Significance of tertiary pattern 5 in patients with gleason score 7 after radical prostatectomy.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 117-117
Author(s):  
Jiakun Li ◽  
Yaochuan Guo ◽  
Shi Qiu ◽  
Mingjing He ◽  
Kun Jin ◽  
...  
Keyword(s):  
Radical Prostatectomy ◽  
Gleason Score ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Statistical Significance ◽  
Strong Association ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Gleason Pattern ◽  
Cox Proportional Hazards Models

117 Background: To evaluate the association between tertiary Gleason pattern (TGP) 5 and the biochemical recurrence (BCR) in patients with prostate cancer (PCa) of Gleason score (GS) 7 after radical prostatectomy(RP). Methods: This retrospective study collected 387 patients received RP and diagnosed GS 7 (3+4 or 4+3) in the West China Hospital from January 2009 to December 2017.Regardlessly the first Gleason pattern, patients were divide into 2 groups: TGP5 absence and TGP5 presence. Furthermore, we added the primary Gleason pattern to divided patients into 4 groups: GS 3+4, GS 3+4/TGP 5, Gleason 4+3, Gleason 4+3/TGP 5. Cox proportional-hazards models was used to evaluate the association between the status of TGP5 and BCR after adjusting the confounding factors with follow-up time as the underlying time scale. All the analyses were conducted with the use of statistical software packages Rnand EmpowerStats and conducted as two sides and P values less than 0.05 were considered statistical significance. Results: In the results by using Cox proportional-hazards model, regardless the primary Gleason pattern, comparing TGP5 absence (89.7%) and presence (10.3%), the risk of BCR for patients with tertiary Gleason pattern 5 presence was statistically significantly higher than absence (P = 0.02, HR = 2.24, 95%Cl: 1.12-4.49). In terms of the patients with primary Gleason pattern 4, the risk of BCR for patients with Gleason 4+3/TGP5 was statistically significantly higher than Gleason 4+3.(P = 0.02, HR = 2.56, 95%Cl: 1.16-5.67). There was a marked trend that patients with Gleason 3+4/TGP 5 has a higher risk of BCR compared with patients with Gleason 3+4, although there was no statistical difference (P = 0.58, HR = 1.82, 95%Cl: 0.22-14.96). Conclusions: The TGP5 in patients with GS 7 had strong association with the risk of BCR and it was an independent predictor for BCR. This result was more obvious in patients with GS 7 (4+3) in our study. Further researches with larger data size were needed to confirm these funding.

Predictive Value of First Posttreatment Imaging Using Standardized Reporting in Head and Neck Cancer

2019 ◽  
Vol 161 (6) ◽  
pp. 978-985 ◽  
Author(s):  
Derek Hsu ◽  
Falgun H. Chokshi ◽  
Patricia A. Hudgins ◽  
Suprateek Kundu ◽  
Jonathan J. Beitler ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Head And Neck ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Strong Association ◽  
Treatment Completion ◽  
Tertiary Hospital ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Increased Risk

Objective The Neck Imaging Reporting and Data System (NI-RADS) is a standardized numerical reporting template for surveillance of head and neck squamous cell carcinoma (HNSCC). Our aim was to analyze the accuracy of NI-RADS on the first posttreatment fluorodeoxyglucose positron emission tomography/contrast-enhanced computed tomography (PET/CECT). Study Design Retrospective cohort study. Setting Academic tertiary hospital. Subject and Methods Patients with HNSCC with a 12-week posttreatment PET/CECT interpreted using the NI-RADS template and 9 months of clinical and radiologic follow-up starting from treatment completion between June 2014 and July 2016 were included. Treatment failure was defined as positive tumor confirmed by biopsy or Response Evaluation Criteria in Solid Tumors criteria. Cox proportional hazards models were performed. Results This study comprised 199 patients followed for a median of 15.5 months after treatment completion (25% quartile, 11.8 months; 75% quartile, 20.2 months). The rates of treatment failure increased with each incremental increase in NI-RADS category from 1 to 3 (4.3%, 9.1%, and 42.1%, respectively). A Cox proportional hazards model demonstrated a strong association between NI-RADS categories and treatment failure at both primary and neck sites (hazard ratio [HR], 2.60 and 5.22, respectively; P < .001). In the smaller treatment subgroup analysis, increasing NI-RADS category at the primary site in surgically treated patients and treatment failure did not achieve statistically significant association (HR, 0.88; P = .82). Conclusion Increasing NI-RADS category at the baseline posttreatment PET/CECT is strongly associated with increased risk of treatment failure in patients with HNSCC.

Serum IGFBP4 levels in combination with miliary disease: A candidate predictor of ovarian cancer progression-free survival.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5079-5079
Author(s):  
Samantha Cohen
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Residual Disease ◽  
Statistical Significance ◽  
Serum Levels ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Separate Analysis

5079 Background: Insulin-like growth factor binding protein, IGFBP4, was shown to be highly expressed across all stages of epithelial ovarian cancer (EOC) and serum levels are elevated in EOC. Moreover, IGFBP4 levels are ~3x greater in women with malignant pelvic masses. We investigated whether ascites volume and the presence of miliary disease in combination with serum levels of IGFBP4 are independent predictors of survival. Methods: A prospective and retrospective analysis was performed. Patients were enrolled at the time of cytoreductive surgery. Ascites volume was either absent, <500 cc (low), or >= 500 cc (high), and the presence of miliary disease was recorded. The IGFBP4 cutoff was 1064.5 ug/ml based upon previous results. The Kaplan-Meier product limit method was used to estimate PFS probabilities. The Cox proportional hazards model was used to estimate hazard ratios (HR) and corresponding 95% CI. Results: 57 cases were included in the analysis of ascites volume and miliary disease. Cytoreductive outcomes were complete gross resection (44.8%), optimal (<=1cm residual disease; 44.8%), and suboptimal ( >1cm residual disease; 10.3%). Histologic subtypes: papillary serous (n=35; 61.4%), mucinous (n=15; 26.3%), endometrioid (n=4; 7.0%), and clear cell (n=3; 5.3%). Stage distribution was 21.1% I/II, and 78.9% III/IV. PFS was unaffected by ascites volume (p=0.341) or miliary disease. Among this cohort, 29 had IGFBP4 levels available for a separate analysis. Patients with high IGFBP4 and miliary disease were 5.5 times as likely to recur compared with patients with miliary disease and low IGFBP4 (HR=5.55 [0.77, 39.82]), and the statistical significance was borderline (p<0.088). No statistically significant differences were detected between rates of recurrence among patients with high and low IGFBP4 values in combination with ascites volume. Conclusions: These exploratory studies suggest that patients with high IGFBP4 serum levels and miliary disease were > 5 times as likely to recur compared to women with miliary disease and low IGFBP4 levels. Future studies examining these variables using a larger population and examining the biologic basis of this relationship are planned.

scholarly journals POS0824 THE LONG-TERM CLINICAL COURSE OF MUSCULAR VASCULITIS DEPENDING ON THE ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY STATUS: A RETROSPECTIVE OBSERVATIONAL STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 665.2-665
Author(s):  
T. Yoshida ◽  
K. Nishimura ◽  
D. Waki ◽  
K. Mizukawa ◽  
N. Tanaka ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Systemic Vasculitis ◽  
Statistical Significance ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Negative Group ◽  
Positive Group

Background:Skeletal muscle is known as one of the organ involvements of primary systemic vasculitis.1,2 Muscle inflammation is detected by magnetic resonance imaging, and necrotizing vasculitis is proved by muscle biopsy.3 As with systemic vasculitis or single organ vasculitis, glucocorticoid (GC) and immunosuppressants are used in its treatment.4 There are not many reports about muscular vasculitis, and its long-term clinical course after initial treatment, including the rates of relapse and mortality, remains unclear.Objectives:To identify the predictors of relapse and mortality in patients with muscular vasculitis, especially focusing on the status of anti-neutrophil cytoplasmic antibody (ANCA).Methods:We retrospectively reviewed patients diagnosed with necrotizing vasculitis with muscle involvements in our hospital between 2004 and 2020. In all cases, muscular vasculitis was identified by muscle biopsy or magnetic resonance imaging. To focus on the clinical features of muscular vasculitis, we excluded patients with such severe organ involvements as cardiovascular, abdominal, cerebral, severe renal, and severe pulmonary involvements. We compared the 5-year cumulative incidence of relapse, the overall survival rate, and the dose of GC over 5 years between the ANCA-positive and ANCA-negative groups. A relapse was defined as any new or worsened state of disease activity requiring an escalation of GC dose. Gray’s method was used for assessing the cumulative incidence of relapse. The log-rank test was used for assessing overall survival. The Mann-Whitney U test was used for assessing the dose of GC. The possible factors for relapse in 5 years in a univariate analysis were selected for a multivariate analysis using the Cox proportional hazards model.Results:Forty-nine patients were enrolled. The median age of onset was 77 (69-82) years and 71.4% were women. There were 30 ANCA-positive patients (90.0% with anti-myeloperoxidase) and 19 ANCA-negative patients. The median age and the number of patients with renal involvements were higher in the ANCA-positive group than in the ANCA-negative group (73.0 ± 9.29 years vs. 79.5 ± 20.28 years, p=0.0062 and 7/30 [23.3%] vs. 0/19 [0.0%], p=0.034, respectively). The Birmingham Vasculitis Activity Score (ver. 3), the induction dose of GC, and the rate of immunosuppressants use were not significantly different between the two groups. During the observational period, 24 patients relapsed. The 5-year cumulative incidence of relapse was significantly higher in the ANCA-positive group than in the ANCA-negative group (p=0.026) (Figure 1). The Cox proportional hazards model revealed that the presence of ANCA was an independent risk factor for relapse (hazard ratio: 3.15; 95% confidence interval 1.06–9.38; p=0.040). During the observational period, 9 patients died (3 died from cancer, 1 from interstitial pneumonia, 1 from cerebral hemorrhage, 1 from infection, and 3 from unknown reasons). The ANCA-positive group exhibited a higher mortality rate than the ANCA-negative group without a statistical significance (p=0.12). The 5-year cumulative dose of GC was larger in the ANCA-positive group than in the ANCA-negative group without a statistical significance (14786 [11246–19138] mg vs. 10088 [7129–12634] mg, p=0.12).Conclusion:In muscular vasculitis, the presence of ANCA is an independent risk factor for long-term relapse. Stratified treatment depending on the ANCA status may reduce the relapse rate and the occurrence of side effects of GC in patients with muscular vasculitis.References:[1]Kitching AR et al. Nat Rev Dis Primers 2020; 6(1): 71.[2]Hernández-Rodríguez J et al. J Autoimmun 2014; 48-49: 84-9.[3]Ushiyama S et al. Rheumatol Int 2020; 40(10): 1667-74.[4]Ganeshanandan LR et al. Semin Arthritis Rheum 2020; 50(3): 503-8.Disclosure of Interests:None declared

MO051EFFECTS OF SEMAGLUTIDE ON CHRONIC KIDNEY DISEASE OUTCOMES: A POST HOC POOLED ANALYSIS FROM THE SUSTAIN 6 AND PIONEER 6 TRIALS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Katherine Tuttle ◽  
David Cherney ◽  
Samy Hadjadj ◽  
Thomas Idorn ◽  
Ofri Mosenzon ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Statistical Significance ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Post Hoc ◽  
Time To Onset

Abstract Background and Aims The SUSTAIN 6 cardiovascular outcomes trial (CVOT) indicated a renal benefit with subcutaneous (s.c.) once-weekly (OW) semaglutide vs placebo. The PIONEER 6 CVOT reported cardiovascular safety with oral semaglutide in a similar cohort using a similar trial design. In the present post hoc study, eGFR data from the SUSTAIN 6 and PIONEER 6 trials were pooled to evaluate the potential benefit of semaglutide (s.c. or oral) vs placebo on chronic kidney disease (CKD) outcomes. Method Data from 6,480 subjects from SUSTAIN 6 (N=3,297; median follow-up, 2.1 years; mean baseline eGFR, 76 mL/min/1.73 m2) and PIONEER 6 (N=3,183; median follow-up, 1.3 years; mean baseline eGFR, 74 mL/min/1.73 m2) were pooled for semaglutide (0.5 mg s.c. OW, 1.0 mg s.c. OW or 14 mg oral once daily) or placebo. We evaluated time to onset of persistent eGFR reduction (thresholds of ≥30%, ≥40%, ≥50% and ≥57% [57% corresponds to a doubling of serum creatinine]) from baseline in the overall pooled population and by baseline CKD subgroups (≥30–&lt;60 mL/min/1.73 m2, n=1,699; ≥60 mL/min/1.73 m2, n=4,762; data were missing for 19 subjects). Analyses were performed using a Cox proportional-hazards model with treatment group (semaglutide vs placebo) and CKD subgroup as fixed factors and the interaction between both stratified by trial. Results In the overall population, the hazard ratios (HRs) for time to onset of persistent eGFR reductions with semaglutide vs placebo were &lt;1.0, but did not achieve statistical significance. In subjects with baseline eGFR ≥30–&lt;60 mL/min/1.73 m2, HRs for semaglutide vs placebo were consistently lower compared with the overall population and, in this subgroup, semaglutide significantly reduced the risk of developing a persistent 30% eGFR reduction vs placebo (Figure; p=0.03). Numerically larger effects were seen with increasing eGFR reduction thresholds in this subgroup, with the exception of the 57% eGFR reduction threshold. No statistically different interactions between treatment and CKD subgroup were observed. Conclusion The findings of this post hoc analysis of pooled data from SUSTAIN 6 and PIONEER 6 on clinically relevant outcomes for CKD support a smaller magnitude of eGFR decline with semaglutide vs placebo, despite relatively short follow-up times. The small number of events at both the 50% and 57% thresholds, and the associated broad confidence intervals, limit the interpretability of the results. In line with previous findings, the data suggest a renal benefit of semaglutide vs placebo in subjects with established CKD. The FLOW trial (ClinicalTrials.gov Identifier: NCT03819153), which is dedicated to exploring CKD outcomes with semaglutide treatment, is ongoing to test this hypothesis in patients with CKD at baseline.

Genotype-Phenotype Associations in Patients with Severe Congenital Neutropenia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 502-502
Author(s):  
Philip S. Rosenberg ◽  
Steven Stein ◽  
Elin Rodger ◽  
Audrey Anna Bolyard ◽  
Mary Ann Bonilla ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Statistical Significance ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Causative Gene ◽  
Distinct Subgroup ◽  
Cell Counts

Abstract BACKGROUND: G-CSF therapy has reduced sepsis mortality in patients with severe congenital neutropenia (SCN), revealing a syndromic predisposition to myelodysplastic syndrome and acute myeloid leukemia (MDS/AML). The MDS/AML risk appears to be higher in SCN patients who are less-responsive to therapy; however, the genetic determinants of susceptibility remain to be elucidated. METHODS: We studied 82 North American and Australian patients with SCN on long-term G-CSF enrolled in the Severe Chronic Neutropenia International Registry. These patients had prospective follow-up, sufficient banked DNA for genotyping, and validated clinical data. RESULTS: Fifty-two patients (63%) were positive for germline mutations in neutrophil elastase (ELA2); the remaining 30 patients (37%) had no detectable mutations. Prior to G-CSF therapy, blood cell counts were significantly different between ELA2 positive and negative patients. Compared with ELA2 positive patients, ELA2 negative patients had significantly higher median absolute neutrophil count (ANC) values (158 versus 53 cells/uL, P=0.02), significantly lower monocyte and eosinophil counts (P&lt;0.001), and significantly lower platelet counts (P=0.002). ELA2 negative patients were maintained on significantly lower doses of G-CSF (5.2 versus 9.9 ug/kg/day, P=0.02), consistent with higher baseline ANC values. However, ELA2 negative patients were significantly less responsive to G-CSF therapy. Compared with ELA2 positive patients, on therapy, ELA2 negative patients had significantly smaller median increases in ANC values (1200 versus 2700 cells/uL, P=0.02); the difference remained significant after controlling for individual G-CSF dose (P=0.04). ELA2 negative patients had 5 MDS/AML events in 132 person-years, versus 8 MDS/AML events in 373 person-years among ELA2 positive patients. Using the Cox proportional hazards model, the hazard of MDS/AML was 3.1-fold higher in ELA2 negative patients compared with ELA2 positive patients. This association was of borderline statistical significance (P=0.08). No patient in either group died of sepsis. We found 34 distinct mutations in 52 ELA2 positive patients. The mutation sites were not clustered in the 8 ELA2 positive patients who developed MDS/AML. We found no associations of phenotype or outcome with specific ELA2 mutations; however, the numbers were limited. CONCLUSIONS: SCN patients without mutations in ELA2 constitute a clinically distinct subgroup. ELA2 negative patients are significantly less responsive to G-CSF therapy than ELA2 positive patients, and they may be at substantially higher risk of leukemia. Additional studies are needed to confirm the latter association and identify the causative gene or genes.

Targeted therapy for renal cell carcinoma (RCC) with brain metastasis: Overall survival (OS) and safety.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15517-e15517
Author(s):  
Diogo Assed Bastos ◽  
Ana M. Molina ◽  
Xiaoyu Jia ◽  
Susanne Velasco ◽  
Sujata Patil ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Local Therapy ◽  
Multimodality Treatment ◽  
Primary Objective ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model

e15517 Background: Brain metastases (b-met) in RCC are associated with poor prognosis and median OS of about 7 months in the pre-targeted therapy (TT) era (Culine, Cancer 1998). The role of TT in this setting is not well established since patients (pts) with b-met were excluded from most clinical trials. The primary objective was to assess OS and central nervous system (CNS) safety of pts with b-met treated with TT. Methods: Pts with mRCC treated with ≥ 28 days of TT after b-met diagnoses were retrospectively identified. Kaplan-Meier method and Cox proportional hazards model were used to analyze the association between clinical features and OS. Results: 65 pts were identified, 52 (80%) treated with anti-angiogenic agents and 13 (20%) treated with mTOR inhibitors. Most pts had extracranial metastasis (98%) and 54% had ≥ 2 brain lesions. Fifty seven pts (88%) had local therapy for b-met before TT including surgery in 3 (5%), radiation therapy (RT) in 36 (55%) and both surgery and RT in 18 (28%). Median follow-up was 12.3 months (1.1 – 58.8) and median time from RCC diagnosis to b-met was 17.8 months (0 – 192.2). Median TT duration was 3.4 months (0.3 – 31.9) for 1st line and 1.9 months (0.2 – 23.6) for 2nd line. Median OS was 12.2 months (95% CI 8.0 to 15.5). On univariate analysis using various clinical and treatment variables, MSKCC risk group (P= 0.001), histology subtype (clear vs other) (P< 0.0001), and number of b-met at diagnosis (P= 0.004) correlated with OS and retained statistical significance on multivariate analysis (Table). CNS complications were identified in 5 pts (8%), including 2 with radiation necrosis and 3 with b-met hemorrhage. Conclusions: The use of TT in the multimodality treatment of pts with RCC and b-met appears safe with OS that compares favorably to historical results in the pre-TT era. Clear cell RCC, favorable MSKCC risk status, and solitary b-met are associated with better outcome. [Table: see text]

Safety and efficacy of targeted therapy for renal cell carcinoma (RCC) with brain metastasis.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 497-497
Author(s):  
Diogo Assed Bastos ◽  
Ana M. Molina ◽  
Xiaoyu Jia ◽  
Susanne Velasco ◽  
Sujata Patil ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Local Therapy ◽  
Mtor Inhibitors ◽  
Primary Objective ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Safety And Efficacy

497 Background: Brain metastases (Bm) in RCC are associated with poor prognosis. The safety and efficacy of TT in this setting is not well established since patients (pts) with Bm were excluded from pivotal clinical trials. The primary objective was to assess safety and efficacy of TT in pts with Bm. Methods: Pts with mRCC treated with ≥ 28 days of TT after Bm diagnoses were retrospectively identified. Kaplan-Meier method and Cox proportional hazards model were used to analyze the association between clinical features and OS. Results: 65 pts were identified, including 52 (80%) treated with anti-angiogenic agents and 13 (20%) treated with mTOR inhibitors. Most pts had extracranial metastasis (98%) and 54% had ≥ 2 brain lesions. Fifty seven pts (88%) had local therapy for Bm before TT including surgery in 3 (5%), radiation therapy (RT) in 36 (55%) and both surgery and RT in 18 (28%). Median follow-up was 12.3 months (1.1 – 58.8). Median treatment duration was 3.4 months (0.3 – 31.9) for 1st line and 1.9 months (0.2 – 23.6) for 2nd line. Median OS was 12.2 months (95% CI 8.0 to 15.5). On univariate analysis using various clinical and treatment variables, MSKCC risk group (p = 0.001), histology subtype (clear vs other) (p < 0.0001), and number of Bm at diagnosis (p = 0.004) correlated with OS and retained statistical significance on multivariate analysis (Table). CNS complications were identified in only 5 pts (8%), including 2 with radiation necrosis and 3 with Bm hemorrhage. Conclusions: The use of targeted agents for pts with RCC and Bm appears safe with OS that compares favorably to historical results in the pre-TT era. Clear cell RCC, favorable MSKCC risk status, and solitary Bm are associated with better outcome. [Table: see text]

Very early PSA response to abiraterone in mCRPC patients: A novel prognostic factor to predict overall survival.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 219-219
Author(s):  
Carla Cavaliere ◽  
Orazio Caffo ◽  
Cinzia Ortega ◽  
Carmine D'aniello ◽  
Sabrina Chiara Cecere ◽  
...  
Keyword(s):  
Time Course ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Statistical Significance ◽  
Significant Proportion ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
New Drugs ◽  
Metastatic Setting ◽  
Psa Response

219 Background: In the last years the therapeutic scenario of mCRPC has undergone a radical change with the approval of new drugs. AA is approved for the treatment of mCRPC after failure of ADT in whom chemotherapy (CT) is not yet clinically indicated and for treatment of mCRPC progressed on or after docetaxel (DTX) based chemotherapy. The aim of this study is to evaluate the role of early PSA decline as a marker of response for an early detection of therapy success in mCRPC patients treated with AA. Methods: We retrospectively evaluated 87 pts with mCRPC treated with AA in compassionate use in Napoli, Trento, and Candiolo, Italy. Serum PSA levels were performed after 15, 90 days and then monthly, a time course of serum PSA was obtained. The PSA flare phenomenon was evaluated, according to a confirmation value at least one week apart. The Cox proportional hazards model was used to test the effect of several variables on survival outcomes in multivariate analyses. Results: We have collected data of 87 patients between Sep 2011 and Sep 2014; 75/87 were eligible for correlation analysis. PSA decline was observed in 78.6 % (59/75) of pts. Early PSA response ( ≥ 50% from baseline at 15 days) was found in 56%(42/75) evaluated patients and confirmed in 29 of them after 90 days. In early responders patients (PSA RR ≥ 50% at 15 days), we found a significant statistical advantage in terms of PFS at 1 year, HR 0.28,95% CI 0.12-0.65, p = 0.003, and OS, HR 0.21 95% CI 0.06-0.72, p = 0.01. The median OS was 17,1 months(8,8-25,2). PFS at 1 year and OS reached statistical significance also in the evaluation at 90 days, HR: 0.23 95% CI 0.07-0.77, p = 0.02 and HR: 0.14 95% CI 0.03-0.70, p = 0.02 respectively. Our analysis showed a positive correlation between OS and duration of AA treatment, previous chemotherapy treatment, cumulative dose of docetaxel ≤ 675 mg/m² and previous hormonal therapy duration ( ≥ 2.5 months) for metastatic setting in early responders group. Conclusions: A significant proportion (78.6%) of patients achieved a rapid response in terms of decline of PSA. Early PSA RR ( ≥ 50% at 15 days after start of AA) can provide clinically meaningful information and could be considered a surrogate of longer PFS and OS.

scholarly journals Duration of natalizumab therapy and reasons for discontinuation in a multiple sclerosis population

2020 ◽  
Vol 6 (1) ◽  
pp. 205521732090248
Author(s):  
Devon S Conway ◽  
Carrie M Hersh ◽  
Haleigh C Harris ◽  
Le H Hua
Keyword(s):  
Multiple Sclerosis ◽  
Disease Duration ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Patient Characteristics ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Cox Proportional Hazards Models ◽  
Natalizumab Treatment ◽  
Relapsing Multiple Sclerosis

Objective To determine multiple sclerosis patient characteristics that predict a shorter duration of natalizumab treatment. Methods The Tysabri Outreach: Unified Commitment to Health database was reviewed to identify patients treated with natalizumab at our centers. Cox proportional hazards models were used to evaluate patient characteristics associated with shorter treatment durations on natalizumab. Associations were also assessed with respect to specific reasons for stopping natalizumab. Results We identified 554 patients who began and stopped natalizumab treatment during the observation period. The average disease duration at natalizumab initiation was 7.6 years, and the average number of infusions was 30. The multivariable Cox proportional hazards model identified greater age ( P = 0.035), longer disease duration ( P < 0.001), progressive relapsing multiple sclerosis phenotype ( P = 0.003), current smoking ( P = 0.031), and greater depression ( P = 0.026) as significant predictors for natalizumab discontinuation. Greater disability levels ( P = 0.022) and gadolinium-enhancing lesions on baseline magnetic resonance imaging ( P < 0.001) were significantly associated with longer natalizumab treatment. Individuals with progressive relapsing multiple sclerosis had a 14-fold increased hazard of discontinuing natalizumab due to inflammatory events ( P < 0.001) than those with relapsing–remitting multiple sclerosis. Smokers had an 80% increased hazard of discontinuation due to intolerance ( P = 0.008). Conclusions Our results suggest that smoking, depression, and a progressive relapsing multiple sclerosis phenotype are associated with shorter natalizumab treatment durations.

Methods for displaying and calibration of Cox proportional hazards models

2017 ◽  
Vol 232 (1) ◽  
pp. 105-115
Author(s):  
Chrianna I Bharat ◽  
Kevin Murray ◽  
Edward Cripps ◽  
Melinda R Hodkiewicz
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Explanatory Power ◽  
Cox Proportional Hazards ◽  
Remaining Useful Life ◽  
Cox Proportional Hazards Model ◽  
Data Set ◽  
Proportional Hazards Models ◽  
Hazards Model ◽  
Cox Proportional Hazards Models

Cox proportional hazards modelling is a widely used technique for determining relationships between observed data and the risk of asset failure when model performance is satisfactory. Cox proportional hazards models possess good explanatory power and are used by asset managers to gain insight into factors influencing asset life. However, validation of Cox proportional hazards models is not straightforward and is seldom considered in the maintenance literature. A comprehensive validation process is a necessary foundation to build trust in the failure models that underpin remaining useful life prediction. This article describes data splitting, model discrimination, misspecification and fit methods necessary to build trust in the ability of a Cox proportional hazards model to predict failures on out-of-sample assets. Specifically, we consider (1) Prognostic Index comparison for training and test sets, (2) Kaplan–Meier curves for different risk bands, (3) hazard ratios across different risk bands and (4) calibration of predictions using cross-validation. A Cox proportional hazards model on an industry data set of water pipe assets is used for illustrative purposes. Furthermore, because we are dealing with a non-statistical managerial audience, we demonstrate how graphical techniques, such as forest plots and nomograms, can be used to present prediction results in an easy to interpret way.

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