NIMG-11. VOLUMETRIC ENDPOINTS IN DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG): COMPARISON TO CROSS-SECTIONAL MEASURES AND CORRELATION WITH OUTCOMES

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi129-vi130
Author(s):  
Margot Lazow ◽  
Martijn Nievelstein ◽  
Adam Lane ◽  
Pratiti Bandopadhayay ◽  
Mariko DeWire-Schottmiller ◽  
...  
Keyword(s):  
Disease Burden ◽  
Cox Regression ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Prognostic Impact ◽  
Cross Sectional ◽  
Volume Increase ◽  
Hazard Ratios ◽  
Post Radiation ◽  
Landmark Analyses ◽  
Volumetric Measures

Abstract INTRODUCTION Cross-sectional tumor measures are used as endpoints in clinical trials of DIPG, but may not capture meaningful changes in disease burden. Volumetric measures may provide a more accurate assessment of tumor growth. We measured the correlation between cross-sectional and volumetric measures and compared their prognostic impact to better understand response evaluation in DIPG. METHODS Patients from the International DIPG Registry with diagnostic and post-radiation MRIs were included. Utilizing mint LesionTM software, tumors were manually contoured by an experienced pediatric neuro-radiologist to extrapolate cross-sectional product (CP) and volume measures. Correlation between CP and volume was assessed by linear regression. Landmark analyses were performed to determine differences in overall survival (OS) (via log-rank) between patients classified as progressive disease (PD) versus non-PD according to CP and volumetric measurements at one-, three-, and five-months post-radiation. Imaging consistent with pseudoprogression was designated non-PD. Hazard ratios (HR) for survival after these timepoints were calculated by Cox regression. RESULTS A total of 317 MRIs from 46 patients were analyzed. When comparing change from smallest previous tumor size, CP increase of 25% (PD by RAPNO) correlated with volume increase of 28% (R2=0.685). There was no difference in OS between patients classified as PD versus non-PD by CP at one-month, three-months, or five-months post-radiation (p >0.05). However, significant differences in OS were observed between patients classified as PD versus non-PD by volume (28% increase) at one-month (2.7 vs. 12.8 months, p=0.005), three-months (1.9 vs. 10.7 months, p=0.036), and five-months post-radiation (3.7 vs. 9.1 months, p=0.023). PD by volume, but not by CP, was predictive of survival at all timepoints (HR: 5.0, 2.4, 2.4). CONCLUSIONS Volumetric assessments of PD correlated better with survival than CP at all post-radiation timepoints. Tumor volume likely represents a more accurate, prognostically-relevant measure of disease burden that deserves investigation in future DIPG trials.

H3K27M-mutant Diffuse Midline Gliomas should be Further Molecularly Stratified: An Integrated Analysis of 669 Patients

2021 ◽  
Author(s):  
Huy Gia Vuong ◽  
Hieu Trong Le ◽  
Tam N.M. Ngo ◽  
Kar-Ming Fung ◽  
James D. Battiste ◽  
...  
Keyword(s):  
Cox Regression ◽  
Fatal Outcome ◽  
Extent Of Resection ◽  
Tumor Location ◽  
Genetic Alterations ◽  
Integrated Analysis ◽  
Prognostic Impact ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
The Impact

Abstract Introduction: H3K27M-mutated diffuse midline gliomas (H3-DMGs) are aggressive tumors with a fatal outcome. This study integrating individual patient data (IPD) from published studies aimed to investigate the prognostic impact of different genetic alterations on survival of these patients.Methods: We accessed PubMed and Web of Science to search for relevant articles. Studies were included if they have available data of follow-up and additional molecular investigation of H3-DMGs. For survival analysis, Kaplan-Meier analysis and Cox regression models were utilized, and corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of genetic events on overall survival (OS).Result: We included 30 studies with 669 H3-DMGs. TP53 mutations were the most common second alteration among these neoplasms. In univariate Cox regression model, TP53 mutation was an indicator of shortened survival (HR = 1.446; 95% CI = 1.143-1.829) whereas ACVR1 (HR = 0.712; 95% CI = 0.518-0.976) and FGFR1 mutations (HR = 0.408; 95% CI = 0.208-0.799) conferred prolonged survival. In addition, ATRX loss was also associated with a better OS (HR = 0.620; 95% CI = 0.386-0.996). Adjusted for age, gender, tumor location, and the extent of resection, the presence of TP53 mutations, the absence of ACVR1 or FGFR1 mutations remained significantly poor prognostic factors.Conclusions: We outlined the prognostic importance of additional genetic alterations in H3-DMGs and recommended that these neoplasms should be further molecularly segregated. It could help neuro-oncologists better evaluate the risk stratification of patients and consider pertinent treatments.

scholarly journals Histopathological and Genomic Grading Provide Complementary Prognostic Information in Breast Cancer: A Study on Publicly Available Datasets

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Nilotpal Chowdhury
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Prognostic Indicator ◽  
Rank Test ◽  
Prognostic Impact ◽  
Prognostic Information ◽  
Free Survival ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Significant Prognostic Indicator

The genomic grade (GG) for breast cancer is thought to be the genomic counterpart of histopathological grade (HG). The motivation behind this study was to see whether HG retains its prognostic impact even when adjusted for GG, or whether it can be replaced by the latter. Four publicly available gene expression datasets were analyzed. Kaplan-Meier curves, log rank test, and Cox regression were used to study recurrence-free survival (RFS) and distant metastasis-free survival (DMFS). HG remained a significant prognostic indicator in low GG tumors (P = 0.003 for DMFS, P< 0.001 for RFS) but not in high GG tumors. HG grade 2 tumors differed significantly from HG grade 1 tumors, underlining the prognostic role of intermediate HG tumors. Additionally, GG could stratify HG 1 as well as HG 2 tumors into distinct prognostic groups. HG and GG add independent prognostic information to each other. However, the prognostic effects of both HG and GG are time varying, with the hazard ratios of high HG and GG tumors being markedly attenuated over time.

scholarly journals Comparison of Time-Varying and Landmark Analysis Methods in Estimating the Association Between Medication Adherence and Outcomes: A Heart Failure Cohort

2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Xiwen Simon Qin ◽  
Matthew W Knuiman ◽  
Joseph Hung ◽  
Tom Briffa ◽  
Tiew-Hwa Katherine Teng ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cox Regression ◽  
Adverse Outcomes ◽  
Time Dependent ◽  
Time Varying ◽  
Landmark Analysis ◽  
Hazard Ratios ◽  
Β Blockers ◽  
Landmark Analyses

IntroductionMedication adherence is associated with a reduction of adverse outcomes in heart failure (HF). However, this association is complex to estimate accurately because adherence (exposure) can vary during the follow-up period. Adherence can be estimated as a fixed exposure to predict outcomes, and this is known as a landmark analysis. In contrast, adherence can also be estimated as a dynamic exposure which varies over time in the follow-up period. This is known as a time-varying analysis and is expected to be the more precise method. Objectives and ApproachWe compared these two methods in a HF cohort. We identified a population-based cohort of 3619 heart failure patients, aged 65-84 years hospitalised in Western Australia from 2003-2007 and who survived to 1-year post-discharge (landmark date). Adherence to renin-angiotensin system inhibitors (RASI) and β-blockers was calculated using proportion of days covered (PDC) expressed either as a fixed time exposure (in landmark analysis) or a varying exposure (in time-dependent analysis). The latter was updated every 30 days after the landmark date. Cox regression models were used to investigate the association between adherence and all-cause death at 1- and 3-years post-landmark date. ResultsFor 1-year outcomes, hazard ratios (HR) for every 10% increase in PDC were similar between models from landmark analyses (RASI adherence: 0.93, 0.90-0.97; β-blocker adherence: 0.96, 0.92-1.0) and time-dependent analyses (RASI adherence: 0.94, 0.91-0.97; β-blockers adherence: 0.95, 0.92 -0.99). However, 95% confidence intervals estimated from time-dependent models were narrower than those from landmark analyses. HRs were slightly closer to the null when estimated from time-dependent models. A similar pattern was seen with 3-year outcomes. Conclusion / ImplicationsTime-dependent analysis of adherence-outcome associations results in more precise estimates of hazard ratios. Estimates of HRs from landmark analysis models were similar but usually lower than those from time-dependent models.

P2612Anaemia and renal impairment in heart failure: prevalence and differential prognostic importance according to the AHA ACC heart failure classification

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Kordsmeyer ◽  
G Gueder ◽  
S Stoerk ◽  
F Edelmann ◽  
R Wachter ◽  
...  
Keyword(s):  
Heart Failure ◽  
Renal Impairment ◽  
Cox Regression ◽  
Heart Association ◽  
Careful Consideration ◽  
Prognostic Impact ◽  
Prevalence Rates ◽  
Cross Sectional ◽  
The Individual

Abstract Background Anaemia (A) and renal impairment (RI) are frequent comorbidities in heart failure (HF) and known to impact adversely on outcome. Purpose In this post-hoc analysis, we allocated HF patients from 4 studies of the Competence Network Heart Failure at baseline to subgroups according to American Heart Association/ American College of Cardiology (AHA/ACC) HF criteria and compared prevalence rates of A and RI at each HF stage and the individual and cumulative long-term impact of these comorbidities on all-cause mortality (ACM) over a 5-year follow-up (FUP) period. Methods To study A and RI prevalence, we performed a cross-sectional analysis in 3344 patients (40.6% female, 65.6±11.2 years, 7.8, 32.3, 38.5, and 21.4% in stages A, B, C1 and C2/D, respectively). FUP data were available for 2496 patients (37.4% female, 66.0±11.3 years, 8.1, 35.3, 32.9, and 23.7% in stages A, B, C1 and C2/D, respectively). A was defined as haemoglobin <13/12 g/dL in men/women and RI as estimated glomerular filtration rate <60 mL/min/1.73m2. Within each HF subgroup, participants were divided in those without these comorbidities (A-/RI-), with either A or RI (A+/RI- and A-/RI+), or with both, A and RI (A+/RI+). For survival analysis log rank tests and multivariable Cox regression models were used. Results Overall prevalence of A in the stages A, B, C1, and C2/D was 3.1, 7.6, 16.5, and 29.8% (p<0.001) and of RI 17.6, 21.3, 24.4, and 46.6% (p<0.001), respectively. In the 4 subgroups, prevalence rates of A-/RI- were 80.2, 74.3, 66.3, and 42.1%, (p<0.001). A+/RI- and A-/RI+ were present in 2.3, 4.4, 9.3, and 11.3% (p<0.001) and 16.8, 18.1, 17.2, and 28.1 (p<0.001). A+/RI+ was found in 0.8, 3.1, 7.1, and 18.5% (p<0.001). Kaplan Meier curves demonstrate the individual and cumulative prognostic impact of A and RI (Figure). Conclusions Our results demonstrate a high prevalence in particular of RI even in asymptomatic HF stages and significant individual and cumulative long-term adverse effects of A and RI across the entire HF continuum. This includes also the clinically asymptomatic HF stages. Both prevalence and the individual and cumulative negative prognostic impact increase with increasing HF severity calling for careful consideration and management of these comorbidities in the frame of holistic HF care.

Analysis of survival and objective response (OR) in patients with hepatocellular carcinoma in a phase III study of lenvatinib (REFLECT).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 186-186 ◽  
Author(s):  
Masatoshi Kudo ◽  
Richard S. Finn ◽  
Shukui Qin ◽  
Kwang-Hyub Han ◽  
Kenji Ikeda ◽  
...  
Keyword(s):  
Cox Regression ◽  
Objective Response ◽  
Fixed Time ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Hazard Ratios ◽  
Independent Review ◽  
Phase Iii Study ◽  
Landmark Analyses ◽  
The Relationship

186 Background: In REFLECT, Lenvatinib (LEN) demonstrated treatment effect on overall survival (OS) by statistical confirmation of noninferiority to sorafenib (SOR). OR rates for LEN versus SOR were: 24% versus 9% by investigator review and 41% versus 12% by independent review (Kudo et al 2018). Since the relationship between OR and OS in phase III HCC studies is unclear, we explored the relationship between OR and OS in REFLECT. Methods: OR assessed by investigators per mRECIST were used to analyze the association between OR and OS of pts treated with LEN or SOR. The median OS of responders (CR or PR) was compared to that of nonresponders (SD, PD, or UNK/NE) irrespective of treatment. Landmark analyses were performed by OR status at several fixed time points as sensitivity analyses, and the effect on OS was evaluated by Cox regression with OR as a time-dependent covariate, with other prognostic factors. Results: Median OS was 22.4 months for responders and 11.4 months for nonresponders. Hazard ratios (HR) of landmark analyses at 2, 4, and 6 months were 0.75 (95% CI, 0.57–0.98), 0.72 (95% CI, 0.56–0.92), and 0.73 (95% CI, 0.57–0.93). Independent predictors of OS based on unstratified Cox regression are in the table. Conclusions: In REFLECT, OR was an independent predictor of OS in pts with HCC regardless of treatment. The results indicate this correlation is worth further investigation. Clinical trial information: NCT01761266. [Table: see text]

Comparison of Non-radiographic Axial Spondyloarthritis and Ankylosing Spondyltis from a Single Rheumatology Hospital in Morocco

2020 ◽  
Vol 16 (3) ◽  
pp. 240-244 ◽  
Author(s):  
Nessrine Akasbi ◽  
Siar Nihad ◽  
Zoukal Sofia ◽  
El Kohen Khadija ◽  
Harzy Taoufik
Keyword(s):  
Disease Burden ◽  
Axial Spondyloarthritis ◽  
Univariate Analysis ◽  
Cross Sectional Study ◽  
Low Back ◽  
New Classification ◽  
Cross Sectional ◽  
Asas Criteria ◽  
History Of ◽  
High Level

Background: According to the new classification criteria developed by The Assessment of SpondyloArthritis International Society, patients with axial spondyloarthritis (axSpA) can be classified in 2 subgroups: Patients with radiographic axial spondyloarthritis: ankylosing spondylitis patients (AS) and those with non-radiographic axial spondyloarthritis (nr-axSpA). Objective: The aim of the present study is to describe and discuss the differences and similarities between the two subgroups. Patients and Methods: A cross-sectional study was conducted in a single rheumatology hospital in Morocco. These included patients diagnosed as having axial spondyloarthritis according to ASAS criteria 2010, during a period of 6 years. The AS and the nr-axSpA subgroups were compared for the various axSpA-related variables. Results: Of the 277 patients with a diagnosis of axial SpA who were included in this study, 160 had AS and 117 had nr-axSpA. AS and nr-ax-SpA shared a similar age at diagnosis, similar prevalence of low back pain, lumbar stiffness, extra-articular manifestations, BASDAI and BASFI. In the multivariate analysis, AS patients were mainly male with cervical stiffness, enthesitis, coxitis and high level of ESR (erythrocyte sedimentation rate). The females generally had a family history of SpA and arthritis and were associated to the nr-axSpA form in the univariate analysis. Conclusion: This was the first study to characterise patients with AS and nr-axSpA in Morocco. Consistent with other studies published, this study showed that patients with nr-axSpA and patients with AS shared a comparable degree of disease burden.

Fracture Risk in Patients with Myasthenia Gravis: A Population-Based Cohort Study

2021 ◽  
pp. 1-8
Author(s):  
Charles Kassardjian ◽  
Jessica Widdifield ◽  
J. Michael Paterson ◽  
Alexander Kopp ◽  
Chenthila Nagamuthu ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Lower Risk ◽  
Cox Regression ◽  
Large Population ◽  
Population Based ◽  
Osteoporosis Prevention ◽  
Inception Cohort ◽  
Hazard Ratios ◽  
Multiple Covariates ◽  
Region Of Residence

Background: Prednisone is a common treatment for myasthenia gravis (MG), and osteoporosis is a known potential risk of chronic prednisone therapy. Objective: Our aim was to evaluate the risk of serious fractures in a population-based cohort of MG patients. Methods: An inception cohort of patients with MG was identified from administrative health data in Ontario, Canada between April 1, 2002 and December 31, 2015. For each MG patient, we matched 4 general population comparators based on age, sex, and region of residence. Fractures were identified through emergency department and hospitalization data. Crude overall rates and sex-specific rates of fractures were calculated for the MG and comparator groups, as well as rates of specific fractures. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression. Results: Among 3,823 incident MG patients (followed for a mean of 5 years), 188 (4.9%) experienced a fracture compared with 741 (4.8%) fractures amongst 15,292 matched comparators. Crude fracture rates were not different between the MG cohort and matched comparators (8.71 vs. 7.98 per 1000 patient years), overall and in men and women separately. After controlling for multiple covariates, MG patients had a significantly lower risk of fracture than comparators (HR 0.74, 95% CI 0.63–0.88). Conclusions: In this large, population-based cohort of incident MG patients, MG patients were at lower risk of a major fracture than comparators. The reasons for this finding are unclear but may highlight the importance osteoporosis prevention.

scholarly journals Prognostic impact of elevated lactate levels on mortality in critically ill patients with and without preadmission metformin treatment: a Danish registry-based cohort study

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rene A. Posma ◽  
Trine Frøslev ◽  
Bente Jespersen ◽  
Iwan C. C. van der Horst ◽  
Daan J. Touw ◽  
...  
Keyword(s):  
Cohort Study ◽  
Mortality Rate ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Cox Regression ◽  
Lower Mortality ◽  
Prognostic Impact ◽  
Icu Admission ◽  
Lactate Levels ◽  
Restricted Cubic Splines

Abstract Background Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher lactate levels at ICU admission without a concomitant increase in mortality. However, this has not been investigated in a larger cohort. We aimed to determine whether the association between lactate levels around ICU admission and mortality is different in metformin users compared to metformin nonusers. Methods This cohort study included patients admitted to ICUs in northern Denmark between January 2010 and August 2017 with any circulating lactate measured around ICU admission, which was defined as 12 h before until 6 h after admission. The association between the mean of the lactate levels measured during this period and 30-day mortality was determined for metformin users and nonusers by modelling restricted cubic splines obtained from a Cox regression model. Results Of 37,293 included patients, 3183 (9%) used metformin. The median (interquartile range) lactate level was 1.8 (1.2–3.2) in metformin users and 1.6 (1.0–2.7) mmol/L in metformin nonusers. Lactate levels were strongly associated with mortality for both metformin users and nonusers. However, the association of lactate with mortality was different for metformin users, with a lower mortality rate in metformin users than in nonusers when admitted with similar lactate levels. This was observed over the whole range of lactate levels, and consequently, the relation of lactate with mortality was shifted rightwards for metformin users. Conclusion In this large observational cohort of critically ill patients, early lactate levels were strongly associated with mortality. Irrespective of the degree of hyperlactataemia, similar lactate levels were associated with a lower mortality rate in metformin users compared with metformin nonusers. Therefore, lactate levels around ICU admission should be interpreted according to metformin use.

scholarly journals Poverty and survival from COVID-19 in Mexico

2020 ◽  
Author(s):  
Rebeca Olivia Millán-Guerrero ◽  
Ramiro Caballero-Hoyos ◽  
Joel Monárrez-Espino
Keyword(s):  
Cox Regression ◽  
Secondary Data ◽  
Multidimensional Poverty ◽  
Preventive Strategy ◽  
Poverty Level ◽  
Factors Affecting ◽  
Extreme Poverty ◽  
Lower Survival ◽  
Hazard Ratios ◽  
Poverty And Inequality

Abstract Background Recent evidence points to the relevance of poverty and inequality as factors affecting the spread and mortality of the COVID-19 pandemic in Latin America. This study aimed to determine whether COVID-19 patients living in Mexican municipalities with high levels of poverty have a lower survival compared with those living in municipalities with low levels. Methods Retrospective cohort study. Secondary data was used to define the exposure (multidimensional poverty level) and outcome (survival time) among patients diagnosed with COVID-19 between 27 February and 1 July 2020. Crude and adjusted hazard ratios (HR) from Cox regression were computed. Results Nearly 250 000 COVID-19 patients were included. Mortality was 12.3% reaching 59.3% in patients with ≥1 comorbidities. Multivariate survival analyses revealed that individuals living in municipalities with extreme poverty had 9% higher risk of dying at any given time proportionally to those living in municipalities classified as not poor (HR 1.09; 95% CI 1.06–1.12). The survival gap widened with the follow-up time up to the third to fourth weeks after diagnosis. Conclusion Evidence suggests that the poorest population groups have a lower survival from COVID-19. Thus, combating extreme poverty should be a central preventive strategy.

scholarly journals Angiogenin—A Proposed Biomarker for Cardiovascular Disease—Is Not Associated With Long-Term Survival in Patients With Peripheral Artery Disease

Angiology ◽  
2021 ◽  
pp. 000331972110043
Author(s):  
Clemens Höbaus ◽  
Gerfried Pesau ◽  
Bernhard Zierfuss ◽  
Renate Koppensteiner ◽  
Gerit-Holger Schernthaner
Keyword(s):  
Peripheral Artery Disease ◽  
Cox Regression ◽  
Ankle Brachial Index ◽  
Limb Ischemia ◽  
Cross Sectional Study ◽  
Enzyme Linked Immunosorbent Assay ◽  
Peripheral Artery ◽  
Cross Sectional ◽  
Term Survival ◽  
Artery Disease

We evaluated angiogenin as a prospective biomarker in peripheral artery disease (PAD) patients with and without claudication symptoms. A pilot study suggested an elevation of angiogenin in critical limb ischemia. However, in PAD patients, the predictive value of angiogenin has not yet been evaluated. For this purpose, 342 patients with PAD (age: 69 ± 10 years, 34.5% women) were followed-up for 7 years in a cross-sectional study. Angiogenin was measured by enzyme-linked immunosorbent assay. All-cause and cardiovascular mortality were analyzed by Cox regression. Angiogenin levels were higher in men ( P = .001) and were associated with patient waist-to-hip ratio ( P < .001), fasting triglycerides ( P = .011), and inversely with estimated glomerular filtration rate ( P = .009). However, angiogenin showed no association with age, characteristics of diabetes, markers of lipid metabolism, or C-reactive protein. Angiogenin did not correlate with markers of angiogenesis such as vascular endothelial growth factor, angiopoietin-2, or tie-2. Furthermore, angiogenin was not associated with PAD Fontaine stages or with patient ankle-brachial index in addition to all-cause mortality (hazard ratio [HR] = 1.09 [95% CI: 0.89-1.34]) or cardiovascular morality (HR = 1.05 [0.82-1.35]). These results suggest that angiogenin does not provide further information regarding outcome prediction in patients with PAD.

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