recipients of a first heart allograft. Patients suffering from DCM had the best survival rates at 3 years (74%) compared with patients suffering from CAD (70%) or from another end-stage heart disease (67%). With advancing age of the adult recipient, the mortality risk increased. Patients aged 16-40 had a 3-year survival rate of 77%, compared with 74%, 70% and 61% for transplant recipients aged 41-55, 56-65 and over age 65, respectively. The 3-year survival rates for adult recipients transplanted with an heart allograft from a donor aged under 16 or between 16-44 were 78% and 74%, compared with 66% and 63% for donors aged 45-55 and over 55, respectively. The 3-year survival rates for recipients of hearts with cold ischemic times under 2 hours, 2-3, 3-4, 4-5, 5-6 and more than 6 hours were 74%, 75%, 70%, 65%, 54% and 40%, respectively. Transplanting a female donor heart into a male recipient was associated with the worst prognosis: the 3-year survival rates were 73%, 71%, 66% and 76%, respectively, for the donor/recipient groups male/male, male/female, female/male and female/female, respectively. When the donor-to-recipient body weight ratio was below 0.8, the 3-year survival rate was 64%, compared to 72% for weight-matched pairs and 74% for patients who received a heart from an oversized donor (p=0.004). Better

  11. Colonoscopic surveillance improves survival after colorectal cancer diagnosis in inflammatory bowel disease.

    PubMed

    Lutgens, M W M D; Oldenburg, B; Siersema, P D; van Bodegraven, A A; Dijkstra, G; Hommes, D W; de Jong, D J; Stokkers, P C F; van der Woude, C J; Vleggaar, F P

    2009-11-17

    Colonoscopic surveillance provides the best practical means for preventing colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients. Strong evidence for improved survival from surveillance programmes is sparse. The aim of this study was to compare tumour stage and survival of IBD patients with CRC who were a part of a surveillance programme with those who were not. A nationwide pathology database (PALGA (pathologisch anatomisch landelijk geautomatiseerd archief)) was consulted to identify IBD patients with CRC treated in all eight university hospitals in The Netherlands over a period of 15 years. Patients were assigned to the surveillance group when they had undergone one or more surveillance colonoscopies before a diagnosis of CRC. Patients who had not undergone surveillance served as controls. Tumour stage and survival were compared between the two groups. A total of 149 patients with IBD-associated CRC were identified. Twenty-three had had colonoscopic surveillance before CRC was discovered. The 5-year CRC-related survival rate of patients in the surveillance group was 100% compared with 74% in the non-surveillance group (P=0.042). In the surveillance group, only one patient died as a consequence of CRC compared with 29 patients in the control group (P=0.047). In addition, more early tumour stages were found in the surveillance group (P=0.004). These results provide evidence for improved survival from colonoscopic surveillance in IBD patients by detecting CRC at a more favourable tumour stage.

  12. Survival outcome of intermediate risk neuroblastoma at Children Cancer Hospital Egypt.

    PubMed

    Elzomor, Hossam; Ahmed, Gehad; Elmenawi, Salma; Elkinaai, Naglaa; Refaat, Amal; Soliman, Sonya; Abdelwahab, Mai Amr; Zaghloul, Mohamed Saad; Fawzy, Mohamed

    2018-03-01

    The study aims to evaluate survival outcome in newly diagnosed pediatric intermediate risk neuroblastoma patients treated at the Children Cancer Hospital - Egypt and their relation to various clinical and pathological factors. The study included stage 3 patients <1.5 years, children 1.5 years or older with stage 3 disease and favorable histopathological features, infants (<1 year) with International Neuroblastoma Staging System (INSS) stage 4 disease, stage 4 children 1-1.5 years with favorable biology, and infants stage 4 s (with unfavorable biologic features). Patients received systemic chemotherapy, in the form of etoposide and carboplatin alternating with cyclophosphamide, doxorubicin and vincristine, administered at 3-week intervals, with a total of 6 or 8 cycles guided by reaching objective overall response (complete/very good partial/partial response). The study included 136 patients, 67 males and 69 females. 101 patients had abdominal primary tumors, 28 had mediastinal masss and 7 with masses in the neck; 68% were stage 3 and the remaining (n = 44) had metastatic disease. The three-year overall survival (OS) and event-free survival (EFS) estimates were 94% ± 2% and 90.9% ± 2.5%, respectively. OS and EFS by gender, age, pathology and INPC were all statistically not significantly different. Moreover, OS for patients having surgery versus no surgery (inoperable residual only) was statistically significant (98.4% ± 1.6% & 88.7% ± 5.3%, respectively, p = .034). A very high rate of survival is currently achievable in patients with intermediate risk neuroblastoma by chemotherapy or chemotherapy and surgery. In addition to response, our plan is to adopt biologically-based treatment to reduce treatment-induced complications among survivors. Copyright © 2018 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

  13. Improved survival with ursodeoxycholic acid prophylaxis in allogeneic stem cell transplantation: long-term follow-up of a randomized study.

    PubMed

    Ruutu, Tapani; Juvonen, Eeva; Remberger, Mats; Remes, Kari; Volin, Liisa; Mattsson, Jonas; Nihtinen, Anne; Hägglund, Hans; Ringdén, Olle

    2014-01-01

    We report the long-term results of a prospective randomized study on the use of ursodeoxycholic acid (UDCA) for prevention of hepatic complications after allogeneic stem cell transplantation. Two hundred forty-two patients, 232 with malignant disease, were randomized to receive (n = 123) or not to receive (n = 119) UDCA from the beginning of the conditioning until 90 days post-transplantation. The results were reported after 1-year follow-up. UDCA administration reduced significantly the proportion of patients developing high serum bilirubin levels as well as the incidence of severe acute graft-versus-host disease (GVHD), liver GVHD, and intestinal GVHD. In the UDCA prophylaxis group, nonrelapse mortality (NRM) was lower and overall survival better than in the control group. After a 10-year follow-up, the difference in the survival and NRM in favor of the UDCA-treated group, seen at 1 year, was maintained (survival 48% versus 38%, P = .037; NRM 28% versus 41%, P = .01). A landmark analysis in patients surviving at 1 year post-transplantation showed no significant differences between the study groups in the long-term follow-up in chronic GVHD, relapse rate, NRM, disease-free survival, or overall survival. These long-term results continue to support the useful role of UDCA in the prevention of transplant-related complications in allogeneic transplantation. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  14. 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

  15. 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.

  16. Urinary and sexual outcomes in long-term (5+ years) prostate cancer disease free survivors after radical prostatectomy

    PubMed Central

    2009-01-01

    Background After long term disease free follow up (FUp) patients reconsider quality of life (QOL) outcomes. Aim of this study is assess QoL in prostate cancer patients who are disease-free at least 5 years after radical prostatectomy (RP). Methods 367 patients treated with RP for clinically localized pCa, without biochemical failure (PSA ≤ 0.2 ng/mL) at the follow up ≥ 5 years were recruited. Urinary (UF) and Sexual Function (SF), Urinary (UB) and Sexual Bother (SB) were assessed by using UCLA-PCI questionnaire. UF, UB, SF and SB were analyzed according to: treatment timing (age at time of RP, FUp duration, age at time of FUp), tumor characteristics (preoperative PSA, TNM stage, pathological Gleason score), nerve sparing (NS) procedure, and hormonal treatment (HT). We calculated the differences between 93 NS-RP without HT (group A) and 274 non-NS-RP or NS-RP with HT (group B). We evaluated the correlation between function and bother in group A according to follow-up duration. Results Time since prostatectomy had a negative effect on SF and a positive effect SB (both p < 0.001). Elderly men at follow up experienced worse UF and SF (p = 0.02 and p < 0.001) and better SB (p < 0.001). Higher stage PCa negatively affected UB, SF, and SB (all: p ≤ 0.05). NS was associated with better UB, SF and SB (all: p ≤ 0.05); conversely, HT was associated with worse UF, SF and SB (all: p ≤ 0.05). More than 8 years after prostatectomy SF of group A and B were similar. Group A subjects (NS-RP without HT) demonstrated worsening SF, but improved SB, suggesting dissociation of the correlation between SF and SB over time. Conclusion Older age at follow up and higher pathological stage were associated with worse QoL outcomes after RP. The direct correlation between UF and age at follow up, with no correlation between UF and age at time of RP suggests that other issues (i.e: vascular or neurogenic disorders), subsequent to RP, are determinant on urinary incontinence. After NS

  17. Our paper 20 years later: 1-year survival and 6-month quality of life after intensive care.

    PubMed

    Capuzzo, Maurizia; Bianconi, Margherita

    2015-04-01

    In the early 1990s, the in-hospital mortality rate of intensive care unit (ICU) patients dropped, and interest in the quality of life (QOL) of ICU survivors increased. In 1996, we published a study to investigate 1-year survival after hospital discharge and 6-month QOL after intensive care. Now, we compare our previous results with those reported in the recent literature to appraise any changes, and new knowledge in the area. The 1-year survival of ICU patients after hospital discharge is substantial, lower than in the general population, and different among subgroups. Some studies showed a reduction in QOL at 6 months, as in our study, while others showed an improvement. Different results seem to be related mainly to the case mix. Studies on different types of patients found long-term cognitive impairment in ICU survivors, possibly not disease specific. The proportions of patients with neuropsychological morbidities such as posttraumatic stress disorder, anxiety, and depression, described after our study, did not show any change over time. Differences between studies on long-term survival and QOL do not allow conclusions to be drawn about change over time. No change was found in neuropsychological morbidities. However, a lack of change may not be viewed negatively, because critically ill patients who survive ICU today may be at higher risk for poor long-term outcome than in the past due to the higher severity of their illness and the more aggressive treatments received. Future studies may provide understanding of the relationships between psychiatric symptoms, cognitive impairment, functional disability, and QOL.

  18. Treatment results of nasopharyngeal carcinoma: a 15-year single institutional experience.

    PubMed

    Khademi, Bijan; Mahmoodi, Jalal; Omidvari, Shapour; Mohammadianpanah, Mohammad

    2006-06-01

    Nasopharyngeal Carcinoma (NPC) is a common malignant neoplasm of the head and neck that occurs most commonly in people in the South Eastern Asia but its condition in Iran is not much clear. In this retrospective study, we evaluated the treatment characteristics determining the outcome in patients with NPC. In this retrospective study, we reviewed the records of one hundred and seven patients with biopsy proven diagnosis of NPC who were referred to the radiation oncology department, Nemazee Hospital, Shiraz University of Medical Sciences, Iran, during the time period from January 1985 to December 2000. Eightyfive patients (79.4%) received 60-70Gy radiation (1.8- 2Gy/fraction, one fraction per day, and 5 fractions per week). Sixty-two patients (57.5%) received radiotherapy combined with adjuvant chemotherapy which consisted of cisplatin and 5-fluorouracil. Eighty-six patients (80.4%) had WHO II-III histopathologic diagnosis. According to the AJCC 1997 staging system, 4 (3.6%), 3 (2.7%), 33 (30.8%) and 67 (62%) patients were in stages I, II, III and IV, respectively. With a median follow-up of 12 months, the 2-year overall and disease-free survival rates were 35% and 21%, respectively. According to the multivariate analysis for overall survival, patients under 40 years had a better prognosis (p=0.041). Node stage and stage of disease were significant prognostic factors (p=0.0001). On multivariate analysis for disease-free survival, age and node stage were significant prognostic factors. The patients who received more than 60Gy radiation had a better prognosis (p=0.02), however; sequential adjuvant chemotherapy had no impact on survival and response (p=0.6). Our experience confirmed earlier reports showing poor outcomes for locoregionally advanced nasopharyngeal carcinomas. This study failed to demonstrate improvement in the outcome regarding overall and disease-free survival by adding sequential adjuvant chemotherapy after radiotherapy for patients with advanced NPC.

  19. Neighborhood socioeconomic deprivation and residential instability: effects on incidence of ischemic heart disease and survival after myocardial infarction.

    PubMed

    Chaix, Basile; Rosvall, Maria; Merlo, Juan

    2007-01-01

    Previous literature has shown that neighborhood socioeconomic position influences the risk of ischemic heart disease, but little is known about the mechanisms linking the residential context to ischemic heart disease incidence and mortality. We examined whether neighborhood socioeconomic position and neighborhood residential stability (as a determinant of social interaction patterns) have an influence on ischemic heart disease risk. Moreover, we investigated whether dissimilar contextual influences operate at different stages of the disease process, ie, on incidence, 1-day case-fatality, and long-term survival after acute myocardial infarction (MI). Using a large 27-year longitudinal cohort (baseline: 1 January 1996) defined in the Scania region, Sweden, we estimated multilevel survival models adjusted for individual sociodemographic factors and previous diseases of the persons. After adjustment, multilevel survival models indicated that the incidence of ischemic heart disease increased with neighborhood socioeconomic deprivation but was only weakly associated with neighborhood residential instability (for high vs low residential instability, hazard ratio = 1.2; 95% credible interval = 1.0-1.4). Conversely, beyond effects of individual and contextual socioeconomic circumstances and distance to the hospital, we saw a markedly higher 1-day case-fatality (4.9; 1.8-15) and shorter survival time after MI among individuals still alive 28 days after MI (4.3; 1.2-17) in neighborhoods with a high versus low residential instability. Effects of residential instability on post-MI survival may be mediated by the lower availability of social support in residentially unstable neighborhoods, suggesting a new class of intermediate processes that should be taken into account when investigating contextual influences on ischemic heart disease. Moreover, dissimilar contextual effects may operate at various stages of the disease process (ie, on incidence, case-fatality, and survival

  20. Discovery of prognostic biomarkers for predicting lung cancer metastasis using microarray and survival data.

    PubMed

    Huang, Hui-Ling; Wu, Yu-Chung; Su, Li-Jen; Huang, Yun-Ju; Charoenkwan, Phasit; Chen, Wen-Liang; Lee, Hua-Chin; Chu, William Cheng-Chung; Ho, Shinn-Ying

    2015-02-21

    Few studies have investigated prognostic biomarkers of distant metastases of lung cancer. One of the central difficulties in identifying biomarkers from microarray data is the availability of only a small number of samples, which results overtraining. Recently obtained evidence reveals that epithelial-mesenchymal transition (EMT) of tumor cells causes metastasis, which is detrimental to patients' survival. This work proposes a novel optimization approach to discovering EMT-related prognostic biomarkers to predict the distant metastasis of lung cancer using both microarray and survival data. This weighted objective function maximizes both the accuracy of prediction of distant metastasis and the area between the disease-free survival curves of the non-distant and distant metastases. Seventy-eight patients with lung cancer and a follow-up time of 120 months are used to identify a set of gene markers and an independent cohort of 26 patients is used to evaluate the identified biomarkers. The medical records of the 78 patients show a significant difference between the disease-free survival times of the 37 non-distant- and the 41 distant-metastasis patients. The experimental results thus obtained are as follows. 1) The use of disease-free survival curves can compensate for the shortcoming of insufficient samples and greatly increase the test accuracy by 11.10%; and 2) the support vector machine with a set of 17 transcripts, such as CCL16 and CDKN2AIP, can yield a leave-one-out cross-validation accuracy of 93.59%, a test accuracy of 76.92%, a large disease-free survival area of 74.81%, and a mean survival prediction error of 3.99 months. The identified putative biomarkers are examined using related studies and signaling pathways to reveal the potential effectiveness of the biomarkers in prospective confirmatory studies. The proposed new optimization approach to identifying prognostic biomarkers by combining multiple sources of data (microarray and survival) can

  1. 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.

  2. Demographic effects of canine parvovirus on a free-ranging wolf population over 30 years

    USGS Publications Warehouse

    Mech, L.D.; Goyal, S.M.; Paul, W.J.; Newton, W.E.

    2008-01-01

    We followed the course of canine parvovinis (CPV) antibody prevalence in a subpopulation of wolves (Canis 1upus) in northeastern Minnesota from 1973, when antibodies were first detected, through 2004. Annual early pup survival was reduced by 70%, and wolf population change was related to CPV antibody prevalence. In the greater Minnesota population of 3,000 wolves, pup survival was reduced by 40-60%. This reduction limited the Minnesota wolf population rate of increase to about 4% per year compared with increases of 16-58% in other populations. Because it is young wolves that disperse, reduced pup survival may have caused reduced dispersal and reduced recolonization of new range in Minnesota. ?? Wildlife Disease Association 2008.

  3. Metastatic neuroblastoma in infants: are survival rates excellent only within the stringent framework of clinical trials?

    PubMed

    Di Cataldo, A; Agodi, A; Balaguer, J; Garaventa, A; Barchitta, M; Segura, V; Bianchi, M; Castel, V; Castellano, A; Cesaro, S; Couselo, J M; Cruz, O; D'Angelo, P; De Bernardi, B; Donat, J; de Andoin, N G; Hernandez, M I; La Spina, M; Lillo, M; Lopez-Almaraz, R; Luksch, R; Mastrangelo, S; Mateos, E; Molina, J; Moscheo, C; Mura, R; Porta, F; Russo, G; Tondo, A; Torrent, M; Vetrella, S; Villegas, J A; Viscardi, E; Zanazzo, G A; Cañete, A

    2017-01-01

    SIOPEN INES protocol yielded excellent 5-year survival rates for MYCN-non-amplified metastatic neuroblastoma. Patients deemed ineligible due to lack or delay of MYCN status or late registration were treated, but not included in the study. Our goal was to analyse survival at 10 years among the whole population. Italian and Spanish metastatic INES patients' data are reported. SPSS 20.0 was used for statistical analysis. Among 98 infants, 27 had events and 19 died, while 79 were disease free. Five- and 10-year event-free survival (EFS) were 73 and 70 %, and overall survival (OS) was 81 and 74 %, respectively. MYCN status was significant for EFS, but not for OS in multivariate analysis. The survival rates of patients who complied with all the inclusion criteria for INES trials are higher compared to those that included also not registered patients. Five-year EFS and OS for INES 99.2 were 87.8 and 95.7 %, while our stage 4s population obtained 78 and 87 %. Concerning 99.3, 5-year EFS and OS were 86.7 and 95.6 %, while for stage 4 we registered 61 and 68 %. MYCN amplification had a strong impact on prognosis and therefore we consider it unacceptable that many patients were not studied for MYCN and probably inadequately treated. Ten-year survival rates were shown to decrease: EFS from 73 to 70 % and OS from 81 to 74 %, indicating a risk of late events, particularly in stage 4s. Population-based registries like European ENCCA WP 11-task 11 will possibly clarify these data.

  4. 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

  5. Serum thymidine kinase 1 levels predict cancer-free survival following neoadjuvant, surgical and adjuvant treatment of patients with locally advanced breast cancer

    PubMed Central

    CHEN, FEIYU; TANG, LILI; XIA, TING; HE, ELLEN; HU, GUOZHU; LI, YUAN; ZHANG, MING; ZHOU, JI; ERIKSSON, STAFFAN; SKOG, SVEN

    2013-01-01

    In this study, the use of serum thymidine kinase 1 protein (STK1p) concentration for the prognosis of the overall survival of patients with locally advanced breast cancer (n=51) following routine treatment (neoadjuvant treatment, surgery and chemotherapy) was investigated. The patients were followed up for 44 months and the STK1p values were determined by a high-sensitivity enhanced chemiluminescence (ECL) dot blot assay. The variables investigated in relation to metastasis and survival were STK1p, clinical stage, tumor size and age, by the Kaplan-Meier method, the log-rank test and Cox uni- and multivariate analyses. Patients with high STK1p values (≥2.0 pM) 3–6 months after surgery exhibited a positive correlation to clinical stage, tumor size, occurrence of metastasis and survival. The hazard risk for the development of metastatic disease and mortality among breast cancer patients was 11–12 times higher in patients with high compared to those with low STK1p values (<2.0 pM). Notably, patients with stage III/IV disease and low STK1p values exhibited statistically significantly improved survival compared to patients with high STK1p values. A multivariate Cox analysis demonstrated that the STK1p levels 6 months after surgery was the only independent prognostic factor for metastasis and survival. In conclusion, STK1p is a prognostic marker in patients with locally advanced breast cancer and it may help identify a subgroup of stage III/IV patients with improved cancer-free survival expectancy, enabling personalized treatment. PMID:24649267

  6. HannaH phase III randomised study: Association of total pathological complete response with event-free survival in HER2-positive early breast cancer treated with neoadjuvant-adjuvant trastuzumab after 2 years of treatment-free follow-up.

    PubMed

    Jackisch, Christian; Hegg, Roberto; Stroyakovskiy, Daniil; Ahn, Jin-Seok; Melichar, Bohuslav; Chen, Shin-Cheh; Kim, Sung-Bae; Lichinitser, Mikhail; Starosławska, Elżbieta; Kunz, Georg; Falcon, Silvia; Chen, Shou-Tung; Crepelle-Fléchais, Aulde; Heinzmann, Dominik; Shing, Mona; Pivot, Xavier

    2016-07-01

    In the phase III, open-label, randomised HannaH study, fixed-dose neoadjuvant-adjuvant subcutaneous trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer was non-inferior to standard weight-based intravenous infusion in terms of serum trough concentration and pathological complete response (pCR). Evidence suggests that pCR, particularly total pCR (tpCR), is likely to predict clinical benefit. We report associations between tpCR and event-free survival (EFS) from HannaH (the largest population from a single study of patients presenting with newly diagnosed HER2-positive breast cancer treated with neoadjuvant-adjuvant trastuzumab to date) plus long-term efficacy and safety. Eligible patients received four cycles of neoadjuvant docetaxel followed by four cycles of fluorouracil/epirubicin/cyclophosphamide administered concurrently with 3-weekly subcutaneous (600 mg fixed dose) or intravenous trastuzumab (8 mg/kg loading, 6 mg/kg maintenance doses). Post-surgery, patients received adjuvant trastuzumab as randomised to complete 1 year of standard treatment. In exploratory analyses, we used Cox regression to assess associations between tpCR and EFS. EFS rates per subgroup were estimated using the Kaplan-Meier method. Three-year EFS rates were 76% for subcutaneous and 73% for intravenous trastuzumab (unstratified hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.69-1.30; intention-to-treat population). Three-year overall survival rates were 92% for subcutaneous and 90% for intravenous trastuzumab (unstratified HR 0.76, 95% CI 0.44-1.32). tpCR was associated with a reduced risk of an EFS event: subcutaneous arm HR 0.38 (95% CI 0.22-0.65); intravenous arm HR 0.32 (95% CI 0.18-0.60). Results were similar for subgroups, including oestrogen receptor status. The few additional adverse events occurring during treatment-free follow-up were balanced between arms. Long-term efficacy supports the established non-inferiority of

  7. 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

  8. Impact of breast cancer subtypes on 3-year survival among adolescent and young adult women

    PubMed Central

    2013-01-01

    Introduction Young women have poorer survival after breast cancer than do older women. It is unclear whether this survival difference relates to the unique distribution of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2)-defined molecular breast cancer subtypes among adolescent and young adult (AYA) women aged 15 to 39 years. The purpose of our study was to examine associations between breast cancer subtypes and short-term survival in AYA women, as well as to determine whether the distinct molecular subtype distribution among AYA women explains the unfavorable overall breast cancer survival statistics reported for AYA women compared with older women. Methods Data for 5,331 AYA breast cancers diagnosed between 2005 and 2009 were obtained from the California Cancer Registry. Survival by subtype (triple-negative; HR+/HER2-; HR+/HER2+; HR-/HER2+) and age-group (AYA versus 40- to 64-year-olds) was analyzed with Cox proportional hazards regression with follow-up through 2010. Results With up to 6 years of follow-up and a mean survival time of 3.1 years (SD = 1.5 years), AYA women diagnosed with HR-/HER + and triple-negative breast cancer experienced a 1.6-fold and 2.7-fold increased risk of death, respectively, from all causes (HR-/HER + hazard ratio: 1.55; 95% confidence interval (CI): 1.10 to 2.18; triple-negative HR: 2.75; 95% CI, 2.06 to 3.66) and breast cancer (HR-/HER + hazard ratio: 1.63; 95% CI, 1.12 to 2.36; triple-negative hazard ratio: 2.71; 95% CI, 1.98 to 3.71) than AYA women with HR+/HER2- breast cancer. AYA women who resided in lower socioeconomic status neighborhoods, had public health insurance, and were of Black, compared with White, race/ethnicity experienced worse survival. This race/ethnicity association was attenuated somewhat after adjusting for breast cancer subtypes (hazard ratio, 1.33; 95% CI, 0.98 to 1.82). AYA women had similar all-cause and breast cancer-specific short-term survival as older women

  9. Free access to medicines for the treatment of chronic diseases in Brazil

    PubMed Central

    Tavares, Noemia Urruth Leão; Luiza, Vera Lucia; Oliveira, Maria Auxiliadora; Costa, Karen Sarmento; Mengue, Sotero Serrate; Arrais, Paulo Sergio Dourado; Ramos, Luiz Roberto; Farias, Mareni Rocha; Pizzol, Tatiane da Silva Dal; Bertoldi, Andréa Dâmaso

    2016-01-01

    ABSTRACT OBJECTIVE To analyze the free access to medicines for the treatment of chronic diseases in the Brazilian population, according to demographic and socioeconomic factors. We also analyzed the most used pharmacological groups, according to funding source: free-of-charge or out-of-pocket paid. METHODS Analysis of data from the Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM – National Survey on Access, Use and Promotion of Rational Use of Medicines), a population-based household survey, of cross-sectional design, based on probabilistic sample of the Brazilian population. We analyzed as outcome the prevalence of free access (free-of-charge) to all medicines for treatment of the reported chronic diseases, in the last 30 days. We studied the following independent variables: sex, age group, education in complete years of school, economic class, health plan, and geographical region of residence. We estimated the prevalences and 95% confidence intervals (95%CI) and applied the Pearson’s Chi-squared test to assess the differences between the groups, considering a 5% significance level. RESULTS About half of adults and older adults who have had full access to the treatment of chronic diseases in Brazil obtained all needed medicines for free (47.5%; 95%CI 45.1–50.0). The prevalences of free access were higher among men (51.4%; 95%CI 48.1–54.8), age group of 40-59 years (51.1%; 95%CI 48.1–54.2), and in the poorest social classes (53.9%; 95%CI 50.2–57.7). The majority of medicines that act on the cardiovascular system, such as diuretics (C03) (78.0%; 95%CI 75.2–80.5), beta-blockers (C07) (62.7%; 95%CI 59.4–65.8), and the agents that work in the renin-angiotensin system (C09) (73.4%; 95%CI 70.8–75.8), were obtained for free. Medicines that act on the respiratory system, such as agents against obstructive airway diseases (R03) (60.0%; 95%CI 52.7–66.9) were mostly paid with own resources. CONCLUSIONS Free

  10. Adjuvant treatment for resected rectal cancer: impact of standard and intensified postoperative chemotherapy on disease-free survival in patients undergoing preoperative chemoradiation-a propensity score-matched analysis of an observational database.

    PubMed

    Garlipp, Benjamin; Ptok, Henry; Benedix, Frank; Otto, Ronny; Popp, Felix; Ridwelski, Karsten; Gastinger, Ingo; Benckert, Christoph; Lippert, Hans; Bruns, Christiane

    2016-12-01

    Adjuvant chemotherapy for resected rectal cancer is widely used. However, studies on adjuvant treatment following neoadjuvant chemoradiotherapy (CRT) and total mesorectal excision (TME) have yielded conflicting results. Recent studies have focused on adding oxaliplatin to both preoperative and postoperative therapy, making it difficult to assess the impact of adjuvant oxaliplatin alone. This study was aimed at determining the impact of (i) any adjuvant treatment and (ii) oxaliplatin-containing adjuvant treatment on disease-free survival in CRT-pretreated, R0-resected rectal cancer patients. Patients undergoing R0 TME following 5-fluorouracil (5FU)-only-based CRT between January 1, 2008, and December 31, 2010, were selected from a nationwide registry. After propensity score matching (PSM), comparison of disease-free survival (DFS) using Kaplan-Meier analysis and log-rank test was performed in (i) patients receiving no vs. any adjuvant treatment and (ii) patients treated with adjuvant 5FU/capecitabine without vs. with oxaliplatin. Out of 1497 patients, 520 matched pairs were generated for analysis of no vs. any adjuvant treatment. Mean DFS was significantly prolonged with adjuvant treatment (81.8 ± 2.06 vs. 70.1 ± 3.02 months, p < 0.001). One hundred forty-eight matched pairs were available for analysis of adjuvant therapy with or without oxaliplatin, showing no improvement in DFS in patients receiving oxaliplatin (76.9 ± 4.12 vs. 79.3 ± 4.44 months, p = 0.254). Local recurrence rate was not significantly different between groups in either analysis. In this cohort of rectal cancer patients treated with neoadjuvant CRT and TME surgery under routine conditions, adjuvant chemotherapy significantly improved DFS. No benefit was observed for the addition of oxaliplatin to adjuvant chemotherapy in this setting.

  11. The Contribution of Specific Diseases to Educational Disparities in Disability-Free Life Expectancy

    PubMed Central

    Nusselder, Wilma J.; Looman, Caspar W.N.; Mackenbach, Johan P.; Huisman, Martijn; van Oyen, Herman; Deboosere, Patrick; Gadeyne, Sylvie; Kunst, Anton E.

    2005-01-01

    Objectives. We examined the contribution that specific diseases, as causes of both death and disability, make to educational disparities in disability-free life expectancy (DFLE). Methods. We used disability data from the Belgian Health Interview Survey (1997) and mortality data from the National Mortality Follow-Up Study (1991–1996) to assess education-related disparities in DFLE and to partition these differences into additive contributions of specific diseases. Results. The DFLE advantage of higher-educated compared with lower-educated persons was 8.0 years for men and 5.9 years for women. Arthritis (men, 1.3 years; women, 2.2 years), back complaints (men, 2.1 years), heart disease/stroke (men, 1.5 years; women, 1.6 years), asthma/chronic obstructive pulmonary disease (COPD) (men, 1.2 years; women, 1.5 years), and “other diseases” (men, 2.4 years) contributed the most to this difference. Conclusions. Disabling diseases, such as arthritis, back complaints, and asthma/COPD, contribute substantially to differences in DFLE by education. Public health policy aiming to reduce existing disparities in the DFLE and to improve population health should not only focus on fatal diseases but also on these nonfatal diseases. PMID:16195519

  12. Anal Carcinoma: Impact of TN Category of Disease on Survival, Disease Relapse, and Colostomy Failure in US Gastrointestinal Intergroup RTOG 98-11 Phase 3 Trial

    PubMed Central

    Gunderson, Leonard L.; Moughan, Jennifer; Ajani, Jaffer A.; Pedersen, John E.; Winter, Kathryn A.; Benson, Al B.; Thomas, Charles R.; Mayer, Robert J.; Haddock, Michael G.; Rich, Tyvin A.; Willett, Christopher G.

    2013-01-01

    Purpose The long-term update of US GI Intergroup RTOG 98-11 anal cancer trial found that concurrent chemoradiation (CCRT) with fluorouracil (5-FU) plus mitomycin had a significant impact on disease-free survival (DFS) and overall survival (OS) compared with induction plus concurrent 5-FU plus cisplatin. The intent of the current analysis was to determine the impact of tumor node (TN) category of disease on survival (DFS and OS), colostomy failure (CF), and relapse (local-regional failure [LRF] and distant metastases [DM]) in this patient group. Methods and Materials DFS and OS were estimated univariately by using the Kaplan-Meier method, and 6 TN categories were compared by the log–rank test (T2N0, T3N0, T4N0, T2N1-3, T3N1-3, and T4N1-3). Time to relapse and colostomy were estimated by the cumulative incidence method, and TN categories were compared using Gray’s test. Results Of 682 patients, 620 were analyzable for outcomes by TN category. All endpoints showed statistically significant differences among the TN categories of disease (OS, P<.0001; DFS, P<.0001; LRF, P<.0001; DM, P=.0011; CF, P=.01). Patients with the poorest OS, DFS, and LRF outcomes were those with T3-4N-positive (+) disease. CF was lowest for T2N0 and T2N+ (11%, 11%, respectively) and worst for the T4N0, T3N+, and T4N+ categories (26%, 27%, 24%, respectively). Conclusions TN category of disease has a statistically significant impact on OS, DFS, LRF, DM, and CF in patients treated with CCRT and provides excellent prognostic information for outcomes in patients with anal carcinoma. Significant challenges remain for patients with T4N0 and T3-4N+ categories of disease with regard to survival, relapse, and CF and lesser challenges for T2-3N0/T2N+ categories. PMID:24035327

  13. 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.

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

    PubMed

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

    2017-08-01

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

  15. Balloon atrial septostomy in pulmonary arterial hypertension: effect on survival and associated outcomes.

    PubMed

    Chiu, Joanne S; Zuckerman, Warren A; Turner, Mariel E; Richmond, Marc E; Kerstein, Diane; Krishnan, Usha; Torres, Alejandro; Vincent, Julie A; Rosenzweig, Erika B

    2015-03-01

    Pulmonary arterial hypertension (PAH) is a progressive disease that, without early identification and treatment, may lead to right heart failure, multi-organ dysfunction and early death. In severe PAH, in addition to maximal medical therapy, balloon atrial septostomy (BAS) may be used for palliation and as a bridge to lung transplantation. We present our contemporary institutional experience utilizing BAS in adult and pediatric patients with severe PAH. We performed a retrospective analysis of 46 BASs performed in 32 patients with PAH from 2002 to 2013. Data obtained included vital status, functional class, medications, hemodynamic measurements from right heart catheterizations and biomarkers. Lung transplantation-free and repeat-BAS-free survival was analyzed. Median age at BAS was 23 (range 1 to 56) years. The most common indications were symptomatic right heart failure (21 of 46 patients) and pre-syncope/syncope (19 of 46 patients); 69% of patients were WHO Functional Class III or IV pre-BAS. There were no procedural complications or deaths. There were no significant differences in biomarkers or hemodynamic findings between pre-BAS and 1 year or latest follow-up. Seven patients were successfully bridged to lung transplantation. Lung transplantation-free and repeat-BAS-free survival at 30 days, 1 year and 5 years was 87%, 61% and 32%, respectively. In our experienced center, BAS was shown to be safe in patients with severe PAH on maximal medical management, with no procedural deaths or complications. BAS was safely used as a bridge to lung transplantation or to alleviate right heart failure symptoms and/or syncope. Other potential benefits for end-organ function and overall survival remain to be determined. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

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

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

    Elshaikh, Mohamed A., E-mail: melshai1@hfhs.org; Vance, Sean; Suri, Jaipreet S.

    2014-02-01

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

  17. The emerging phenotype of long-term survivors with infantile Pompe disease

    PubMed Central

    Prater, Sean N.; Banugaria, Suhrad G.; DeArmey, Stephanie M.; Botha, Eleanor G.; Stege, Erin M.; Case, Laura E.; Jones, Harrison N.; Phornphutkul, Chanika; Wang, Raymond Y.; Young, Sarah P.; Kishnani, Priya S.

    2013-01-01

    Purpose Enzyme replacement therapy with alglucosidase alfa for infantile Pompe disease has improved survival creating new management challenges. We describe an emerging phenotype in a retrospective review of long-term survivors. Methods Inclusion criteria included ventilator-free status and age ≤6 months at treatment initiation, and survival to age ≥5 years. Clinical outcome measures included invasive ventilator-free survival and parameters for cardiac, pulmonary, musculoskeletal, gross motor and ambulatory status; growth; speech, hearing, and swallowing; and gastrointestinal and nutritional status. Results Eleven of 17 patients met study criteria. All were cross-reactive immunologic material-positive, alive, and invasive ventilator-free at most recent assessment, with a median age of 8.0 years (range: 5.4 to 12.0 years). All had marked improvements in cardiac parameters. Commonly present were gross motor weakness, motor speech deficits, sensorineural and/or conductive hearing loss, osteopenia, gastroesophageal reflux disease, and dysphagia with aspiration risk. Seven of 11 patients were independently ambulatory and four required the use of assistive ambulatory devices. All long-term survivors had low or undetectable anti-alglucosidase alfa antibody titers. Conclusions Long-term survivors exhibited sustained improvements in cardiac parameters and gross motor function. Residual muscle weakness, hearing loss, risk for arrhythmias, hypernasal speech, dysphagia with risk for aspiration, and osteopenia were commonly observed findings. PMID:22538254

  18. Adoptive TIL Transfer in the Adjuvant Setting for Melanoma: Long-Term Patient Survival

    PubMed Central

    Khammari, Amir; Knol, Anne-Chantal; Nguyen, Jean-Michel; Bossard, Céline; Denis, Marc-Guillaume; Pandolfino, Marie-Christine; Quéreux, Gaëlle; Bercegeay, Sylvain; Dréno, Brigitte

    2014-01-01

    Two first analyses of our clinical trial on TIL as adjuvant therapy for melanoma were published in 2002 and 2007. We present here an update of the clinical results after a 17-year median followup. In this trial, disease-free patients were randomly assigned to receive either TIL/IL-2 or IL-2. The relapse-free survival (RFS) was the primary objective. Eighty-eight patients were enrolled. A new analysis performed in May 2013 did not show significant changes in RFS or OS duration. However, our first finding on the association between the number of invaded lymph nodes and TIL effectiveness was strengthened. The Cox model adjusted on this interaction showed for the first time a significant treatment effect when considering the overall population, both on the RFS and OS. Patients treated with TIL had a longer RFS (P = 0.023) or OS (P = 0.020). This study being with a very long followup (17 years), confirmed the association between TIL effectiveness and the number of invaded lymph nodes, indicating that a low tumor burden could be a crucial factor enhancing the curative effect of TIL in possible microscopic residual disease. Moreover, we confirmed that a prolonged survival was associated with the presence of specific TIL and a decrease in Foxp3 expression. PMID:24741578

  19. Adoptive TIL transfer in the adjuvant setting for melanoma: long-term patient survival.

    PubMed

    Khammari, Amir; Knol, Anne-Chantal; Nguyen, Jean-Michel; Bossard, Céline; Denis, Marc-Guillaume; Pandolfino, Marie-Christine; Quéreux, Gaëlle; Bercegeay, Sylvain; Dréno, Brigitte

    2014-01-01

    Two first analyses of our clinical trial on TIL as adjuvant therapy for melanoma were published in 2002 and 2007. We present here an update of the clinical results after a 17-year median followup. In this trial, disease-free patients were randomly assigned to receive either TIL/IL-2 or IL-2. The relapse-free survival (RFS) was the primary objective. Eighty-eight patients were enrolled. A new analysis performed in May 2013 did not show significant changes in RFS or OS duration. However, our first finding on the association between the number of invaded lymph nodes and TIL effectiveness was strengthened. The Cox model adjusted on this interaction showed for the first time a significant treatment effect when considering the overall population, both on the RFS and OS. Patients treated with TIL had a longer RFS (P = 0.023) or OS (P = 0.020). This study being with a very long followup (17 years), confirmed the association between TIL effectiveness and the number of invaded lymph nodes, indicating that a low tumor burden could be a crucial factor enhancing the curative effect of TIL in possible microscopic residual disease. Moreover, we confirmed that a prolonged survival was associated with the presence of specific TIL and a decrease in Foxp3 expression.

  20. Effect of age on biochemical disease-free outcome in patients with T1-T3 prostate cancer treated with definitive radiotherapy in an equal-access health care system: a radiation oncology report of the Department of Defense Center for Prostate Disease Research.

    PubMed

    Johnstone, Peter A S; Riffenburgh, Robert H; Moul, Judd W; Sun, Leon; Wu, Hongyu; McLeod, David G; Kane, Christopher J; Martin, Douglas D; Kusuda, Leo; Lance, Raymond; Douglas, Robert; Donahue, Timothy; Beat, Michael G; Foley, John; Chung, Andrew; Soderdahl, Douglas; Do, Jason; Amling, Christopher L

    2003-03-15

    It has traditionally been a common perception that young age is a negative prognostic factor in prostate cancer (CaP). Furthermore, many urologists believe that younger patients are better suited to surgery rather than radiotherapy (RT) because of this perception. However, the data on the effect of age on outcome in patients with CaP are unclear. The records of the Department of Defense Center for Prostate Disease Research were queried for the biochemical disease-free results of patients after definitive RT and analyzed by age. The records of 1018 patients with T1-T3 CaP treated with definitive RT between 1988 and 2000 were reviewed. The records of patients receiving adjuvant hormonal therapy or adjuvant or salvage RT postoperatively were excluded. Biochemical failure was calculated by the American Society for Therapeutic Radiology and Oncology criteria. The median potential follow-up was 85.3 months as of December 31, 2001. Age did not affect biochemical disease-free survival significantly when considered as <60 vs. >/=60 years (p = 0.646), by decade (p = 0.329), or as a continuous variable (correlation coefficient r = 0.017, regression slope = 0.007, with p = 0.588 and R(2) < 0.001). Using multiple regression analysis, age was still not significant (p = 0.408). Other variables analyzed were pretreatment prostate-specific antigen level (p < 0.001), Gleason sum (p = 0.023), stage (p = 0.828), and RT dose (p = 0.033). Age and biochemical disease-free survival after RT for CaP are not related. Age may not be a valid factor in choosing between primary treatment options for CaP.

  1. Dynamic prognostication using conditional survival analysis for patients with operable lung adenocarcinoma

    PubMed Central

    Kim, Wooil; Lee, Ho Yun; Jung, Sin-Ho; Woo, Min-Ah; Kim, Hong Kwan; Choi, Yong Soo; Kim, Jhingook; Zo, Jae Ill; Shim, Young Mog; Han, Joungho; Jeong, Ji Yun; Choi, Joon Young; Lee, Kyung Soo

    2017-01-01

    Purpose To evaluate conditional survival among patients with surgically resected stage I-IIIa lung adenocarcinoma and identify changes in prognostic contributions for various prognostic factors over time. Patients and Methods We performed conditional survival analysis at each t0 (=0, 1, 2, 3, 4, 5 years) for 723 consecutive patients who underwent surgical resection for lung adenocarcinoma, stratified by various clinico-demographic features, as well as pathologic and imaging (tumor-shadow disappearance ratio [TDR] on CT and maximum standardized uptake value [SUVmax] on PET) characteristics. Uni- and multivariableCox regression analyses were performed to evaluate relationships between those variables and conditional survival. Results Three-year conditional overall survival (OS) and disease-free survival (DFS) were 92.12% and 75.51% at baseline, but improved steadily up to 98.33% and 95.95% at 5 years after surgery. In contrast to demographic factors, pathologic (stage, subtype, pathologic grade and differentiation) and radiologic factors (TDR and SUVmax) maintained a statistically significant association with subseqeunt 3-year OS until 3 years after surgery. According to the multivariableanalysis, high SUVmax and low TDR value were independent predictors of subsequent 3-year OS and DFS at baseline, 1 and 2 years after surgery, respectively. Conclusion Our findings based on CS provide theoretical background for clinicians to plan longer period of surveillance following lung adenocarcinoma resection in survivors with preoperatively high SUVmax and low TDR on PET-CT and chest CT, respectively. PMID:27793026

  2. Surgery Increases Survival in Patients With Gastrinoma

    PubMed Central

    Norton, Jeffrey A.; Fraker, Douglas L.; Alexander, H R.; Gibril, Fathia; Liewehr, David J.; Venzon, David J.; Jensen, Robert T.

    2006-01-01

    Objective: To determine whether the routine use of surgical exploration for gastrinoma resection/cure in 160 patients with Zollinger-Ellison syndrome (ZES) altered survival compared with 35 ZES patients who did not undergo surgery. Summary Background Data: The role of routine surgical exploration for resection/cure in patients with ZES has been controversial since the original description of this disease in 1955. This controversy continues today, not only because medical therapy for acid hypersecretion is so effective, but also in large part because no studies have shown an effect of tumor resection on survival. Methods: Long-term follow-up of 160 ZES patients who underwent routine surgery for gastrinoma/resection/cure was compared with 35 patients who had similar disease but did not undergo surgery for a variety of reasons. All patients had preoperative CT, MRI, ultrasound; if unclear, angiography and somatostatin receptor scintigraphy since 1994 to determine resectability. At surgery, all had the same standard ZES operation. All patients were evaluated yearly with imaging studies and disease activity studies. Results: The 35 nonsurgical patients did not differ from the 160 operated in clinical, laboratory, or tumor imaging results. The 2 groups did not differ in follow-up time since initial evaluation (range, 11.8–12 years). At surgery, 94% had a tumor removed, 51% were cured immediately, and 41% at last follow-up. Significantly more unoperated patients developed liver metastases (29% vs. 5%, P = 0.0002), died of any cause (54 vs. 21%, P = 0.0002), or died a disease-related death (23 vs. 1%, P < 0.00001). Survival plots showed operated patients had a better disease-related survival (P = 0.0012); however, there was no difference in non-disease-related survival. Fifteen-year disease-related survival was 98% for operated and 74% for unoperated (P = 0.0002). Conclusions: These results demonstrate that routine surgical exploration increases survival in patients with

  3. MiR-21 Expression in the Tumor Stroma of Oral Squamous Cell Carcinoma: An Independent Biomarker of Disease Free Survival

    PubMed Central

    Specht, Lena; Fiehn, Anne-Marie K.; Therkildsen, Marianne H.; Friis-Hansen, Lennart; Dabelsteen, Erik; von Buchwald, Christian

    2014-01-01

    Oral squamous cell carcinoma (OSCC) patients have a high mortality rate; thus, new clinical biomarkers and therapeutic options are needed. MicroRNAs (miRNAs) are short noncoding RNAs that regulate posttranscriptional gene expression and are commonly deregulated in OSCC and other cancers. MicroRNA-21 (miR-21) is the most consistently overexpressed miRNA in several types of cancer, and it might be a useful clinical biomarker and therapeutic target. To better understand the role of miR-21 in OSCC, paraffin-embedded tumor tissue samples from 86 patients with primary OSCC were analyzed by in situ hybridization. We found that miR-21 was primarily expressed in the tumor stroma and in some tumor-associated blood vessels with no expression in the adjacent normal epithelia or stroma. Using image analysis, we quantitatively estimated miR-21 expression levels specifically in the stroma of a cohort of OSCC samples. These miR-21 levels significantly correlated with disease free survival with the highest levels being located in the stroma. Stromal miR-21 expression was independently associated with a poorer prognosis, even after adjusting for clinical parameters (perineural invasion and N-stage) in a multivariate analysis. In summary, we have shown that miR-21 is located in the carcinoma cells, stroma and blood vessels of tumors, and its expression specifically in the stromal compartment has a negative prognostic value in OSCC. PMID:24755828

  4. Twenty-year survival analysis in total knee arthroplasty by a single surgeon.

    PubMed

    Bae, Dae Kyung; Song, Sang Jun; Park, Man Jun; Eoh, Jae Hyung; Song, Jong Hoon; Park, Cheol Hee

    2012-08-01

    Between January 1988 and December 2006, a total of 3014 primary total knee arthroplasties (TKAs) in 2042 patients were performed, and survivorship analysis was performed. Survivorship analysis showed a 10-year survival of 93.8% and a 20-year survival of 70.9%. There was no significant difference in the survival rate according to sex and diagnosis (P = .142 and .443, respectively). The survival rate was higher in the patients older than 60 years (P < .001). The survival rate of Total Condylar IV (TC-IV) was higher than that of Ortholoc (Dow Corning Wright Medical, Arlington, Tenn) (P < .001). Total knee arthroplasty results in satisfactory long-term survival rates. However, the survival rate decreases over time. The risk of requiring revision TKA was related to age and type of implants. Careful consideration is necessary to decide the time for TKA and select type of implants. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  5. High-volume ovarian cancer care: survival impact and disparities in access for advanced-stage disease.

    PubMed

    Bristow, Robert E; Chang, Jenny; Ziogas, Argyrios; Randall, Leslie M; Anton-Culver, Hoda

    2014-02-01

    To characterize the impact of hospital and physician ovarian cancer case volume on survival for advanced-stage disease and investigate socio-demographic variables associated with access to high-volume providers. Consecutive patients with stage IIIC/IV epithelial ovarian cancer (1/1/96-12/31/06) were identified from the California Cancer Registry. Disease-specific survival analysis was performed using Cox-proportional hazards model. Multivariate logistic regression analyses were used to evaluate for differences in access to high-volume hospitals (HVH) (≥20 cases/year), high-volume physicians (HVP) (≥10 cases/year), and cross-tabulations of high- or low-volume hospital (LVH) and physician (LVP) according to socio-demographic variables. A total of 11,865 patients were identified. The median ovarian cancer-specific survival for all patients was 28.2 months, and on multivariate analysis the HVH/HVP provider combination (HR = 1.00) was associated with superior ovarian cancer-specific survival compared to LVH/LVP (HR = 1.31, 95%CI = 1.16-1.49). Overall, 2119 patients (17.9%) were cared for at HVHs, and 1791 patients (15.1%) were treated by HVPs. Only 4.3% of patients received care from HVH/HVP, while 53.1% of patients were treated by LVH/LVP. Both race and socio-demographic characteristics were independently associated with an increased likelihood of being cared for by the LVH/LVP combination and included: Hispanic race (OR = 1.72, 95%CI = 1.22-2.42), Asian/Pacific Islander race (OR = 1.57, 95%CI = 1.07-2.32), Medicaid insurance (OR = 2.51, 95%CI = 1.46-4.30), and low socioeconomic status (OR = 2.84, 95%CI = 1.90-4.23). Among patients with advanced-stage ovarian cancer, the provider combination of HVH/HVP is an independent predictor of improved disease-specific survival. Access to high-volume ovarian cancer providers is limited, and barriers are more pronounced for patients with low socioeconomic status, Medicaid insurance, and racial minorities. Copyright © 2013

  6. Thirteen-year nationwide trends in use of implantable cardioverter-defibrillators and subsequent long-term survival.

    PubMed

    Schmidt, Morten; Pedersen, Susanne Bendesgaard; Farkas, Dóra Körmendiné; Hjortshøj, Søren Pihlkjær; Bøtker, Hans Erik; Nielsen, Jens Cosedis; Sørensen, Henrik Toft

    2015-09-01

    Long-term trends in use of implantable cardioverter-defibrillators (ICDs) and outcomes are rare. We examined 13-year nationwide trends in ICD implantation and survival rates in Denmark. Using medical databases, we identified all first time ICD recipients in Denmark during 2000-2012 (N = 8460) and ascertained all-cause mortality. We computed standardized annual implantation rates and mortality rate ratios according to age, sex, comorbidity level, indication, and device type. The standardized annual implantation rate increased from 42 per million persons in 2000 to 213 per million persons in 2012 (from 34 to 174 for men and from 8 to 39 for women). The increase was driven by secondary prophylactic ICDs until 2006 and primary prophylactic ICDs thereafter. The increase occurred particularly in older patients and those with a high level of comorbidity. Independent of indication, 76% of all patients with ICD were alive after 5 years. Men had a higher mortality rate compared with women (mortality rate ratio 1.28; 95% confidence interval 1.10-1.49). Compared with low comorbidity level, moderate, severe, and very severe comorbidity levels were associated with 1.6-, 2.5-, and 4.9-fold increased mortality rates, respectively. The most influential individual comorbidities were heart failure, diabetes, liver disease, and renal disease. The annual implantation rate of ICDs increased 5-fold in Denmark between 2000 and 2012. The rate increase occurred for both men and women, but particularly in the elderly and patients with severe comorbidity. Five-year survival probability was high, but severe comorbidity and male sex were associated with shorter survival. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  7. Hostility as a predictor of survival in patients with coronary artery disease.

    PubMed

    Boyle, Stephen H; Williams, Redford B; Mark, Daniel B; Brummett, Beverly H; Siegler, Ilene C; Helms, Michael J; Barefoot, John C

    2004-01-01

    This article presents a reanalysis of an earlier study that reported a nonsignificant relation between the 50-item Cook-Medley Hostility Scale (CMHS) and survival in a sample of coronary patients. Since publication of those results, there have been significant developments in the measurement of hostility that suggest that an abbreviated scale may be a better predictor of health outcomes. This study examined the ability of the total CMHS and an abbreviated form of the CMHS (ACM) to predict survival in a sample of patients with documented coronary artery disease (CAD) with increased statistical power. Nine hundred thirty-six patients (83% were male; mean age = 51.48) with CAD who were followed for an average of 14.9 years. The ACM consisted of the combination of the cynicism, hostile attribution, hostile affect, and aggressive responding subscales that were identified in an earlier study (Barefoot et al. [1989]) by a rational analysis of the item content. The relation between hostility and survival was examined with Cox proportional hazard models (hazard ratios [HRs] based on a two standard deviation difference). Controlling for disease severity, the ACM was a significant predictor for both CHD mortality (HR = 1.33, p <.009) and total mortality (HR = 1.28, p <.02). The total CMHS was only a marginally significant predictor of either outcome (p values < 0.06). The results of this study suggest that hostility is associated with poorer survival in CAD patients, and it may be possible to refine measures of hostility in order to improve prediction of health outcomes.

  8. Survival with breast cancer: the importance of estrogen receptor quantity.

    PubMed

    Shek, L L; Godolphin, W

    1989-02-01

    The survival of 1184 British Columbian women whose primary breast cancers were diagnosed and assayed for estrogen receptor (ER) between 1975 and 1981 was studied. Median follow-up was 60 months. ER concentrations yielded greater prognostic information than simple positive and negative categories. When ER data were divided into four strata: less than or equal to 1, 2-9, 10-159 and greater than or equal to 160 fmol/mg cytosol protein, the association of higher ER with prolonged survival was highly significant (P less than 0.0001) and independent of TNM stage, nodal status and menopausal status. ER less than or equal to 1 and ER = 2-9 groups were distinct with respect to overall disease-specific survival. Patient age did not predict survival when controlled for ER. Prolonged recurrence-free survival was associated with higher ER (P = 0.0001) for at least 5 years after diagnosis. This significant trend persisted after adjustments for nodal status, TNM stage, menopausal status and the type of systemic adjuvant therapy.

  9. 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.

  10. Pretreatment Serum Testosterone and Androgen Deprivation: Effect on Disease Recurrence and Overall Survival in Prostate Cancer Patients Treated With Brachytherapy

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

    Taira, Al V.; Merrick, Gregory S.; Galbreath, Robert W.

    Purpose: Low testosterone has been implicated as a possible adverse prognostic factor in patients with newly diagnosed prostate cancer. We evaluated the impact of pretreatment serum testosterone on survival after prostate brachytherapy. Methods and Materials: From October 2001 to November 2004, 619 patients underwent brachytherapy and 546 had a pretreatment serum testosterone level measured. Pretreatment serum testosterone levels were assigned by the following criteria: below-normal (n = 105), low normal (n = 246), mid normal (n = 132), high normal (n = 50), and above normal (n = 13). Median follow-up was 5.2 years. Cause of death was determined formore » each deceased patient. Results: Six-year biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) were 97.7%, 99.8%, and 89.2%. When comparing patients with low or low normal testosterone with those with average or higher testosterone, there was no significant difference in bPFS (97.6% vs. 98.4%; p = 0.72), CSS (99.8% vs. 100%; p = 0.72), or OS (88.9% vs. 90.8%; p = 0.73). Among patients with average and higher pretreatment testosterone, there was no significant difference in outcomes when comparing patients who did and did not receive androgen deprivation therapy (ADT). For patients with low or low normal testosterone levels, there was no significant difference in bPFS or CSS when comparing patients who did and did not receive ADT. However, there was a trend toward lower OS in patients with baseline lower testosterone levels who also received ADT (83.9% vs. 91.3%, p = 0.075). Conclusions: Low pretreatment testosterone levels alone did not affect disease recurrence or OS. Patients with baseline low testosterone who also were treated with ADT had a trend toward decreased OS.« less

  11. Implantable Cardioverter Defibrillator Programming Characteristics, Shocked Rhythms, and Survival Among Patients Under Thirty Years of Age.

    PubMed

    Chang, Philip M; Powell, Brian D; Jones, Paul W; Carter, Nathan; Hayes, David L; Saxon, Leslie A

    2016-10-01

    Indications for implantable cardioverter defibrillators (ICDs) in young patients have expanded and differ from those in older adults. We sought to provide descriptive characteristics and data regarding ICD therapy and outcomes among younger and older ICD recipients. Demographics, device type and programming, remotely transmitted data, shock events, and survival were compared among younger (≤30 years) and older (>30 years) cohorts with ICDs from a single manufacturer followed on a remote network. The younger cohort included 904 patients (1.6% of all implants). This group had more females (46% vs. 25%; P < 0.01), single-coil leads (21% vs. 4%; P < 0.01), and single-chamber devices (46% vs. 34%; P < 0.01). Shock incidence was higher (40% younger vs. 32% older at 4 years; P < 0.01) and survival was better over comparable follow-up (88% vs. 72%; P < 0.01). Remote monitoring was associated with improved survival in both groups (93% vs. 86% ≤ 30 years, P < 0.01; 73% vs. 66% > 30 years, P < 0.01). Shock for polymorphic ventricular tachycardia/fibrillation (VT/VF) was more frequent in younger patients (12% vs. 5%; P < 0.01); 39% of all shocks were inappropriate. A 10-fold increased risk of mortality was seen among young patients with shocks for atrial fibrillation/flutter (AF/AFL). Differences in survival, shock incidence, and prognostic significance of VT/VF and AF/AFL exist between younger and older ICD recipients. These suggest distinct differences in myocardial substrates and diseases that ultimately impact ICD management. © 2016 Wiley Periodicals, Inc.

  12. Cognitive decline and survival in Alzheimer's disease according to education level.

    PubMed

    Bruandet, A; Richard, F; Bombois, S; Maurage, C A; Masse, I; Amouyel, P; Pasquier, F

    2008-01-01

    We tested the hypothesis that a higher education level is associated with faster cognitive decline and lower survival in a cohort of 670 Alzheimer's disease patients, followed for 3.5 years at the Lille-Bailleul memory centre. The patients were categorized in 3 groups according to educational levels: low (years), intermediate (9-12 years) and high (>12 years). Cognitive function was measured with the Mini Mental State Examination (MMSE) and the Mattis Dementia Rating Scale (DRS). Survival was analyzed with a Cox model. Analyses were adjusted for age, sex, cholinesterase inhibitor treatment, diabetes, hypertension, visible vascular lesions on MRI, baseline DRS and MMSE. The adjusted mixed random model showed that MMSE declined faster for patients with high and intermediate educational levels compared with those with a low educational level (p < 0.0001). The mean annually adjusted DRS decline was highest for the groups with the most education (p = 0.05). The mortality risk was not higher in the better-educated groups (high vs. low: RR = 0.84; 95% CI = 0.35-1.99, intermediate vs. low: RR = 0.82; 95% CI = 0.41-1.63). In our cohort, highly educated patients had a faster cognitive decline than less educated patients but similar mortality rates. Our findings support the cognitive reserve hypothesis. (c) 2007 S. Karger AG, Basel.

  13. Concomitant coronary artery bypass graft and aortic and mitral valve replacement for rheumatic heart disease: short- and mid-term outcomes.

    PubMed

    Davarpasand, Tahereh; Hosseinsabet, Ali; Jalali, Arash

    2015-09-01

    It has been reported that the short-term mortality of concomitant aortic and mitral valve replacement (AVR and MVR) is considerable and concomitant coronary artery bypass graft (CABG) has adverse effects on the survival of patients with valve replacement surgery. We summarize the short- and mid-term outcome after concomitant CABG, AVR and MVR in our centre. Between 2003 and 2013, 103 patients (68 males, 35 females, age: 60.1 ± 10.1 years) underwent CABG, AVR and MVR for rheumatic heart disease (RHD) and coronary artery disease (CAD). The median follow-up was 47.6 months. Most of the patients were asymptomatic at rest. We analysed demographic, clinical and operative data of patients to define independent predictors of overall survival, cardiac event-free survival as well as cardiac death. The rate of 30-day survival was 93% (n = 96). The corresponding rates of overall survival and cardiac event-free survival and the cumulative incidence rate of cardiac death at 1 year were 80.2, 77.3 and 10.9%; the same at 4 years were 73.7, 64.6 and 15.8%. The corresponding freedom rates from anticoagulation-associated major haemorrhage; a composite of major bleeding events, thromboemboli and valvular thrombosis; cardiac rehospitalization; major adverse valve-associated events; and significant malfunction of the prosthetic valve were 96.2, 95.3, 94.7, 81.6 and 97.7% at 1 year. The corresponding freedom rates from anticoagulation-associated major haemorrhage; a composite of major bleeding events, thromboemboli and valvular thrombosis; cardiac rehospitalization; major adverse valve-associated events; and significant malfunction of the prosthetic valve were 93.5, 91.0, 91.4, 73.5 and 95.5% at 4 years. The independent predictors of overall survival were age, cigarette smoking, chronic kidney diseases and balloon pump insertion. The independent predictors of cardiac event-free survival were age and previous myocardial infarction, while age, cigarette smoking, history of cerebrovascular

  14. Radiotherapy for stage I Hodgkin's disease: 20 years experience at St Bartholomew's Hospital.

    PubMed Central

    Ganesan, T. S.; Wrigley, P. F.; Murray, P. A.; Stansfeld, A. G.; d'Ardenne, A. J.; Arnott, S.; Jones, A.; Shand, W. S.; Malpas, J. S.; Lister, T. A.

    1990-01-01

    One hundred and one consecutive patients with newly diagnosed stage I Hodgkin's disease (HD) received treatment at St Bartholomew's Hospital, between 1968 and 1987, with a median follow-up of 12 years. Eleven patients have been excluded from detailed analysis because they either received involved field radiotherapy (RT) or radiotherapy with chemotherapy or were lost to follow-up. Actuarial analysis predicts 78% to be alive and without relapse of Hodgkin's disease at 15 years. Ninety evaluable patients (clinical stage (CS) 24; pathological stage (PS) 66) received either mantle or inverted 'Y' RT and form the basis of this analysis. The median age was 33 years (63 men, 27 women). Histology at presentation was nodular sclerosing (39), lymphocytic predominant (27) or mixed cellularity (24). The presenting site was neck (78), axilla (6) groin (4) and mediastinum (2). Complete remission was achieved in all evaluable patients, the actuarial proportion in remission being 75% at 15 years. Factors predictive of a prolonged remission were pathological staging versus clinical staging (P = 0.02) and lymph node size less than 3 cm (P = 0.04). Actuarial overall survival in these 90 patients was 75% at 15 years and none of the above factors correlated with survival. Relapse of HD has occurred in 18 patients (5 within RT field, 10 without and 3 in both). Second remission was achieved in 15/18. The actuarial rate of second remission and survival was 40% at 10 years. Sixteen patients have died, 7 of Hodgkin's disease, 7 of unrelated causes and 2 of second malignancy. A further 3 patients who developed second malignancy are still alive. At 15 years the actuarial mortality related to HD was 12%. These results confirm the importance of long follow up to assess the efficacy of primary therapy. PMID:2386750

  15. Vulnerabilities in Older Patients when Cancer Treatment is Initiated: Does a Cognitive Impairment Impact the Two-Year Survival?

    PubMed Central

    Borghgraef, Cindy; Etienne, Anne-Marie; Merckaert, Isabelle; Paesmans, Marianne; Reynaert, Christine; Roos, Myriam; Slachmuylder, Jean-Louis; Vandenbossche, Sandrine; Bron, Dominique; Razavi, Darius

    2016-01-01

    Introduction Dementia is a known predictor of shorter survival times in older cancer patients. However, no empirical evidence is available to determine how much a cognitive impairment shortens survival in older patients when cancer treatment is initiated. Purpose To longitudinally investigate how much a cognitive impairment detected at the initiation of cancer treatment influences survival of older patients during a two-year follow-up duration and to compare the predictive value of a cognitive impairment on patients survival with the predictive value of other vulnerabilities associated with older age. Methods Three hundred and fifty-seven consecutive patients (≥65 years old) admitted for breast, prostate, or colorectal cancer surgeries were prospectively recruited. A cognitive impairment was assessed with the Montreal Cognitive Assessment (MoCA<26). Socio-demographic, disease-related, and geriatric vulnerabilities were assessed using validated tools. Univariate and subsequent multivariate Cox proportional hazards models stratified for diagnosis (breast/prostate cancer versus colorectal cancer) and disease status (metastatic versus non-metastatic) were used. Results A cognitive impairment was detected in 46% (n = 163) of patients. Survival was significantly influenced by a cognitive impairment (HR = 6.13; 95% confidence interval [CI] = 2.07–18.09; p = 0.001), a loss in instrumental autonomy (IADL ≤7) (HR = 3.06; 95% CI = 1.31–7.11; p = 0.009) and fatigue (Mob-T<5) (HR = 5.98; 95% CI = 2.47–14.44; p <0.001). Conclusions During the two years following cancer treatment initiation, older patients with a cognitive impairment were up to six times more likely to die than patients without. Older patients should be screened for cognitive impairments at cancer treatment initiation to enable interventions to reduce morbidity and mortality. Further studies should address processes underlying the relationship between cognitive impairments and an increased risk of dying

  16. MicroRNA-137 promoter methylation is associated with poorer overall survival in patients with squamous cell carcinoma of the head and neck

    PubMed Central

    Langevin, Scott M.; Stone, Roslyn A.; Bunker, Clareann H.; Lyons-Weiler, Maureen A.; LaFramboise, William A.; Kelly, Lori; Seethala, Raja R.; Grandis, Jennifer R.; Sobol, Robert W.; Taioli, Emanuela; PhD, MD

    2010-01-01

    BACKGROUND The overall 5-year survival rate of approximately 60% for head and neck cancer patients has remained essentially unchanged over the past 30 years. MicroRNA-137 (miR-137) plays an essential role in cell cycle control at the G1/S phase checkpoint. However, aberrant miR-137 promoter methylation observed in squamous cell carcinoma of the head and neck (SCCHN) suggests a tumor-specific molecular defect that may contribute to disease progression. METHODS The goal of this study is to assess, in formalin-fixed paraffin-embedded tumor tissue, the association between miR-137 promoter methylation and survival (both overall and disease-free) and with prognostic factors including stage, tumor size, nodal positivity, tumor grade and surgical tumor margin positivity. RESULTS Promoter methylation status of miR-137 was ascertained by methylation-specific PCR and detected in 11/67 SCCHN patients (16.4%), with no significant differences according to site (oral cavity, pharynx, larynx). Methylation of the miR-137 promoter was significantly associated with overall survival (Hazard Ratio = 3.68, 95% Confidence Interval: 1.01–13.38) but not with disease-free survival or any of the prognostic factors evaluated. CONCLUSIONS This study indicates that miR-137 is methylated in tumor tissue from pharyngeal and laryngeal squamous cancers, in addition to oral squamous cell carcinoma; and that miR-137 promoter methylation has potential utility as a prognostic marker for SCCHN. PMID:21425146

  17. Mesorectal Invasion Depth in Rectal Carcinoma Is Associated With Low Survival.

    PubMed

    Lino-Silva, Leonardo S; Loaeza-Belmont, Reynaldo; Gómez Álvarez, Miguel A; Vela-Sarmiento, Itzel; Aguilar-Romero, José M; Domínguez-Rodríguez, Jorge A; Salcedo-Hernández, Rosa A; Ruiz-García, Erika B; Maldonado-Martínez, Héctor A; Herrera-Gómez, Ángel

    2017-03-01

    Most cases of rectal cancer (RC) in our institution are in pathologic stage T3. They are a heterogeneous group but have been classified in a single-stage category. We performed the present study to validate the prognostic significance of the mesorectal extension depth (MED) in T3 RC measured in millimeters beyond the muscularis propria plane. We performed a retrospective analysis of 104 patients with T3 RC who had undergone curative surgery after a course of preoperative chemoradiotherapy at a tertiary referral cancer hospital. The patients were grouped by MED (T3a, < 1 mm; T3b, 1-5 mm; T3c > 5-10 mm; and T3d > 10 mm). The clinicopathologic data and disease-free survival were analyzed. The 5-year disease-free survival rate according to the T3 subclassification was 87.5% for those with T3a, 57.9% for T3b, 38.7% for T3c, and 40.3% for those with T3d tumors (P = .050). On univariate and multivariate analysis, the prognostic factors affecting survival were overall recurrence (hazard ratio [HR], 3.670; 95% confidence interval [CI], 1.710-7.837; P = .001), histologic grade (HR, 2.204; 95% CI, 1.156-4.199; P = .016), mesorectal invasion depth (HR, 1.885; 95% CI, 1.164-3.052; P = .010), and lymph node metastasis (HR, 1.211; 95% CI, 1.015-1.444; P = .033). MED is a significant prognostic factor in patients with T3 RC who have undergone neoadjuvant chemoradiotherapy, especially when the MED is > 5 mm. The MED could be as important as other clinicopathologic factors in predicting disease-specific survival. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Primary Sinonasal Malignant Melanoma: Effect of Clinical and Histopathologic Prognostic Factors on Survival.

    PubMed

    Göde, Sercan; Turhal, Göksel; Tarhan, Ceyda; Yaman, Banu; Kandiloğlu, Gülşen; Öztürk, Kerem; Kaya, İsa; Midilli, Raşit; Karcı, Bülent

    2017-05-05

    Mucosal melanoma is a rare malignancy arising from melanocytes of the mucosal surfaces. The pattern and frequency of oncogenic mutations and histopathological biomarkers have a role on distinct tumour behaviour and survival. To assess the rate of C-KIT positivity and its effect on survival of surgically treated sinonasal malignant melanoma patients with other histopathological biomarkers and clinical features. Retrospective cross-sectional study. Seventeen sinonasal malignant melanoma patients with a mean age of 65.41 (39-86) years were included. Overall survival and disease-specific survival rates were calculated. The impact of age, gender, stage and extent of the disease, type of surgery, and adjuvant therapies were also taken into consideration. The effect of mitotic index, pigmentation, S100, HMB-45, Melan-A and C-KIT on survival were evaluated. Median tumour size was 20 mm (interquartile range=27.5 mm). Pigmentation was present in 7 (41.2%) cases. Median number of mitoses per millimetre squared was 11 (interquartile range=13). Melan A was positive in 7 (41.2%) patients, ulceration was present in 6 cases (35.3%), and necrosis was present in (47.1%) 8 cases. Six patients (35.3%) were positive for S100, 14 (82.4%) specimens stained positive for HMB-45 and C-KIT (CD117) was positive in 9 cases (52.9%). Three patients (16.7%) developed distant metastasis. Five year overall and disease free survival rates were 61.4% and 43.8%, respectively. Although C-KIT positive sinonasal malignant melanoma patients (52.9%) can be candidates for targeted tumour therapies, the studied clinical or histopathological features along with C-KIT seem to have no significant effect on survival in a small group of patients with sinonasal malignant melanoma.

  19. Neoadjuvant rectal score as individual-level surrogate for disease-free survival in rectal cancer in the CAO/ARO/AIO-04 randomized phase 3 trial.

    PubMed

    Fokas, E; Fietkau, R; Hartmann, A; Hohenberger, W; Grützmann, R; Ghadimi, M; Liersch, T; Ströbel, P; Grabenbauer, G G; Graeven, U; Hofheinz, R-D; Köhne, C-H; Wittekind, C; Sauer, R; Kaufmann, M; Hothorn, T; Rödel, C

    2018-04-27

    Surrogate endpoints in rectal cancer after preoperative chemoradiation are lacking as their statistical validation poses major challenges, including confirmation based on large phase 3 trials. We examined the prognostic role and individual-level surrogacy of neoadjuvant rectal (NAR) score that incorporates weighted cT, ypT and ypN categories for disease-free survival (DFS) in 1191 patients with rectal carcinoma treated within the CAO/ARO/AIO-04 phase 3 trial. Cox regression models adjusted for treatment arm, resection status, and NAR score were used in multivariable analysis. The four Prentice criteria (PC1-4) were used to assess individual-level surrogacy of NAR for DFS. After a median follow-up of 50 months, the addition of oxaliplatin to fluorouracil-based chemoradiotherapy (CRT) significantly improved 3-year DFS (75.9% [95% CI 72.30-79.50] vs 71.3% [95% CI 67.60-74.90]; P = 0.034; PC 1) and resulted in a shift towards lower NAR groups (P = 0.034, PC 2) compared to fluorouracil-only CRT. The 3-year DFS was 91.7% (95% CI, 88.2 95.2), 81.8% (95% CI, 78.4-85.1) and 58.1 (95% CI 52.4-63.9) for low, intermediate and high NAR score, respectively (P < 0.001; PC 3). NAR score remained an independent prognostic factor for DFS (low vs high NAR: HR 4.670; 95% CI 3.106-7.020; P < 0.001; low vs intermediate NAR: HR 1.971; 95% CI 1.303-2.98; P = 0.001) in multivariable analysis. Notwithstanding the inherent methodological difficulty in interpretation of PC 4 to establish surrogacy, the treatment effect on DFS was captured by NAR, supporting satisfaction of individual-level PC4. Our study validates the prognostic role and individual-level surrogacy of NAR score for DFS within a large randomized phase 3 trial. NAR score could help oncologists to speed up response-adapted therapeutic decision, and further large phase 3 trial datasets should aim to confirm trial-level surrogacy.

  20. Associations of centrally acting ACE inhibitors with cognitive decline and survival in Alzheimer’s disease

    PubMed Central

    Fazal, Karim; Khondoker, Mizanur; Howard, Robert; Stewart, Robert

    2017-01-01

    Background Cognitive improvement has been reported in patients receiving centrally acting angiotensin-converting enzyme inhibitors (C-ACEIs). Aims To compare cognitive decline and survival after diagnosis of Alzheimer’s disease between people receiving C-ACEIs, non-centrally acting angiotensin-converting enzyme inhibitors (NC-ACEIs), and neither. Method Routine Mini-Mental State Examination (MMSE) scores were extracted in 5260 patients receiving acetylcholinesterase inhibitors and analysed against C-/NC-ACEI exposure at the time of Alzheimer’s disease diagnosis. Results In the 9 months after Alzheimer’s disease diagnosis, MMSE scores significantly increased by 0.72 and 0.19 points per year in patients on C-ACEIs and neither respectively, but deteriorated by 0.61 points per year in those on NC-ACEIs. There were no significant group differences in score trajectories from 9 to 36 months and no differences in survival. Conclusions In people with Alzheimer’s disease receiving acetylcholinesterase inhibitors, those also taking C-ACEIs had stronger initial improvement in cognitive function, but there was no evidence of longer-lasting influence on dementia progression. Declaration of interest R.S. has received research funding from Pfizer, Lundbeck, Roche, Janssen and GlaxoSmithKline. Copyright and usage © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:28713585

  1. Sinonasal mucosal melanoma: retrospective survival study of 25 patients.

    PubMed

    Vandenhende, C; Leroy, X; Chevalier, D; Mortuaire, G

    2012-02-01

    To determine potential prognostic factors for survival in patients with mucosal malignant melanoma of the sinonasal tract. Patients managed between 1991 and 2008 were assessed retrospectively. The seventh edition Union for International Cancer Control (7th UICC) tumour-node-metastasis classification was used for tumour staging. Kaplan-Meier and log rank tests were used for survival analysis. Twenty-five patients were studied (six were tumour stage three, eight tumour stage four(a) and 11 tumour stage four(b)). Surgery was performed on 23 patients (92 per cent). Fifteen received post-operative radiotherapy. Mean follow up was 31.3 months (range, two to 99 months). Three-year disease-free survival was improved in patients with stage four tumour arising from the nasal fossa, versus other sites, and in those with stage four tumour treated with surgery plus adjuvant radiotherapy, versus other treatments. Patients with melanoma of the nasal cavity have very poor survival rates. Treatment is still based on adequate surgical resection with safe margins. In this study, post-operative radiotherapy improved local control only for stage four tumours.

  2. Pre-treatment plasma proteomic markers associated with survival in oesophageal cancer.

    PubMed

    Kelly, P; Paulin, F; Lamont, D; Baker, L; Clearly, S; Exon, D; Thompson, A

    2012-02-28

    The incidence of oesophageal adenocarcinoma is increasing worldwide but survival remains poor. Neoadjuvant chemotherapy can improve survival, but prognostic and predictive biomarkers are required. This study built upon preclinical approaches to identify prognostic plasma proteomic markers in oesophageal cancer. Plasma samples collected before and during the treatment of oesophageal cancer and non-cancer controls were analysed by surface-enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) mass spectroscopy (MS). Protein peaks were identified by MS in tryptic digests of purified fractions. Associations between peak intensities obtained in the spectra and clinical endpoints (survival, disease-free survival) were tested by univariate (Fisher's exact test) and multivariate analysis (binary logistic regression). Plasma protein peaks were identified that differed significantly (P<0.05, ANOVA) between the oesophageal cancer and control groups at baseline. Three peaks, confirmed as apolipoprotein A-I, serum amyloid A and transthyretin, in baseline (pre-treatment) samples were associated by univariate and multivariate analysis with disease-free survival and overall survival. Plasma proteins can be detected prior to treatment for oesophageal cancer that are associated with outcome and merit testing as prognostic and predictive markers of response to guide chemotherapy in oesophageal cancer.

  3. Gluten-free diet may improve obstructive sleep apnea-related symptoms in children with celiac disease.

    PubMed

    Yerushalmy-Feler, Anat; Tauman, Riva; Derowe, Ari; Averbuch, Eran; Ben-Tov, Amir; Weintraub, Yael; Weiner, Dror; Amir, Achiya; Moran-Lev, Hadar; Cohen, Shlomi

    2018-02-07

    Enlarged tonsils and adenoids are the major etiology of obstructive sleep apnea (OSA) in children. Lymphatic hyperplasia is common to both OSA and celiac disease. We aimed to investigate the effect of a gluten-free diet on OSA symptoms in children with celiac disease. Children with celiac disease aged 2-18 years were prospectively recruited before the initiation of a gluten-free diet. Children with negative celiac serology who underwent gastrointestinal endoscopies for other indications served as controls. All participants completed a validated OSA-related symptoms questionnaire and the pediatric sleep questionnaire (PSQ) at baseline and 6 months later. Thirty-four children with celiac disease (mean age 6.6 ± 3.5 years) and 24 controls (mean age 7.3 ± 4.6 years, P = 0.5) were recruited. There were no significant differences in gender, body mass index or season at recruitment between the two groups. The rate of positive PSQ scores was higher (more OSA-related symptoms) in the control group compared to the celiac group, both at recruitment and at the 6-month follow-up (33.3% vs. 11.8%, P = 0.046, and 16.7% vs. 0, P = 0.014, respectively). PSQ scores improved significantly in both groups at the 6-month follow-up (P < 0.001 for both). Improvement was significantly higher in the celiac group compared to controls (0.1 ± 0.09 vs.0.06 ± 0.06, respectively, P = 0.04). Children with celiac disease had fewer OSA-related symptoms than controls, but the degree of improvement following the initiation of a gluten-free diet was significantly higher. These findings suggest that a gluten-free diet may improve OSA-related symptoms in children with celiac disease.

  4. Ovarian Suppression With Triptorelin During Adjuvant Breast Cancer Chemotherapy and Long-term Ovarian Function, Pregnancies, and Disease-Free Survival: A Randomized Clinical Trial.

    PubMed

    Lambertini, Matteo; Boni, Luca; Michelotti, Andrea; Gamucci, Teresa; Scotto, Tiziana; Gori, Stefania; Giordano, Monica; Garrone, Ornella; Levaggi, Alessia; Poggio, Francesca; Giraudi, Sara; Bighin, Claudia; Vecchio, Carlo; Sertoli, Mario Roberto; Pronzato, Paolo; Del Mastro, Lucia

    Whether the administration of luteinizing hormone-releasing hormone analogues (LHRHa) during chemotherapy is a reliable strategy to preserve ovarian function is controversial owing to both the lack of data on long-term ovarian function and pregnancies and the safety concerns about the potential negative interactions between endocrine therapy and chemotherapy. To evaluate long-term results of LHRHa-induced ovarian suppression during breast cancer chemotherapy. Parallel, randomized, open-label, phase 3 superiority trial conducted at 16 Italian sites. Between October 2003 and January 2008, 281 premenopausal women with stage I to III hormone receptor-positive or hormone receptor-negative breast cancer were enrolled. Last annual follow-up was June 3, 2014. Patients were randomized to receive adjuvant or neoadjuvant chemotherapy alone (control group) or chemotherapy plus triptorelin (LHRHa group). The primary planned end point was incidence of chemotherapy-induced early menopause. Post hoc end points were long-term ovarian function (evaluated by yearly assessment of menstrual activity and defined as resumed by the occurrence of at least 1 menstrual cycle), pregnancies, and disease-free survival (DFS). A total of 281 women (median age, 39 [range, 24-45] years) were randomized. Median follow-up was 7.3 years (interquartile range, 6.3-8.2 years). The 5-year cumulative incidence estimate of menstrual resumption was 72.6% (95% CI, 65.7%-80.3%) among the 148 patients in the LHRHa group and 64.0% (95% CI, 56.2%-72.8%) among the 133 patients in the control group (hazard ratio [HR], 1.28 [95% CI, 0.98-1.68]; P = .07; age-adjusted HR, 1.48 [95% CI, 1.12-1.95]; P = .006). Eight pregnancies (5-year cumulative incidence estimate of pregnancy, 2.1% [95% CI, 0.7%-6.3%]) occurred in the LHRHa group and 3 (5-year cumulative incidence estimate of pregnancy, 1.6% [95% CI, 0.4%-6.2%]) in the control group (HR, 2.56 [95% CI, 0.68-9.60]; P = .14; age-adjusted HR, 2.40 [95% CI, 0

  5. Vaccination of free-living juvenile wild rabbits (Oryctolagus cuniculus) against myxomatosis improved their survival.

    PubMed

    Guitton, Jean-Sébastien; Devillard, Sébastien; Guénézan, Michel; Fouchet, David; Pontier, Dominique; Marchandeau, Stéphane

    2008-04-17

    For several decades, the populations of the European wild rabbit (Oryctolagus cuniculus) have declined, which is partly due to myxomatosis. Vaccination against this disease is expected to contribute to restoration of rabbit populations but the actual impact of myxomatosis is not well known and vaccination might have some negative effects. We analyzed the capture-mark-recapture data obtained in a 4-year field experiment (1991-1994) in a park near Paris, France wherein 300 out of 565 seronegative juvenile rabbits were vaccinated at first capture against myxomatosis with the nontransmissible Dervaximyxo SG33 vaccine. After accounting for weight at first capture, age-class (juvenile/adult), "trap-happiness" and season (spring/autumn) of the capture event, vaccinated rabbits had 1.8-fold greater odds of surviving than the unvaccinated rabbits. The average summer survival risk for vaccinated juveniles was 0.63 (+/-0.08 S.E.) whereas it was 0.48 (+/-0.08 S.E.) for unvaccinated juvenile rabbits.

  6. Fifteen-Year Survival of Endoscopic Anterior Cruciate Ligament Reconstruction in Patients Aged 18 Years and Younger.

    PubMed

    Morgan, Matthew D; Salmon, Lucy J; Waller, Alison; Roe, Justin P; Pinczewski, Leo A

    2016-02-01

    The current body of literature surrounding anterior cruciate ligament (ACL) survival and the variables contributing to further ACL injuries after primary ACL reconstruction in children and adolescents is limited, with no long-term evidence examining the incidence and contributing factors of further ACL injuries in this younger patient population. To determine the long-term survival of the ACL graft and the contralateral ACL (CACL) after primary reconstruction in patients aged ≤18 years and to identify the factors that increase the odds of subsequent ACL injuries. Case series; Level of evidence, 4. Patients having undergone primary ACL reconstruction at age ≤18 years between 1993 and 1998 who were included in a prospective database by a single surgeon were considered for this study. Single-incision endoscopic ACL reconstruction was performed with either an autologous bone-patellar tendon-bone graft or a hamstring tendon graft. At a minimum of 15 years after ACL reconstruction, patients completed a subjective survey involving the International Knee Documentation Committee (IKDC) questionnaire in addition to questions regarding current symptoms, further ACL injuries, family history of ACL injury, and current level of activity. A total of 288 adolescents (age range, 13-18 years) met the inclusion criteria, of whom 242 (84%) were reviewed at a mean of 16 years and 6 months after ACL reconstruction. Of these patients, 75 (31%) sustained a further ACL injury: 27 (11.2%) suffered an ACL graft rupture, 33 suffered a CACL injury (13.6%), and 15 sustained both an ACL graft rupture and a CACL injury (6.2%) over 15 years. Survival of the ACL graft was 95%, 92%, 88%, 85%, and 83% at 1, 2, 5, 10, and 15 years, respectively, and survival of the CACL was 99%, 98%, 90%, 83%, and 81%, respectively. Survival of the ACL graft was less favorable in those with a family history of ACL injury than in those without a family history (69% vs 90%, respectively; hazard ratio [HR], 3.6; P

  7. The lyme disease pathogen has no effect on the survival of its rodent reservoir host.

    PubMed

    Voordouw, Maarten J; Lachish, Shelly; Dolan, Marc C

    2015-01-01

    Zoonotic pathogens that cause devastating morbidity and mortality in humans may be relatively harmless in their natural reservoir hosts. The tick-borne bacterium Borrelia burgdorferi causes Lyme disease in humans but few studies have investigated whether this pathogen reduces the fitness of its reservoir hosts under natural conditions. We analyzed four years of capture-mark-recapture (CMR) data on a population of white-footed mice, Peromyscus leucopus, to test whether B. burgdorferi and its tick vector affect the survival of this important reservoir host. We used a multi-state CMR approach to model mouse survival and mouse infection rates as a function of a variety of ecologically relevant explanatory factors. We found no effect of B. burgdorferi infection or tick burden on the survival of P. leucopus. Our estimates of the probability of infection varied by an order of magnitude (0.051 to 0.535) and were consistent with our understanding of Lyme disease in the Northeastern United States. B. burgdorferi establishes a chronic avirulent infection in their rodent reservoir hosts because this pathogen depends on rodent mobility to achieve transmission to its sedentary tick vector. The estimates of B. burgdorferi infection risk will facilitate future theoretical studies on the epidemiology of Lyme disease.

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

    PubMed

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

    2018-01-01

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

  9. Vaccination With Patient-Specific Tumor-Derived Antigen in First Remission Improves Disease-Free Survival in Follicular Lymphoma

    PubMed Central

    Schuster, Stephen J.; Neelapu, Sattva S.; Gause, Barry L.; Janik, John E.; Muggia, Franco M.; Gockerman, Jon P.; Winter, Jane N.; Flowers, Christopher R.; Nikcevich, Daniel A.; Sotomayor, Eduardo M.; McGaughey, Dean S.; Jaffe, Elaine S.; Chong, Elise A.; Reynolds, Craig W.; Berry, Donald A.; Santos, Carlos F.; Popa, Mihaela A.; McCord, Amy M.; Kwak, Larry W.

    2011-01-01

    Purpose Vaccination with hybridoma-derived autologous tumor immunoglobulin (Ig) idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) and administered with granulocyte-monocyte colony-stimulating factor (GM-CSF) induces follicular lymphoma (FL) –specific immune responses. To determine the clinical benefit of this vaccine, we conducted a double-blind multicenter controlled phase III trial. Patients and Methods Treatment-naive patients with advanced stage FL achieving complete response (CR) or CR unconfirmed (CRu) after chemotherapy were randomly assigned two to one to receive either Id vaccine (Id-KLH + GM-CSF) or control (KLH + GM-CSF). Primary efficacy end points were disease-free survival (DFS) for all randomly assigned patients and DFS for randomly assigned patients receiving at least one dose of Id vaccine or control. Results Of 234 patients enrolled, 177 (81%) achieved CR/CRu after chemotherapy and were randomly assigned. For 177 randomly assigned patients, including 60 patients not vaccinated because of relapse (n = 55) or other reasons (n = 5), median DFS between Id-vaccine and control arms was 23.0 versus 20.6 months, respectively (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.16; P = .256). For 117 patients who received Id vaccine (n = 76) or control (n = 41), median DFS after randomization was 44.2 months for Id-vaccine arm versus 30.6 months for control arm (HR, 0.62; 95% CI, 0.39 to 0.99; P = .047) at median follow-up of 56.6 months (range, 12.6 to 89.3 months). In an unplanned subgroup analysis, median DFS was significantly prolonged for patients receiving IgM-Id (52.9 v 28.7 months; P = .001) but not IgG-Id vaccine (35.1 v 32.4 months; P = .807) compared with isotype-matched control-treated patients. Conclusion Vaccination with patient-specific hybridoma-derived Id vaccine after chemotherapy-induced CR/CRu may prolong DFS in patients with FL. Vaccine isotype may affect clinical outcome and explain differing results between this and other

  10. Impact of age and sex on survival and causes of death in adults with congenital heart disease.

    PubMed

    Oliver, Jose Maria; Gallego, Pastora; Gonzalez, Ana Elvira; Garcia-Hamilton, Diego; Avila, Pablo; Alonso, Andres; Ruiz-Cantador, Jose; Peinado, Rafael; Yotti, Raquel; Fernandez-Aviles, Francisco

    2017-10-15

    The impact of gender and aging on relative survival and causes of death in adults with congenital heart disease (ACHD) are not well known. Single center observational longitudinal study of 3311 consecutive ACHD (50.5% males) followed up to 25years. Patients were divided by the age at last follow-up into three groups: <40, 40-65 and >65years old. Their vital status was verified by crosschecking the Spanish National Death Index. Regression model for relative survival from reference population was performed. Cause of death was classified according to the International Classification of Diseases (ICD-10). Patients who died from cardiovascular (CV) causes were further investigated on a case-by-case basis. During a cumulative follow-up time of 37,608 person-years 336 patients died (10%). Age-adjusted relative survival in females was significantly worse than in males (hazard ratio [HR] 1.25; 95% confidence interval [CI] 1.0-1.6; p=0.046), and sex-adjusted relative survival improved across the three group of ages (HR 0.98; 95% CI 0.97-0.99; p<0.001). There was a temporal decline of CV deaths with aging in both genders (p<0.001). The leading cause of CV death was heart failure but sudden death prevailed in subjects <40years (p=0.004). While sudden death progressively declined with aging heart failure significantly increased (p<0.001). Women with CHD fare worse than men. There are a decline in CV deaths and a major temporal shift in the causes of CV deaths with aging. Heart failure surpasses sudden death as the primary cause of death in survivors over 40years. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Radiotherapy timing in the treatment of limited-stage small cell lung cancer: the impact of thoracic and brain irradiation on survival.

    PubMed

    Scotti, Vieri; Meattini, Icro; Franzese, Ciro; Saieva, Calogero; Bertocci, Silvia; Meacci, Fiammetta; Furfaro, Ilaria; Scartoni, Daniele; Cecchini, Sara; Desideri, Isacco; Ferrari, Katia; Bruni, Alessio; De Luca Cardillo, Carla; Bastiani, Paolo; Agresti, Benedetta; Mangoni, Monica; Livi, Lorenzo; Biti, Giampaolo

    2014-01-01

    Small cell lung cancer is an aggressive histologic subtype of lung cancer in which the role of chemotherapy and radiotherapy has been well established in limited-stage disease. We retrospectively reviewed a series of limited-stage small cell lung cancers treated with chemotherapy and thoracic and brain radiotherapy. A total of 124 patients affected by limited-stage small cell lung cancer has been treated over 10 years in our Institute. Fifty-three patients (42.8%) had concomitant radio-chemotherapy treatment and 71 patients (57.2%) a sequential treatment. Eighty-eight patients (70.9%) underwent an association of a platinum-derived drug (cisplatinum or carboplatinum) and etoposide. Prophylactic cranial irradiation was planned in all patients with histologically proven complete response to primary radio-chemotherapy. With a mean follow-up of 2.2 years, complete response was obtained in 50.8% of cases. We found a significant difference between different radio-chemotherapy association approaches (P = 0.007): percentages of overall survival were respectively 10.0%, 12.9% and 5.6% in early, late concomitant and sequential radio-chemotherapy timing. Cranial prophylaxis did not seem to influence overall survival (P = 0.21) or disease-free survival for local relapse (P = 0.34). Concomitant radio-chemotherapy is the best approach according to our experience. Our results show a benefit of prophylactic cranial irradiation in distant metastasis-free survival.

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

    PubMed

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

    2015-11-01

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

  13. Impact of Blood Transfusions on Survival of Locally Advanced Cervical Cancer Patients Undergoing Neoadjuvant Chemotherapy Plus Radical Surgery.

    PubMed

    Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Lopez, Carlos; Indini, Alice; Leone Roberti Maggiore, Umberto; Sabatucci, Ilaria; Lorusso, Domenica; Raspagliesi, Francesco

    2017-03-01

    Transfusions represent one of the main progresses of modern medicine. However, accumulating evidence supports that transfusions correlate with worse survival outcomes in patients affected by solid cancers. In the present study, we aimed to investigate the effects of perioperative blood transfusion in locally advanced cervical cancer. Data of consecutive patients affected by locally advanced cervical cancer scheduled to undergo neoadjuvant chemotherapy plus radical surgery were retrospectively searched to test the impact of perioperative transfusions on survival outcomes. Five-year survival outcomes were evaluated using Kaplan-Meier and Cox models. The study included 275 patients. Overall, 170 (62%) patients had blood transfusion. Via univariate analysis, we observed that transfusion correlated with an increased risk of developing recurrence (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.09-4.40; P = 0.02). Other factors associated with 5-year disease-free survival were noncomplete clinical response after neoadjuvant chemotherapy (HR, 2.99; 95% CI, 0.92-9.63; P = 0.06) and pathological (P = 0.03) response at neoadjuvant chemotherapy as well as parametrial (P = 0.004), vaginal (P < 0.001), and lymph node (P = 0.002) involvements. However, via multivariate analysis, only vaginal (HR, 3.07; 95% CI, 1.20-7.85; P = 0.01) and lymph node involvements (HR, 2.4; 95% CI, 1.00-6.06; P = 0.05) correlate with worse disease-free survival. No association with worse outcomes was observed for patients undergoing blood transfusion (HR, 2.71; 95% CI, 0.91-8.03; P = 0.07). Looking at factors influencing overall survival, we observed that lymph node status (P = 0.01) and vaginal involvement (P = 0.06) were independently associated with survival. The role of blood transfusions in increasing the risk of developing recurrence in LAAC patients treated by neoadjuvant chemotherapy plus radical surgery remains unclear; further prospective studies are warranted.

  14. Pelvis Ewing sarcoma: Local control and survival in the modern era.

    PubMed

    Ahmed, Safia K; Robinson, Steven I; Arndt, Carola A S; Petersen, Ivy A; Haddock, Michael G; Rose, Peter S; Issa Laack, Nadia N

    2017-09-01

    Local control for Ewing sarcoma (ES) has improved in modern studies. However, it is unclear if these gains have also been achieved for pelvis tumors. The purpose of this study is to evaluate local control and survival in pelvis ES patients treated in the modern era. All pelvis ES patients diagnosed from 1990 to 2012 and seen at Mayo Clinic were identified. Factors relevant to survival and local control were analyzed. The cohort consisted of 48 patients. Fifty-two percent had metastatic disease at diagnosis. The 5-year overall survival and event-free survival was 73% and 65%, respectively, for localized disease. The 5-year cumulative incidence of local recurrence was 19%, with a 26% incidence for radiation, 13% for surgery, and 0% for surgery + radiation (P = 0.54). All local failures occurred in-field. Sacral involvement by tumor trended toward a higher incidence of local recurrence (hazard ratio 3.06, P = 0.09). Patients treated with definitive radiation doses ≥5,600 cGy had a lower incidence of local recurrence (17% vs. 28%, P = 0.61). Our study demonstrates excellent survival for localized tumors in the modern era. Anatomical localization within the pelvis likely correlates with outcomes. Local control remains problematic, especially for patients treated with definitive radiation. Though statistically not significant, surgery + radiation and definitive radiation dose ≥5,600 cGy were associated with the lowest incidence of local failure, suggesting treatment intensification may improve local control for pelvis ES. © 2017 Wiley Periodicals, Inc.

  15. 5-Fluorouracil Adjuvant Chemotherapy Does Not Increase Survival in Patients with CpG Island Methylator Phenotype Colorectal Cancer

    PubMed Central

    Jover, Rodrigo; Nguyen, Thuy-Phuong; Pérez-Carbonell, Lucía; Zapater, Pedro; Payá, Artemio; Alenda, Cristina; Rojas, Estefanía; Cubiella, Joaquín; Balaguer, Francesc; Morillas, Juan D.; Clofent, Juan; Bujanda, Luis; Reñé, Josep M; Bessa, Xavier; Xicola, Rosa M.; Nicolás-Pérez, David; Castells, Antoni; Andreu, Montserrat; Llor, Xavier; Boland, C. Richard; Goel, Ajay

    2011-01-01

    Background & Aims 5-FU-based adjuvant chemotherapy does not increase survival times of patients with colorectal tumors with microsatellite instability. We determined the response of patients with colorectal tumors with the CpG island methylator phenotype (CIMP) to 5-FU-based therapy. Methods We analyzed a population-based cohort of 302 patients with colorectal cancer (CRC) for a median follow-up time of 50.7 months. CIMP status was determined by analysis of the CACNAG1, SOCS1, RUNX3, NEUROG1, and MLH1 promoters; tumors were considered to be CIMP-positive (CIMP+) if at least 3 promoters were methylated. Results Tumors from 29.5% (89/302) of patients were CIMP+; this did not influence disease-free survival (log rank=.26). Of tumors of TNM stages II–III (n=196), 32.7% were CIMP+. Among patients with CRC stages II–III who did not receive adjuvant 5-FU chemotherapy, those with CIMP+ tumors had longest times of disease-free survival (log rank=.04); patients with CIMP+ tumors who received chemotherapy had shorter times of disease-free survival (log rank=0.02). In patients with CIMP-negative tumors, adjuvant 5-FU chemotherapy significantly increased time of disease-free survival (log-rank=.00001). However, in patients with CIMP+ tumors, adjuvant 5-FU chemotherapy did not affect time of disease-free survival (log rank=.7). Multivariate analysis showed a significant, independent interaction between 5-FU treatment and CIMP status (hazard ratio [HR]=0.6; 95% confidence interval [CI], .5–.8). Among patients with CIMP+ tumors, adjuvant chemotherapy was not an independent predictor of outcome (HR=0.8; 95% CI, 0.3–2.0). In patients who did not receive adjuvant 5-FU chemotherapy, CIMP status was the only independent predictor of survival (HR=2.0; 95% CI, 1.1–3.8) Conclusion Patients with CIMP+ colorectal tumors do not benefit from 5-FU–based adjuvant chemotherapy. PMID:21185836

  16. Survival Benefit of Japanese Extended Lymphadenectomy for Clinically Node-Negative and Node-Positive Colorectal Cancers.

    PubMed

    Ouchi, Akira; Komori, Koji; Kimura, Kenya; Kinoshita, Takashi; Shimizu, Yasuhiro; Nagino, Masato

    2018-02-01

    The impact of extended lymphadenectomy for colorectal cancer is still not sufficiently clear. The aim of the present study was to evaluate the survival benefit of extended lymphadenectomy compared with nonextended lymphadenectomy for clinically node-negative and node-positive colorectal cancers. The present study was a retrospective cohort study that used prospectively collected data and a propensity score matching method. The present study was conducted at a single specialized colorectal surgery department. Of the 1314 patients who underwent radical resection with nonextended or extended lymphadenectomy between 1988 and 2007, we included 711 and 603 patients in the cN0 and cN1/2 series. Propensity score matching was applied, and 141 and 63 pairs were extracted from the cN0 and cN1/2 series. Disease-free survival, cancer-specific survival, and overall survival of the 2 groups were calculated and compared. In the cN0 series, no differences were observed in the long-term outcomes between the nonextended and extended groups. In the cN1/2 series, the disease-free survival, cancer-specific survival and overall survival were significantly higher (log rank, p = 0.04, p = 0.02, and p = 0.01, respectively), and the frequency of local recurrence was significantly lower (p = 0.04) in the extended group. The present study was limited by its nonrandomized retrospective design. Extended lymphadenectomy demonstrated a good inhibitory effect on the local recurrence rate and led to improved disease-free survival, cancer-specific survival, and overall survival of patients in the cN1/2 series. See Video Abstract at http://links.lww.com/DCR/A517.

  17. Differences in patterns of survival in metastatic adenoid cystic carcinoma of the head and neck.

    PubMed

    van Weert, Stijn; Reinhard, Rinze; Bloemena, Elisabeth; Buter, Jan; Witte, Birgit I; Vergeer, Marije R; Leemans, C René

    2017-03-01

    We examined the assumption in conventional teaching about metastatic adenoid cystic carcinoma (ACC) being an indolent type of disease. A single center analysis of 105 cases of ACC was performed. Radiographs were reviewed and tumor response to chemotherapy was measured. Distant disease-free survival (DDFS) and time to death since distant metastases diagnosis were analyzed. Forty-two percent of the patients were diagnosed with distant metastases. DDFS showed significant negative associations with advanced T classification, N+ classification, solid type tumor, and positive surgical margins. Distant metastases (91%) developed in the first 5 years after presentation. Median distant metastatic survival was 13.8 months. The most frequent organ sited was the lung. Solid type ACC showed a preponderance for multiorgan metastases (17/28; 61%). Distant metastases seemed not to occur in case of clear surgical margins. Solid type ACC had a significant poorer survival after development of distant metastases. Metastatic ACC is not always an indolent disease. © 2016 Wiley Periodicals, Inc. Head Neck 39: 456-463, 2017. © 2016 Wiley Periodicals, Inc.

  18. Survival period after tube feeding in bedridden older patients.

    PubMed

    Kosaka, Yoichi; Nakagawa-Satoh, Takuma; Ohrui, Takashi; Fujii, Masahiko; Arai, Hiroyuki; Sasaki, Hidetada

    2012-04-01

    We prospectively studied survival periods after tube feeding. Participants were 163 bedridden older patients suffering from dysphagia. A wide range of survival periods after tube feeding were observed within half a year without tube feeding after being bedridden. After this initial period, survival periods after tube feeding were limited to approximately half a year. Survival periods after tube feeding were positively proportional to the length of time patients were free from pneumonia after tube feeding. After tube feeding, patients died from pneumonia within half a year, and the frequency of pneumonia was 3.1 ± 2.7 times (mean ± SD) before death. Survival periods after tube feeding for less than 1 year were primarily determined by being bedridden for more than half a year without tube feeding and once pneumonia occurred; patients who were tube fed did not survive for more than half a year. © 2012 Japan Geriatrics Society.

  19. 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

  20. Disease-free and overall survival of patients diagnosed with HPV-associated or HPV-negative cervical cancer

    NASA Astrophysics Data System (ADS)

    Ibragimova, M. K.; Tsyganov, M. M.; Karabut, I. V.; Kolomiets, L. A.; Choynzonov, E. L.; Litviakov, N. V.

    2015-11-01

    The real-time PCR method is used to study scrapings of cervical epithelium and outer portion of the cervix in 116 patients aged 24-79 years with stage I-IV primary cervical cancer. The comprehensive survey included colposcopy, cytological and histological analysis, detection and genotyping of high-risk human papillomavirus. In 84 patients (72.4%) the presence of human papillomavirus (HPV) of high carcinogenic risk (HCR) is found, in 32 patients (27.6%) the presence of the virus has not been inspected in the tumor. A significant decrease in the survival rate as well as the prevalence of the worst prognosis for patients with HPV-negative cervical cancer are shown.

  1. Favorable Local Control From Consolidative Radiation Therapy in High-Risk Neuroblastoma Despite Gross Residual Disease, Positive Margins, or Nodal Involvement

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

    Ferris, Matthew J., E-mail: mjferri@emory.edu; Winship Cancer Institute, Emory University, Atlanta, Georgia; Danish, Hasan

    Purpose: To report the influence of radiation therapy (RT) dose and surgical pathology variables on disease control and overall survival (OS) in patients treated for high-risk neuroblastoma at a single institution. Methods and Materials: We conducted a retrospective study of 67 high-risk neuroblastoma patients who received RT as part of definitive management from January 2003 until May 2014. Results: At a median follow-up of 4.5 years, 26 patients (38.8%) failed distantly; 4 of these patients also failed locally. One patient progressed locally without distant failure. Local control was 92.5%, and total disease control was 59.5%. No benefit was demonstrated for RT doses over 21.6 Gymore » with respect to local relapse–free survival (P=.55), disease-free survival (P=.22), or OS (P=.72). With respect to local relapse–free survival, disease-free survival, and OS, no disadvantage was seen for positive lymph nodes on surgical pathology, positive surgical margins, or gross residual disease. Of the patients with gross residual disease, 75% (6 of 8) went on to have no evidence of disease at time of last follow-up, and the 2 patients who failed did so distantly. Conclusions: Patients with high-risk neuroblastoma in this series maintained excellent local control, with no benefit demonstrated for radiation doses over 21.6 Gy, and no disadvantage demonstrated for gross residual disease after surgery, positive surgical margins, or pathologic lymph node positivity. Though the limitations of a retrospective review for an uncommon disease must be kept in mind, with small numbers in some of the subgroups, it seems that dose escalation should be considered only in exceptional circumstances.« less

  2. 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

  3. 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.

  4. 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.

  5. Alternative Lengthening of Telomeres and Loss of DAXX/ATRX Expression Predicts Metastatic Disease and Poor Survival in Patients with Pancreatic Neuroendocrine Tumors.

    PubMed

    Singhi, Aatur D; Liu, Ta-Chiang; Roncaioli, Justin L; Cao, Dengfeng; Zeh, Herbert J; Zureikat, Amer H; Tsung, Allan; Marsh, J Wallis; Lee, Kenneth K; Hogg, Melissa E; Bahary, Nathan; Brand, Randall E; McGrath, Kevin M; Slivka, Adam; Cressman, Kristi L; Fuhrer, Kimberly; O'Sullivan, Roderick J

    2017-01-15

    Pancreatic neuroendocrine tumors (PanNET) are a heterogeneous group of neoplasms with increasing incidence and unpredictable behavior. Whole-exome sequencing has identified recurrent mutations in the genes DAXX and ATRX, which correlate with loss of protein expression and alternative lengthening of telomeres (ALT). Both ALT and DAXX/ATRX loss were initially reported to be associated with a favorable prognosis; however, recent studies suggest the contrary. Our aims were to assess the prevalence and prognostic significance of ALT and DAXX/ATRX in both primary and metastatic PanNETs. Telomere-specific FISH and DAXX/ATRX IHC was performed on a multi-institutional cohort of 321 patients with resected PanNET and 191 distant metastases from 52 patients. These results were correlated with clinicopathologic features, including disease-free survival (DFS) and disease-specific survival (DSS). The prevalence of ALT and DAXX/ATRX loss in resected PanNETs was 31% and 26%, respectively, and associated with larger tumor size, higher WHO grade, lymph node metastasis, and distant metastasis (P < 0.001). The 5-year DFS and 10-year DSS of patients with ALT-positive and DAXX/ATRX-negative PanNETs were 40% and 50%, respectively, as compared with 96% and 89%, respectively, for wild-type PanNETs. Among distant metastases, ALT and DAXX/ATRX loss was 67% and 52%, respectively, and only occurred in the setting of an ALT-positive and DAXX/ATRX-negative primary PanNET. By multivariate analysis, both ALT and DAXX/ATRX loss were negative, independent prognostic factors for DFS. ALT and DAXX/ATRX loss in PanNETs was associated with shorter DFS and DSS and likely plays a significant role in driving metastatic disease. Clin Cancer Res; 23(2); 600-9. ©2016 AACR. ©2016 American Association for Cancer Research.

  6. Sex and the city: differences in disease- and disability-free life years, and active community participation of elderly men and women in 7 cities in Latin America and the Caribbean.

    PubMed

    Rose, Angela M C; Hennis, Anselm J; Hambleton, Ian R

    2008-04-21

    The world's population is ageing, and four of the top 10 most rapidly ageing developing nations are from the region of Latin America and the Caribbean (LAC). Although an ageing population heralds likely increases in chronic disease, disability-related dependence, and economic burden, the societal contribution of the chronically ill or those with disability is not often measured. We calculated country-specific prevalences of 'disability' (difficulty with at least one activity of daily living), 'disease' and 'co-morbidity' (presence of at least one, and at least two, of seven chronic diseases/conditions, respectively), and 'active community engagement' (using five levels of community participation, from less than weekly community contact to voluntary or paid work) in seven LAC cities. We estimated remaining life expectancy (LE) with and without disability, disease and co-morbidity, and investigated age, sex, and regional variations in disability-free LE. Finally, we modeled the association of disease, co-morbidity and disability with active community participation using an ordinal regression model, adjusted for depression. Overall, 77% of the LAC elderly had at least one chronic disease/condition, 44% had co-morbidity and 19% had a disability. The proportion of disability-free LE declined between the youngest (60-64 years) and the eldest (90 years and over) age-groups for both men (from 85% to 55%) and women (from 75% to 45%). Disease-free and co-morbidity-free LE, however, remained at approximately 30% and 62%, respectively, for men (20% and 48% for women), until 80-84 years of age, then increased. Only Bridgetown's participants had statistically significantly longer disability-free LE than the regional average (IRR = 1.08; 95%CI 1.05-1.10; p < 0.001). Only Santiago's participants had disability-free LE which was shorter than the regional average (IRR = 0.94; 95%CI 0.92-0.97; p < 0.001). There was 75% active community participation overall, with more women than men

  7. Sex and the city: Differences in disease- and disability-free life years, and active community participation of elderly men and women in 7 cities in Latin America and the Caribbean

    PubMed Central

    Rose, Angela MC; Hennis, Anselm J; Hambleton, Ian R

    2008-01-01

    Background The world's population is ageing, and four of the top 10 most rapidly ageing developing nations are from the region of Latin America and the Caribbean (LAC). Although an ageing population heralds likely increases in chronic disease, disability-related dependence, and economic burden, the societal contribution of the chronically ill or those with disability is not often measured. Methods We calculated country-specific prevalences of 'disability' (difficulty with at least one activity of daily living), 'disease' and 'co-morbidity' (presence of at least one, and at least two, of seven chronic diseases/conditions, respectively), and 'active community engagement' (using five levels of community participation, from less than weekly community contact to voluntary or paid work) in seven LAC cities. We estimated remaining life expectancy (LE) with and without disability, disease and co-morbidity, and investigated age, sex, and regional variations in disability-free LE. Finally, we modeled the association of disease, co-morbidity and disability with active community participation using an ordinal regression model, adjusted for depression. Results Overall, 77% of the LAC elderly had at least one chronic disease/condition, 44% had co-morbidity and 19% had a disability. The proportion of disability-free LE declined between the youngest (60–64 years) and the eldest (90 years and over) age-groups for both men (from 85% to 55%) and women (from 75% to 45%). Disease-free and co-morbidity-free LE, however, remained at approximately 30% and 62%, respectively, for men (20% and 48% for women), until 80–84 years of age, then increased. Only Bridgetown's participants had statistically significantly longer disability-free LE than the regional average (IRR = 1.08; 95%CI 1.05–1.10; p < 0.001). Only Santiago's participants had disability-free LE which was shorter than the regional average (IRR = 0.94; 95%CI 0.92–0.97; p < 0.001). There was 75% active community participation

  8. Pretreatment Evaluation of Microcirculation by Dynamic Contrast-Enhanced Magnetic Resonance Imaging Predicts Survival in Primary Rectal Cancer Patients

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

    DeVries, Alexander Friedrich; Piringer, Gudrun, E-mail: gudrun.piringer@hotmail.com; Kremser, Christian

    2014-12-01

    Purpose: To investigate the prognostic value of the perfusion index (PI), a microcirculatory parameter estimated from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), which integrates information on both flow and permeability, to predict overall survival and disease-free survival in patients with primary rectal cancer. Methods and Materials: A total of 83 patients with stage cT3 rectal cancer requiring neoadjuvant chemoradiation were investigated with DCE-MRI before start of therapy. Contrast-enhanced dynamic T{sub 1} mapping was obtained, and a simple data analysis strategy based on the calculation of the maximum slope of the tissue concentration–time curve divided by the maximum of the arterial inputmore » function was used as a measure of tumor microcirculation (PI), which integrates information on both flow and permeability. Results: In 39 patients (47.0%), T downstaging (ypT0-2) was observed. During a mean (±SD) follow-up period of 71 ± 29 months, 58 patients (69.9%) survived, and disease-free survival was achieved in 45 patients (54.2%). The mean PI (PImean) averaged over the group of nonresponders was significantly higher than for responders. Additionally, higher PImean in age- and gender-adjusted analyses was strongly predictive of therapy nonresponse. Most importantly, PImean strongly and significantly predicted disease-free survival (unadjusted hazard ratio [HR], 1.85 [ 95% confidence interval, 1.35-2.54; P<.001)]; HR adjusted for age and sex, 1.81 [1.30-2.51]; P<.001) as well as overall survival (unadjusted HR 1.42 [1.02-1.99], P=.040; HR adjusted for age and sex, 1.43 [1.03-1.98]; P=.034). Conclusions: This analysis identifies PImean as a novel biomarker that is predictive for therapy response, disease-free survival, and overall survival in patients with primary locally advanced rectal cancer.« less

  9. First-Year Growth and Survival Of Long Cottonwood Cuttings

    Treesearch

    W.K. Randall; R.M. Krinard

    1977-01-01

    When five Stoneville cottonwood clones were grown in a nursery for one season, lifted with about a foot of root, and planted in 3-foot deep holes, they averaged 9.6 feet in height growth and 92 percent survival after 1 year in the field. Planted height averaged 8.3 feet. The same clonal material planted without roots averaged only 36 percent survival. These results...

  10. A 20-Year Review of 75 Cases of Salivary Duct Carcinoma.

    PubMed

    Gilbert, Mark R; Sharma, Arun; Schmitt, Nicole C; Johnson, Jonas T; Ferris, Robert L; Duvvuri, Umamaheswar; Kim, Seungwon

    2016-05-01

    Salivary duct carcinoma is a rare, aggressive malignancy of the salivary glands. Owing to its rare nature, clinical data are limited, and only a few clinical studies comprise more than 50 patients. To review the University of Pittsburgh Medical Center's experience with salivary duct carcinoma over a 20-year period, focusing on demographics, presentation, treatment, and outcome. This investigation was a retrospective cohort study in a multihospital institution with tertiary referral. A pathology database was reviewed for all cases of histopathologically diagnosed salivary duct carcinoma from January 1, 1995, to October 20, 2014. Patients who were referrals for pathology review only and were never seen at the institution were excluded. In total, 75 study patients were identified. The electronic medical record was reviewed for details regarding demographics, presentation, treatment, and outcome, including overall survival (OS) and disease-free survival (DFS). This study was supplemented with a review of the institution's Head and Neck Oncology Database for further clinical details. Primary outcome measures consisted of OS and DFS. The study sample comprised 75 participants with a mean age at diagnosis of 66.0 years (age range, 33-93 years), and 29% (n = 22) were female. Most primary tumors were from the parotid gland (83%), with the next most frequent site being the submandibular gland (12%). Overall, 41% of the cases were carcinoma ex pleomorphic adenoma. Rates of other histologic features included the following: perineural invasion (69%), extracapsular spread (58%), ERBB2 (formerly HER2) positivity (31%) (62% of those who were tested), and vascular invasion (61%). The median OS was 3.1 years, and the median DFS was 2.7 years. Univariate Kaplan-Meier survival analyses demonstrated that facial nerve sacrifice and extracapsular spread were associated with lower OS (2.38 vs 5.11 years and 2.29 vs 6.56 years, respectively) and DFS (2.4 vs 3.88 years and 1.44 vs 4

  11. No harm from five year ingestion of oats in coeliac disease

    PubMed Central

    Janatuinen, E K; Kemppainen, T A; Julkunen, R J K; Kosma, V-M; Mäki, M; Heikkinen, M; Uusitupa, M I J

    2002-01-01

    Background: Six to 12 months of ingestion of moderate amounts of oats does not have a harmful effect in adult patients with coeliac disease. As the safety of long term intake of oats in coeliac patients is not known, we continued our previous 6–12 month study for five years. Aim: To assess the safety of long term ingestion of oats in the diet of coeliac patients. Patients: In our previous study, the effects of a gluten free diet and a gluten free diet including oats were compared in a randomised trial involving 92 adult patients with coeliac disease (45 in the oats group, 47 in the control group). After the initial phase of 6–12 months, patients in the oats group were allowed to eat oats freely in conjunction with an otherwise gluten free diet. After five years, 35 patients in the original oats group (23 still on an oats diet) and 28 in the control group on a conventional gluten free diet were examined. Methods: Clinical and nutritional assessment, duodenal biopsies for conventional histopathology and histomorphometry, and measurement of antiendomysial, antireticulin, and antigliadin antibodies. Results: There were no significant differences between controls and those patients consuming oats with respect to duodenal villous architecture, inflammatory cell infiltration of the duodenal mucosa, or antibody titres after five years of follow up. In both groups histological and histomorphometric indexes improved equally with time. Conclusions: This study provides the first evidence of the long term safety of oats as part of a coeliac diet in adult patients with coeliac disease. It also appears that the majority of coeliac patients prefer oats in their diet. PMID:11839710

  12. Do Ultrasensitive Prostate Specific Antigen Measurements Have a Role in Predicting Long-Term Biochemical Recurrence-Free Survival in Men after Radical Prostatectomy?

    PubMed

    Sokoll, Lori J; Zhang, Zhen; Chan, Daniel W; Reese, Adam C; Bivalacqua, Trinity J; Partin, Alan W; Walsh, Patrick C

    2016-02-01

    In this study we evaluate an ultrasensitive prostate specific antigen assay in patients with prostate cancer after radical prostatectomy to predict long-term biochemical recurrence-free survival. A total of 754 men who underwent radical prostatectomy and had an undetectable prostate specific antigen after surgery (less than 0.1 ng/ml) were studied. Prostate specific antigen was measured in banked serum specimens with an ultrasensitive assay (Hybritech® PSA, Beckman Coulter Access® 2) using a cutoff of 0.01 ng/ml. Prostate specific antigen was also measured in 44 men after cystoprostatectomy who had no pathological evidence of prostate cancer with the Hybritech assay and with the Quanterix AccuPSA™ assay. Of the 754 men 17% (131) experienced biochemical recurrence (median 4.0 years). Those men without biochemical recurrence (83%, 623) had a minimum of 5 years of followup (median 11). Prostate specific antigen was less than 0.01 ng/ml in 93.4% of men with no biochemical recurrence, whereas 30.5% of men with biochemical recurrence had a prostate specific antigen of 0.01 ng/ml or greater. On multivariate analysis postoperative prostate specific antigen at a 0.01 ng/ml cutoff, pathological stage and Gleason score, and surgical margins were significant independent predictors of biochemical recurrence risk. Kaplan-Meier estimates for mean biochemical recurrence-free survival were 15.2 years (95% CI 14.9-15.6) for prostate specific antigen less than 0.01 ng/ml and 10.0 years (95% CI 8.4-11.5) for prostate specific antigen 0.01 ng/ml or greater (p <0.0001). Biochemical recurrence-free rates 11 years after surgery were 86.1% (95% CI 83.2-89.0) for prostate specific antigen less than 0.01 ng/ml and 48.9% (95% CI 37.5-60.3) for prostate specific antigen 0.01 ng/ml or greater (p <0.0001). Prostate specific antigen concentrations in 44 men after cystoprostatectomy were all less than 0.03 ng/ml, with 95.4% less than 0.01 ng/ml. In men with a serum prostate specific antigen

  13. High-Dose-Rate Monotherapy for Localized Prostate Cancer: 10-Year Results

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

    Hauswald, Henrik; Kamrava, Mitchell R.; Fallon, Julia M.

    2016-03-15

    Purpose: High-dose-rate (HDR) brachytherapy was originally used with external beam radiation therapy (EBRT) to increase the dose to the prostate without injuring the bladder or rectum. Numerous studies have reported HDR brachytherapy is safe and effective. We adapted it for use without EBRT for cases not requiring lymph node treatment. Patients and Methods: We entered the patient demographics, disease characteristics, and treatment parameters into a prospective registry and serially added follow-up data for 448 men with low-risk (n=288) and intermediate-risk (n=160) prostate cancer treated from 1996 to 2009. Their median age was 64 years (range 42-90). The median prostate-specific antigen (PSA)more » level was 6.0 ng/mL (range 0.2-18.2). The Gleason score was ≤6 in 76% and 7 in 24%. The median dose was 43.5 Gy in 6 fractions. The clinical and biochemical disease control and survival rates were calculated. Adverse events were graded according to the Common Toxicity Criteria of Adverse Events. Results: The median follow-up period was 6.5 years (range 0.3-15.3). The actuarial 6- and 10-year PSA progression-free survival was 98.6% (95% confidence interval [CI] 96.9%-99.4%) and 97.8% (95% CI 95.5%-98.9%). Overall survival at 10 years was 76.7% (95% CI 69.9%-82.2%). The local control, distant metastasis-free survival, and cause-specific survival were 99.7% (95% CI 97.9%-99.9%), 98.9% (95% CI 96.3%-99.7%), and 99.1% (95% CI 95.8%-99.8%). T stage, initial PSA level, Gleason score, National Comprehensive Cancer Network risk group, patient age, and androgen deprivation therapy did not significantly correlate with disease control or survival. No late grade 3 to 4 rectal toxicities developed. Late grade 3 to 4 genitourinary toxicity occurred in 4.9% (grade 3 in 4.7%). Conclusions: HDR monotherapy is a safe and highly effective treatment of low- and intermediate-risk prostate cancer.« less

  14. Hemodialysis versus Peritoneal Dialysis: A Comparison of Survival Outcomes in South-East Asian Patients with End-Stage Renal Disease.

    PubMed

    Yang, Fan; Khin, Lay-Wai; Lau, Titus; Chua, Horng-Ruey; Vathsala, A; Lee, Evan; Luo, Nan

    2015-01-01

    Studies comparing patient survival of hemodialysis (HD) and peritoneal dialysis (PD) have yielded conflicting results and no such study was from South-East Asia. This study aimed to compare the survival outcomes of patients with end-stage renal disease (ESRD) who started dialysis with HD and PD in Singapore. Survival data for a maximum of 5 years from a single-center cohort of 871 ESRD patients starting dialysis with HD (n = 641) or PD (n = 230) from 2005-2010 was analyzed using the flexible Royston-Parmar (RP) model. The model was also applied to a subsample of 225 propensity-score-matched patient pairs and subgroups defined by age, diabetes mellitus, and cardiovascular disease. After adjusting for the effect of socio-demographic and clinical characteristics, the risk of death was higher in patients initiating dialysis with PD than those initiating dialysis with HD (hazard ratio [HR]: 2.08; 95% confidence interval [CI]: 1.67-2.59; p<0.001), although there was no significant difference in mortality between the two modalities in the first 12 months of treatment. Consistently, in the matched subsample, patients starting PD had a higher risk of death than those starting HD (HR: 1.73, 95% CI: 1.30-2.28, p<0.001). Subgroup analysis showed that PD may be similar to or better than HD in survival outcomes among young patients (≤65 years old) without diabetes or cardiovascular disease. ESRD patients who initiated dialysis with HD experienced better survival outcomes than those who initiated dialysis with PD in Singapore, although survival outcomes may not differ between the two dialysis modalities in young and healthier patients. These findings are potentially confounded by selection bias, as patients were not randomized to the two dialysis modalities in this cohort study.

  15. 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

  16. 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.

  17. Diagnostic value of inflammatory cell infiltrates, tumor stroma percentage and disease-free survival in patients with colorectal cancer

    PubMed Central

    Jakubowska, Katarzyna; Kisielewski, Wojciech; Kańczuga-Koda, Luiza; Koda, Mariusz; Famulski, Waldemar

    2017-01-01

    disease-free survival (DFS) time (P=0.004). Inflammatory cell infiltrate in the invasive front was identified as an independent predictive factor in CRC (P=0.041). In conclusion, the degree of inflammatory cell infiltration in the invasive front of the primary tumor significantly affects various variables that determine disease progression and DFS rates of patients with CRC. Furthermore, the routine histopathological assessment of this parameter in tissue stained with H&E may have potential prognostic value. PMID:28927159

  18. Breast-conserving therapy versus mastectomy in T1-2N2 stage breast cancer: a population-based study on 10-year overall, relative, and distant metastasis-free survival in 3071 patients.

    PubMed

    van Maaren, M C; de Munck, L; Jobsen, J J; Poortmans, P; de Bock, G H; Siesling, S; Strobbe, L J A

    2016-12-01

    Our previous study demonstrated breast-conserving surgery with radiation therapy (BCT) to be at least equivalent to mastectomy in T1-2N0-1 breast cancer. Yet, 10-year survival rates after BCT and mastectomy with radiation therapy (MAST) in T1-2N2 breast cancer specifically have not been examined. Our study aimed to determine 10-year overall (OS), relative (RS), and distant metastasis-free survival (DMFS) in T1-2N2 breast cancer after BCT and MAST, stratified for T category. All women diagnosed with primary invasive T1-2N2 breast cancer in 2000-2004, treated with BCT or MAST, both with axillary dissection and RT, were selected from the Netherlands Cancer Registry. Ten-year OS and DMFS were estimated using multivariable Cox regression. Excess mortality ratios (EMR) were calculated to estimate RS, using life tables of the general population. OS and RS were determined on the whole cohort, and DMFS on the 2003 cohort with completed follow-up. Missing data were imputed. Of 3071 patients, 1055 (34.4 %) received BCT and 2016 (65.7 %) MAST. BCT and MAST showed equal 10-year OS and RS. After stratification, BCT was significantly associated with improved 10-year OS [HR adjusted 0.82 (95 % CI 0.71-0.96)] and RS (EMR adjusted 0.81 (95 % CI 0.67-0.97]) in T2N2, but not in T1N2. Ten-year DMFS was equal for both treatments [HR adjusted 0.87 (95 % CI 0.64-1.18)] in the 2003 cohort (n = 594), which was representative for the full cohort. BCT showed at least equal 10-year OS, RS, and DMFS compared to MAST. These results confirm that BCT is a good treatment option in T1-2N2 breast cancer.

  19. Nursing diagnoses in children with congenital heart disease: a survival analysis.

    PubMed

    Martins da Silva, Viviane; Lopes, Marcos Venícios de Oliveira; Leite de Araujo, Thelma

    2007-01-01

    To analyze the relationship between nursing diagnoses and survival rates in children with congenital heart disease. A total of 270 observations were carried out in 45 children with congenital heart disease who were followed for 15 days. Differences in mean survival times were identified in children not more than 4 months of age with respect to the following diagnoses: impaired gas exchange, ineffective breathing pattern, activity intolerance, delayed growth and development, and decreased cardiac output. The main diagnoses are identified early in the hospitalization period and are conditions resulting from hemodynamic alterations and prescribed medical treatment. Congenital heart disease provokes serious hemodynamic alterations that generate human responses, which should be treated proactively.

  20. Discrepancy between recurrence-free survival and overall survival in patients with resectable colorectal liver metastases: a potential surrogate endpoint for time to surgical failure.

    PubMed

    Oba, Masaru; Hasegawa, Kiyoshi; Matsuyama, Yutaka; Shindoh, Junichi; Mise, Yoshihiro; Aoki, Taku; Sakamoto, Yoshihiro; Sugawara, Yasuhiko; Makuuchi, Masatoshi; Kokudo, Norihiro

    2014-06-01

    Recurrence-free survival (RFS) may not be a surrogate for overall survival (OS) in patients with resectable colorectal liver metastases (CLM). We investigated whether a new composite tool-time to surgical failure (TSF)-is a suitable endpoint. The medical records of consecutive patients who underwent curative resection for CLM at our center over a 17-year period were reviewed. Patients with liver-limited tumors (n = 371) who had not received previous treatment for metastasis were eligible for analysis. TSF was defined as the time until unresectable relapse or death. The correlations between TSF and OS, and between RFS and OS, were assessed for all the eligible patients. The median OS, TSF, and RFS were 5.7, 2.7, and 0.7 years, respectively, and the 5-year OS, TSF, and RFS rates were 52.6, 39.8, and 23.7 %, respectively, for all patients. The rates of first, second, and third relapse were 75.5, 77.6, and 70.8 %, respectively, and repeat resections were performed in 54.3 % (first relapses), 40.7 % (second relapses), and 47.1 % (third relapses) of patients. The concordance proportions of TSF and RFS for OS events were 0.83 and 0.65, respectively. The correlation between TSF and OS was stronger than that between RFS and OS in terms of the predicted probabilities. The correlation between TSF and OS was stronger than that between RFS and OS after curative hepatic resection. TSF could be a suitable endpoint for CLM overall management.

  1. Survival after Radiofrequency Ablation in 122 Patients with Inoperable Colorectal Lung Metastases

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

    Gillams, Alice, E-mail: alliesorting@gmail.com; Khan, Zahid; Osborn, Peter

    2013-06-15

    Purpose. To analyze the factors associated with favorable survival in patients with inoperable colorectal lung metastases treated with percutaneous image-guided radiofrequency ablation. Methods. Between 2002 and 2011, a total of 398 metastases were ablated in 122 patients (87 male, median age 68 years, range 29-90 years) at 256 procedures. Percutaneous CT-guided cool-tip radiofrequency ablation was performed under sedation/general anesthesia. Maximum tumor size, number of tumors ablated, number of procedures, concurrent/prior liver ablation, previous liver or lung resection, systemic chemotherapy, disease-free interval from primary resection to lung metastasis, and survival from first ablation were recorded prospectively. Kaplan-Meier analysis was performed, andmore » factors were compared by log rank test. Results. The initial number of metastases ablated was 2.3 (range 1-8); the total number was 3.3 (range 1-15). The maximum tumor diameter was 1.7 (range 0.5-4) cm, and the number of procedures was 2 (range 1-10). The major complication rate was 3.9 %. Overall median and 3-year survival rate were 41 months and 57 %. Survival was better in patients with smaller tumors-a median of 51 months, with 3-year survival of 64 % for tumors 2 cm or smaller versus 31 months and 44 % for tumors 2.1-4 cm (p = 0.08). The number of metastases ablated and whether the tumors were unilateral or bilateral did not affect survival. The presence of treated liver metastases, systemic chemotherapy, or prior lung resection did not affect survival. Conclusion. Three-year survival of 57 % in patients with inoperable colorectal lung metastases is better than would be expected with chemotherapy alone. Patients with inoperable but small-volume colorectal lung metastases should be referred for ablation.« less

  2. Adults surviving lung cancer two or more years: A systematic review.

    PubMed

    Rhea, Deborah J; Lockwood, Suzy

    Lung cancer has had a low survival rate throughout the years. Some studies have shown that psychological variables such as hardiness and resiliency may play a role in the meaningfulness of survival among lung cancer patients. The objective of this systematic review was to synthesize the best available evidence on the experiences of surviving lung cancer (including psychological/affective well-being dimensions such as resiliency, optimism, quality of life, and coping strategies) in adults over the age of 18, two or more years after diagnosis. The review considered adults (18 years and older) who have survived lung cancer two or more years post diagnosis.The review included studies that examined the experiences (including psychological/affective well-being dimensions such as resiliency, optimism, quality of life, and coping strategies) of surviving lung cancer two or more years post diagnosis.The review considered patients' experiences of surviving lung cancer post two years diagnosis, including the examination of specific psychological/affective well-being aspects such as resiliency, optimism, quality of life and coping strategies.The review included quantitative descriptive studies and qualitative studies. A search for published and unpublished studies in English language from January 1999 through December 2010 was undertaken in multiple databases including MEDLINE, CINAHL, ProQuest and Psyc INFO. Assessment of methodological quality of studies was undertaken using critical appraisal tools from the Joanna Briggs Institute. Data was extracted using the Joanna Briggs Institute Data Extraction forms. Results were presented in a narrative format as the synthesis of qualitative or quantitative data was not appropriate. 13 studies were included in the review: one mixed methods study (including a qualitative research component) and 12 quantitative studies.The qualitative component of the included mixed methods study identified five findings related to the meaningfulness

  3. Pre-treatment plasma proteomic markers associated with survival in oesophageal cancer

    PubMed Central

    Kelly, P; Paulin, F; Lamont, D; Baker, L; Clearly, S; Exon, D; Thompson, A

    2012-01-01

    Background: The incidence of oesophageal adenocarcinoma is increasing worldwide but survival remains poor. Neoadjuvant chemotherapy can improve survival, but prognostic and predictive biomarkers are required. This study built upon preclinical approaches to identify prognostic plasma proteomic markers in oesophageal cancer. Methods: Plasma samples collected before and during the treatment of oesophageal cancer and non-cancer controls were analysed by surface-enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) mass spectroscopy (MS). Protein peaks were identified by MS in tryptic digests of purified fractions. Associations between peak intensities obtained in the spectra and clinical endpoints (survival, disease-free survival) were tested by univariate (Fisher's exact test) and multivariate analysis (binary logistic regression). Results: Plasma protein peaks were identified that differed significantly (P<0.05, ANOVA) between the oesophageal cancer and control groups at baseline. Three peaks, confirmed as apolipoprotein A-I, serum amyloid A and transthyretin, in baseline (pre-treatment) samples were associated by univariate and multivariate analysis with disease-free survival and overall survival. Conclusion: Plasma proteins can be detected prior to treatment for oesophageal cancer that are associated with outcome and merit testing as prognostic and predictive markers of response to guide chemotherapy in oesophageal cancer. PMID:22294182

  4. 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

  5. Improving outcomes in heart failure in the community: long-term survival benefit of a disease-management program.

    PubMed

    Akosah, Kwame O; Schaper, Ana M; Haus, Lindsay M; Mathiason, Michelle A; Barnhart, Sharon I; McHugh, Vicki L

    2005-06-01

    The purpose of our current study was to determine whether our disease-management model was associated with long-term survival benefits. A secondary objective was to determine whether program involvement was associated with medication maintenance and reduced hospitalization over time compared to usual care management of heart failure. A retrospective chart review was conducted in patients who had been hospitalized for congestive heart failure between April 1999 and March 31, 2000, and had been discharged from the hospital for follow-up in the Heart Failure Clinic vs usual care. An integrated health-care center serving a tristate area. Patients (n = 101) were followed up for 4 years after their index hospitalization for congestive heart failure. The patients followed up in the Heart Failure Clinic comprised group 1 (n = 38), and the patients receiving usual care made up group 2 (n = 63). The mean (+/- SD) age of the patients in group 1 was 68 +/- 16 years compared to 76 +/- 11 years for the patients in group 2 (p = 0.002). The patients in group 1 were more likely to have renal failure (p = 0.035), a lower left ventricular ejection fraction (p = 0.005), and hypotension at baseline (p = 0.002). At year 2, more patients in group 1 were maintained by therapy with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) [p = 0.036]. The survival rate over 4 years was better for group 1. Univariate Cox proportional hazard ratios revealed that age, not receiving ACEIs or ARBs, and renal disease or cancer at baseline were associated with mortality. When controlling for these variables in a multivariate Cox proportional hazards ratio model, survival differences between groups remained significant (p = 0.021). Subjects in group 2 were 2.4 times more likely to die over the 4-year period than those in group 1. Our study demonstrated that, after controlling for baseline variables, patients participating in a heart failure clinic enjoyed improved

  6. Adjuvant tamoxifen and exemestane in women with postmenopausal early breast cancer (TEAM): 10-year follow-up of a multicentre, open-label, randomised, phase 3 trial.

    PubMed

    Derks, Marloes G M; Blok, Erik J; Seynaeve, Caroline; Nortier, Johan W R; Kranenbarg, Elma Meershoek-Klein; Liefers, Gerrit-Jan; Putter, Hein; Kroep, Judith R; Rea, Daniel; Hasenburg, Annette; Markopoulos, Christos; Paridaens, Robert; Smeets, Jan B E; Dirix, Luc Y; van de Velde, Cornelis J H

    2017-09-01

    After 5 years of median follow-up, the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial reported no difference in disease-free survival between exemestane monotherapy and a sequential scheme of tamoxifen followed by exemestane in postmenopausal patients with early-stage, hormone receptor-positive breast cancer. As recurrence risk in hormone receptor-positive breast cancer remains linear beyond 5 years after diagnosis, we analysed long-term follow-up outcomes of this trial. The TEAM trial, a multicentre, open-label, randomised, controlled, phase 3 trial, included postmenopausal patients with early-stage hormone receptor-positive breast cancer from nine countries. Patients were randomly allocated (1:1) by a computer-generated random permuted block method (block sizes 4-8) to either 5 years of oral exemestane monotherapy (25 mg once a day) or a sequential scheme of oral tamoxifen (20 mg once a day) followed by exemestane for a total duration of 5 years. After the publication of the IES trial, the protocol was amended (Dec 13, 2004). Patients assigned to tamoxifen were switched after 2·5-3·0 years to exemestane therapy for a total duration of 5·0 years of treatment. Randomisation was done centrally in each country. Long-term follow-up data for disease recurrence and survival was collected in six participating countries and analysed by intention to treat. The primary endpoint was disease-free survival at 10 years of follow-up. The trial is registered with ClinicalTrials.gov, numbers NCT00279448 and NCT00032136; with Netherlands Trial Register, number NTR 267; and the Ethics Commission Trial, number 27/2001. 6120 patients of the original 9776 patients in the TEAM trial were included in the current intention-to-treat analysis. Median follow-up was 9·8 years (IQR 8·0-10·3). During follow-up, 921 (30%) of 3075 patients in the exemestane group and 929 (31%) of 3045 patients in the sequential group had a disease-free survival event. Disease-free survival at 10

  7. Effect of Occult Metastases on Survival in Node-Negative Breast Cancer

    PubMed Central

    Weaver, Donald L.; Ashikaga, Takamaru; Krag, David N.; Skelly, Joan M.; Anderson, Stewart J.; Harlow, Seth P.; Julian, Thomas B.; Mamounas, Eleftherios P.; Wolmark, Norman

    2011-01-01

    BACKGROUND Retrospective and observational analyses suggest that occult lymph-node metastases are an important prognostic factor for disease recurrence or survival among patients with breast cancer. Prospective data on clinical outcomes from randomized trials according to sentinel-node involvement have been lacking. METHODS We randomly assigned women with breast cancer to sentinel-lymph-node biopsy plus axillary dissection or sentinel-lymph-node biopsy alone. Paraffin-embedded tissue blocks of sentinel lymph nodes obtained from patients with pathologically negative sentinel lymph nodes were centrally evaluated for occult metastases deeper in the blocks. Both routine staining and immunohistochemical staining for cytokeratin were used at two widely spaced additional tissue levels. Treating physicians were unaware of the findings, which were not used for clinical treatment decisions. The initial evaluation at participating sites was designed to detect all macrometastases larger than 2 mm in the greatest dimension. RESULTS Occult metastases were detected in 15.9% (95% confidence interval [CI], 14.7 to 17.1) of 3887 patients. Log-rank tests indicated a significant difference between patients in whom occult metastases were detected and those in whom no occult metastases were detected with respect to overall survival (P = 0.03), disease-free survival (P = 0.02), and distant-disease–free interval (P = 0.04). The corresponding adjusted hazard ratios for death, any outcome event, and distant disease were 1.40 (95% CI, 1.05 to 1.86), 1.31 (95% CI, 1.07 to 1.60), and 1.30 (95% CI, 1.02 to 1.66), respectively. Five-year Kaplan-Meier estimates of overall survival among patients in whom occult metastases were detected and those without detectable metastases were 94.6% and 95.8%, respectively. CONCLUSIONS Occult metastases were an independent prognostic variable in patients with sentinel nodes that were negative on initial examination; however, the magnitude of the difference in

  8. INFLUENCE OF HEPATOCELLULAR CARCINOMA ETIOLOGY IN THE SURVIVAL AFTER RESECTION.

    PubMed

    Lopes, Felipe de Lucena Moreira; Coelho, Fabricio Ferreira; Kruger, Jaime Arthur Pirolla; Fonseca, Gilton Marques; Araujo, Raphael Leonardo Cunha de; Jeismann, Vagner Birk; Herman, Paulo

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and its incidence is increasing around the world in the last decades, making it the third cause of death by cancer in the world. Hepatic resection is one of the most effective treatments for HCC with five-year survival rates from 50-70%, especially for patients with a single nodule and preserved liver function. Some studies have shown a worse prognosis for HCC patients whose etiology is viral. That brings us to the question about the existence of a difference between the various causes of HCC and its prognosis. To compare the prognosis (overall and disease-free survival at five years) of patients undergoing hepatectomy for the treatment of HCC with respect to various causes of liver disease. Was performed a review of medical records of patients undergoing hepatectomy between 2000 and 2014 for the treatment of HCC. They were divided into groups according to the cause of liver disease, followed by overall and disease-free survival analysis for comparison. There was no statistically significant difference in the outcomes of the groups of patients divided according to the etiology of HCC. Overall and disease-free survival at five years of the patients in this sample were 49.9% and 40.7%, respectively. From the data of this sample, was verified that there was no prognostic differences among the groups of HCC patients of the various etiologies. O carcinoma hepatocelular (CHC) é o mais frequente tipo de câncer primário do fígado e a sua incidência vem aumentando nas últimas décadas, tornando-o hoje a terceira causa de morte por câncer no mundo. A ressecção hepática é um dos tratamentos mais eficazes para ele com taxas de sobrevida em cinco anos de 50-70%, especialmente para pacientes com nódulo único e função hepática preservada. Alguns estudos mostraram pior prognóstico para os pacientes com CHC cuja causa é a infecção por vírus B ou C. Isso leva à questão sobre a

  9. Using Survival Analysis to Improve Estimates of Life Year Gains in Policy Evaluations.

    PubMed

    Meacock, Rachel; Sutton, Matt; Kristensen, Søren Rud; Harrison, Mark

    2017-05-01

    Policy evaluations taking a lifetime horizon have converted estimated changes in short-term mortality to expected life year gains using general population life expectancy. However, the life expectancy of the affected patients may differ from the general population. In trials, survival models are commonly used to extrapolate life year gains. The objective was to demonstrate the feasibility and materiality of using parametric survival models to extrapolate future survival in health care policy evaluations. We used our previous cost-effectiveness analysis of a pay-for-performance program as a motivating example. We first used the cohort of patients admitted prior to the program to compare 3 methods for estimating remaining life expectancy. We then used a difference-in-differences framework to estimate the life year gains associated with the program using general population life expectancy and survival models. Patient-level data from Hospital Episode Statistics was utilized for patients admitted to hospitals in England for pneumonia between 1 April 2007 and 31 March 2008 and between 1 April 2009 and 31 March 2010, and linked to death records for the period from 1 April 2007 to 31 March 2011. In our cohort of patients, using parametric survival models rather than general population life expectancy figures reduced the estimated mean life years remaining by 30% (9.19 v. 13.15 years, respectively). However, the estimated mean life year gains associated with the program are larger using survival models (0.380 years) compared to using general population life expectancy (0.154 years). Using general population life expectancy to estimate the impact of health care policies can overestimate life expectancy but underestimate the impact of policies on life year gains. Using a longer follow-up period improved the accuracy of estimated survival and program impact considerably.

  10. Fisics-Incor bovine pericardial bioprostheses: 15 year results.

    PubMed

    Pomerantzeff, P M; Brandao, C M; Cauduro, P; Puig, L B; Grinberg, M; Tarasoutchi, F; Cardoso, L F; Lerner, A; Stolf, N A; Verginelli, G; Jatene, A D

    1998-01-01

    From March 1982 to December 1995, 2,607 Fisics-Incor bovine pericardial bioprostheses were implanted in 2,259 patients. Mean age was 47.2 +/- 17.5 years, and 55% were male. Rheumatic fever was present in 1,301 (45.7%) patients. One thousand and seventy-three aortic valve replacements, 1,085 mitral replacements, 27 tricuspid replacements, 195 mitral-aortic replacements, and 16 other combined valve replacements were carried out. Combined procedures were performed in 788 (32.9%) patients, the most frequent being tricuspid valve repair (9.2%) and coronary artery bypass grafting (7.7%). Hospital mortality was 8.6% (194 patients), 8.6% for the mitral group, 4.7% for the aortic group, and 12.8% for double-valve replacements. The linear rates for calcification, thromboembolism, rupture, leak and endocarditis were, respectively, 1.1%, 0.2%, 0.9%, 0.1% and 0.5% patient-year. The actuarial survival curve was 56.7 +/- 5.4% in 15 years. Survival free from endocarditis was 91.92%, survival free from thromboembolism was 95 +/- 1.7%, survival free from rupture was 43.7 +/- 9.8%, survival free from leak was 98.9 +/- 4.5%, and survival free from calcification was 48.8 +/- 7.9% in 15 years. In the late postoperative period, 1,614 (80.6%) patients were in New York Heart Association functional Class I. We conclude that the results with the Fisics-Incor bovine pericardial prostheses were satisfactory in our group of patients.

  11. Controls on Arctic sea ice from first-year and multi-year survival rates

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

    Hunke, Jes

    2009-01-01

    The recent decrease in Arctic sea ice cover has transpired with a significant loss of multi year ice. The transition to an Arctic that is populated by thinner first year sea ice has important implications for future trends in area and volume. Here we develop a reduced model for Arctic sea ice with which we investigate how the survivability of first year and multi year ice control the mean state, variability, and trends in ice area and volume.

  12. 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.

  13. Young breast cancer patients who develop distant metastasis after surgery have better survival outcomes compared with elderly counterparts.

    PubMed

    Wang, Jingjing; Wang, Jiayu; Li, Qing; Zhang, Pin; Yuan, Peng; Ma, Fei; Luo, Yang; Cai, Ruigang; Fan, Ying; Chen, Shanshan; Li, Qiao; Xu, Binghe

    2017-07-04

    To investigate the recurrence pattern and subsequent survival outcomes in young breast cancer population, 483 young patients (≤ 35) and 739 elderly patients (≥ 65), who received mastectomy or breast-conserving surgery from 2008 to 2012, were included in this study. The young population presented with a higher rate of pathologic tumor stage (P < 0.001), positive pathologic lymph node (P < 0.001), grade III tumors (P < 0.001), and lymphovascular invasion (P < 0.001). With a median follow-up of 56.5 months, young patients had a significantly lower 5-year disease-free survival (73.7% vs 83.4%, P = 0.001), while no difference in 5-year overall survival was observed (91.7% vs 91.7%, P = 0.721). The 5-year cumulative incidences of locoregional relapse (8.9% vs 4.3%, P = 0.009) and distant metastasis (18.8% vs 9.5%, P < 0.001) were significantly higher in the young population. However, for patients with distant metastasis, the survival outcomes were significantly better in the young patients (5-year overall survival since diagnosis: 60.0% vs 47.3%, P = 0.025; 5-year overall survival after recurrence: 31.0% vs 24.3%, P = 0.001). Young breast cancer patients present with more aggressive clinicopathological features and have poor prognosis compared with elderly. But young patients with distant metastasis might have better survival outcomes.

  14. [Association between metabolic syndrome and the 10 years mortality of cerebro-cardiovascular diseases in the senile population].

    PubMed

    Jin, Meng-meng; Pan, Chang-Yu; Tian, Hui; Liu, Min; Su, Hai-yan

    2008-02-01

    To assess the prevalence of metabolic syndrome (MS) and its association with mortality of cerebro-cardiovascular diseases in senile population. Data were collected from 1926 people aged 60 and over, who took part in routine health examination in our hospital from 1996 to 1997. All subjects were followed up for 10 years. MS was diagnosed by using the definition recommended by Chinese Diabetic Society in 2004. Cox-proportional hazards models were used in survival analyses and to calculate the relative risk (RR) of cerebro-cardiovascular diseases mortality. The prevalence of MS was 25.03% (n = 482, Group 2) in this population. The 10 year mortality of cerebro-cardiovascular diseases was significantly higher (6.82/1000-person year vs. 2.55/1000-person year, P < 0.05) and the cumulative survival rate was significantly lower (92.46%vs. 97.14%, P < 0.05) in group 2 compared that in group 1 (non-MS, n = 1444). Compared with group 1, RR of cerebro-cardiovascular diseases mortality was 2.52 (95% CI 1.367 - 4.661, P < 0.05) in group 2. There was a high prevalence of MS in the senile population and MS was associated with higher 10 years mortality of cerebro-cardiovascular diseases.

  15. Disease Characteristics, Patterns of Care, and Survival in Very Elderly Patients with Diffuse Large B-Cell Lymphoma

    PubMed Central

    Williams, Jessica N.; Rai, Ashish; Lipscomb, Joseph; Koff, Jean L.; Nastoupil, Loretta J.; Flowers, Christopher R.

    2015-01-01

    Background Although rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is considered standard therapy for diffuse large B-cell lymphoma (DLBCL), patterns of use and the impact of R-CHOP on survival in patients >80 years are less clear. Methods We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to characterize presentation, treatment, and survival patterns in DLBCL patients diagnosed from 2002–2009. Chi-squared tests compared characteristics and initial treatments of DLBCL patients >80 years and ≤80 years. Multivariable logistic regression models examined factors associated with treatment selection in patients >80 years; standard and propensity score-adjusted multivariable Cox proportional hazards models examined relationships between treatment regimen, treatment duration, and survival. Results Among 4,635 patients with DLBCL, 1,156 (25%) were >80 years. Patients >80 were less likely to receive R-CHOP and more likely to be observed or receive rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP); both p<0.0001. Marital status, stage, disease site, performance status, radiation therapy, and growth factor support were associated with initial R-CHOP in patients >80. In propensity score-matched multivariable Cox proportional hazards models examining relationships between treatment regimen and survival, R-CHOP was the only regimen associated with improved OS (hazard ratio (HR) = 0.45, 95% confidence interval (CI) = 0.33–0.62) and LRS (HR=0.58, 95% CI 0.38–0.88). Conclusions Although DLBCL patients >80 years were less likely to receive R-CHOP, this regimen conferred the longest survival and should be considered for this population. Further studies are needed to characterize the impact of DLBCL treatment on quality of life in this age group. PMID:25675909

  16. γ-amino butyric acid (GABA) level as an overall survival risk factor in breast cancer.

    PubMed

    Brzozowska, Anna; Burdan, Franciszek; Duma, Dariusz; Solski, Janusz; Mazurkiewicz, Maria

    2017-09-21

    The γ-amino butyric acid (GABA) plays important role in the proliferation and migration of cancer cells. The aim of the study was to evaluate the level of GABA in breast cancer, in relation to clinical and epidemiological data. The study was conducted on 89 patients with breast cancer in stage I-II. GABA level was assessed using spectrofluorometric method in tumour homogenates. Immunoexpression of E-cadherin was evaluated histologically on paraffin fixed specimens. Overall and disease-free survival was assessed for a 15-year interval period. Median overall survival was significantly longer (127.2 months) in patients with a high level of GABA (>89.3 μg/1), compared with a group with a low level of the amino acid (106.4 months). Disease-free survival was insignificantly different - 99 and 109 months, respectively. A significantly longer overall survival (131.2 months) was seen among patients with a high level of GABA and positive E-cadherin immunoexpression, compared with a group characterized by a low level of GABA and lack of E-cadherin immunorectivity (98.1 months). The co-existence of negative immunoexpression of E-cadherin and low GABA concentration resulted in a six-fold increase in the risk of death (HR=6.03). GABA has a significant prognostic value in breast cancer. Co-existence of a low level of GABA and loss of E-cadherin immune-expression seems to be a new, independent, and negative prognostic marker of the neoplasm.

  17. The presence of anaemia negatively influences survival in patients with POLG disease.

    PubMed

    Hikmat, Omar; Charalampos, Tzoulis; Klingenberg, Claus; Rasmussen, Magnhild; Tallaksen, Chantal M E; Brodtkorb, Eylert; Fiskerstrand, Torunn; McFarland, Robert; Rahman, Shamima; Bindoff, Laurence A

    2017-11-01

    Mitochondria play an important role in iron metabolism and haematopoietic cell homeostasis. Recent studies in mice showed that a mutation in the catalytic subunit of polymerase gamma (POLG) was associated with haematopoietic dysfunction including anaemia. The aim of this study was to analyse the frequency of anaemia in a large cohort of patients with POLG related disease. We conducted a multi-national, retrospective study of 61 patients with confirmed, pathogenic biallelic POLG mutations from six centres, four in Norway and two in the United Kingdom. Clinical, laboratory and genetic data were collected using a structured questionnaire. Anaemia was defined as an abnormally low haemoglobin value adjusted for age and sex. Univariate survival analysis was performed using log-rank test to compare differences in survival time between categories. Anaemia occurred in 67% (41/61) of patients and in 23% (14/61) it was already present at clinical presentation. The frequency of anaemia in patients with early onset disease including Alpers syndrome and myocerebrohepatopathy spectrum (MCHS) was high (72%) and 35% (8/23) of these had anaemia at presentation. Survival analysis showed that the presence of anaemia was associated with a significantly worse survival (P = 0.004). Our study reveals that anaemia can be a feature of POLG-related disease. Further, we show that its presence is associated with significantly worse prognosis either because anaemia itself is impacting survival or because it reflects the presence of more serious disease. In either case, our data suggests anaemia is a marker for negative prognosis.

  18. Renal transplantation in systemic lupus erythematosus: Comparison of graft survival with other causes of end-stage renal disease.

    PubMed

    Horta-Baas, Gabriel; Camargo-Coronel, Adolfo; Miranda-Hernández, Dafhne Guadalupe; Gónzalez-Parra, Leslie Gabriela; Romero-Figueroa, María Del Socorro; Pérez-Cristóbal, Mario

    2017-08-14

    End-stage renal disease (ESRD) due to lupus nephritis (LN) occurs in 10%-30% of patients. Initially systemic lupus erythematosus (SLE) was a contraindication for kidney transplantation (KT). Today, long-term graft survival remains controversial. Our objective was to compare the survival after KT in patients with SLE or other causes of ESRD. All SLE patients who had undergone KT in a retrospective cohort were included. Renal graft survival was compared with that of 50 controls, matched for age, sex, and year of transplantation. Survival was evaluated by the Kaplan-Meier test and the Cox proportional hazards model. Twenty-five subjects with SLE were included. The estimated 1-year, 2- and 5-year survival rates for patients with SLE were 92%, 66% and 66%. Renal graft survival did not differ between patients with SLE and other causes of ESRD (P=.39). The multivariate analysis showed no significant difference in graft survival between the two groups (hazard ratio, HR=1.95, 95% confidence interval [CI] 0.57-6.61, P=.28). The recurrence rate of LN was 8% and was not associated with graft loss. Acute rejection was the only variable associated with graft loss in patients with SLE (HR=16.5, 95% CI 1.94-140.1, P=.01). Renal graft survival in SLE patients did not differ from that reported for other causes of ESRD. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  19. Radiotherapy for early infradiaphragmatic Hodgkin's disease: the Australasian experience.

    PubMed

    Barton, M; Boyages, J; Crennan, E; Davis, S; Fisher, R J; Hook, C; Johnson, N; Joseph, D; Khoo, V; Liew, K H; Morgan, G; O'Brien, P; Pendlebury, S; Pratt, G; Quong, G; Roos, D E; Thornton, D; Trotter, G; Walker, Q; Wallington, M

    1996-04-01

    To review the Australasian results of Stage I and IIA Infradiaphragmatic Hodgkin's Disease (IHD) treated solely by irradiation. Eligible patients had IHD only and were treated by irradiation with curative intent over the period of 1969 to 1988. Ten radiation oncology centres from within Australia and New Zealand were surveyed for patient, tumour and treatment variables. Disease free rates, survival and complications were analysed. 106 patients with IHD were studied. The average potential follow up was 9.4 years. The male to female ratio was 3.3:1. The median age was 37.5 years. Histological subgroups were as follows; lymphocyte predominant 43%, mixed cellularity 21%, lymphocyte depleted 5%, nodular sclerosing 27% and unclassifiable 4%. Fifty nine patients had laparotomy of which 22 (37%) were positive for tumour. Nine laparotomies were performed for diagnosis and the remainder for staging. One patient was up-staged by laparotomy and three were down-staged. Sixty-eight patients presented with inguinal disease alone, five with abdominal disease alone, 19 with two sites of involvement and 12 with inguinal, pelvic and abdominal disease. In two patients the site was unknown. There was no correlation between site of involvement, age, sex or histological subtype. Forty seven cases were clinically staged (CS) as follows: CS IA-23, CS IIA-24. The other 59 were pathologically staged (PS) as follows: PS IA-37, PS IB-1, PS IIA-21. Treatment consisted of involved field alone (16), inverted Y (68), inverted Y and spleen (13), para-aortic irradiation only (3), or total nodal irradiation (6). Mean dose was 37 Gy. There were 30 recurrences to give an acturial 10-year disease-free rate of 70%. In multivariate analysis lower number of tumour sites, lymphocyte predominant histology and higher dose were all significantly correlated with higher disease free rates. Eight patients died of Hodgkin's disease and 19 of other causes. The 10-year overall survival rate was 71%. Older age and

  20. Does aggressive surgical resection improve survival in advanced stage 3 and 4 neuroblastoma? A systematic review and meta-analysis.

    PubMed

    Mullassery, Dhanya; Farrelly, Paul; Losty, Paul D

    2014-11-01

    The role of surgery in the management of advanced staged neuroblastoma (NBL) is controversial. A systematic review and meta-analysis is reported to address robust evidence for curative "gross total tumor resection" (GTR) in Stage 3 and Stage 4 neuroblastoma. Studies were identified using Medline, Embase, and Cochrane databases using pre-specified search terms. Primary outcomes were 5-year overall (OS) and disease-free survival (DFS) after GTR and subtotal resection (STR) in Stage 3 or 4 NBL. Data were analyzed using Review Manager. The Mantel-Haenszel method and a random effects model was utilized to calculate odds ratios (95% CI). Fifteen studies (five Stage 3 and 13 Stage 4) met full inclusion criteria. The pooled odds ratio for 5 year OS in Stage 3 following GTR compared to STR was 2.4 (95% CI 1.19-4.85). In Stage 4 disease, the pooled odds ratio for 5 year overall survival (OS) following GTR compared to STR was 1.65 (95% CI 0.96-1.91); a pooled odds ratio for 5 year DFS following GTR compared to STR was 1.55 (95% CI 1.12-2.14). A clear survival benefit is shown for GTR over STR in Stage 3 NBL only. Though some advantage can be demonstrated for GTR as defined by DFS in Stage 4 NBL GTR did not significantly improve OS in Stage 4 disease.

  1. Prognostic Score of Long-Term Survival After Surgery for Malignant Pleural Mesothelioma: A Multicenter Analysis.

    PubMed

    Leuzzi, Giovanni; Rea, Federico; Spaggiari, Lorenzo; Marulli, Giuseppe; Sperduti, Isabella; Alessandrini, Gabriele; Casiraghi, Monica; Bovolato, Pietro; Pariscenti, Gianluca; Alloisio, Marco; Infante, Maurizio; Pagan, Vittore; Fontana, Paolo; Oliaro, Alberto; Ruffini, Enrico; Ratto, Giovanni Battista; Leoncini, Giacomo; Sacco, Rocco; Mucilli, Felice; Facciolo, Francesco

    2015-09-01

    Despite ongoing efforts to improve therapy in malignant pleural mesothelioma, few patients undergoing extrapleural pneumonectomy experience long-term survival (LTS). This study aims to explore predictors of LTS after extrapleural pneumonectomy and to define a prognostic score. From January 2000 to December 2010, we retrospectively reviewed clinicopathologic and oncological factors in a multicenter cohort of 468 malignant pleural mesothelioma patients undergoing extrapleural pneumonectomy. LTS was defined as survival longer than 3 years. Associations were evaluated using χ(2), Student's t, and Mann-Whitney U tests. Logistic regression, Cox regression hazard model, and bootstrap analysis were applied to identify outcome predictors. Survival curves were calculated by the Kaplan-Meier method. Receiver operating characteristic analyses were used to estimate optimal cutoff and area under the curve for accuracy of the model. Overall, 107 patients (22.9%) survived at least 3 years. Median overall, cancer-specific, and disease-free survival times were 60 (95% confidence interval [CI], 51 to 69), 63 (95% CI, 54 to 72), and 49 months (95% CI, 39 to 58), respectively. At multivariate analysis, age (odds ratio, 0.51; 95% CI, 0.31 to 0.82), epithelioid histology (odds ratio, 7.07; 95% CI, 1.56 to 31.93), no history of asbestos exposure (odds ratio, 3.13; 95% CI, 1.13 to 8.66), and the ratio between metastatic and resected lymph nodes less than 22% (odds ratio, 4.12; 95% CI, 1.68 to 10.12) were independent predictors of LTS. According to these factors, we created a scoring system for LTS that allowed us to correctly predict overall, cancer-specific, and disease-free survival in the total sample, obtaining two different groups with favorable or poor prognosis (area under the curve, 0.74; standard error, 0.04; p < 0.0001). Our prognostic model facilitates the prediction of LTS after surgery for malignant pleural mesothelioma and can help to stratify the outcome and, eventually

  2. Automated digital volume measurement of melanoma metastases in sentinel nodes predicts disease recurrence and survival.

    PubMed

    Riber-Hansen, Rikke; Nyengaard, Jens R; Hamilton-Dutoit, Stephen J; Sjoegren, Pia; Steiniche, Torben

    2011-09-01

    Total metastatic volume (TMV) is an important prognostic factor in melanoma sentinel lymph nodes (SLNs) that avoids both the interobserver variation and unidirectional upstaging seen when using semi-quantitative size estimates. However, it is somewhat laborious for routine application. Our aim was to investigate whether digital image analysis can estimate TMV accurately in melanoma SLNs. TMV was measured in 147 SLNs from 95 patients both manually and by automated digital image analysis. The results were compared by Bland-Altman plots (numerical data) and kappa statistics (categorical data). In addition, disease-free and melanoma-specific survivals were calculated. Mean metastatic volume per patient was 10.6 mm(3) (median 0.05 mm(3); range 0.0001-621.3 mm(3)) and 9.62 mm(3) (median 0.05 mm(3); range 0.00001-564.3 mm(3)) with manual and digital measurement, respectively. The Bland-Altman plot showed an even distribution of the differences, and the kappa statistic was 0.84. In multivariate analysis, both manual and digital metastasis volume measurements were independent progression markers when corrected for primary tumour thickness [manual: hazard ratio (HR): 1.21, 95% confidence interval (CI): 1.07-1.36, P = 0.002; digital: HR: 1.21, 95% CI: 1.06-1.37, P = 0.004]. Stereology-based, automated digital metastasis volume measurement in melanoma SLNs predicts disease recurrence and survival. © 2011 Blackwell Publishing Limited.

  3. Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma: 9 years of follow-up.

    PubMed

    Finocchiaro, L M E; Glikin, G C

    2012-12-01

    We present here the updated results after 9 years of the beginning of a trial on canine patients with malignant melanoma. This surgery adjuvant approach combined local suicide gene therapy with a subcutaneous vaccine composed by tumor cells extracts and xenogeneic cells producing human interleukin-2 and granulocyte-macrophage colony-stimulating factor. Toxicity was absent or minimal in all patients (0≤VCOG-CTCAE grade≤1). With respect to surgery-treated controls (ST), the complete surgery (CS) arm of this combined treatment (CT) significantly increased the fraction of local disease-free patients from 13 to 81% and distant metastases free from 32 to 84%. Even though less effective than the CS arm, the partial surgery (PS) arm of this CT was significantly better controlling the disease than only surgery (14% while PS-ST: 0%, P<0.01 and CS-ST: 5%, P<0.05). In addition, CT produced a significant sevenfold (CS) and threefold (PS) increase in overall survival. The CS-CT arm significantly improved both CS-ST metastasis-free- and melanoma overall survival from 99 days (respective ranges: 11-563 and 10-568) to >2848 days (81-2848 and 35-2848). Thus, more of 50% of our CT patients died of melanoma unrelated causes, transforming a lethal disease into a chronic one. Finally, surgery adjuvant CT delayed or prevented post-surgical recurrence and distant metastasis, significantly improved disease-free and overall survival maintaining the quality of life. Long-term safety and efficacy of this treatment are supported by the high number of CT patients (283) and extensive follow-up (>9 years). The successful clinical outcome encourages the further translation of similar approaches to human gene therapy trials.

  4. Association between Free Triiodothyronine Levels and Peripheral Arterial Disease in Euthyroid Participants.

    PubMed

    Wang, Po; DU, Rui; Lin, Lin; Ding, Lin; Peng, Kui; Xu, Yu; Xu, Min; Bi, Yu Fang; Wang, Wei Qing; Ning, Guang; Lu, Jie Li

    2017-02-01

    This current cross-sectional study investigates the relationship between thyroid hormones and peripheral artery disease (PAD) among euthyroid Chinese population aged 40 years and above. Serum free triiodothyronine (FT3), free thyroxin (FT4), thyroid-stimulating hormone (TSH), and thyroid antibodies were measured. PAD was defined as ankle-brachial index (ABI) < 0.9. There were 91 (2.9%) PAD cases among the 3,148 euthyroid study participants. Participants in the highest quartile of FT3 and free-triiodothyronine-to-free-thyroxin (FT3/FT4 ratio) had a decreased risk of prevalent PAD (multivariate-adjusted odds ratio, 95% confidence interval: 0.32, 0.15-0.62, P for trend = 0.01 and 0.31, 0.13-0.66, P for trend = 0.004, respectively) compared to those in the lowest quartile. To conclude, FT3 levels and the FT3/FT4 ratio was inversely associated with prevalent PAD in euthyroid Chinese population aged 40 years and above. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  5. 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.

  6. Ozone and Survival in Four Cohorts with Potentially Predisposing Diseases

    PubMed Central

    Schwartz, Joel

    2011-01-01

    Rationale: Time series studies have reported associations between ozone and daily deaths. Only one cohort study has reported the effect of long-term exposures on deaths, and little is known about effects of chronic ozone exposure on survival in susceptible populations. Objectives: We investigated whether ozone was associated with survival in four cohorts of persons with specific diseases in 105 United States cities, treating ozone as a time varying exposure. Methods: We used Medicare data (1985–2006), and constructed cohorts of persons hospitalized with chronic conditions that might predispose to ozone effects: chronic obstructive pulmonary disease, diabetes, congestive heart failure, and myocardial infarction. Yearly warm-season average ozone was merged to the individual follow-up in each city. We applied Cox proportional hazard model for each cohort within each city, adjusting for individual risk factors, temperature, and city-specific long-term trends. Measurements and Main Results: We found significant associations with a hazard ratio for mortality of 1.06 (95% confidence interval [CI], 1.03–1.08) per 5-ppb increase in summer average ozone for persons with congestive heart failure; of 1.09 (95% CI, 1.06–1.12) with myocardial infarction; of 1.07 (95% CI, 1.04–1.09) with chronic obstructive pulmonary disease; and of 1.07 (95% CI, 1.05–1.10) for diabetics. We also found that the effect varied by region, but that this was mostly explained by mean temperature, which is likely a surrogate of air conditioning use, and hence exposure. Conclusions: This is the first study that follows persons with specific chronic conditions, and shows that long-term ozone exposure is associated with increased risk of death in these groups. PMID:21700916

  7. Immediate Implants Placed in Fresh Sockets Associated with Periapical Pathology: A Split-Mouth Design and Survival Evaluation after 1-Year Follow-Up.

    PubMed

    Hita-Iglesias, Cristina; Sánchez-Sánchez, Francisco J; Montero, Javier; Galindo-Moreno, Pablo; Mesa, Francisco; Martínez-Lara, Ildefonso; Sánchez-Fernández, Elena

    2016-12-01

    To compare the immediate implant success rates between sites with chronic apical lesions and healthy sites in the same patients 1 year postdelayed loading. One hundred sixty-eight immediate implants were placed in sixty patients at upper incisor, canine, and premolar sites. A split-mouth design was used, placing a minimum of two implants, one in a fresh socket associated with chronic periapical disease, the average lesion size was larger than 4 mm and less than 8 mm (test group), and the other(s) in a healthy fresh socket (control group). Implant survival rate at 1 year postloading delayed was compared between the groups. The implant survival rate was 98.2% for the total sample (n = 168); out of the three implants lost, two were from the test group, and one was from the control group (in the same patient as one of the former). Among the surviving implants, five were also considered failures due to excessive bone loss (n = 3) and also because of the recurrence of the periapical lesions (n = 2). Survival rates were significantly lower in the test than control sites at 12 months postloading. Implant survival rates were significantly lower after the immediate implantation in postextraction sockets associated with chronic periapical disease (90.8%) than in healthy postextraction sockets (98.1%). © 2015 Wiley Periodicals, Inc.

  8. Movement Disorders in Adult Surviving Patients with Maple Syrup Urine Disease

    PubMed Central

    Carecchio, Miryam; Schneider, Susanne A.; Chan, Heidi; Lachmann, Robin; Lee, Philip J.; Murphy, Elaine; Bhatia, Kailash P.

    2014-01-01

    Maple syrup urine disease is a rare metabolic disorder caused by mutations in the branched-chain α-keto acid dehydrogenase complex gene. Patients generally present early in life with a toxic encephalopathy because of the accumulation of the branched-chain amino acids leucine, isoleucine, and valine and the corresponding ketoacids. Movement disorders in maple syrup urine disease have typically been described during decompensation episodes or at presentation in the context of a toxic encephalopathy, with complete resolution after appropriate dietary treatment. Movement disorders in patients surviving childhood are not well documented. We assessed 17 adult patients with maple syrup urine disease (mean age, 27.5 years) with a special focus on movement disorders. Twelve (70.6%) had a movement disorder on clinical examination, mainly tremor and dystonia or a combination of both. Parkinsonism and simple motor tics were also observed. Pyramidal signs were present in 11 patients (64.7%), and a spastic-dystonic gait was observed in 6 patients (35.2%). In summary, movement disorders are common in treated adult patients with maple syrup urine disease, and careful neurological examination is advisable to identify those who may benefit from specific therapy. PMID:21484869

  9. Comparison of Biochemical Recurrence-Free Survival after Radical Prostatectomy Triggered by Grade Reclassification during Active Surveillance and in Men Newly Diagnosed with Similar Grade Disease.

    PubMed

    Diniz, Clarissa P; Landis, Patricia; Carter, H Ballentine; Epstein, Jonathan I; Mamawala, Mufaddal

    2017-09-01

    We compared biochemical recurrence between men on active surveillance who underwent radical prostatectomy triggered by grade reclassification and men diagnosed with similar grade disease treated with immediate radical prostatectomy. We retrospectively analyzed the records of men who underwent surgery from 1995 to 2015 at our institution. We identified 4 groups, including 94 and 56 men on active surveillance who underwent radical prostatectomy following reclassification to Gleason 7 (3 + 4) or greater (grade groups 2 or greater) and Gleason 7 (3 + 4) (grade group 2), and 3,504 and 1,979 in the immediate prostatectomy group diagnosed with grade group 2 or greater and 2, respectively. Biochemical recurrence was assessed by Kaplan-Meir analysis and a multivariable Cox model. Men on active surveillance had a lower incidence of biochemical recurrence than men in the immediate radical prostatectomy groups for biopsy grade groups 2 or greater and 2 (each p <0.05). One, 5 and 10-year biochemical recurrence-free survival for men in the active surveillance group vs the immediate radical prostatectomy group was 97.9% vs 85.5%, 76.6% vs 65.1% and 69.0% vs 54.2% in biopsy grade groups 2 or greater (p = 0.009) and 96.4% vs 91.2%, 89.6% vs 74.0% and 89.6% vs 63.9%, respectively, in biopsy grade group 2 (p = 0.071). For biopsy grade groups 2 or greater there was no significant difference in the risk of biochemical recurrence between the groups after adjusting for age, biopsy extent of cancer and prostate specific antigen density. Patients on active surveillance reclassified to grade groups 2 or greater are at no greater risk for treatment failure than men newly diagnosed with similar grades. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  10. Five year survival analysis of an oxidised zirconium total knee arthroplasty.

    PubMed

    Holland, Philip; Santini, Alasdair J A; Davidson, John S; Pope, Jill A

    2013-12-01

    Zirconium total knee arthroplasties theoretically have a low incidence of failure as they are low friction, hard wearing and hypoallergenic. We report the five year survival of 213 Profix zirconium total knee arthroplasties with a conforming all polyethylene tibial component. Data was collected prospectively and multiple strict end points were used. SF12 and WOMAC scores were recorded pre-operatively, at three months, at twelve months, at 3 years and at 5 years. Eight patients died and six were "lost to follow-up". The remaining 199 knees were followed up for five years. The mean WOMAC score improved from 56 to 35 and the mean SF12 physical component score improved from 28 to 34. The five year survival for failure due to implant related reasons was 99.5% (95% CI 97.4-100). This was due to one tibial component becoming loose aseptically in year zero. Our results demonstrate that the Profix zirconium total knee arthroplasty has a low medium term failure rate comparable to the best implants. Further research is needed to establish if the beneficial properties of zirconium improve long term implant survival. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. End-stage renal disease and survival in people with diabetes: a national database linkage study

    PubMed Central

    Fletcher, E.H.; Brady, I.; Looker, H.C.; Levin, D.; Joss, N.; Traynor, J.P.; Metcalfe, W.; Conway, B.; Livingstone, S.; Leese, G.; Philip, S.; Wild, S.; Halbesma, N.; Sattar, N.; Lindsay, R.S.; McKnight, J.; Pearson, D.; Colhoun, H.M.

    2015-01-01

    Background: Increasing prevalence of diabetes worldwide is projected to lead to an increase in patients with end-stage renal disease (ESRD) requiring renal replacement therapy (RRT). Aim: To provide contemporary estimates of the prevalence of ESRD and requirement for RRT among people with diabetes in a nationwide study and to report associated survival. Methods: Data were extracted and linked from three national databases: Scottish Renal Registry, Scottish Care Initiative-Diabetes Collaboration and National Records of Scotland death data. Survival analyses were modelled with Cox regression. Results: Point prevalence of chronic kidney disease (CKD)5 in 2008 was 1.63% of 19 414 people with type 1 diabetes (T1DM) compared with 0.58% of 167 871 people with type 2 diabetes (T2DM) (odds ratio for DM type 0.97, P = 0.77, on adjustment for duration. Although 83% of those with T1DM and CKD5 and 61% of those with T2DM and CKD5 were receiving RRT, there was no difference when adjusted for age, sex and DM duration (odds ratio for DM type 0.83, P = 0.432). Diabetic nephropathy was the primary renal diagnosis in 91% of people with T1DM and 58% of people with T2DM on RRT. Median survival time from initiation of RRT was 3.84 years (95% CI 2.77, 4.62) in T1DM and 2.16 years (95% CI: 1.92, 2.38) in T2DM. Conclusion: Considerable numbers of patients with diabetes continue to progress to CKD5 and RRT. Almost half of all RRT cases in T2DM are considered to be due to conditions other than diabetic nephropathy. Median survival time for people with diabetes from initiation of RRT remains poor. These prevalence data are important for future resource planning. PMID:25140030

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

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

    Malagari, Katerina, E-mail: kmalag@otonet.gr; Pomoni, Mary; Moschouris, Hippocrates, E-mail: hipmosch@gmail.com

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

  13. Survival Outcomes for Patients With Indeterminate 18FDG-PET Scan for Extrahepatic Disease Before Liver Resection for Metastatic Colorectal Cancer: A Retrospective Cohort Study Using a Prospectively Maintained Database to Analyze Survival Outcomes for Patients With Indeterminate Extrahepatic Disease on 18FDG-PET Scan Before Liver Resection for Metastatic Colorectal Cancer.

    PubMed

    Wong, Geoffrey Yuet Mun; Kumar, Rajiv; Beeke, Carol; Ullah, Shahid; Chen, John; Karapetis, Christos; Price, Timothy; Padbury, Rob

    2018-05-01

    The aim of this study was to evaluate overall survival (OS) and cancer recurrence for patients with indeterminate positron emission tomography (PET) scan for extrahepatic disease (EHD) before liver resection (LR) for colorectal liver metastases (CLMs). Indeterminate EHD as determined by PET imaging indicates a probability of extrahepatic malignancy and potentially excludes patients from undergoing LR for CLM. In a retrospective analysis of prospectively collected data from February 2006 to December 2014, OS for patients with indeterminate EHD on FDG-PET scan before LR for CLM was performed using standard survival analysis methods, including Kaplan-Meier estimator and Cox proportional hazard models for multivariate analyses. Postoperative imaging was used as reference to evaluate the association between indeterminate EHD and recurrence. Of 267 patients with PET scans before LR, 197 patients had no EHD and 70 patients had indeterminate EHD. Median follow-up was 33 months. The estimated 5-year OS was 60.8% versus 59.4% for indeterminate and absent EHD, respectively (P = 0.625). Disease-free survival was comparable between both groups (P = 0.975) and overall recurrence was 57.1% and 59.5% for indeterminate and absent EHD, respectively (P = 0.742). About 16.9% of recurrence was associated with the site of indeterminate EHD, with 80% of associated recurrence occurring in the thorax. The site of indeterminate EHD appears to have a predictive value for recurrence, with indeterminate EHD in the thorax having a higher probability of malignancy. The evidence in this report supports the critical evaluation of PET scan results and that patients are not denied potential curative LR unless the evidence for unresectable EHD is certain.

  14. Transoral laser microsurgery for locally advanced (T3-T4a) supraglottic squamous cell carcinoma: Sixteen years of experience.

    PubMed

    Vilaseca, Isabel; Blanch, José Luis; Berenguer, Joan; Grau, Juan José; Verger, Eugenia; Muxí, África; Bernal-Sprekelsen, Manuel

    2016-07-01

    Controversy exists regarding treatment of advanced laryngeal cancer. The purpose of this study was to evaluate the oncologic and functional outcomes of T3 to T4a supraglottic squamous carcinomas treated with transoral laser microsurgery (TLM). We conducted a retrospective analysis from an SPSS database. Primary outcomes were: locoregional control, overall survival (OS), disease-specific survival (DSS), laryngectomy-free survival, and function-preservation rates. Secondary objectives were: rate of tracheostomies and gastrostomies according to age. Risk factors for local control and larynx preservation were also evaluated. One hundred fifty-four consecutive patients were chosen for this study. Median follow-up was 40.7 + /- 32.8 months. Five and 10-year OS, DSS, and laryngectomy-free survival were 55.6% and 47%, 67.6% and 58.6%, and 75.2% and 59.5%, respectively. Paraglottic involvement was an independent factor for larynx preservation. Six patients (3.9%) needed a definitive tracheostomy, a gastrostomy, or both. The gastrostomy rate was higher in the group of patients above 65 years of age (p = .03). Five-year laryngectomy-free survival with preserved function was 74.5%. TLM constitutes a true alternative for organ preservation in locally advanced supraglottic carcinomas with good oncologic and functional outcomes. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1050-1057, 2016. © 2016 Wiley Periodicals, Inc.

  15. Secondary free-flap reconstruction following ablation for acute invasive fungal sinusitis.

    PubMed

    Allensworth, Jordan J; Troob, Scott H; Weaver, Tyler S; Gonzalez, Javier D; Petrisor, Daniel; Wax, Mark K

    2017-04-01

    Acute invasive fungal sinusitis (AIFS) is a frequently fatal infection for which extensive and debilitating surgical debridement is a mainstay of therapy. Resulting defects are often composite in nature, mandating free tissue-transfer reconstruction. Outcomes data for free flap reconstruction are limited. The purpose of this study was to examine surgical outcomes and survival in patients undergoing free flap transfer following invasive fungal sinusitis. Retrospective case series. Between 1995 and 2015, patients undergoing operative debridement for AIFS were identified. Surgical records were used to identify survivors of acute infection who subsequently underwent free flap reconstructive surgery. Patient demographics, cause of immune compromise, defect description, flap type, perioperative complications, indications for revision surgery, functional outcomes, and long-term survival were reviewed. Forty-four patients were treated for AIFS, of those, 30 (68%) survived acute infection. Ten patients underwent maxillectomy, six with orbital exenteration, and were designated candidates for reconstruction. Eight patients underwent reconstruction. Median time from debridement to reconstruction was 67.5 days. Flap types included latissimus dorsi, scapula, anterolateral thigh, rectus, radial forearm, and fibula. Median follow-up was 7.7 months. No perioperative complications were encountered, and all subjects remained disease-free, able to speak and eat normally without prosthetic supplementation. Seven patients (87%) are currently alive. Reconstruction of defects left by invasive fungal sinusitis using free-tissue transfer resulted in successful flap survival, with no disease recurrence for all defects and flap types reviewed. Survivors of AIFS are able to tolerate midface reconstruction, with favorable functional outcomes and survival rates. 4. Laryngoscope, 127:815-819, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  16. Analysis of Survival Rates Following Primary Surgery of 178 Consecutive Patients with Oral Cancer in a Large District General Hospital.

    PubMed

    Stathopoulos, Panagiotis; Smith, William P

    2017-06-01

    The aim of this study is to present the survival rates in patients treated for oral cancer with primary surgery in a large district general hospital. We discuss the influence of the most significant prognostic factors on survival and compare our results with larger centres specializing in the management of oral cancer. All patients diagnosed with oral cancer from 1995 to 2006 and were treated in the Department had their details entered prospectively onto a computerized database. Demographic details of patients, type of treatment, pathological stage of tumor (TNM), local and regional recurrence rate, overall survival, disease specific survival and incidence of involved margins were recorded and calculated. Of the 178 patients, 96 (54 %) were alive and free of oral cancer 5 years after surgery. Forty-four patients died of oral cancer (24.7 %) but 38 (21.3 %) died of other causes. The overall survival rate after primary surgery in relation to stage was: I 84 %, II 71 %, III 36 % and IV 28 %. As almost half of our patients presented with advanced cancer and had discouraging survival rates, we emphasize the need for early recognition of the disease. Advanced disease signifies difficulty in obtaining clear margins which actually indicates a higher recurrence rate. 25 % of our patients died of oral cancer within 5 years of surgery which highlights the poor prognosis that recurrence carries after treatment. Effective educational campaign with purpose to raise oral cancer awareness and earlier referral may result in improvement of survival.

  17. Free radicals: properties, sources, targets, and their implication in various diseases.

    PubMed

    Phaniendra, Alugoju; Jestadi, Dinesh Babu; Periyasamy, Latha

    2015-01-01

    Free radicals and other oxidants have gained importance in the field of biology due to their central role in various physiological conditions as well as their implication in a diverse range of diseases. The free radicals, both the reactive oxygen species (ROS) and reactive nitrogen species (RNS), are derived from both endogenous sources (mitochondria, peroxisomes, endoplasmic reticulum, phagocytic cells etc.) and exogenous sources (pollution, alcohol, tobacco smoke, heavy metals, transition metals, industrial solvents, pesticides, certain drugs like halothane, paracetamol, and radiation). Free radicals can adversely affect various important classes of biological molecules such as nucleic acids, lipids, and proteins, thereby altering the normal redox status leading to increased oxidative stress. The free radicals induced oxidative stress has been reported to be involved in several diseased conditions such as diabetes mellitus, neurodegenerative disorders (Parkinson's disease-PD, Alzheimer's disease-AD and Multiple sclerosis-MS), cardiovascular diseases (atherosclerosis and hypertension), respiratory diseases (asthma), cataract development, rheumatoid arthritis and in various cancers (colorectal, prostate, breast, lung, bladder cancers). This review deals with chemistry, formation and sources, and molecular targets of free radicals and it provides a brief overview on the pathogenesis of various diseased conditions caused by ROS/RNS.

  18. Analysis of survival after pancreatic resection for oncological pathologies.

    PubMed

    Benzoni, Enrico; Rossit, Luca; Cojutti, Alessandro; Favero, Alessandro; Saccomano, Enrico; Zompicchiatti, Aron; Noce, Luigi; Bresadola, Fabrizio; Intini, Sergio

    2007-01-01

    Surgical treatment of pancreatic cancer is to date the only modality that offers a chance of long-term survival. Potentially curative surgery is an option for only about 15% of patients with pancreatic adenocarcinoma. The aim of this study was to determine the survival and to assess the association of clinical, pathological, and treatment features with survival of patients who underwent resection of pancreatic cancer at the Department of Surgery of Udine University Hospital. From November 1989 to December 2005, 137 consecutive patients, who underwent surgical procedures for pancreatic cancer, were followed in our department. We performed 76 pancreatico-duodenectomy, 26 distal pancreatectomies and 35 total pancreatectomies. The surgical reconstruction after pancreatico-duodenectomy was as follows: 11 closures of the main duct with manual nonabsorbable stitches, 24 closures of the main duct with a linear stapler, 17 occlusions of the main duct with neoprene glue and 24 duct-to-mucosa anastomoses. Mean survival time was 27.7 +/- 26.93 months (mean +/- SD) and mean disease-free survival time was 25.4 +/- 23.06 months (mean +/- SD). 1, 3, 5, 7 and 9-year survival rates were 63.9, 33.7, 21.17, 12.7 and 10.2%, respectively. Significant differences in survival were recorded by the Log-rank test for age > 70 (p = 0.001), surgical procedures (p = 0.00046) and presence of metastases (p = 0.0055) The treatment of pancreatic cancer is undertaken with two different aims. The first is radical surgery for patients with early-stage disease, mainly stage I and partly stage II. In all other cases, the aim of treatment is the palliation of the several distressing symptoms related to this cancer. The standard treatment option for resectable tumours is radical pancreatic resection according to the Whipple procedure or total pancreatectomy.

  19. Avoiding the Major Causes of Death: Does Childhood Misfortune Reduce the Likelihood of Being Disease Free in Later Life?

    PubMed

    Williams, Monica M; Kemp, Blakelee R; Ferraro, Kenneth F; Mustillo, Sarah A

    2018-04-03

    Although previous research reveals the detrimental effects of early misfortune on the development of chronic diseases in later life, few studies have investigated its effects on remaining disease free. This study draws on cumulative inequality theory to investigate whether experiencing childhood misfortune reduces the likelihood of remaining disease free over time. This study utilizes five waves of data from the Health and Retirement Study to test whether five domains of childhood misfortune predict being disease free at baseline (2004) and developing disease over time (2004-2012). Respondents reporting risky parental behaviors during childhood were less likely to be disease free at baseline and had an increased risk of disease onset over time, the latter driven by having a guardian who smoked in combination with more pack-years smoked in adulthood. Furthermore, we find that adult resources, i.e. wealth, help to mitigate the noxious effects of other misfortunes, notably poor socioeconomic conditions. Consistent with cumulative inequality theory, these findings reveal that experiencing multiple types of misfortune during childhood decreases the likelihood of remaining disease free in later life, but engaging in health behaviors, such as physical activity, can help to ameliorate some of the noxious effects of early misfortune.

  20. 9 CFR 92.4 - Reestablishment of a region's disease-free status.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Reestablishment of a region's disease... Reestablishment of a region's disease-free status. This section applies to regions that are designated in this subchapter D as free of a specific animal disease and then experience an outbreak of that disease. (a...

  1. 9 CFR 92.4 - Reestablishment of a region's disease-free status.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Reestablishment of a region's disease... Reestablishment of a region's disease-free status. This section applies to regions that are designated in this subchapter D as free of a specific animal disease and then experience an outbreak of that disease. (a...

  2. 9 CFR 92.4 - Reestablishment of a region's disease-free status.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Reestablishment of a region's disease... Reestablishment of a region's disease-free status. This section applies to regions that are designated under this subchapter as free of a specific animal disease and then experience an outbreak of that disease. (a) Interim...

  3. 9 CFR 92.4 - Reestablishment of a region's disease-free status.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Reestablishment of a region's disease... Reestablishment of a region's disease-free status. This section applies to regions that are designated in this subchapter D as free of a specific animal disease and then experience an outbreak of that disease. (a...

  4. A study of risk factors associated with Newcastle disease epidemics in village free-range chickens in Uganda.

    PubMed

    Otim, M O; Kabagambe, E K; Mukiibi, G M; Christensen, H; Bisgaard, M

    2007-01-01

    A prospective study of risk factors associated with outbreaks of Newcastle disease (ND) in indigenous free-range chickens was carried out in three agro-ecological zones in eastern Uganda. Sixty households keeping chickens were randomly selected and studied from March 2004 to February 2005, covering rainy and dry seasons. Data on ND outbreaks, risk factors and flock dynamics were collected using an interviewer-administered questionnaire, while ND outbreaks were confirmed by haemagglutination inhibition test. Multivariate survival analyses were performed to identify the risk factors for Newcastle disease outbreaks. Although the survival time against ND was longer (> 100 days) in the dry compared to the rainy season, incidence in the two seasons was not significantly different (p > 0.05). None of the factors investigated was significantly associated with ND. However, purchasing of restocking chickens from the market and neighbourhood (hazard ratio [HR] = 1.79; 95% confidence interval [CI] 0.89-3.60), the presence of migratory wild birds (HR = 1.70; 95% CI 0.65-4.48) and being in agro-ecological zone 1 (HR = 1.48; 95% CI 0.66-3.36) showed a positive but non-significant association with risk for ND. To understand the roles of other domestic poultry species in the epidemiology of ND in rural free-range chickens, virus isolation and molecular characterization of isolates in addition to more prospective cohort studies with a larger sample size and similarly long period of follow-up are needed.

  5. Association Between Change in Body Mass Index, Unified Parkinson’s Disease Rating Scale Scores, and Survival Among Persons With Parkinson Disease

    PubMed Central

    Wills, Anne-Marie A.; Pérez, Adriana; Wang, Jue; Su, Xiao; Morgan, John; Rajan, Suja S.; Leehey, Maureen A.; Pontone, Gregory M.; Chou, Kelvin L.; Umeh, Chizoba; Mari, Zoltan; Boyd, James

    2017-01-01

    IMPORTANCE Greater body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) is associated with improved survival among persons with Huntington disease or amyotrophic lateral sclerosis. Weight loss is common among persons with Parkinson disease (PD) and is associated with worse quality of life. OBJECTIVE To explore the association between change in BMI, Unified Parkinson’s Disease Rating Scale (UPDRS) motor and total scores, and survival among persons with PD and to test whether there is a positive association between BMI at randomization and survival. DESIGN, SETTING, AND PARTICIPANTS Secondary analysis (from May 27, 2014, to October 13, 2015) of longitudinal data (3–6 years) from 1673 participants who started the National Institute of Neurological Disorders and Stroke Exploratory Trials in PD Long-term Study-1 (NET-PD LS-1). This was a double-blind randomized placebo-controlled clinical trial of creatine monohydrate (10 g/d) that was performed at 45 sites throughout the United States and Canada. Participants with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) PD were enrolled from March 2007 to May 2010 and followed up until September 2013. MAIN OUTCOMES AND MEASURES Change across time in motor UPDRS score, change across time in total UPDRS score, and time to death. Generalized linear mixed models were used to estimate the effect of BMI on the change in motor and total UPDRS scores after controlling for covariates. Survival was analyzed using Cox proportional hazards models of time to death. A participant’s BMI was measured at randomization, and BMI trajectory groups were classified according to whether participants experienced weight loss (“decreasing BMI”), weight stability (“stable BMI”), or weight gain (“increasing BMI”) during the study. RESULTS Of the 1673 participants (mean [SD] age, 61.7 [9.6] years; 1074 [64.2%] were male), 158 (9.4%) experienced weight loss

  6. Improvement in initial survival of spinal injuries: a 10-year audit.

    PubMed

    Tan, H B; Sloan, J P; Barlow, I F

    2005-08-01

    A 10-year retrospective study of all spinal injuries presenting to the Leeds Teaching Hospitals between 1991 and 2001. The hospitals provide secondary care to a population of 750,000 and tertiary care to a population of 2-3 million. In total 1119 spinal injuries were studied. The overall survival rate was 89%. The commonest age group for presentation was 25-29 years with a secondary peak in the seventh decade, a mean overall of 43 years. 66% of injuries occurred in males. The commonest cause was a fall from a height (44%), with road traffic accidents (RTA) causing 43%. Pedestrians were most at risk within the road traffic group, making up 63% of cases. Isolated cervical spine injuries made up 37% of all cases. Cervical fractures were most associated with neurological injury (50%). Immediate survival has increased over the decade from 83% in 1991 to 93% in 2001. The probability of survival was significant at P = 0.006 and actual survival at P = 0.012 (Pearson correlation). The causal analysis has not been carried out but it is thought likely that improved quality of care is responsible.

  7. Comparison of peritonitis rates and patient survival in automated and continuous ambulatory peritoneal dialysis: a 10-year single center experience.

    PubMed

    El-Reshaid, Wael; Al-Disawy, Hanan; Nassef, Hossameldeen; Alhelaly, Usama

    2016-09-01

    Peritonitis is a common complication in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD). In this retrospective study, peritonitis rates and patient survival of 180 patients on CAPD and 128 patients on APD were compared in the period from January 2005 to December 2014 at Al-Nafisi Center in Kuwait. All patients had prophylactic topical mupirocin at catheter exit site. Patients on CAPD had twin bag system with Y transfer set. The peritonitis rates were 1 in 29 months in CAPD and 1 in 38 months in APD (p < 0.05). Percentage of peritonitis free patients over 10-year period in CAPD and APD were 49 and 60%, respectively (p < 0.05). Time to develop peritonitis was 10.25 ± 3.1 months in CAPD compared to 16.1 ± 4 months in APD (p < 0.001). Relapse and recurrence rates were similar in both groups. Median patient survival in CAPD and APD groups with peritonitis was 13.1 ± 1 and 14 ± 1.4 months respectively (p = 0.3) whereas in peritonitis free patients it was 15 ± 1.4 months in CAPD and 23 ± 3.1 months in APD (p = 0.025). APD had lower incidence rate of peritonitis than CAPD. Patient survival was better in APD than CAPD in peritonitis free patients but was similar in patients who had peritonitis.

  8. Sentinel lymph node biopsy in thick malignant melanoma: A 16-year single unit experience.

    PubMed

    Hunger, Robert E; Michel, Aude; Seyed Jafari, S Morteza; Shafighi, Maziar

    2015-01-01

    The role of sentinel lymph node biopsy (SLNB) and its benefits in patients with thick melanoma is still controversial. We evaluated the clinical effect of SLNB in patients with thick melanoma. We performed a retrospective cohort review (1996-2012) of thick melanomas. Collected data included the patient and tumour characteristics. Locoregional recurrence, distant metastases, disease free and overall survival were compared between the patients with positive and negative SLNB. 126 thick melanomas with a mean age of 64.09 years were included in the study. Positive SLNB were found in 47 (37.3%) patients. Significantly more locoregional recurrence (P = 0.002) and distant metastases (P = 0.030) were detected in the patients with positive SLNB. Furthermore, the patients with negative SLNB showed significantly better disease free survival (P = 0.021). Positive SLNB might be prognostic factor in thick melanoma and aggravates the outcome of thick melanomas.

  9. A retrospective study on the role of diabetes and metformin in colorectal cancer disease survival

    PubMed Central

    Ramjeesingh, R.; Orr, C.; Bricks, C.S.; Hopman, W.M.; Hammad, N.

    2016-01-01

    Background Recent studies have suggested an effect of metformin on mortality for patients with both diabetes and colorectal cancer (crc). However, the literature is contradictory, with both positive and negative effects being identified. We set out to determine the effect of metformin with respect to prognosis in crc patients. Methods After a retrospective chart review of crc patients treated at the Cancer Centre of Southeastern Ontario, Kaplan–Meier analyses and Cox proportional hazards regression models were used to compare overall survival (os) in patients with and without diabetes. Results We identified 1304 crc patients treated at the centre. No significant differences between the diabetic and nondiabetic groups were observed with respect to tumour pathology, extent of metastatic disease, time or toxicity of chemotherapy, and the os rate (1-year os: 85.6% vs. 86.4%, p = 0.695; 2-year os: 73.6% vs. 77.0%, p = 0.265). In subgroup analysis, diabetic patients taking metformin survived significantly longer than their counterparts taking other diabetes treatments (os for the metformin group: 91% at 1 year; 80.5% at 2 years; os for the group taking other treatments, including diet control: 80.6% at 1 year, 67.4% at 2 years). Multivariate analysis suggests that patients with diabetes taking treatments other than metformin experience worse survival (p = 0.025). Conclusions Our results suggest that crc patients with diabetes, excluding those taking metformin, might have a worse crc prognosis. Taking metformin appears to have a positive association with prognosis. The protective nature of metformin needs further evaluation in prospective analyses. PMID:27122979

  10. Over 25 years survival after Charnley's total hip arthroplasty.

    PubMed

    Caton, Jacques; Prudhon, Jean Louis

    2011-02-01

    Since 1962, the low friction arthroplasty (LFA) developed by Sir John Charnley has spread widely throughout the world. Many series have reported long-term results. Polyethylene (PE) wear is well known. The average wear ratio is about 0.1 mm a year. Many factors may influence that wear process. The authors describe two different series of patients operated upon with Charnley's total hip arthroplasty (THA) using the original cemented stem and a non modular 22.2-mm head, with a cemented full polyethylene acetabular socket. Outcomes confirm excellent patient function after 25 years. They emphasise the fact that PE is the weak point of total hip arthroplasty. Function may be excellent even though PE wear is significant. In several cases, no wear at the maximum follow-up was detectable. This study confirms different publications relating long-term follow-up with LFA. During a Charnley meeting in Lyon, we published a survival curve of 85% after 25 years. Berry et al. published a 86.5% survival curve (J Bone Joint Surg Am 84:171-177, 2002). In 1995, Luc and Marcel Kerboul published a 77% survival rate after 20 years in young patients under 40 years old at the time of the surgery. In 2009, Callaghan et al. published a series of 35 years follow-up with a ratio of 78% survivorship (J Bone Joint Surg Br 91:2617-2621). Could the long-term results be improved? Through recent decades, many solutions have been introduced to improve the survivorship of THA including bearing surfaces such as alumina-on-alumina and metal-on-metal. Different problems have occurred with these solutions. LFA might be improved by working on the nature and the quality of the head. Improvements might also be obtained by working on the quality and the hardness of the acetabular socket.

  11. Impact of testosterone replacement therapy on thromboembolism, heart disease and obstructive sleep apnoea in men.

    PubMed

    Cole, Alexander P; Hanske, Julian; Jiang, Wei; Kwon, Nicollette K; Lipsitz, Stuart R; Kathrins, Martin; Learn, Peter A; Sun, Maxine; Haider, Adil H; Basaria, Shehzad; Trinh, Quoc-Dien

    2018-05-01

    To assess the association of testosterone replacement therapy (TRT) with thromboembolism, cardiovascular disease (stroke, coronary artery disease and heart failure) and obstructive sleep apnoea (OSA). A cohort of 3 422 male US military service members, retirees and their dependents, aged 40-64 years, was identified, who were prescribed TRT between 2006 and 2010 for low testosterone levels. The men in this cohort were matched on a 1:1 basis for age and comorbidities to men without a prescription for TRT. Event-free survival and rates of thromboembolism, cardiovascular events and OSA were compared between men using TRT and the control group, with a median follow-up of 17 months. There was no difference in event-free survival with regard to thromboembolism (P = 0.239). Relative to controls, men using TRT had improved cardiovascular event-free survival (P = 0.004), mainly as a result of lower incidence of coronary artery disease (P = 0.008). The risk of OSA was higher in TRT users (2-year risk 16.5% [95% confidence interval 15.1-18.1] in the TRT group vs 12.7% [11.4-14.1] in the control group. This study adds to growing evidence that the cardiovascular risk associated with TRT may be lower than once feared. The elevated risk of OSA in men using TRT is noteworthy. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

  12. Comparative Study of Survival following Videothoracoscopic Lobectomy Procedures for Lung Cancer: Single- versus Multiple-port Approaches.

    PubMed

    Borro, José M; Regueiro, Francisco; Pértega, Sonia; Constenla, Manuel; Pita, Salvador

    2017-04-01

    Video-assisted thoracoscopic surgery has become the technique of choice in the early stages of lung cancer in many centers although there is no evidence that all of the surgical approaches achieve the same long-term survival. We carried out a retrospective review of 276 VATS lobectomies performed in our department, analyzing age, sex, comorbidities, current smoker, FEV1 and FCV, surgical approach, TNM and pathological stage, histologic type, neoadjuvant or coadjuvant chemotherapy, relapse and metastasis time, with the main aim of evaluating the survival rate and disease-free time, especially with regard to the two/three versus single port approach. The one/four year global survival rate was 88.1 and 67.6% respectively. Bivariate analysis found that the variables associated with survival are comorbidity, histological type, stage, surgical approach and need for chemotherapy. When we independently analyzed the surgical approach, we found a lower survival rate in the single-port group vs. the two/three-port group (VATS). Stratifying by tumoral stage (stage I) and by tumor size (T2) survival was significantly lower for patients with single-port group in comparison to VATS approach. In the multivariate analysis, single-port group is associated with a higher risk of death (HR=1.78). In analyzing disease-free survival, differences were found in both cases in favor of two/three port VATS: p=.093 for local relapses and p=.091 for the development of metastasis. These results challenge the use of the single port technique in malignant lung pathologies, suggesting the need for clinical trials in order to identify the role this technique may have in lung cancer surgery. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Survival analysis of biliary tract cancer cases in Turkey.

    PubMed

    Akca, Zeki; Mutlu, Hasan; Erden, Abdulsamet; Buyukcelik, Abdullah; Cihan, Yasemin Benderli; Goksu, Sema Sezgin; Aslan, Tuncay; Sezer, Emel Yaman; Inal, Ali

    2014-01-01

    Because of the relative rarity of biliary tract cancers (BTCs), defining long term survival results is difficult. In the present study, we aimed to evaluate the survival of a series of cases in Turkey. A totally of 47 patients with billiary tract cancer from Mersin Goverment Hospital, Acibadem Kayseri Hospital and Kayseri Training and Research Hospital were analyzed retrospectively using hospital records between 2006-2012. The median overall survival was 19.3±3.9 months for all patients. The median disease free and overall survivals were 24.3±5.3 and 44.1±12.9 months in patients in which radical surgery was performed , but in those with with inoperable disease they were only 5.3±1.5 and 10.7±3.2 months, respectively. BTCs have a poor prognosis. Surgery with a microscopic negative margin is still the only curative treatment.

  14. [Five-year survival analysis in patients with penile cancer].

    PubMed

    Montiel-Jarquín, Álvaro José; Contreras-Díaz, Antonio Jesús; Vázquez-Cruz, Eduardo; Chopin-Gazga, Marco Antonio; Romero-Figueroa, María Socorro; Etchegaray-Morales, Ivet; Alvarado-Ortega, Ivan

    2017-01-01

    Short-term survival of penile cancer is poor. The objective was to describe the 5-years penile cancer survival. Retrospective cohort study. We included patients with penile cancer managed surgically from 2010 to 2014. Descriptive statistics were used for socio-demographic variables and the Kaplan-Meier estimator for survival function. We studied 22 patients with a mean age of 64.95 years and a time of evolution of 25 months after the diagnosis. 68.2% of patients smoked or had human papillomavirus (HPV); they all presented phimosis; 72.7% had pain in the penis and the groin area; 81.8% had palpable lymph nodes and 45.5% lesions ≥ 3 cm; 86.3% were diagnosed in clinical stage IIIa. 59.1% underwent partial penectomy and 86.4% had squamous cell variety. 40.9% of patients died six months after the surgery. 66% of the smokers presented metastasis; all of the patients that smoked and had HPV infection had neurovascular invasion and died; 83.3% of the patients (n = 6) who underwent partial penectomy and positive lymph node dissection due to metastases died. The 5-years mortality of patients with penile cancer was 40.9%. Tobacco use and HPV increase morbidity and mortality in patients with penile cancer; lesions greater than 5 cm are more common in smokers. The size of the lesion increases with the delay in treatment.

  15. Free radicals and related reactive species as mediators of tissue injury and disease: implications for Health.

    PubMed

    Kehrer, James P; Klotz, Lars-Oliver

    2015-01-01

    A radical is any molecule that contains one or more unpaired electrons. Radicals are normal products of many metabolic pathways. Some exist in a controlled (caged) form as they perform essential functions. Others exist in a free form and interact with various tissue components. Such interactions can cause both acute and chronic dysfunction, but can also provide essential control of redox regulated signaling pathways. The potential roles of endogenous or xenobiotic-derived free radicals in several human pathologies have stimulated extensive research linking the toxicity of numerous xenobiotics and disease processes to a free radical mechanism. In recent years, improvements in analytical methodologies, as well as the realization that subtle effects induced by free radicals and oxidants are important in modulating cellular signaling, have greatly improved our understanding of the roles of these reactive species in toxic mechanisms and disease processes. However, because free radical-mediated changes are pervasive, and a consequence as well as a cause of injury, whether such species are a major cause of tissue injury and human disease remains unclear. This concern is supported by the fact that the bulk of antioxidant defenses are enzymatic and the findings of numerous studies showing that exogenously administered small molecule antioxidants are unable to affect the course of most toxicities and diseases purported to have a free radical mechanism. This review discusses cellular sources of various radical species and their reactions with vital cellular constituents, and provides examples of selected disease processes that may have a free radical component.

  16. Smoking, physical inactivity and obesity as predictors of healthy and disease-free life expectancy between ages 50 and 75: a multicohort study.

    PubMed

    Stenholm, Sari; Head, Jenny; Kivimäki, Mika; Kawachi, Ichiro; Aalto, Ville; Zins, Marie; Goldberg, Marcel; Zaninotto, Paola; Magnuson Hanson, Linda; Westerlund, Hugo; Vahtera, Jussi

    2016-08-01

    Smoking, physical inactivity and obesity are modifiable risk factors for morbidity and mortality. The aim of this study was to examine the extent to which the co-occurrence of these behaviour-related risk factors predict healthy life expectancy and chronic disease-free life expectancy in four European cohort studies. Data were drawn from repeated waves of four cohort studies in England, Finland, France and Sweden. Smoking status, physical inactivity and obesity (body mass index ≥30 kg/m 2 ) were examined separately and in combination. Health expectancy was estimated by using two health indicators: suboptimal self-rated health and having a chronic disease (cardiovascular disease, cancer, respiratory disease and diabetes). Multistate life table models were used to estimate sex-specific healthy life expectancy and chronic disease-free life expectancy from ages 50 to 75 years. Compared with men and women with at least two behaviour-related risk factors, those with no behaviour-related risk factors could expect to live on average8 years longer in good health and 6 years longer free of chronic diseases between ages 50 and 75. Having any single risk factor was also associated with reduction in healthy years. No consistent differences between cohorts were observed. Data from four European countries show that persons with individual and co-occurring behaviour-related risk factors have shorter healthy life expectancy and shorter chronic disease-free life expectancy. Population level reductions in smoking, physical inactivity and obesity could increase life-years lived in good health. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association.

  17. Incidence and survival of hematological cancers among adults ages ≥75 years.

    PubMed

    Krok-Schoen, Jessica L; Fisher, James L; Stephens, Julie A; Mims, Alice; Ayyappan, Sabarish; Woyach, Jennifer A; Rosko, Ashley E

    2018-04-13

    Evaluating population-based data of hematologic malignancies (HMs) in older adults provides prognostic information for this growing demographic. Incidence rates and one- and five-year relative survival rates were examined for specific HMs among adults ages ≥75 years using data from the Surveillance, Epidemiology and End Results (SEER) Program. Hematologic malignancy cases (Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), multiple myeloma (MM), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML)) were reported to one of 18 SEER registries. Recent average annual (2010-2014) incidence rates and incidence trends from 1973 to 2014 were examined for cases ages ≥75 years. One- and five-year relative cancer survival rates were examined for adults ages ≥75 years diagnosed 2007-2013, with follow-up into 2014. From 1973 to 2014, incidence rates increased for NHL, MM, and AML, decreased for HL, and remained relatively stable for ALL, CLL, and CML among adults ages ≥75 years. The highest one- and five-year relative survival rates were observed among adults with CLL ages 75-84 years (1 year: 91.8% (95% CI = 91.8-90.8)) and 5 years: 76.5% (95% CI = 74.2-78.6)). The lowest one- and five-year survival rates were observed among adults with AML ages 75-84 (1 year: 18.2% (95% CI = 74.2-78.6) and 5 years: 2.7% (95% CI = 2.0-3.6)). Survival for older adults ages ≥75 years with HMs is poor, particularly for acute leukemia. Understanding the heterogeneity in HM outcomes among older patients may help clinicians better address the hematological cancer burden and mortality in the aging population. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  18. Conditional survival in patients with chronic myeloid leukemia in chronic phase in the era of tyrosine kinase inhibitors.

    PubMed

    Sasaki, Koji; Kantarjian, Hagop M; Jain, Preetesh; Jabbour, Elias J; Ravandi, Farhad; Konopleva, Marina; Borthakur, Gautam; Takahashi, Koichi; Pemmaraju, Naveen; Daver, Naval; Pierce, Sherry A; O'Brien, Susan M; Cortes, Jorge E

    2016-01-15

    Tyrosine kinase inhibitors (TKIs) significantly improve survival in patients with chronic myeloid leukemia in chronic phase (CML-CP). Conditional probability provides survival information in patients who have already survived for a specific period of time after treatment. Cumulative response and survival data from 6 consecutive frontline TKI clinical trials were analyzed. Conditional probability was calculated for failure-free survival (FFS), transformation-free survival (TFS), event-free survival (EFS), and overall survival (OS) according to depth of response within 1 year of the initiation of TKIs, including complete cytogenetic response, major molecular response, and molecular response with a 4-log or 4.5-log reduction. A total of 483 patients with a median follow-up of 99.4 months from the initiation of treatment with TKIs were analyzed. Conditional probabilities of FFS, TFS, EFS, and OS for 1 additional year for patients alive after 12 months of therapy ranged from 92.0% to 99.1%, 98.5% to 100%, 96.2% to 99.6%, and 96.8% to 99.7%, respectively. Conditional FFS for 1 additional year did not improve with a deeper response each year. Conditional probabilities of TFS, EFS, and OS for 1 additional year were maintained at >95% during the period. In the era of TKIs, patients with chronic myeloid leukemia in chronic phase who survived for a certain number of years maintained excellent clinical outcomes in each age group. Cancer 2016;122:238-248. © 2015 American Cancer Society. © 2015 American Cancer Society.

  19. Texture analysis for survival prediction of pancreatic ductal adenocarcinoma patients with neoadjuvant chemotherapy

    NASA Astrophysics Data System (ADS)

    Chakraborty, Jayasree; Langdon-Embry, Liana; Escalon, Joanna G.; Allen, Peter J.; Lowery, Maeve A.; O'Reilly, Eileen M.; Do, Richard K. G.; Simpson, Amber L.

    2016-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States. The five-year survival rate for all stages is approximately 6%, and approximately 2% when presenting with distant disease.1 Only 10-20% of all patients present with resectable disease, but recurrence rates are high with only 5 to 15% remaining free of disease at 5 years. At this time, we are unable to distinguish between resectable PDAC patients with occult metastatic disease from those with potentially curable disease. Early classification of these tumor types may eventually lead to changes in initial management including the use of neoadjuvant chemotherapy or radiation, or in the choice of postoperative adjuvant treatments. Texture analysis is an emerging methodology in oncologic imaging for quantitatively assessing tumor heterogeneity that could potentially aid in the stratification of these patients. The present study derives several texture-based features from CT images of PDAC patients, acquired prior to neoadjuvant chemotherapy, and analyzes their performance, individually as well as in combination, as prognostic markers. A fuzzy minimum redundancy maximum relevance method with leave-one-image-out technique is included to select discriminating features from the set of extracted features. With a naive Bayes classifier, the proposed method predicts the 5-year overall survival of PDAC patients prior to neoadjuvant therapy and achieves the best results in terms of the area under the receiver operating characteristic curve of 0:858 and accuracy of 83:0% with four-fold cross-validation techniques.

  20. Survival in patients with metachronous second primary lung cancer.

    PubMed

    Ha, Duc; Choi, Humberto; Chevalier, Cory; Zell, Katrina; Wang, Xiao-Feng; Mazzone, Peter J

    2015-01-01

    Four to 10% of patients with non-small cell lung cancer subsequently develop a metachronous second primary lung cancer. The decision to perform surveillance or screening imaging for patients with potentially cured lung cancer must take into account the outcomes expected when detecting metachronous second primaries. To assess potential survival differences between patients with metachronous second primary lung cancer compared to matched patients with first primary lung cancer. We retrospectively reviewed patients diagnosed with lung cancer at the Cleveland Clinic (2006-2010). Metachronous second primary lung cancer was defined as lung cancer diagnosed after a 4-year, disease-free interval from the first lung cancer, or if there were two different histologic subtypes diagnosed at different times. Patients with first primary lung cancer diagnosed in the same time period served as control subjects. Propensity score matching was performed using age, sex, smoking history, histologic subtype, and collaborative stage, with a 1:3 case-control ratio. Survival analyses were performed by Cox proportional hazards modeling and Kaplan-Meier estimates. Forty-four patients met criteria for having a metachronous second primary lung cancer. There were no statistically significant differences between case subjects and control subjects in prognostic variables. The median survival time and 2-year overall survival rate for the metachronous second primary group, compared with control subjects, were as follows: 11.8 versus 18.4 months (P = 0.18) and 31.0 versus 40.9% (P = 0.28). The survival difference was largest in those with stage I metachronous second primaries (median survival time, 26.8 vs. 60.4 mo, P = 0.09; 2-year overall survival, 56.3 vs. 71.2%, P = 0.28). Patients with stage I metachronous second primary lung cancer may have worse survival than those who present with a first primary lung cancer. This could influence the benefit-risk balance of screening the high-risk cohort with

  1. Graft-versus-Host Disease Treatment: Predictors of Survival

    PubMed Central

    Levine, John E.; Logan, Brent; Wu, Juan; Alousi, Amin M.; Ho, Vincent; Bolaños-Meade, Javier; Weisdorf, Daniel

    2010-01-01

    Acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic cell transplant (HCT) is the major reason for non-relapse mortality and thus is a major determinant of long term survival. Clinical trials of new aGVHD treatments are needed in order to identify approaches that will ultimately improve upon HCT survival. At present it is not clear how quickly response to GVHD treatment needs to be established in order to reliably categorize patients at high risk for death or to promptly identify those who might benefit from alternate treatment. Therefore, we analyzed time to response from onset of aGVHD treatment in 180 patients who were enrolled on a national, randomized, phase II aGVHD treatment clinical trial whose initial treatment of GVHD consisted of high dose steroids plus a second immunosuppressive agent. The aim of this analysis was to determine whether time to aGVHD treatment response predicts patient outcomes, especially survival. We used response at 14, 28 and 56 days from initiation of aGVHD treatment to categorize patients for non-relapse mortality and survival. Multivariate analyses and specificity/sensitivity analyses identified that day 28 response (complete or partial response) best categorized patients by non-relapse mortality and survival at 9 months from start of aGVHD treatment. If verified as a reliable predictor of late outcomes following other aGVHD treatment approaches, day 28 response should serve as a standard early endpoint for future trials of aGVHD therapy. PMID:20541024

  2. Association of ITPA Genotype with Event-Free Survival and Relapse Rates in Children with Acute Lymphoblastic Leukemia Undergoing Maintenance Therapy

    PubMed Central

    Smid, Alenka; Karas-Kuzelicki, Natasa; Milek, Miha; Jazbec, Janez; Mlinaric-Rascan, Irena

    2014-01-01

    Although the treatment of acute lymphoblastic leukemia (ALL) has improved significantly over recent decades, failure due to treatment-related toxicities and relapse of the disease still occur in about 20% of patients. This retrospective study included 308 pediatric ALL patients undergoing maintenance therapy and investigated the effects of genetic variants of enzymes involved in the 6-mercaptopurine (6-MP) metabolism and folate pathway on survival and relapse rates. The presence of at least one of the non-functional ITPA alleles (94C>A and/or IVS2+21A>C variant) was associated with longer event-free survival compared to patients with the wild-type ITPA genotype (p = 0.033). Furthermore, patients carrying at least one non-functional ITPA allele were shown to be at a lower risk of suffering early (p = 0.003) and/or bone marrow relapse (p = 0.017). In conclusion, the ITPA genotype may serve as a genetic marker for the improvement of risk stratification and therapy individualization for patients with ALL. PMID:25303517

  3. Analysis of prognostic factors after resection of solitary liver metastasis in colorectal cancer: a 22-year bicentre study.

    PubMed

    Acciuffi, Sara; Meyer, Frank; Bauschke, Astrid; Settmacher, Utz; Lippert, Hans; Croner, Roland; Altendorf-Hofmann, Annelore

    2018-03-01

    The investigation of the predictors of outcome after hepatic resection for solitary colorectal liver metastasis. We recruited 350 patients with solitary colorectal liver metastasis at the University Hospitals of Jena and Magdeburg, who underwent curative liver resection between 1993 and 2014. All patients had follow-up until death or till summer 2016. The follow-up data concern 96.6% of observed patients. The 5- and 10-year overall survival rates were 47 and 28%, respectively. The 5- and 10-year disease-free survival rates were 30 and 20%, respectively. The analysis of the prognostic factors revealed that the pT category of primary tumour, size and grade of the metastasis and extension of the liver resection had no statistically significant impact on survival and recurrence rates. In multivariate analysis, age, status of lymph node metastasis at the primary tumour, location of primary tumour, time of appearance of the metastasis, the use of preoperative chemotherapy and the presence of extrahepatic tumour proved to be independent statistically significant predictors for the prognosis. Moreover, patients with rectal cancer had a lower intrahepatic recurrence rate, but a higher extrahepatic recurrence rate. The long-term follow-up of patients with R0-resected liver metastasis is multifactorially influenced. Age and comorbidity have a role only in the overall survival. More than three lymph node metastasis reduced both the overall and disease-free survival. Extrahepatic tumour had a negative influence on the extrahepatic recurrence and on the overall survival. Neither overall survival nor recurrence rates was improved using neoadjuvant chemotherapy.

  4. Self-Regulation and Executive Functioning as Related to Survival in Motor Neuron Disease: Preliminary Findings.

    PubMed

    Garcia-Willingham, Natasha E; Roach, Abbey R; Kasarskis, Edward J; Segerstrom, Suzanne C

    2018-05-16

    Disease progression varies widely among patients with motor neuron disease (MND). Patients with MND and coexisting dementia have shorter survival. However, implications of mild cognitive and behavioral difficulties are unclear. The present study examined the relative contribution of executive functioning and self-regulation difficulties on survival over a 6-year period among patients with MND, who scored largely within normal limits on cognitive and behavioral indices. Patients with MND (N=37, age=59.97±11.57, 46% female) completed the Wisconsin Card Sorting Task (WCST) as an executive functioning perseveration index. The Behavior Rating Inventory of Executive Functions (BRIEF-A) was used as a behavioral measure of self-regulation in two subdomains self-regulatory behavior (Behavioral Regulation) and self-regulatory problem-solving (Metacognition). Cox proportional hazard regression analyses were used. In total, 23 patients died during follow-up. In Cox proportional hazard regressions adjusted for a priori covariates, each 10-point T-score increment in patient-reported BRIEF-A self-regulatory behavior and problem-solving difficulties increased mortality risk by 94% and103%, respectively (adjusted HR=1.94, 95% CI [1.07, 3.52]; adjusted HR=2.03, 95% CI [1.19, 3.48]). In sensitivity analyses, patient-reported self-regulatory problem-solving remained significant independent of disease severity and a priori covariates (adjusted HR=1.68, 95% CI [1.01, 2.78], though the predictive value of self-regulatory behavior was attenuated in adjusted models (HR=1.67, 95% CI [0.85, 3.27). Caregiver-reported BRIEF-A ratings of patients and WCST perseverative errors did not significantly predict survival. Preliminary evidence suggests patient-reported self-regulatory problem-solving difficulties indicate poorer prognosis in MND. Further research is needed to uncover mechanisms that negatively affect patient survival.

  5. Survival and Associated Risk Factors for Mortality Among Infants with Critical Congenital Heart Disease in a Developing Country.

    PubMed

    Mat Bah, Mohd Nizam; Sapian, Mohd Hanafi; Jamil, Mohammad Tamim; Alias, Amelia; Zahari, Norazah

    2018-05-14

    Critical congenital heart disease (CCHD) is associated with significant morbidity and mortality. However, data on survival of CCHD and the risk factors associated with its mortality are limited. This study examined CCHD survival and the risk factors for CCHD mortality. Using a retrospective cohort study of infants born with CCHD from 2006 to 2015, survival over 10 years was estimated using Kaplan-Meier analysis, and the risk factors for mortality were analyzed using multivariate Cox proportional hazards regression. A total of 491 CCHD cases were included in the study, with an overall mortality rate of 34.8% (95% confidence interval [CI] 30.6-39.2). The intervention/surgical mortality rate was 9.8% ≤ 30 days and 11.5% > 30 days after surgery, and 17% died before surgery or intervention. The median age at death was 2.7 months [first quartile: 1 month, third quartile: 7.3 months]. The CCHD survival rate was 90.4% (95% CI 89-91.8%) at 1 month, 69.3% (95% CI 67.2-71.4%) at 1 year, 63.4% (95% CI 61.1-65.7%) at 5 years, and 61.4% (95% CI 58.9-63.9%) at 10 years. Weight of < 2 kg at diagnosis, associated syndromes, poor pre-operative condition, and non-duct-dependent CCHD were independent risk factors for poor survival, with hazard ratios of 2.61, 2.10, 2.22, and 1.70, respectively. CCHD is associated with a high mortality rate. Low weight, poor pre-operative condition, associated syndromes, and non-duct-dependent CCHD are significant risk factors affecting the survival of infants with CCHD.

  6. Long-term survival after uvulopalatopharyngoplasty in nonobese heavy snorers: a 5- to 9-year follow-up of 400 consecutive patients.

    PubMed

    Lysdahl, M; Haraldsson, P O

    2000-09-01

    Heavy snoring and the obstructive sleep apnea syndrome are associated with increased morbidity and mortality in patients with cardiovascular disease. The effect of uvulopalatopharyngoplasty on mortality has been questioned. To investigate long-term survival after palatal surgery. An observational retrospective case-control study with a 5- to 9-year follow-up. A university medical center. Four hundred consecutive heavy snorers (median age, 47 years), 256 of whom had obstructive sleep apnea syndrome. The mean +/- SD body mass index (calculated as weight in kilograms divided by the square of height in meters) of all included patients was 27.1+/-4.2. Comparison was made with 744 control patients (median age, 43 years) who underwent nasal surgery during the same period and a matched general control population. Uvulopalatopharyngoplasty or laser uvulopalatoplasty between 1986 and 1990. Mortality and causes of death up to 9 years after surgery. High blood pressure at the time of surgery and subsequent death due to cardiovascular disease were 3 times more frequent in the patients with obstructive sleep apnea syndrome than in both control groups (P<.01), but the overall long-term mortality was not increased either in snorers or in persons with sleep apnea. The cumulative survival rate was more than 96% for the 400 patients, the 744 controls, and the matched general population. No increased mortality was seen following palatal surgery in this long-term follow-up of 400 consecutive, on average, nonobese snorers, 256 of whom had obstructive sleep apnea syndrome. This might indicate a positive survival effect of surgery.

  7. Celiac disease: understanding the gluten-free diet.

    PubMed

    Bascuñán, Karla A; Vespa, María Catalina; Araya, Magdalena

    2017-03-01

    The only effective and safe treatment of celiac disease (CD) continues being strict exclusion of gluten for life, the so-called gluten-free diet (GFD). Although this treatment is highly successful, following strict GFD poses difficulties to patients in family, social and working contexts, deteriorating his/her quality of life. We aimed to review main characteristics of GFD with special emphasis on factors that may interfere with adherence to it. We conducted a search of various databases, such as PubMed, Google Scholar, Embase, and Scielo, with focus on key words such as "gluten-free diet", "celiac disease", "gluten" and "gluten-free diet adherence". Available literature has not reached definitive conclusions on the exact amount of gluten that is harmless to celiac patients, although international agreements establish cutoff points for gluten-free products and advise the use of clinical assessment to tailor the diet according to individual needs. Following GFD must include eliminating gluten as ingredient as well as hidden component and potential cross contamination in foods. There are numerous grains to substitute wheat but composition of most gluten-free products tends to include only a small number of them, especially rice. The diet must be not only free of gluten but also healthy to avoid nutrient, vitamins and minerals deficiencies or excess. Overweight/obesity frequency has increased among celiac patients so weight gain deserves attention during follow up. Nutritional education by a trained nutritionist is of great relevance to achieve long-term satisfactory health status and good compliance. A balanced GFD should be based on a combination of naturally gluten-free foods and certified processed gluten-free products. How to measure and improve adherence to GFD is still controversial and deserves further study.

  8. MDM2 promoter polymorphism and p53 codon 72 polymorphism in chronic myeloid leukemia: the association between MDM2 promoter genotype and disease susceptibility, age of onset, and blast-free survival in chronic phase patients receiving imatinib.

    PubMed

    Liu, Yi-Chang; Hsiao, Hui-Hua; Yang, Wen-Chi; Liu, Ta-Chih; Chang, Chao-Sung; Yang, Ming-Yu; Lin, Pai-Mei; Hsu, Jui-Feng; Lee, Ching-Ping; Lin, Sheng-Fung

    2014-12-01

    The genetic or functional inactivation of the p53 pathway plays an important role with regards to disease progression from the chronic phase (CP) to blast phase (BP) and imatinib treatment response in chronic myeloid leukemia (CML). Two functional single nucleotide polymorphisms (SNPs), p53 R72P and MDM2 SNP309, are associated with alternation of p53 activity, however the association regarding CML susceptibility and BP transformation under imatinib treatment is unclear. The MDM2 SNP309 genotype was determined by polymerase chain reaction-restriction fragment length polymorphism and confirmed by direct sequencing from 116 CML patients, including 104 in the CP at diagnosis, and 162 healthy Taiwanese controls. The p53 R72P polymorphism was examined in all CML patients. The SNP309 G/G genotype was associated with an increased risk of CML susceptibility (OR: 1.82, 95% CI: 1.03-3.22, P = 0.037), and an earlier age of disease onset (log-rank P = 0.005) compared with the T/T + T/G genotypes. Higher MDM2 mRNA expression was found in G/G genotype compared with T/T (P = 0.034) and T/T + T/G (P = 0.056) genotypes. No associations were found between the p53 R72P genotypes and clinical parameters and survival outcomes. Among 62 CP patients receiving imatinib as first-line therapy, the G/G genotype was associated with a shorter blast-free survival (log-rank P = 0.048) and more clonal evolution compared with the T/T + T/G genotypes. In patients with advanced diseases at diagnosis, the G/G genotype was associated with a poor overall survival (log-rank P = 0.006). Closely monitoring CML patients harboring the G/G genotype and further large-scale studies are warranted. © 2013 Wiley Periodicals, Inc.

  9. Low lean tissue mass can be a predictor of one-year survival in hemodialysis patients.

    PubMed

    Rymarz, Aleksandra; Gibińska, Julia; Zajbt, Maria; Piechota, Wiesław; Niemczyk, Stanisław

    2018-11-01

    Nutritional status has a significant impact on the outcomes in the dialysis population. The aim of this study was to evaluate the association between body composition and a one-year survival of hemodialysis patients. Forty-eight patients with chronic kidney disease stage V treated with hemodialysis for more than three months were included. Body composition was assessed by bioimpedance spectroscopy (Body Composition Monitor, Fresenius Medical Care). Blood samples for serum creatinine, serum albumin, serum prealbumin, high sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), insulin-like growth factor 1(IGF-1) concentrations were taken before the midweek dialysis session. Over the course of a one-year observation, seven patients died. We observed a significantly lower lean tissue index (LTI) (p = .013) and higher IL-6 (p = .032) and hsCRP levels (p = .011) among the patients who died. The remaining biochemical markers did not differ between these two groups. Kapplan-Meier analysis revealed a worse survival rate in patients with sarcopenia (lower than the 10th percentile for their age and gender) in comparison with those with normal LTI. However, it was not of statistical significance (p = .055). LTI inversely correlated with age and IL-6 and positively with IGF-1. Sarcopenia defined as decreased LTI, is a relatively common condition among patients undergoing maintenance hemodialysis, it can also be associated with a lower one-year survival rate. Decreased lean tissue mass can be associated with old age, lower IGF-1 levels and higher IL-6 levels. Body composition assessment may provide prognostic data for hemodialysis patients.

  10. Survival analysis of high-intensity focused ultrasound ablation in patients with small hepatocellular carcinoma.

    PubMed

    Cheung, Tan To; Fan, Sheung Tat; Chu, Ferdinand S K; Jenkins, Caroline R; Chok, Kenneth S H; Tsang, Simon H Y; Dai, Wing Chiu; Chan, Albert C Y; Chan, See Ching; Yau, Thomas C C; Poon, Ronnie T P; Lo, Chung Mau

    2013-08-01

    High-intensity focused ultrasound (HIFU) ablation is a non-invasive treatment for hepatocellular carcinoma (HCC). At present, data on the treatment's long-term outcome are limited. This study analysed the survival outcome of HIFU ablation for HCCs smaller than 3 cm. Forty-seven patients with HCCs smaller than 3 cm received HIFU treatment between October 2006 and September 2010. Fifty-nine patients who received percutaneous radiofrequency ablation (RFA) were selected for comparison. The two groups of patients were compared in terms of pre-operative variables and survival. More patients in the HIFU group patients had Child-Pugh B cirrhosis (34% versus 8.5%; P = 0.001). The 1- and 3-year overall survival rates of patients whose tumours were completely ablated in the HIFU group compared with the RFA group were 97.4% versus 94.6% and 81.2% versus 79.8%, respectively (P = 0.530). The corresponding 1- and 3-year disease-free survival rates were 63.6% versus 62.4% and 25.9% versus 34.1% (P = 0.683). HIFU ablation is a safe and effective method for small HCCs. It can achieve survival outcomes comparable to those of percutaneous RFA and thus serves as a good alternative ablation treatment for patients with cirrhosis. © 2012 International Hepato-Pancreato-Biliary Association.

  11. 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.

  12. The survival of platypuses in captivity.

    PubMed

    Whittington, R J

    1991-01-01

    Data are presented on the duration of survival of 228 platypuses at six Australian zoos between 1934 and 1988. Only 22.4% of all platypuses survived more than 1 year in captivity. Of 15 living platypuses, 3 had been held in captivity for less than 1 year, 5 for between 1 and 5 years, 6 for between 5 and 10 years and 1 for 21 years. Of 213 platypuses that died in captivity, 81.7% had died within 1 year; most within the first month. The duration of survival was unrelated to the age of animals at acquisition or to sex. The survival rate of animals donated to zoos, including "refugees", was similar to that of purpose-caught animals. Clearly, only a small proportion of platypuses adapted to captive husbandry. The cause of death of most platypuses was not established. However, infectious disease did not appear to be significant. Approximately 28% of deaths were related to inadequate husbandry. Recommendations are made to improve the survival of platypuses in captivity. Research has commenced in zoos to facilitate this goal.

  13. Aleutian Disease: An Emerging Disease in Free-Ranging Striped Skunks (Mephitis mephitis) From California.

    PubMed

    LaDouceur, E E B; Anderson, M; Ritchie, B W; Ciembor, P; Rimoldi, G; Piazza, M; Pesti, D; Clifford, D L; Giannitti, F

    2015-11-01

    Aleutian disease virus (ADV, Amdovirus, Parvoviridae) primarily infects farmed mustelids (mink and ferrets) but also other fur-bearing animals and humans. Three Aleutian disease (AD) cases have been described in captive striped skunks; however, little is known about the relevance of AD in free-ranging carnivores. This work describes the pathological findings and temporospatial distribution in 7 cases of AD in free-ranging striped skunks. All cases showed neurologic disease and were found in a 46-month period (2010-2013) within a localized geographical region in California. Lesions included multisystemic plasmacytic and lymphocytic inflammation (ie, interstitial nephritis, myocarditis, hepatitis, meningoencephalitis, pneumonia, and splenitis), glomerulonephritis, arteritis with or without fibrinoid necrosis in several organs (ie, kidney, heart, brain, and spleen), splenomegaly, ascites/hydrothorax, and/or encephalomalacia with cerebral microangiopathy. ADV infection was confirmed in all cases by specific polymerase chain reaction and/or in situ hybridization. The results suggest that AD is an emerging disease in free-ranging striped skunks in California. © The Author(s) 2014.

  14. Heart Transplantation for Congenital Heart Disease in the First Year of Life

    PubMed Central

    Chinnock, Richard E; Bailey, Leonard L

    2011-01-01

    Successful infant heart transplantation has now been performed for over 25 years. Assessment of long term outcomes is now possible. We report clinical outcomes for322 patients who received their heart transplant during infancy. Actuarial graft survival for newborn recipients is 59% at 25 years. Survival has improved in the most recent era. Cardiac allograft vasculopathy is the most important late cause of death with an actuarial incidence at 25 years of 35%. Post-transplant lymphoma is estimated to occur in 20% of infant recipients by25 years. Chronic kidney disease grade 3 or worse is present in 31% of survivors. The epidemiology of infant heart transplantation has changed through the years as the results for staged repair improved and donor resources remained stagnant. Most centers now employ staged repair for hypoplastic left heart syndrome and similar extreme forms of congenital heart disease. Techniques for staged repair, including the hybrid procedure, are described. The lack of donors is described with particular note regarding decreased donors due to newer programs for appropriate infant sleep positioning and infant car seats. ABO incompatible donors are a newer resource for maximizing donor resources, as is donation after circulatory determination of death and techniques to properly utilize more donors by expanding the criteria for what is an acceptable donor. An immunological advantage for the youngest recipients has long been postulated, and evaluation of this phenomenon may provide clues to the development of accommodation and/or tolerance. PMID:22548030

  15. A multi-year analysis of passage and survival at McNary Dam, 2004-09

    USGS Publications Warehouse

    Adams, Noah S.; Walker, C.E.; Perry, R.W.

    2011-01-01

    We analyzed 6 years (2004–09) of passage and survival data collected at McNary Dam to determine how dam operations and environmental conditions affect passage and survival of juvenile salmonids. A multinomial logistic regression was used to examine how environmental variables and dam operations relate to passage behavior of juvenile salmonids at McNary Dam. We used the Cormack-Jolly-Seber release-recapture model to determine how the survival of juvenile salmonids passing through McNary Dam relates to environmental variables and dam operations. Total project discharge and the proportion of flow passing the spillway typically had a positive effect on survival for all species and routes. As the proportion of water through the spillway increased, the number of fish passing the spillway increased, as did overall survival. Additionally, survival generally was higher at night. There was no meaningful difference in survival for fish that passed through the north or south portions of the spillway or powerhouse. Similarly, there was no difference in survival for fish released in the north, middle, or south portions of the tailrace. For subyearling Chinook salmon migrating during the summer season, increased temperatures had a drastic effect on passage and survival. As temperature increased, survival of subyearling Chinook salmon decreased through all passage routes and the number of fish that passed through the turbines increased. During years when the temporary spillway weirs (TSWs) were installed, passage through the spillway increased for spring migrants. However, due to the changes made in the location of the TSW between years and the potential effect of other confounding environmental conditions, it is not certain if the increase in spillway passage was due solely to the presence of the TSWs. The TSWs appeared to improve forebay survival during years when they were operated.

  16. Two-year survival of Ahmed valve implantation in the first 2 years of life with and without intraoperative mitomycin-C.

    PubMed

    Al-Mobarak, Faisal; Khan, Arif O

    2009-10-01

    To evaluate the effect of intraoperative mitomycin-C (MMC) on polypropylene Ahmed glaucoma valve (AGV) survival 2 years after implantation during the first 2 years of life. Retrospective institutional comparative series (1995-2005). Thirty-one eyes of 27 patients (23 unilateral, 4 bilateral; 16 boys, 11 girls) undergoing AGV implantation at a mean age of 11.1 months (standard deviation [SD], 5.46), all of which had 2 years of regular postoperative follow-up. MMC was applied intraoperatively in those cases in the area of AGV implantation in 16 (52%) and was not applied in 15 (48%). In some eyes, MMC was applied intraoperatively in cases done by the surgeons who routinely used MMC for all AGV implantation in young children. Failure was defined as intraocular pressure (IOP) > 22 mmHg with or without glaucoma medications, the need for an additional procedure for IOP control, or the occurrence of significant complications (e.g., endophthalmitis, retinal detachment, persistent hypotony [IOP < 5 mmHg]). Survival was the absence of failure. Failure or significant complications as defined. Mean survival for the non-MMC eyes (22.15 months; standard error [SE], 1.93) was significantly longer than survival for the MMC eyes (16.25 months; SE, 2.17) by the log-rank test (P = 0.025). The difference in cumulative survival at 2 years was also significantly different by log-rank test (P = 0.001): 80.0% (SE 10.3) and 31.3% (SE 11.6), respectively. Rather than improved survival, intraoperative use of MMC was associated with shorter survival 2 years after AGV implantation during the first 2 years of life. We speculate that MMC-induced tissue death can stimulate a reactive fibrosis around the AGV in very young eyes.

  17. Report: Study is about the prevalence of the HCV disease and survival of HCV patients with associated factors in the population of district Multan.

    PubMed

    Tabassum, Hina; Amin, Muhammad; Amanullah, Muhammad; Tabassum, Sana

    2015-09-01

    To find out the significant factors associated with HCV disease and evaluate the impact of these factors on the survival pattern of HCV patients in district Multan. The study was conducted in Nishter Hospital of Multan district from 1st January 2011 to 1st October 2012. To see a significant difference between the survival rates of patients with associated factors, non-parametric Cox- proportional hazard model with their graphical results were used. All the patients above 11 years old of both sexes were included in the study. All those who were surviving with HCV disease were studied with their associated factors such as age, family history (FH) barber/parlor services, blood group (BG) types weight loss (WL), Gender and drug use were collected from Nishter Hospital Multan. Results indicated that age, blood group types and gender are the most significant factors in the patients who are surviving with HCV disease. It was also observed that survival rate of female patients is high as compare to male patients.

  18. Survival Outcomes in Split Compared to Whole Liver Transplantation.

    PubMed

    Yoon, Kyung Chul; Song, Sanghee; Jwa, Eun-Kyoung; Lee, Sanghoon; Kim, Jong Man; Kim, Ok-Kyoung; Hong, Suk Kyun; Yi, Nam-Joon; Lee, Kwang-Woong; Kim, Myoung Soo; Hwang, Shin; Suh, Kyung-Suk; Lee, Suk-Koo

    2018-05-10

    Split liver transplantation (SLT) should be cautiously considered because the right tri-sectional (RTS) graft can be a marginal graft in adult recipients. Herein, we analyzed the outcomes of RTS-SLT in Korea, where > 75% of adult liver transplantations are performed by living donor liver transplantation. Among 2,462 patients who underwent deceased donor liver transplantations (DDLT) from 2005 to 2014, we retrospectively reviewed 86 adult patients (3.4%) who received a RTS graft (RTS-SLT group). The outcomes of the RTS-SLT group were compared to those of 303 recipients of whole liver (WL-DDLT group). Recipients' age, laboratory Model for End-Stage-Liver Disease (L-MELD) score, ischemic time, and donor recipient weight ratio (DRWR) were not different between the two groups (P >0.05). However, malignancy was uncommon (4.7 vs. 36.3%), and donor was younger (25.2 vs. 42.7 years) in the RST-SLT group than in the WL-DDLT group (P <0.05). The technical complication rates and the 5-year graft survival rates (89.0 vs. 92.8%) were not different between the two groups (P >0.05). The 5-year overall survival rate (OS) (63.1%) and graft-failure-free survival rate (63.1%) of the RTS-SLT group were worse than that of the WL-DDLT group (79.3% and 79.3%) (P <0.05). The factors affecting graft survival rates were not definite. However, the factors affecting OS in the RTS-SLT group were L-MELD score >30 and DRWR ≤1.0. In the subgroup analysis, OS was not different between the two groups if the DRWR was >1.0, regardless of the L-MELD score (P >0.05). In conclusion, sufficient volume of the graft estimated from DRWR-matching could lead to better outcomes of adult SLTs with a RTS graft, even in patients with high L-MELD scores. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

  19. Hodgkin disease survival in Europe and the U.S.: prognostic significance of morphologic groups.

    PubMed

    Allemani, Claudia; Sant, Milena; De Angelis, Roberta; Marcos-Gragera, Rafael; Coebergh, Jan Willem

    2006-07-15

    The survival of patients with Hodgkin disease (HD) varies markedly across Europe and generally is shorter than the survival of patients in the U.S. To investigate these differences, the authors compared population-based HD survival in relation to morphologic type among populations in Europe and the U.S. The authors analyzed 6726 patients from 37 cancer registries that participated in EUROCARE-3 and 3442 patients from 9 U.S. Surveillance, Epidemiology, and End Results (SEER) registries. Patients were diagnosed during 1990 to 1994 and were followed for at least 5 years. The European registries were grouped into EUROCARE West, EUROCARE UK, and EUROCARE East. Morphologic groups were nodular sclerosis, mixed cellularity, lymphocyte depletion, lymphocyte predominance, and not otherwise specified (NOS). The influence of morphology on geographic differences in 5-year relative survival was explored by using multiple regression analysis. In the model that was adjusted by age, gender, and years since diagnosis, the relative excess risk (RER) of death was 0.93 (95% confidence interval [95% CI], 0.81-1.05) in EUROCARE West, 1.15 (95% CI, 1.04-1.28) in EUROCARE UK, and 1.39 (95% CI, 1.21-1.60) in EUROCARE East (compared with the SEER data). When morphology was included, EUROCARE UK and SEER no longer differed (RER, 1.06; 95% CI, 0.95-1.18). Morphology distribution varied markedly across Europe and much less in the U.S., with nodular sclerosis less common in Europe (45.9%) than the U.S. (61.7%). The RER data showed that patients who had lymphocyte depletion, NOS, and mixed cellularity had a significantly worse prognoses compared with patients who had nodular sclerosis, whereas patients who had lymphocyte predominance had the best prognosis. The current results provide population-based evidence that morphology strongly influences the prognosis of patients with HD. However differences in the morphologic case mix explains only some of the geographic variations observed in survival.

  20. Movement disorders in adult surviving patients with maple syrup urine disease.

    PubMed

    Carecchio, Miryam; Schneider, Susanne A; Chan, Heidi; Lachmann, Robin; Lee, Philip J; Murphy, Elaine; Bhatia, Kailash P

    2011-06-01

    Maple syrup urine disease is a rare metabolic disorder caused by mutations in the branched-chain α-keto acid dehydrogenase complex gene. Patients generally present early in life with a toxic encephalopathy because of the accumulation of the branched-chain amino acids leucine, isoleucine, and valine and the corresponding ketoacids. Movement disorders in maple syrup urine disease have typically been described during decompensation episodes or at presentation in the context of a toxic encephalopathy, with complete resolution after appropriate dietary treatment. Movement disorders in patients surviving childhood are not well documented. We assessed 17 adult patients with maple syrup urine disease (mean age, 27.5 years) with a special focus on movement disorders. Twelve (70.6%) had a movement disorder on clinical examination, mainly tremor and dystonia or a combination of both. Parkinsonism and simple motor tics were also observed. Pyramidal signs were present in 11 patients (64.7%), and a spastic-dystonic gait was observed in 6 patients (35.2%). In summary, movement disorders are common in treated adult patients with maple syrup urine disease, and careful neurological examination is advisable to identify those who may benefit from specific therapy. © 2011 Movement Disorder Society. Copyright © 2011 Movement Disorder Society.

  1. 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

  2. Outcome of heart transplants 15 to 20 years ago: graft survival, post-transplant morbidity, and risk factors for mortality.

    PubMed

    Roussel, Jean C; Baron, Olivier; Périgaud, Christian; Bizouarn, Philippe; Pattier, Sabine; Habash, Oussama; Mugniot, Antoine; Petit, Thierry; Michaud, Jean L; Heymann, Marie Françoise; Treilhaud, Michèle; Trochu, Jean N; Gueffet, Jean P; Lamirault, Guillaume; Duveau, Daniel; Despins, Philippe

    2008-05-01

    The study was conducted to determine the long-term outcome of patients who underwent heart transplantation 15 to 20 years ago, in the cyclosporine era, and identify risk factors for death. A retrospective analysis was done of 148 patients who had undergone heart transplantation between 1985 and 1991 at a single center. Operative technique and immunosuppressive treatment were comparable in all patients. Actuarial survival rates were 75% (n = 111), 58% (n = 86), and 42% (n = 62) at 5, 10, and 15 years, respectively. The mean follow-up period was 12.1 +/- 5.6 years for patients who survived more than 3 months after transplantation (n = 131). The major causes of death were malignancy (35.8%) and cardiac allograft vasculopathy (24.7%). No death related to acute rejection was reported after the first month of transplantation. Graft coronary artery disease was detected on angiography in 66 (50.3%), and 7 (5.3%) had retransplantation. Malignancies developed in 131 patients (48.1%), including skin cancers in 31 (23.6%), solid tumors in 26 (19.8%), and hematologic malignancies in 14 (10.6%). Severe renal function requiring dialysis or renal transplantation developed in 27 patients (20.6%). By multivariable analysis, the only pre-transplant risk factor found to affect long-term survival was a history of cigarette use (p < 0.0004). Long-term survival at 15 years after cardiac transplantation remains excellent in the cyclosporine era. Controlling acute allograft rejection can be achieved but seems to carry a high rate of cancers and renal dysfunction. History of cigarette use affects significantly long-term survival in our study.

  3. Immune Biomarkers Predictive for Disease-Free Survival with Adjuvant Sunitinib in High-Risk Locoregional Renal Cell Carcinoma: From Randomized Phase III S-TRAC Study.

    PubMed

    George, Daniel J; Martini, Jean-François; Staehler, Michael; Motzer, Robert J; Magheli, Ahmed; Escudier, Bernard; Gerletti, Paola; Li, Sherry; Casey, Michelle; Laguerre, Brigitte; Pandha, Hardev S; Pantuck, Allan J; Patel, Anup; Lechuga, Maria J; Ravaud, Alain

    2018-04-01

    Purpose: Adjuvant sunitinib therapy compared with placebo prolonged disease-free survival (DFS) in patients with locoregional high-risk renal cell carcinoma (RCC) in the S-TRAC trial (ClinicalTrials.gov number NCT00375674). A prospectively designed exploratory analysis of tissue biomarkers was conducted to identify predictors of treatment benefit. Experimental Design: Tissue blocks were used for immunohistochemistry (IHC) staining of programmed cell death ligand 1 (PD-L1), CD4, CD8, and CD68. DFS was compared between < versus ≥ median IHC parameter using the Kaplan-Meier method. For biomarkers with predictive potential, receiver operating characteristics curves were generated. Results: Baseline characteristics were similar in patients with ( n = 191) and without ( n = 419) IHC analysis. Among patients with IHC, longer DFS was observed in patients with tumor CD8 + T-cell density ≥ versus < median [median (95% CI), not reached (6.83-not reached) versus 3.47 years (1.73-not reached); hazard ratio (HR) 0.40 (95% CI, 0.20-0.81); P = 0.009] treated with sunitinib ( n = 101), but not with placebo ( n = 90). The sensitivity and specificity for CD8 + T-cell density in predicting DFS were 0.604 and 0.658, respectively. Shorter DFS was observed in placebo-treated patients with PD-L1 + versus PD-L1 - tumors (HR 1.75; P = 0.103). Among all patients with PD-L1 + tumors, DFS was numerically longer with sunitinib versus placebo (HR 0.58; P = 0.175). Conclusions: Greater CD8 + T-cell density in tumor tissue was associated with longer DFS with sunitinib but not placebo, suggesting predictive treatment effect utility. Further independent cohort validation studies are warranted. The prognostic value of PD-L1 expression in primary tumors from patients with high-risk nonmetastatic RCC should also be further explored. Clin Cancer Res; 24(7); 1554-61. ©2018 AACR . ©2018 American Association for Cancer Research.

  4. 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

  5. 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

  6. Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial: An intention-to-treat analysis of amputation-free and overall survival in patients randomized to a bypass surgery-first or a balloon angioplasty-first revascularization strategy.

    PubMed

    Bradbury, Andrew W; Adam, Donald J; Bell, Jocelyn; Forbes, John F; Fowkes, F Gerry R; Gillespie, Ian; Ruckley, Charles Vaughan; Raab, Gillian M

    2010-05-01

    A 2005 interim analysis of the Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial showed that in patients with severe lower limb ischemia (SLI; rest pain, ulceration, gangrene) due to infrainguinal disease, bypass surgery (BSX)-first and balloon angioplasty (BAP)-first revascularization strategies led to similar short-term clinical outcomes, although BSX was about one-third more expensive and morbidity was higher. We have monitored patients for a further 2.5 years and now report a final intention-to-treat (ITT) analysis of amputation-free survival (AFS) and overall survival (OS). Of 452 enrolled patients in 27 United Kingdom hospitals, 228 were randomized to a BSX-first and 224 to a BAP-first revascularization strategy. All patients were monitored for 3 years and more than half for >5 years. At the end of follow-up, 250 patients were dead (56%), 168 (38%) were alive without amputation, and 30 (7%) were alive with amputation. Four were lost to follow-up. AFS and OS did not differ between randomized treatments during the follow-up. For those patients surviving 2 years from randomization, however, BSX-first revascularization was associated with a reduced hazard ratio (HR) for subsequent AFS of 0.85 (95% confidence interval [CI], 0.5-1.07; P = .108) and for subsequent OS of 0.61 (95% CI, 0.50-0.75; P = .009) in an adjusted, time-dependent Cox proportional hazards model. For those patients who survived for 2 years after randomization, initial randomization to a BSX-first revascularization strategy was associated with an increase in subsequent restricted mean overall survival of 7.3 months (95% CI, 1.2-13.4 months, P = .02) and an increase in restricted mean AFS of 5.9 months (95% CI, 0.2-12.0 months, P = .06) during the subsequent mean follow-up of 3.1 years (range, 1-5.7 years). Overall, there was no significant difference in AFS or OS between the two strategies. However, for those patients who survived for at least 2 years after randomization, a

  7. An elevated serum beta-2-microglobulin level is an adverse prognostic factor for overall survival in patients with early-stage Hodgkin disease.

    PubMed

    Chronowski, Gregory M; Wilder, Richard B; Tucker, Susan L; Ha, Chul S; Sarris, Andreas H; Hagemeister, Fredrick B; Barista, Ibrahim; Hess, Mark A; Cabanillas, Fernando; Cox, James D

    2002-12-15

    The relative importance of prognostic factors in patients with early-stage Hodgkin disease remains controversial. The purpose of this study was to evaluate prognostic factors among patients who received chemotherapy before radiotherapy. From 1987 to 1995, 217 consecutive patients ranging in age from 16 to 88 years (median, 28 years) with Ann Arbor Stage I (n = 55) or II (n = 162) Hodgkin disease underwent chemotherapy before radiotherapy at a single center. Most were treated on prospective studies. Patients received a median of three cycles of induction chemotherapy. Mitoxantrone, vincristine, vinblastine, and prednisone (NOVP), doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), cyclophosphamide, vinblastine, procarbazine, prednisone, doxorubicin, bleomycin, dacarbazine, and CCNU (CVPP/ABDIC), or other chemotherapeutic regimens were given to 160, 18, 15, 10, and 14 patients, respectively. The median radiotherapy dose was 40 Gy. Serum beta-2-microglobulin (beta-2M) levels ranged from 1.0 to 4.1 mg/L (median, 1.7 mg/L; upper limit of normal, 2.0 mg/L). We studied univariate and multivariate associations between survival and the following clinical features: serum beta-2M level above 1.25 times the upper limit of normal (n = 12), male gender (n = 113), hypoalbuminemia (n = 11), and bulky mediastinal disease (n = 94). Follow-up of surviving patients ranged from 0.9 to 13.4 years (median, 6.6 years) and 92% were observed for 3.0 or more years. Nineteen patients have died. Only elevation of the serum beta-2M level was an independent adverse prognostic factor for overall survival (P = 0.0009). The prognostic significance of a simple, widely available, and inexpensive blood test, beta-2M, has not been studied routinely in patients with Hodgkin disease and should be tested prospectively in large, cooperative group trials. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10998

  8. Factors associated with villus atrophy in symptomatic coeliac disease patients on a gluten-free diet.

    PubMed

    Mahadev, S; Murray, J A; Wu, T-T; Chandan, V S; Torbenson, M S; Kelly, C P; Maki, M; Green, P H R; Adelman, D; Lebwohl, B

    2017-04-01

    Duodenal injury persists in some coeliac disease patients despite gluten-free diet, and is associated with adverse outcomes. To determine the prevalence and clinical risk factors for persistent villus atrophy among symptomatic coeliac disease patients. A nested cross-sectional analysis was performed on coeliac disease patients with self-reported moderate or severe symptoms while following a gluten-free diet, who underwent protocol-mandated duodenal biopsy upon enrolment in the CeliAction clinical trial. Demographic factors, symptom type, medication use, and serology were examined to determine predictors of persistent villus atrophy. Of 1345 symptomatic patients, 511 (38%, 95% CI, 35-41%) were found to have active coeliac disease with persistent villus atrophy, defined as average villus height to crypt depth ratio ≤2.0. On multivariable analysis, older age (OR, 5.1 for ≥70 vs. 18-29 years, 95% CI, 2.5-10.4) was a risk factor while longer duration on gluten-free diet was protective (OR, 0.37, 95% CI, 0.24-0.55 for 4-5.9 vs. 1-1.9 years). Villus atrophy was associated with use of proton-pump inhibitors (PPIs; OR, 1.6, 95% CI, 1.1-2.3), non-steroidal anti-inflammatory drugs (NSAIDs; OR, 1.64, 95% CI, 1.2-2.2), and selective serotonin reuptake inhibitors (SSRIs; OR, 1.74, 95% CI, 1.2-2.5). Symptoms were not associated with villus atrophy after adjusting for covariates. Conclusions A majority of symptomatic coeliac disease patients did not have active disease on follow-up histology. Symptoms were poorly predictive of persistent mucosal injury. The impact of NSAIDs, PPIs, and SSRIs on mucosal healing in coeliac disease warrants further study. © 2017 John Wiley & Sons Ltd.

  9. 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.

  10. Prognostic Factors for Hormone Sensitive Metastatic Prostate Cancer: Impact of Disease Volume

    PubMed

    Alhanafy, Alshimaa Mahmoud; Zanaty, Fouad; Ibrahem, Reda; Omar, Suzan

    2018-04-27

    Background and Aim: The optimal management of metastatic hormone-sensitive prostate cancer has been controversial in recent years with introduction of upfront chemohormonal treatment based on results of several Western studies. This changing landscape has renewed interest in the concept “disease volume”, the focus of the present study is the Egyptian patients. Methods: Patients with hormone sensitive metastatic prostate cancer presenting at Menoufia University Hospital, Egypt, during the period from June 2013 to May 2016, were enrolled. All received hormonal treatment. Radiologic images were evaluated and patients were stratified according to their disease volume into high or low, other clinical and pathological data that could affect survival also being collected and analyzed. Results: A total of 128 patients were included, with a median age of 70 years (53.9% ≥70). About 46% had co-morbidities, 62% having high volume disease. During the median follow up period of 28 months about half of the patients progressed and one third received chemotherapy. On univariate analysis, disease volume, performance status (PS), prostate specific antigen level (PSA) and presence of pain at presentation were identified as factors influencing overall survival. Multivariate analysis revealed the independent predictor factors for survival to be PS, PSA and disease volume. The median overall survival with 27 months was high volume versus 49 with low volume disease (hazard ratio 2.1; 95% CI 1.2 - 4.4; P=0.02). Median progression free survival was 19 months in the high volume, as compared with 48 months in the low volume disease patients (hazard ratio, 2.44; 95% CI, 1.42 – 7.4; P=0.009). Conclusions: Disease volume is a reliable predictor of survival which should be incorporated with other important factors as; patient performance status and comorbidities in treatment decision-making. Creative Commons Attribution License

  11. Impact of Nurse-Led, Multidisciplinary Home-Based Intervention on Event-Free Survival Across the Spectrum of Chronic Heart Disease: Composite Analysis of Health Outcomes in 1226 Patients From 3 Randomized Trials.

    PubMed

    Stewart, Simon; Wiley, Joshua F; Ball, Jocasta; Chan, Yih-Kai; Ahamed, Yasmin; Thompson, David R; Carrington, Melinda J

    2016-05-10

    We sought to determine the overall impact of a nurse-led, multidisciplinary home-based intervention (HBI) adapted to hospitalized patients with chronic forms of heart disease of varying types. Prospectively planned, combined, secondary analysis of 3 randomized trials (1226 patients) of HBI were compared with standard management. Hospitalized patients presenting with heart disease but not heart failure, atrial fibrillation but not heart failure, and heart failure, as well, were recruited. Overall, 612 and 614 patients, respectively, were allocated to a home visit 7 to 14 days postdischarge by a cardiac nurse with follow-up and multidisciplinary support according to clinical need or standard management. The primary outcome of days-alive and out-of-hospital was examined on an intention-to-treat basis. During 1371 days (interquartile range, 1112-1605) of follow-up, 218 patients died and 17 917 days of hospital stay were recorded. In comparison with standard management, HBI patients achieved significantly prolonged event-free survival (90.1% [95% confidence interval, 88.2-92.0] versus 87.2% [95% confidence interval, 85.1-89.3] days-alive and out-of-hospital; P=0.020). This reflected less all-cause mortality (adjusted hazard ratio, 0.67; 95% confidence interval, 0.50-0.88; P=0.005) and unplanned hospital stay (median, 0.22 [interquartile range, 0-1.3] versus 0.36 [0-2.1] days/100 days follow-up; P=0.011). Analyses of the differential impact of HBI on all-cause mortality showed significant interactions (characterized by U-shaped relationships) with age (P=0.005) and comorbidity (P=0.041); HBI was most effective for those aged 60 to 82 years (59%-65% of individual trial cohorts) and with a Charlson Comorbidity Index Score of 5 to 8 (36%-61%). These data provide further support for the application of postdischarge HBI across the full spectrum of patients being hospitalized for chronic forms of heart disease. URL: http://www.anzctr.org.au. Unique identifiers

  12. Improved Survival After Heart Failure: A Community‐Based Perspective

    PubMed Central

    Joffe, Samuel W.; Webster, Kristy; McManus, David D.; Kiernan, Michael S.; Lessard, Darleen; Yarzebski, Jorge; Darling, Chad; Gore, Joel M.; Goldberg, Robert J.

    2013-01-01

    Background Heart failure is a highly prevalent, morbid, and costly disease with a poor long‐term prognosis. Evidence‐based therapies utilized over the past 2 decades hold the promise of improved outcomes, yet few contemporary studies have examined survival trends in patients with acute heart failure. The primary objective of this population‐based study was to describe trends in short‐ and long‐term survival in patients hospitalized with acute decompensated heart failure (ADHF). A secondary objective was to examine patient characteristics associated with decreased long‐term survival. Methods and Results We reviewed the medical records of 9748 patients hospitalized with ADHF at all 11 medical centers in central Massachusetts during 1995, 2000, 2002, and 2004. Patients hospitalized with ADHF were more likely to be elderly and to have been diagnosed with multiple comorbidities in 2004 compared with 1995. Over this period, survival was significantly improved in‐hospital, and at 1, 2, and 5 years postdischarge. Five‐year survival rates increased from 20% in 1995 to 29% in 2004. Although survival improved substantially over time, older patients and patients with chronic kidney disease, chronic obstructive pulmonary disease, anemia, low body mass index, and low blood pressures had consistently lower postdischarge survival rates than patients without these comorbidities. Conclusion Between 1995 and 2004, patients hospitalized with ADHF have become older and increasingly comorbid. Although there has been a significant improvement in survival among these patients, their long‐term prognosis remains poor, as fewer than 1 in 3 patients hospitalized with ADHF in 2004 survived more than 5 years. PMID:23676294

  13. 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

  14. 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.

  15. Improved disease-free-survival after transplantation of peripheral blood stem cells as compared with bone marrow from HLA-identical unrelated donors in patients with first chronic phase chronic myeloid leukemia.

    PubMed

    Elmaagacli, Ahmet H; Basoglu, Semiha; Peceny, Rudolf; Trenschel, Rudolf; Ottinger, Hellmut; Lollert, Andre; Runde, Volker; Grosse-Wilde, Hans; Beelen, Dietrich W; Schaefer, Ulrich W

    2002-02-15

    Outcomes after peripheral blood stem cell transplantation (PBSCT) for chronic phase chronic myeloid leukemia (n = 37) were compared with outcomes after bone marrow transplantation (BMT) (n = 54) in the HLA-compatible unrelated donor setting. Median follow-up was 17 months after PBSCT and 29 months after BMT. Both neutrophil and platelet recovery were faster after PBSCT (P <.05). PBSCT was associated with improved immune reconstitution, with higher peripheral blood naive (CD4(+)CD45RA(+)) and memory (CD4(+) CD45RO(+)) helper T cells at 3 months and 12 months after transplantation (P <.03). The cumulative incidence of acute (grades II-IV) and chronic graft-versus-host disease (GVHD) were similar, but BMT was associated with a higher cumulative incidence of severe, acute (grade III-IV) GVHD at 24% as compared with 8% with PBSCT (P <.05). Molecular relapse, defined by 2 consecutive positive polymerase chain reaction assays for bcr-abl within a 4-week interval, occurred in 12 of 45 evaluable patients (27%) after BMT and in 4 of 37 (11%) after PBSCT (not significant). Cytogenetic relapse occurred in 5 of 54 patients after BMT (9%) and in 1 of the 37 (3%) patients after PBSCT (not significant). Seventeen of the 54 patients died after BMT (31%), as compared with 2 of 37 patients after PBSCT (5%). Deaths in the BMT group were associated mainly with infections and severe, acute GVHD. The estimated probability of transplant-related mortality (TRM) and disease-free survival at 1000 days after receiving the transplant were 30% and 64% in the BMT group and 5% and 91% in the PBSCT group (P <.03). Overall survival 1000 days after receiving the transplant was 66% after BMT and 94% after PBSCT (P <.02). In the multivariate analysis, only acute GVHD significantly influenced TRM (P <.01).

  16. The efficacy of edaravone (radicut), a free radical scavenger, for cardiovascular disease.

    PubMed

    Kikuchi, Kiyoshi; Tancharoen, Salunya; Takeshige, Nobuyuki; Yoshitomi, Munetake; Morioka, Motohiro; Murai, Yoshinaka; Tanaka, Eiichiro

    2013-07-04

    Edaravone was originally developed as a potent free radical scavenger, and has been widely used to treat acute ischemic stroke in Japan since 2001. Free radicals play an important role in the pathogenesis of a variety of diseases, such as cardiovascular diseases and stroke. Therefore, free radicals may be targets for therapeutic intervention in these diseases. Edaravone shows protective effects on ischemic insults and inflammation in the heart, vessel, and brain in experimental studies. As well as scavenging free radicals, edaravone has anti-apoptotic, anti-necrotic, and anti-cytokine effects in cardiovascular diseases and stroke. Edaravone has preventive effects on myocardial injury following ischemia and reperfusion in patients with acute myocardial infarction. Edaravone may represent a new therapeutic intervention for endothelial dysfunction in the setting of atherosclerosis, heart failure, diabetes, or hypertension, because these diseases result from oxidative stress and/or cytokine-induced apoptosis. This review evaluates the potential of edaravone for treatment of cardiovascular disease, and covers clinical and experimental studies conducted between 1984 and 2013. We propose that edaravone, which scavenges free radicals, may offer a novel option for treatment of cardiovascular diseases. However, additional clinical studies are necessary to verify the efficacy of edaravone.

  17. The Efficacy of Edaravone (Radicut), a Free Radical Scavenger, for Cardiovascular Disease

    PubMed Central

    Kikuchi, Kiyoshi; Tancharoen, Salunya; Takeshige, Nobuyuki; Yoshitomi, Munetake; Morioka, Motohiro; Murai, Yoshinaka; Tanaka, Eiichiro

    2013-01-01

    Edaravone was originally developed as a potent free radical scavenger, and has been widely used to treat acute ischemic stroke in Japan since 2001. Free radicals play an important role in the pathogenesis of a variety of diseases, such as cardiovascular diseases and stroke. Therefore, free radicals may be targets for therapeutic intervention in these diseases. Edaravone shows protective effects on ischemic insults and inflammation in the heart, vessel, and brain in experimental studies. As well as scavenging free radicals, edaravone has anti-apoptotic, anti-necrotic, and anti-cytokine effects in cardiovascular diseases and stroke. Edaravone has preventive effects on myocardial injury following ischemia and reperfusion in patients with acute myocardial infarction. Edaravone may represent a new therapeutic intervention for endothelial dysfunction in the setting of atherosclerosis, heart failure, diabetes, or hypertension, because these diseases result from oxidative stress and/or cytokine-induced apoptosis. This review evaluates the potential of edaravone for treatment of cardiovascular disease, and covers clinical and experimental studies conducted between 1984 and 2013. We propose that edaravone, which scavenges free radicals, may offer a novel option for treatment of cardiovascular diseases. However, additional clinical studies are necessary to verify the efficacy of edaravone. PMID:23880849

  18. The challenge in treating locally recurrent T3-4 nasopharyngeal carcinoma: the survival benefit and severe late toxicities of re-irradiation with intensity-modulated radiotherapy.

    PubMed

    Tian, Yun-Ming; Huang, Wei-Zeng; Yuan, Xia; Bai, Li; Zhao, Chong; Han, Fei

    2017-06-27

    Effective treatments for patients with advanced locally recurrent nasopharyngeal carcinoma (NPC) are limited. This investigation was to determine the potential benefits from re-irradiation by intensity-modulated radiotherapy (IMRT) on survival and the effects of severe late toxicities. A retrospective study was conducted in 245 patients diagnosed with locally recurrent T3-T4 NPC who had undergone re-irradiation with IMRT. Follow-up data was colletedand factors associated with survival and severe late toxicities were analyzed. The 5-year local-regional failure-free survival, distant failure-free survival and overall survival rates were 60.9%, 78.3% and 27.5%, respectively. The presence of severe late complications, recurrent T4 disease and gross tumor volume >30 cm3 were associated with poor survival. The incidences of mucosal necrosis, temporal lobe necrosis, cranial neuropathy and trismus were 22.0%, 14.6%, 27.0% and 14.6% respectively. Re-irradiation with IMRT is an effective choice in patients with locally recurrent T3-T4 NPC. However, the survival benefits can be partly offset by severe late complications and optimum treatments in these patients remain a challenge.

  19. Survival of macrovascular disease, chronic kidney disease, chronic respiratory disease, cancer and smoking in patients with type 2 diabetes: BioBank Japan cohort.

    PubMed

    Yokomichi, Hiroshi; Nagai, Akiko; Hirata, Makoto; Kiyohara, Yutaka; Muto, Kaori; Ninomiya, Toshiharu; Matsuda, Koichi; Kamatani, Yoichiro; Tamakoshi, Akiko; Kubo, Michiaki; Nakamura, Yusuke; Yamagata, Zentaro

    2017-03-01

    The number of patients with diabetes is increasing worldwide. Macrovascular disease, chronic kidney disease, chronic respiratory disease, cancer and smoking frequently accompany type 2 diabetes. Few data are available related to mortality of Asians with diabetes associated with these serious comorbidities. The present study aimed to quantify the excess mortality risks of type 2 diabetic patients with comorbidities. We analysed the available records of 30,834 Japanese patients with type 2 diabetes from the BioBank Japan Project between 2003 and 2007. Men and women were followed up for median 8.03 and 8.30 years, respectively. We applied Cox proportional hazard model and Kaplan-Meier estimates for survival curves to evaluate mortality in diabetic patients with or without macrovascular disease, chronic respiratory disease, chronic kidney disease, cancer and smoking. Adjusted hazard ratios (HRs) for mortality were 1.39 (95% CI, 1.09-1.78) for male sex, 2.01 (95% CI, 1.78-2.26) per 10-year increment of age. Adjusted HRs of primary interest were 1.77 (95% CI, 1.42-2.22), macrovascular disease; 1.58 (95% CI, 1.08-2.31), chronic respiratory disease; 2.03 (95% CI, 1.67-2.47), chronic kidney disease; 1.16 (95% CI, 0.86-1.56), cancer; and 1.74 (95% CI, 1.30-2.31), current smoking. Diabetic patients with a past or current history of chronic kidney, macrovascular or respiratory diseases or smoking habit have exhibited the highest risk of mortality. Data were limited to those of survivors of comorbidities but we propose the need to improve comorbidities and terminate cigarette smoking for better prognosis in patients with diabetes. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  20. Alveolar Ridge Contouring with Free Connective Tissue Graft at Implant Placement: A 5-Year Consecutive Clinical Study.

    PubMed

    Hanser, Thomas; Khoury, Fouad

    2016-01-01

    This study evaluated volume stability after alveolar ridge contouring with free connective tissue grafts at implant placement in single-tooth gaps. A total of 52 single-tooth gaps with labial volume deficiencies in the maxilla (incisors, canines, and premolars) were consecutively treated with implants and concomitant free palatal connective tissue grafts in 46 patients between 2006 and 2009. Implants had to be covered with at least 2 mm peri-implant local bone after insertion. At implant placement, a free connective tissue graft from the palate was fixed inside a labial split-thickness flap to form an existing concave buccal alveolar ridge contour due to tissue volume deficiency into a convex shape. Standardized volumetric measurements of the labial alveolar contour using a template were evaluated before connective tissue grafting and at 2 weeks, 1 year, and 5 years after implantprosthetic incorporation. Tissue volume had increased significantly (P < .05) in all six reference points representing the outer alveolar soft tissue contour of the implant before connective tissue grafting to baseline (2 weeks after implant-prosthetic incorporation). Statistically, 50% of the reference points (P > .05) kept their volume from baseline to 1 year after prosthetic incorporation and from baseline to 5 years after prosthetic incorporation, respectively, whereas reference points located within the area of the implant sulcus showed a significant (P < .05) decrease in volume. Clinically, 5 years after prosthetic incorporation the originally concave buccal alveolar contour was still convex in all implants, leading to a continuous favorable anatomical shape and improved esthetic situation. Intraoral radiographs confirmed osseointegration and stable peri-implant parameters with a survival rate of 100% after a follow-up of approximately 5 years. Implant placement with concomitant free connective tissue grafting appears to be an appropriate long-term means to contour preexisting buccal

  1. A retrospective analysis of the role of proton pump inhibitors in colorectal cancer disease survival

    PubMed Central

    Graham, C.; Orr, C.; Bricks, C.S.; Hopman, W.M.; Hammad, N.; Ramjeesingh, R.

    2016-01-01

    Background Proton pump inhibitors (ppis) are a commonly used medication. A limited number of studies have identified a weak-to-moderate association between ppi use and colorectal cancer (crc) risk, but none to date have identified an effect of ppi use on crc survival. We therefore postulated that an association between ppi use and crc survival might potentially exist. Methods We performed a retrospective chart review of 1304 crc patients diagnosed from January 2005 to December 2011 and treated at the Cancer Centre of Southeastern Ontario. Kaplan–Meier analysis and Cox proportional hazards regression models were used to evaluate overall survival (os). Results We identified 117 patients (9.0%) who were taking ppis at the time of oncology consult. Those taking a ppi were also more often taking asa or statins (or both) and had a statistically significantly increased rate of cardiac disease. No identifiable difference in tumour characteristics was evident in the two groups, including tumour location, differentiation, lymph node status, and stage. Univariate analysis identified a statistically nonsignificant difference in survival, with those taking a ppi experiencing lesser 1-year (82.1% vs. 86.7%, p = 0.161), 2-year (70.1% vs. 76.8%, p = 0.111), and 5-year os (55.2% vs. 62.9%, p = 0.165). When controlling for patient demographics and tumour characteristics, multivariate Cox regression analysis identified a statistically significant effect of ppi in our patient population (hazard ratio: 1.343; 95% confidence interval: 1.011 to 1.785; p = 0.042). Conclusions Our results suggest a potential adverse effect of ppi use on os in crc patients. These results need further evaluation in prospective analyses. PMID:28050148

  2. Cure model survival analysis after hepatic resection for colorectal liver metastases.

    PubMed

    Cucchetti, Alessando; Ferrero, Alessandro; Cescon, Matteo; Donadon, Matteo; Russolillo, Nadia; Ercolani, Giorgio; Stacchini, Giacomo; Mazzotti, Federico; Torzilli, Guido; Pinna, Antonio Daniele

    2015-01-01

    Statistical cure is achieved when a patient population has the same mortality as cancer-free individuals; however, data regarding the probability of cure after hepatectomy of colorectal liver metastases (CLM) have never been provided. We aimed to assess the probability of being statistically cured from CLM by hepatic resection. Data from 1,012 consecutive patients undergoing curative resection for CLM (2001-2012) were used to fit a nonmixture cure model to compare mortality after surgery to that expected for the general population matched by sex and age. The 5- and 10-year disease-free survival was 18.9 and 15.8 %; the corresponding overall survival was 44.3 and 32.7 %. In the entire study population, the probability of being cured from CLM was 20 % (95 % confidence interval 16.5-23.5). After the first year, the mortality excess of resected patients, in comparison to the general population, starts to decline until it approaches zero 6 years after surgery. After 6.48 years, patients alive without tumor recurrence can be considered cured with 99 % certainty. Multivariate analysis showed that cure probabilities range from 40.9 % in patients with node-negative primary tumors and metachronous presentation of a single lesion <3 cm, to 1.5 % in patients with node positivity, and synchronous presentation of multiple, large CLMs. A model for the calculation of a cure fraction for each possible clinical scenario is provided. Using a cure model, the present results indicate that statistical cure of CLM is possible after hepatectomy; providing this information can help clinicians give more precise answer to patients' questions.

  3. The Tumour Response to Induction Chemotherapy has Prognostic Value for Long-Term Survival Outcomes after Intensity-Modulated Radiation Therapy in Nasopharyngeal Carcinoma.

    PubMed

    Peng, Hao; Chen, Lei; Zhang, Yuan; Li, Wen-Fei; Mao, Yan-Ping; Liu, Xu; Zhang, Fan; Guo, Rui; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2016-04-21

    The prognostic value of the tumour response to induction chemotherapy (IC) for long-term survival outcomes after intensity-modulated radiation therapy in nasopharyngeal carcinoma (NPC) remains unknown. We retrospectively reviewed 1811 consecutive patients with newly diagnosed NPC treated using IMRT, and 399 eligible patients with pre- and post-induction chemotherapy magnetic resonance images were recruited. The clinicopathological features of patients with different tumour responses were compared using the Chi-square test or Fisher's exact test. Prognostic value was assessed using a multivariate Cox proportional hazards model. After IC, 101/399 (25.3%) patients had a complete tumour response overall (CR), 262 (65.7%) had a partial response (PR) and 36 (9.0%) had stable disease (SD). The 4-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) rates for CR vs. PR vs. SD were 90.0% vs. 79.0% vs. 58.2% (CR vs. PR: P1 = 0.007; CR vs. SD: P2 < 0.001; PR vs. SD: P3 = 0.004), 95.7% vs. 88.7% vs. 70.2% (P1 = 0.017, P2 < 0.001, P3 = 0.005), 92.0% vs. 87.4% vs. 74.3% (P1 = 0.162, P2 = 0.005, P3 = 0.029) and 95.9% vs. 88.8% vs. 81.8% (P1 = 0.024, P2 = 0.006, P3 = 0.268), respectively. Multivariate analysis identified that the tumour response to IC was an independent prognostic factor for DFS, OS and LRRFS.

  4. 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.

  5. Lymph Nodes and Survival in Pancreatic Neuroendocrine Tumors (pNET)

    PubMed Central

    Krampitz, Geoffrey W.; Norton, Jeffrey A.; Poultsides, George A.; Visser, Brendan C.; Sun, Lixian; Jensen, Robert T.

    2012-01-01

    Background The significance of lymph node metastases on survival of patients with pNET is controversial. Hypothesis Lymph node metastases decrease survival in patients with pNET. Design Prospective databases of the National Institutes of Health (NIH) and Stanford University Hospital (SUH) were queried. Main Outcome Measures Overall survival, disease-related survival, and time to development of liver metastases Results 326 underwent surgical exploration for pNET at the NIH (n=216) and SUH (n=110). 40 (13%) and 305 (94%) underwent enucleation and resection, respectively. Of the patients who underwent resection, 117 (42%) had partial pancreatectomy and 30 (11%) had a Whipple procedure. 41 also had liver resections, 21 wedge resections and 20 lobectomies. Average follow-up was 8 years (range 0.3–28.6 years). The 10-year overall survival for patients with no metastases or lymph node metastases only was similar at 80%. As expected, patients with liver metastases had a significantly decreased 10-year survival of 30% (p<0.001). The time to development of liver metastases was significantly reduced for patients with lymph node metastases alone compared to those with none (p<0.001). For the NIH cohort with longer follow-up, disease-related survival was significantly different for those patients with no metastases, lymph node metastases alone, and liver metastases (p<0.0001). Extent of lymph node involvement in this subgroup showed that disease-related survival decreased as a function of number of lymph nodes involved (p=0.004). Conclusion As expected, liver metastases decrease survival of patients with pNET. Patients with lymph node metastases alone have a shorter time to development of liver metastases that is dependent on the number of lymph nodes involved. With sufficient long-term follow-up, lymph node metastases decrease disease-related survival. Careful evaluation of number and extent of lymph node involvement is warranted in all surgical procedures for pNET. PMID

  6. 5-year survival and rehospitalization due to stroke recurrence among patients with hemorrhagic or ischemic strokes in Singapore.

    PubMed

    Sun, Yan; Lee, Sze Haur; Heng, Bee Hoon; Chin, Vivien S

    2013-10-03

    Stroke is the 4th leading cause of death and 1st leading cause of disability in Singapore. However the information on long-term post stroke outcomes for Singaporean patients was limited. This study aimed to investigate the post stroke outcomes of 5-year survival and rehospitalization due to stroke recurrence for hemorrhagic and ischemic stroke patients in Singapore. The outcomes were stratified by age, ethnic group, gender and stroke types. The causes of death and stroke recurrence were also explored in the study. A multi-site retrospective cohort study. Patients admitted for stroke at any of the three hospitals in the National Healthcare Group of Singapore were included in the study. All study patients were followed up to 5 years. Kaplan-Meier was applied to study the time to first event, death or rehospitalization due to stroke recurrence. Cox proportional hazard model was applied to study the time to death with adjustment for stroke type, age, sex, ethnic group, and admission year. Cumulative incidence model with competing risk was applied for comparing the risks of rehospitalization due to stroke recurrence with death as the competing risk. Totally 12,559 stroke patients were included in the study. Among them, 59.3% survived for 5 years; 18.4% were rehospitalized due to stroke recurrence in 5 years. The risk of stroke recurrence and mortality increased with age in all stroke types. Gender, ethnic group and admitting year were not significantly associated with the risk of mortality or stroke recurrence in hemorrhagic stroke. Male or Malay patient had higher risk of stroke recurrence and mortality in ischemic stroke. Hemorrhagic stroke had higher early mortality while ischemic stroke had higher recurrence and late mortality. The top cause of death among died stroke patients was cerebrovascular diseases, followed by pneumonia and ischemic heart diseases. The recurrent stroke was most likely to be the same type as the initial stroke among rehospitalized stroke

  7. Does minimalist transfemoral transcatheter aortic valve replacement produce better survival in patients with severe chronic obstructive pulmonary disease?

    PubMed

    Condado, Jose F; Haider, Moosa N; Lerakis, Stamatios; Keegan, Patricia; Caughron, Hope; Thourani, Vinod H; Devireddy, Chandan; Leshnower, Bradley; Mavromatis, Kreton; Sarin, Eric L; Stewart, James; Guyton, Robert; Forcillo, Jessica; Patel, Ateet; Simone, Amy; Block, Peter C; Babaliaros, Vasilis

    2017-03-01

    To compare outcomes after minimalist and standard transfemoral transcatheter aortic valve replacement (TF-TAVR) in patients with severe chronic obstructive pulmonary disease (COPD). TF-TAVR is increasingly performed with conscious sedation and transthoracic echocardiography guidance (minimalist). The safety/efficacy of this technique in patients with severe COPD is unknown. We compared demographics, 30-day outcomes and 1-year survival of patients with severe COPD (FEV1% ≤50) who underwent minimalist vs. standard TF-TAVR between 2008 and 2015 at our institution. Of 88 patients with severe COPD, 46 underwent minimalist and 42 underwent standard TF-TAVR. There were no differences on baseline characteristics, except for more history of coronary artery bypass grafting (45.5% vs. 20.6%, P = 0.03) and less history of cerebrovascular disease (16.7% vs. 45.5%, P = 0.03) in the standard TF-TAVR. Seventeen minimalist TF-TAVR patients (41.0%) were transferred directly to the general medical ward with telemetry monitoring (without ICU stay); all standard TF-TAVR patients went to the ICU. Minimalist TF-TAVR patients had shorter procedure time (97 vs. 129 min, P < 0.001), ICU time (21.8 vs. 29.8 hr, P = 0.001) and length of stay (2 vs. 5 days, P = 0.001). There were no differences in procedure complications and 30-day mortality between groups. In our multivariate analysis, minimalist TF-TAVR (HR 0.28, 95%CI 0.08-0.97) and previous coronary revascularization (HR 0.24, 95%CI 0.09-0.65) were associated with increased 1-year survival. In contrast, moderate paravalvular leak (HR 7.73, 95%CI 1.94-30.84) was associated with decreased 1-year survival. In patients with severe COPD, Minimalist TF-TAVR results in less resource utilization and improved 1-year survival compared to standard approach. Our findings should be validated in a larger cohort of patients with severe COPD. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Survival and complications in thalassemia.

    PubMed

    Borgna-Pignatti, C; Cappellini, M D; De Stefano, P; Del Vecchio, G C; Forni, G L; Gamberini, M R; Ghilardi, R; Origa, R; Piga, A; Romeo, M A; Zhao, H; Cnaan, A

    2005-01-01

    The life expectancy of patients with thalassemia major has significantly increased in recent years, as reported by several groups in different countries. However, complications are still frequent and affect the patients' quality of life. In a recent study from the United Kingdom, it was found that 50% of the patients had died before age 35. At that age, 65% of the patients from an Italian long-term study were still alive. Heart disease is responsible for more than half of the deaths. The prevalence of complications in Italian patients born after 1970 includes heart failure in 7%, hypogonadism in 55%, hypothyroidism in 11%, and diabetes in 6%. Similar data were reported in patients from the United States. In the Italian study, lower ferritin levels were associated with a lower probability of experiencing heart failure and with prolonged survival. Osteoporosis and osteopenia are common and affect virtually all patients. Hepatitis C virus antibodies are present in 85% of multitransfused Italian patients, 23% of patients in the United Kingdom, 35% in the United States, 34% in France, and 21% in India. Hepatocellular carcinoma can complicate the course of hepatitis. A survey of Italian centers has identified 23 such cases in patients with a thalassemia syndrome. In conclusion, rates of survival and complication-free survival continue to improve, due to better treatment strategies. New complications are appearing in long-term survivors. Iron overload of the heart remains the main cause of morbidity and mortality.

  9. 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.

  10. Year of treatment as independent predictor of relapse-free survival in patients with localized prostate cancer treated with definitive radiotherapy in the PSA era.

    PubMed

    Kupelian, Patrick; Thames, Howard; Levy, Larry; Horwitz, Eric; Martinez, Alvaro; Michalski, Jeff; Pisansky, Thomas; Sandler, Howard; Shipley, William; Zelefsky, Michael; Zietman, Anthony; Kuban, Deborah

    2005-11-01

    To study the use of the year of therapy as an independent predictor of outcomes, serving as a proxy for time-related changes in therapy and tumor factors in the treatment of prostate cancer. Accounting for these changes would facilitate the retrospective comparison of outcomes for patients treated in different periods. Nine institutions combined data on 4,537 patients with Stages T1 and T2 adenocarcinoma of the prostate who had a pretherapy prostate-specific antigen (PSA) level and biopsy Gleason score, and who had received > or = 60 Gy external beam radiotherapy without neoadjuvant androgen deprivation or planned adjuvant androgen deprivation. All patients were treated between 1986 and 1995. Two groups were defined: those treated before 1993 (Yr < or = 92) vs. 1993 and after (Yr > or = 93). Patients treated before 1993 had their follow-up truncated to make the follow-up time similar to that for patients treated in 1993 and after. Therefore, the median follow-up time was 6.0 years for both groups (Yr < or = 92 and Yr > or = 93). Two separate biochemical failure endpoints were used. Definition A consisted of the American Society for Therapeutic Radiology Oncology endpoint (three PSA rises backdated, local failure, distant failure, or hormonal therapy). Definition B consisted of PSA level greater than the current nadir plus two, local failure, distant failure, or hormonal therapy administered. Multivariate analyses for factors affecting PSA disease-free survival (PSA-DFS) rates using both endpoints were performed for all cases using the following variables: T stage (T1b, T1c, T2a vs. T2b, T2c), pretreatment PSA (continuous variable), biopsy Gleason score (continuous variable), radiation dose (continuous variable), and year of treatment (continuous variable). The year variable (defined as the current year minus 1960) ranged from 26 to 35. To evaluate the effect of radiation dose, the multivariate analyses were repeated with the 3,897 cases who had received < 72 Gy

  11. Central pancreatectomy for pancreatoblastoma in a 16-year-old girl.

    PubMed

    Dumitrascu, Traian; Stanciulea, Oana; Herlea, Vlad; Tomulescu, Victor; Ionescu, Mihnea

    2011-08-01

    Long-term functional results after standard pancreatic resections are a major concern, especially in children. An alternative pancreas-sparing procedure (such as central pancreatectomy) should be taken into consideration whenever it is feasible, and a prolonged survival is expected. Pancreatoblastoma is an unusual malignant tumor in childhood. However, in initially resectable tumors, the 15-year survival is more than 80%. Thus, there is a potential role of a conservative pancreatic resection in successful treatment of pancreatoblastoma. The management in a case of a 16-year-old girl with a pancreatoblastoma in the body of pancreas is presented. Complete surgical resection by central pancreatectomy followed by chemotherapy led to a prolonged disease-free survival, with good functional results. Central pancreatectomy could be an alternative surgical technique in some selected cases of pancreatoblastoma, having the lowest incidence of postoperative exocrine and endocrine insufficiency rate and offering the best nutritional status. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Ten-year follow-up of pediatric patients with non-Hodgkin lymphoma treated with allogeneic or autologous stem cell transplantation.

    PubMed

    Giulino-Roth, Lisa; Ricafort, Rosanna; Kernan, Nancy A; Small, Trudy N; Trippett, Tanya M; Steinherz, Peter G; Prockop, Susan E; Scaradavou, Andromachi; Chiu, Michelle; O'Reilly, Richard J; Boulad, Farid

    2013-12-01

    Autologous or allogeneic hematopoietic stem cell transplant (SCT) is often considered in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) but there are limited data on the use of SCT for the treatment of NHL in the pediatric setting. To evaluate the role of SCT for children with NHL, we reviewed 36 consecutive pediatric patients with NHL who underwent an allogeneic (n = 21) or autologous (n = 15) SCT at our institution between 1982 and 2004. Pathologic classification included: lymphoblastic lymphoma (n = 12), Burkitt lymphoma (BL) (n = 5), diffuse large B-cell lymphoma (n = 4), anaplastic large cell lymphoma (ALCL) (n = 13), peripheral T cell lymphoma (n = 1), and undifferentiated NHL (n = 1). Donor source for allogeneic-SCT recipients was an HLA-matched related donor (n = 15), a matched unrelated donor (n = 4), or a mismatched donor (related n = 1; unrelated n = 1). Twenty-eight patients (78%) had chemotherapy responsive disease at the time of transplant (either CR or PR). Overall survival (OS) and disease-free survival (DFS) were 55% and 53% with a median follow-up of 9.75 years. Outcomes were similar in patients receiving autologous and allogeneic-SCT (DFS 53% in both groups). Patients with ALCL had a DFS of 76.9%. In contrast, of five patients transplanted for BL, none survived. DFS among patients with chemotherapy sensitive disease was 61%, compared with 25% among patients with relapsed/refractory disease (P = 0.019). Allogeneic and autologous SCT offer the prospect of durable, disease-free survival for a significant proportion of pediatric patients with relapsed or refractory NHL. Survival is superior among patients with chemotherapy sensitive disease. © 2013 Wiley Periodicals, Inc.

  13. 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.

  14. Allogeneic hematopoietic stem cell transplantation for poor-risk CLL: dissecting immune-modulating strategies for disease eradication and treatment of relapse.

    PubMed

    Hahn, M; Böttcher, S; Dietrich, S; Hegenbart, U; Rieger, M; Stadtherr, P; Bondong, A; Schulz, R; Ritgen, M; Schmitt, T; Tran, T H; Görner, M; Herth, I; Luft, T; Schönland, S; Witzens-Harig, M; Zenz, T; Kneba, M; Ho, A D; Dreger, P

    2015-10-01

    To elucidate factors contributing to the effectiveness of allogeneic hematopoietic stem cell transplantation (alloHCT) in high-risk CLL, immune interventions, GvHD and clinical outcome of 77 consecutive patients allografted for CLL were analyzed. Immune modulation (immunosuppression tapering, rituximab-augmented donor lymphocyte infusions) was guided by minimal residual disease (MRD) monitoring and commenced at a median of 91 (22-273) days after alloHCT, resulting in a probability of being event free and MRD-negative 1 year after transplant of 57% (84% in those encountering chronic GvHD). Patients who were event free and MRD-negative at the 12-month landmark had a 4-year PFS of 77% and largely remained durably MRD-negative if MRD clearance had occurred subsequent to immune modulation. Three-year overall survival, PFS, relapse incidence and non-relapse mortality of all 77 patients were 69, 57, 26 and 24%, respectively. Survival was not affected by EBMT risk category but by active disease at alloHCT, which could not be overcome by intensification of conditioning. Twenty-three patients who experienced relapse post alloHCT had a survival of 56% at 2 years after CLL recurrence. In conclusion, MRD-guided immune modulation after alloHCT for high-risk CLL can provide durable MRD clearance in more than half of the patients.

  15. Does a Coeliac School increase psychological well-being in women suffering from coeliac disease, living on a gluten-free diet?

    PubMed

    Ring Jacobsson, Lisa; Friedrichsen, Maria; Göransson, Anne; Hallert, Claes

    2012-03-01

    To assess the effects of an active method of patient education on the psychological well-being of women with coeliac disease in remission. Despite remission with a gluten-free diet, adults with coeliac disease and especially women experience a subjective poor health. Self-management education seems to be promising tool to help patients suffering from coeliac disease to cope with their disorder. A randomised controlled trial. A total of 106 women, ≥ 20 years, with confirmed coeliac disease, who had been on a gluten-free diet for a minimum of five years. The intervention group (n = 54) underwent a 10-session educational programme, 'Coeliac School', based on problem-based learning. The controls (n = 52) received information regarding coeliac disease sent home on a regular basis. The primary outcomes were psychological general well-being measured with a validated questionnaire. Participants in the Coeliac School reported a significant improvement in psychological well-being at 10 weeks, whereas the controls given usual care reported a worsening in psychological well-being. After six months, a significant improvement remained for the index of vitality. Patient education increased psychological well-being in women with coeliac disease. There is a need to refine the methods of patient education to make the effects of well-being more pronounced over time. Patient education using problem-based learning promotes self-management in coeliac disease by improving the well-being of patients who have been struggling with the gluten-free diet for years. © 2011 Blackwell Publishing Ltd.

  16. Impact of gluten-free camp on quality of life of children and adolescents with celiac disease.

    PubMed

    Bongiovanni, Tasce R Simon; Clark, Ann L; Garnett, Elizabeth A; Wojcicki, Janet M; Heyman, Melvin B

    2010-03-01

    A gluten-free camp allows children with celiac disease (CD) to enjoy a camp experience without concern and preoccupation with foods they eat or the stigma of their underlying disease. The objective of this study was to evaluate the impact of gluten-free camp on quality-of-life indicators for children and adolescents with CD. Children aged 7 to 17 years with CD were administered a 14-question survey at the beginning and the end of a 7-day gluten-free camp. Surveys used a Likert scale to examine general well-being, emotional outlook, and self-perception for the week before each survey. Differences between the time points were compared. Data were analyzed by paired t test. Of the 104 campers who attended camp, 77 (21 male) completed the survey at both time points. Most (70%) had been on a gluten-free diet (GFD) for <4 years. All seemed to benefit from camp, no longer feeling different from other kids or feeling frustrated with a restricted diet. A more beneficial impact was found for campers who were on a GFD for <4 years. Overall, campers reported an improvement in 11 of 14 questions, statistically significant (P < .05) for 8 of those 11 questions. Improvement was observed in each of the 3 categories of questions: well-being, self-perception, and emotional outlook. Children who had CD and attended a week-long gluten-free camp demonstrated improvement in well-being, self-perception, and emotional outlook. The positive effects of camp were more apparent among campers who had been on a GFD for <4 years compared with those who had been on a GFD for > or =4 years, suggesting an adaptation to CD with time. A gluten-free camp that provides an environment of unrestricted foods can at least temporarily alleviate stress and anxiety around food and social interactions. Durability of these observations on return to daily life requires additional study.

  17. Serum CA125 predicts extrauterine disease and survival in uterine carcinosarcoma

    PubMed Central

    Huang, Gloria S.; Chiu, Lydia G.; Gebb, Juliana S.; Gunter, Marc J.; Sukumvanich, Paniti; Goldberg, Gary L.; Einstein, Mark H.

    2009-01-01

    Objective The purpose of this study was to determine the clinical utility of CA125 measurement in patients with uterine carcinosarcoma (CS). Methods Ninety-five consecutive patients treated for CS at a single institution were identified. All 54 patients who underwent preoperative CA125 measurement were included in the study. Data were abstracted from the medical records. Tests of association between preoperative CA125 and previously identified clinicopathologic prognostic factors were performed using Fisher’s exact test and Pearson chi-square test. To evaluate relationship of CA125 elevation and survival, a Cox proportional hazard model was used for multivariate analysis, incorporating all of prognostic factors identified by univariate analysis. Results Preoperative CA125 was significantly associated with the presence of extrauterine disease (P<0.001), deep myometrial invasion (P<0.001), and serous histology of the epithelial component (P=0.005). Using univariate survival analysis, stage (HR=1.808, P=0.004), postoperative CA125 level (HR=9.855, P<0.001), and estrogen receptor positivity (HR=0.314, P=0.029) were significantly associated with survival. In the multivariate model, only postoperative CA125 level remained significantly associated with poor survival (HR=5.725, P=0.009). Conclusion Preoperative CA125 elevation is a marker of extrauterine disease and deep myometrial invasion in patients with uterine CS. Postoperative CA125 elevation is an independent prognostic factor for poor survival. These findings indicate that CA125 may be a clinically useful serum marker in the management of patients with CS. PMID:17935762

  18. Survival of ovarian cancer patients in Denmark: excess mortality risk analysis of five-year relative survival in the period 1978-2002.

    PubMed

    Hannibal, Charlotte Gerd; Cortes, Rikke; Engholm, Gerda; Kjaer, Susanne Krüger

    2008-01-01

    To explore the variation in ovarian cancer survival in Denmark in the period 1978-2002 in relation to time since diagnosis, age at diagnosis, period of diagnosis, stage and histology. Register-based cohort study. Denmark in the period 1978-2002. Using the nationwide Danish Cancer Registry, we included a total of 13,035 women diagnosed with invasive ovarian cancer in Denmark in the period 1978-2002. Excess mortality risk analyses of five-year relative survival of ovarian cancer patients diagnosed in the period 1978-2002 with follow-up through 2006 were made based on data from the NORDCAN database. Five-year relative survival, excess mortality rate (ER) and relative excess mortality risk (RER) after an ovarian cancer diagnosis. The relative survival of Danish ovarian cancer patients slightly increased in the period 1978-2002. The ERs were highest in the first year following diagnosis, in particular in the first three months, and among older patients, even for localized and regional tumors. The pattern remained the same when stratified by histological subgroup. Older age at diagnosis, earlier period of diagnosis, more advanced stage at diagnosis and being diagnosed with undifferentiated carcinoma predicted poorer survival among Danish ovarian cancer patients diagnosed in the period 1978-2002. The survival of Danish ovarian cancer patients has slightly increased from 1978 through 2002. Despite this, the mortality rate of ovarian cancer in Denmark is still higher than in the other Nordic countries. Explanations for these differences are still to be identified.

  19. Chronic obstructive pulmonary disease: getting it right. Does optimal management of chronic obstructive pulmonary disease alter disease progression and improve survival?

    PubMed

    Russell, Richard E

    2014-03-01

    We live in a world where people live longer lives. The standardized mortality rate for many diseases is decreasing. Chronic obstructive pulmonary disease (COPD) is not following this trend. Over the last 10 years, interventions for COPD have been developed, but have any changed the prognosis or trajectory of this modern epidemic? We review the most recent and classical literature in order to answer this question. Recent analyses of data have clarified which interventions are effective in COPD and which are not. New studies have defined what is achievable with the current therapies. Only two interventions have been demonstrated to improve survival: smoking cessation and long-term oxygen therapy. Other treatments do reduce exacerbations, improve lung function and improve the patient's quality of life, but do not affect physiological disease progression or mortality. There is much work to do, not only to improve the treatments we have for this disease, but also to diagnose it early, intervene at the right time, reduce the treatment side-effects and most importantly understand the pathophysiology better. Moreover, we are duty bound to look at each patient and review what we are trying to achieve for each one through appropriate phenotyping as well as sometimes taking a more palliative approach.

  20. Celiac Disease Associated with a Benign Granulomatous Mass Demonstrating Self-Regression after Initiation of a Gluten-Free Diet.

    PubMed

    Tiwari, Abhinav; Sharma, Himani; Qamar, Khola; Khan, Zubair; Darr, Umar; Renno, Anas; Nawras, Ali

    2017-01-01

    Celiac disease is a chronic immune-mediated enteropathy in which dietary gluten induces an inflammatory reaction predominantly in the duodenum. Celiac disease is known to be associated with benign small bowel thickening and reactive lymphadenopathy that often regresses after the institution of a gluten-free diet. A 66-year-old male patient with celiac disease presented with abdominal pain and diarrheal illness. Computerized tomography of the abdomen revealed a duodenal mass. Endoscopic ultrasound-guided fine needle aspiration of the mass revealed bizarre stromal cells which represent a nonspecific tissue reaction to inflammation. This inflammatory mass regressed after the institution of a gluten-free diet. This case report describes a unique presentation of celiac disease in the form of a granulomatous self-regressing mass. Also, this is the first reported case of bizarre stromal cells found in association with celiac disease. In addition to lymphoma and small bowel adenocarcinoma, celiac disease can present with a benign inflammatory mass, which should be serially monitored for resolution with a gluten-free diet.