scholarly journals Post-load glucose spike is a determinant of post-MI prognosis in patients without known or newly diagnosed diabetes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Chattopadhyay ◽  
A George ◽  
J John ◽  
T Sathyapalan
Keyword(s):  
Plasma Glucose ◽  
Cohort Analysis ◽  
Categorical Variables ◽  
Rank Test ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Free Survival ◽  
Net Reclassification Improvement ◽  
Group 2 ◽  
Group 1

Abstract Background Post-prandial plasma glucose spikes contribute to the progression of atherosclerosis. Glycaemic variability may predict post-ACS prognosis. A third to two-thirds of these patients had diabetes mellitus (DM). Post-ACS prognosis is worse in DM than in those without. This has not been tested in patients without DM. Purpose To test whether post-load spike in plasma glucose in patients without known or newly diagnosed DM adversely affects prognosis. Methods Retrospective cohort analysis of 847 MI survivors without known or newly diagnosed DM who were followed up for MACE (death and non-fatal MI). The median post-glucose spike (PGS, defined as the difference between the 2h-PG and FPG) was 2.4 mmol/l for the whole cohort and 1.5 mmol/l for the patients with normal glucose tolerance (NGT). Group 1: PGS ≤2.4 mmol/l and Group 2: PGS >2.4 mmom/l were compared using Mann-Whitney test for continuous variables and chi-squared test for categorical variables. Event free survival in the two groups was estimated from the Kaplan–Meier curves and compared using log-rank test. Cox proportional hazard regression identified predictors of MACE. Continuous net reclassification improvement (NRI>0) and integrated discrimination improvement (IDI) and c-statistics determined the added predictive value of glycaemic matrices Results MACE was higher in group 2 (OR 1.99, 95% CI 1.36 to 2.91, p=0.0004) compared to group 1. In patients with NGT, MACE was higher in patients with PGS ≥1.5 mmol/l vs those below (OR 2.37, 95% CI 1.31 to 4.26, p=0.0041). Event free survival was worse in pre-diabetes than in the NGT groups (HR 1.57, 95% CI 1.17 to 2.12, p=0.003). and in group 2 than 1 (HR 2.01, 95% CI 1.49 to 2.71, p<0.001). Amongst the patients with NGT, event free survival was worse in patients with PGS ≥1.5 mmol/l (HR 2.09, 95% CI 1.35 to 3.25, p<0.001). PGS independently predicted MACE in the whole cohort (HR 1.16, 95% CI 1.06 to 1.26, p=0.002) and NGT group (HR 2.06, 95% 1.51 to 2.79, p<0.000). Group 2 independently predicted MACE in the whole cohort (HR 1.75, 95% CI 1.26 to 2.42, p<0.001). In the NGT group, PGS >median, independently predicted of MACE (HR 2.67, 95% CI 1.54 to 4.61, p<0.001). The c-statistic a model containing GRS only increased on addition of PGS (δAUC 0.0134, p=0.046) but not on addition of FPG. Within the whole cohort, PGS improved the net reclassification by 28% when added to the model containing GRS only. NGT cohort had higher net improvement at 46.6%. Addition of PGS to the model containing GRS and FPG resulted in NRI>0 of 25.5% in the whole cohort and 56.3% in the NGT cohort. Similar changes were seen in the IDI. Conclusion(s) PGS predicts post MI prognosis in patients without known or newly diagnosed DM including in patients with NGT. This suggests that PGS is a more powerful indicator of post-MI prognosis than FPG Funding Acknowledgement Type of funding source: None

Does high-normal 2-hour post load plasma glucose after myocardial infarction in patients with normal glucose tolerance adversely affect prognosis?

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Chattopadhyay ◽  
A George ◽  
J John ◽  
T Sathyapalan
Keyword(s):  
Glucose Tolerance ◽  
Plasma Glucose ◽  
Cohort Analysis ◽  
Normal Glucose Tolerance ◽  
Rank Test ◽  
Free Survival ◽  
Net Reclassification Improvement ◽  
Normal Glucose ◽  
Group 2 ◽  
Group 1

Abstract Background Type 2 diabetes mellitus (DM) and pre-DM, newly diagnosed after MI in patients without known DM adversely affects prognosis. 2-hour post-load glucose (2h-PG) predicts post-MI prognosis better than fasting plasma glucose (FPG). Plasma glucose below the conventional threshold for the diagnosis of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), affects post-MI prognosis. Purpose To test whether high-normal post-load plasma glucose in patients with normal glucose tolerance (NGT) would affect post-MI prognosis and whether FPG or 2h-PG increases this risk. Methods Retrospective cohort analysis of 425 MI survivors without known DM and with NGT followed up for (death and non-fatal MI) as MACE. MACE in patients with 2h-PG > median for the whole cohort (Group 2), was compared with those at or below (Group 1). Event free survival in the two groups was estimated from the Kaplan–Meier curves and compared using log-rank test. Cox proportional hazard regression identified predictors of MACE. Continuous net reclassification improvement (NRI>0) and integrated discrimination improvement (IDI) and c-statistics determined the added predictive value of glycaemic matrices. Results Median 2h-PG was 6.3 mmol/l. 219 patients in Group 1 and 206 in Group 2. Group 2 had higher age, prevalence of hypertension, hypercholesterolaemia, ST-segment depression and higher heart rate and GRACE scores. Median follow-up was 40.6 months. MACE was more frequent in Group 2 than Group 1 (OR 2.82, 95% CI 1.55 to 5.16, p<0.001). MACE-free survival was higher in Group 1 (HR 2.43, 95% CI 1.53 to 3.85, p<0.001). Group 2 (HR 2.42, 95% CI 1.44 to 4.04, p<0.001) predicted the MACE-free survival. 2h-PG, but not the FPG independently predicted of MACE (HR 1.73, 95% CI 1.31 to 2.30, p<0.001). Addition of 2h-PG to models containing FPG and other variables improved their predictive performance (NRI>0 0.5062, p<0.001; IDI 0.0376, p=0.003). The c-statistic increased when 2h-PG was added to the GRACE score only model (δAUC 0.037, 95% CI 0.012 to 0.081, p=0.046). Conclusion(s) This study suggests that “high-normal” 2h-PG is an independent predictor of post-MI prognosis. Normoglycaemic patients with 2h-PG ≥6.4 mmol/l, had worse post-MI prognosis compared to those with 2h-PG ≤6.3 mmol/l. The risk of MACE increased with increasing 2h-PG within the normal range. FPG had no effect on prognosis. Funding Acknowledgement Type of funding source: None

Abstract 3652: Coronary Heart Disease Prevention in Women: The Prognostic Significance of Subclinical Atherosclerosis by Carotid Ultrasound

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Kwame O Akosah ◽  
Vicki L McHugh ◽  
Michelle A Mathiason
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Carotid Atherosclerosis ◽  
Prognostic Significance ◽  
Main Body ◽  
Carotid Ultrasound ◽  
Event Free Survival ◽  
Free Survival ◽  
Group 2 ◽  
Group 1

Background : The difficulty of coronary heart disease (CHD) prevention in women is recognized. Reasons include gender disparities in accuracy rates of current diagnostic tests and clinical presentation. Objective : Assess the utility and prognostic significance of carotid atherosclerosis in predicting CHD in women. Methods : Women (n=140) scheduled for elective coronary angiography underwent carotid ultrasound and fasting lipid analysis. Subjects were excluded for age (≥ 65), prior history of CHD, and anti-lipid therapy. Severe coronary artery disease (CAD) was defined as stenosis ≥ 50%. Carotid atherosclerosis was defined as IMT ≥ 1 mm in the main body or focal plaque in the main body or bulb. Subjects were followed for a median of 50 months. Future cardiovascular events (CVEs) were defined as Major (death, MI, and stroke), and Any event (Major, revascularization, and new onset heart failure). Results: 136 women (mean age 53 ± 8) had all data available. 80% (n=108) of subjects were classified as low risk and 1% (n=2) as intermediate risk per Framingham score, with an additional 19% (n=26) having CHD equivalent conditions. Severe CAD was present in 39 (28%) subjects. Carotid atherosclerosis had a sensitivity of 74%, specificity of 49%, and negative predictive value of 83% for CAD. Subjects were categorized into Group 1 (Carotid atherosclerosis, n=79) and Group 2 (no carotid atherosclerosis, n=57). After median follow-up of 50 months, 6 women experienced Major CVEs (Group 1 n = 5; Group 2 n=1). Major event rate for Group 1 was 6.3% vs. 1.8% for Group 2. For Any event, the rates were 22% for Group 1 compared to 9% for Group 2 (p=0.046). The event rates were similar between high-risk (3.8%) and low-risk (3.7%) for Major and 12% vs. 16 % for Any event. Kaplan-Meier survival analysis reveals that women without diagnosis of carotid atherosclerosis enjoyed significantly better event free survival. Negative predictive values for carotid atherosclerosis in predicting angiographic disease, Major events and Any event were 83%, 91% and 98%, respectively. Conclusion : Carotid atherosclerosis predicts CVEs in young to middle-aged women without high-risk clinical scores. Women without diagnosis of carotid atherosclerosis enjoy excellent long-term event free survival.

Comparison of biochemical recurrence free survival after radical prostatectomy triggered by grade reclassification on active surveillance, and men newly diagnosed with similar grade disease.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5047-5047
Author(s):  
Clarissa P. Diniz ◽  
Ballentine Carter ◽  
Jonathan I. Epstein ◽  
Mufaddal Mamawala
Keyword(s):  
Radical Prostatectomy ◽  
Biochemical Recurrence ◽  
Rank Test ◽  
Recurrence Free Survival ◽  
Newly Diagnosed ◽  
Grade Group ◽  
Free Survival ◽  
Log Rank Test ◽  
Grade Groups ◽  
Group 2

5047 Background: Evaluate the biochemical recurrence free survival (bRFS) in men after radical prostatectomy (RP) triggered by Gleason score (GS) grade reclassification (GR) during active surveillance (AS) in order to inform patient decisions. Methods: We conducted a retrospective analysis of men undergoing RP from 1995 - 2015 at Johns Hopkins and identified 4 groups; 94 men in AS that underwent RP following GR from Gleason score (GS) 6 to GS ≥ 7(3+4) [grade groups ≥ 2], 3,504 men that underwent IRP following a diagnosis of grade groups ≥ 2, 56 men in AS that underwent RP following GR to GS 7(3+4) [grade group 2], and 1,979 men that underwent IRP following a diagnosis of grade group 2. The outcome of interest was bRFS, assessed using Kaplan Meir analysis and a multivariate Cox regression model. Results: Men on AS had a lower PSA density distribution (0.11 vs. 0.13, p = 0.022; 0.12 vs. 0.12, p = 0.043), and a higher proportion of low volume cancers (46.2% vs. 15.3%, 46.4% vs. 16.7%, both p < 0.001) as compared to the IRP groups for both biopsy grade groups ≥ 2 and biopsy grade group 2, respectively. The proportions of men with biochemical recurrence (BCR) in the AS and IRP groups were 13.8% vs. 29.1% (p = 0.008 for grade groups ≥ 2) and 8.9% vs. 21.7% (p = 0.022 for grade group 2), respectively. One, 5, 10-year bRFS for men in the AS group vs the IRP group was 97.9%, 76.6%, 69.0% vs 85.5%, 65.1% ,54.2%%, respectively for biopsy grade groups ≥ 2 (log-rank test, p = 0.009), and 96.4%, 89.6%, 89.6% vs 91.2%, 74.0%, 63.9%, respectively for biopsy grade group 2 (log-rank test, p = 0.071). For biopsy grade groups ≥ 2, there was no significant difference in BCR between groups after adjustment for age at treatment, biopsy extent of cancer, and PSA density; HR = 0.78 (95% CI 0.43 – 1.43, p = 0.426). Conclusions: AS patients that are reclassified to grade groups ≥ 2 have no greater risk of treatment failure as compared to men newly diagnosed with similar grades. These data could help inform decisions regarding management of low grade prostate cancer.

Continued improvement in survival in multiple myeloma (MM) including high-risk patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8039-8039 ◽  
Author(s):  
Bharat Nandakumar ◽  
Moritz Binder ◽  
Angela Dispenzieri ◽  
Prashant Kapoor ◽  
Francis Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Staging System ◽  
Initial Therapy ◽  
Rank Test ◽  
Newly Diagnosed ◽  
Group 3 ◽  
Group 2 ◽  
Improvement In Survival ◽  
Group 1

8039 Background: Treatment of MM has evolved significantly over the past decade, with increasing use of multi-drug combinations for initial therapy. In addition, supportive care approaches have also improved. We examined how these improvements have translated to survival outcomes in patients with newly diagnosed MM. Methods: Patients (n=3449) with a diagnosis of MM made between 2004 and 2017 and seen at Mayo Clinic within six months of the diagnosis, were included in this analysis. Patients were divided into three groups based on the year of diagnosis; group 1- 2004-07 (n=831), group 2-2008-12 (n=1161), and group 3-2013-17 (n=1457). Survival of the groups were estimated using Kaplan-Meier method, and compared using log rank test. Results: The median age was 64 years (22 to 96); 60% were male and 40% were female. 14% were >75 years, 33% were aged 65-75 and 53% were <65 years. The median overall survival for the whole cohort was 5.7 years (95%CI; 5.4, 6.3). The median OS for the groups 1, 2 and 3 were 3.9, 6.3 and NR, respectively; p<0.001. The 4-year survival estimates were 50%, 62%, and 75%, respectively. We then explored the improvements in patient subgroups. While all patients experienced improvements in OS over time, improvement in group 3 was most prominent for those >75 years. In patients <65 years, the 4-yr OS for groups 1, 2 and 3 were 57, 71, and 79% respectively. In patients 65-75 years of age, the 4-yr OS for groups 1, 2 and 3 were 48, 60, and 75% respectively. In patients >75 years, the 4-yr OS for groups 1, 2 and 3 were 24, 35, and 56% respectively. While patients with high-risk disease did not see as much benefit in the earlier period, substantial progress was seen in the last group. The 3-yr OS for patients with high-risk cytogenetics were 52, 55, and 73% for groups 1, 2 and 3 compared to 67, 75, and 85% for standard-risk cytogenetics respectively. 2067 patients were staged according to the International Staging System and the median OS for stages 1, 2 and 3 were 6.5, 4.6 and 2.4 in group 1; 9.2, 6.6 and 3.5 in group 2 and NR for any of the stages in group 3. Conclusions: The results confirm continued improvement in survival of newly diagnosed multiple myeloma patients, including elderly and high-risk MM.

scholarly journals Blunted heart rate reserve during dobutamine stress echocardiography is a predictor of outcome in diabetes and/or chronic kidney disease

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
C C A Bellagamba ◽  
M A R Torres
Keyword(s):  
Beta Blockers ◽  
Dobutamine Stress ◽  
Heart Rate Reserve ◽  
Event Free Survival ◽  
Free Survival ◽  
Inducible Ischemia ◽  
Group 3 ◽  
Group 2 ◽  
Post Hoc ◽  
Group 1

Abstract Funding Acknowledgements Type of funding sources: None. Background A blunted heart rate reserve (HRR) during dobutamine stress echo (DSE) is an index of altered cardiac sympathetic reserve, which is frequently present in diabetes mellitus (DM) or chronic kidney disease (CKD). Aim To assess the prognostic value of HRR during DSE. Methods We recruited 280 patients (pts) (mean age 62.9 ± 13.1 years); 128 (45.7%) male; 28.2% on beta-blockers at the time of testing) who underwent DSE for known or suspected coronary artery disease and/or heart failure and were followed-up. Four subsets were identified: Group 1 (111 pts without DM or CKD); group 2 (37 with DM without CKD); group 3 (90 with CKD with or without DM); and group 4 (42 with CKD on dialysis). HRR was calculated by EKG as the peak/rest HR ratio. Results Ischemia was identified in 34/280 (12.1%) pts. During a median follow-up time of 40.3 ± 30.5 months, 120 events occurred: 46 deaths, 15 non-fatal myocardial infarctions, 23 hospital admissions for acute decompensated heart failure, and 36 myocardial revascularizations. Multivariable comparison of HRR among the 4 groups using post hoc test showed a blunted HRR in group 3 (1.66 ± 0.32) and 4 (1.65 ± 0.27) when compared with group 1 (HRR 1.85 ± 0.35), p &lt; 0.01. Group 2 (1.73 ± 0.28) was not different from any group (p = ns). Groups 3 and 4 were not different between them (p = ns). A post hoc Tukey test for HRR separated in tercils, 1st: HRR &lt; 1.59, 2nd: 1.59 &lt; HRR &lt; 1.86 and 3rd: HRR &gt; 1.86 (p &lt; 0.000). Kaplan-Meier curves showed blunted HRR as an independent predictor of event-free survival in the overall group - 1st: 66.08 ± 5.9 months, 95% CI 54.3-77.7; 2nd: 69.52 ± 6.5, 95% CI 56.6-82.3; 3rd: 90.05 ± 5.3, 95% CI 79.5-100.5. See Figure. HRR was comparable in patients with and without inducible ischemia and off or on beta-blockers. Conclusion A blunted HRR during DSE is frequent in patients with DM and CKD, independent of inducible ischemia and use of beta-blockers, and is a useful non-imaging predictor of adverse events. Abstract Figure. HR ratio and event-free survival curves

Immediate and long-term results of the first line chemotherapy in patients with metastatic triple negative breast cancer. Final analysis of randomized study

2020 ◽  
pp. 75-80
Author(s):  
S.A. Lyalkin ◽  
◽  
L.A. Syvak ◽  
N.O. Verevkina ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Randomized Study ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Group 2 ◽  
Line Chemotherapy ◽  
Group 1

The objective: was to evaluate the efficacy of the first line chemotherapy in patients with metastatic triple negative breast cancer (TNBC). Materials and methods. Open randomized study was performed including 122 patients with metastatic TNBC. The efficacy and safety of the first line chemotherapy of regimens АТ (n=59) – group 1, patients received doxorubicine 60 мг/м2 and paclitaxel 175 мг/м2 and ТР (n=63) – group 2, patients received paclitaxel 175 мг/м2 and carboplatin AUC 5 were evaluated. Results. The median duration of response was 9.5 months (4.5–13.25 months) in patients received AT regimen and 8.5 months (4.7–12.25 months), in TP regimen; no statistically significant differences were observed, р=0.836. The median progression free survival was 7 months (95% CI 5–26 months) in group 1 and 7.5 months (95% CI 6–35 months) in group 2, p=0.85. Both chemotherapy regimens (AT and TP) had mild or moderate toxicity profiles (grade 1 or 2 in most patients). No significant difference in gastrointestinal toxicity was observed. The incidence of grade 3–4 neutropenia was higher in patients of group 2 (TP regimen): 42.8% versus 27% (р<0.05). Conclusions. Both regimens of chemotherapy (AT and TP) are appropriate to use in the first line setting in patients with metastatic TNBC. Key words: metastatic triple negative breast cancer, chemotherapy, progression free survival, chemotherapy toxicity.

The Relationship between Serum Ferritin Levels and 5-Year All-Cause Mortality in Hemodialysis Patients

2021 ◽  
pp. 1-7
Author(s):  
Emre Erdem ◽  
Ahmet Karatas ◽  
Tevfik Ecder
Keyword(s):  
Serum Ferritin ◽  
Hemodialysis Patients ◽  
Rank Test ◽  
Significant Difference ◽  
All Cause Mortality ◽  
Group 3 ◽  
Group 2 ◽  
The Relationship ◽  
Group 1

<b><i>Introduction:</i></b> The effect of high serum ferritin levels on long-term mortality in hemodialysis patients is unknown. The relationship between serum ferritin levels and 5-year all-cause mortality in hemodialysis patients was investigated in this study. <b><i>Methods:</i></b> A total of 173 prevalent hemodialysis patients were included in this study. The patients were followed for up to 5 years and divided into 3 groups according to time-averaged serum ferritin levels (group 1: serum ferritin &#x3c;800 ng/mL, group 2: serum ferritin 800–1,500 ng/mL, and group 3: serum ferritin &#x3e;1,500 ng/mL). Along with the serum ferritin levels, other clinical and laboratory variables that may affect mortality were also included in the Cox proportional-hazards regression analysis. <b><i>Results:</i></b> Eighty-one (47%) patients died during the 5-year follow-up period. The median follow-up time was 38 (17.5–60) months. The 5-year survival rates of groups 1, 2, and 3 were 44, 64, and 27%, respectively. In group 3, the survival was lower than in groups 1 and 2 (log-rank test, <i>p</i> = 0.002). In group 1, the mortality was significantly lower than in group 3 (HR [95% CI]: 0.16 [0.05–0.49]; <i>p</i> = 0.001). In group 2, the mortality was also lower than in group 3 (HR [95% CI]: 0.32 [0.12–0.88]; <i>p</i> = 0.026). No significant difference in mortality between groups 1 and 2 was found (HR [95% CI]: 0.49 [0.23–1.04]; <i>p</i> = 0.063). <b><i>Conclusion:</i></b> Time-averaged serum ferritin levels &#x3e;1,500 ng/mL in hemodialysis patients are associated with an increased 5-year all-cause mortality risk.

scholarly journals Oral Metronomic Maintenance Therapy Can Improve Survival in High-Risk Neuroblastoma Patients Not Treated with ASCT or Anti-GD2 Antibodies

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3494
Author(s):  
Xiaofei Sun ◽  
Zijun Zhen ◽  
Ying Guo ◽  
Yuanhong Gao ◽  
Juan Wang ◽  
...  
Keyword(s):  
High Risk ◽  
Conventional Treatment ◽  
Maintenance Treatment ◽  
Antibody Therapy ◽  
Aggressive Treatment ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Free Survival ◽  
Stage 4 ◽  
Risk Patients

Despite aggressive treatment, the prognosis of high-risk NB patients is still poor. This retrospective study investigated the benefits of metronomic maintenance treatment (MT) in high-risk NB patients without ASCT or GD2 antibody therapy. Patients aged ≤ 21 years with newly diagnosed high-risk NB were included. Patients with complete/very good partial remission (CR/VGPR/PR) to conventional treatment received, or not, oral metronomic MT for 1 year. Two hundred and seventeen high-risk NB patients were enrolled. One hundred and eighty-five (85%) had a CR/VGPR/PR to conventional treatment, of the patients with stage 4, 106 receiving and 61 not receiving oral metronomic MT, and the 3-year event-free survival (EFS) rate was 42.5 ± 5.1% and 29.6 ± 6%, respectively (p = 0.017), and overall survival (OS) rate was 71.1 ± 4.7% and 59.4 ± 6.4%, respectively (p = 0.022). A total of 117 high-risk patients with oral metronomic MT had EFS rate of 42.7 ± 4.8%. The toxicity of MT was mild. For high-risk NB patients without ASCT or anti-GD2 antibody therapy, stage 4, MYCN amplication and patients with stage 4 not receiving oral metronomic MT after CR/VGPR/PR were independent adverse prognostic factors. Oral metronomic MT can improve survival in high-risk NB patients in CR/VGPR/PR without ASCT or anti-GD2 antibodies therapy.

Retrospective cohort analysis of real-world clinical outcomes in nonmetastatic (M0) castration-resistant prostate cancer (CRPC) treated with novel androgen receptor pathway inhibitors (ARPI).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 51-51
Author(s):  
Richard Gagnon ◽  
Nimira S. Alimohamed ◽  
Alexander Watson ◽  
Eugene Batuyong ◽  
Alyssa Chow ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Real World ◽  
Retrospective Cohort ◽  
Cohort Analysis ◽  
Progression Free Survival ◽  
Rank Test ◽  
Castration Resistant Prostate Cancer ◽  
Survival Times ◽  
Free Survival

51 Background: The landscape of M0 CRPC has changed with the recent demonstration of metastasis-free survival (MFS) and overall survival (OS) improvements with the use of ARPIs in clinical trial settings. However, the extrapolation of this data to clinical practice is limited by strict exclusion criteria in these trials, including prior or concurrent malignancy, cardiovascular disease, or hypertension. The purpose of this study was to assess real-world outcomes in patients with M0 CRPC treated with ARPIs compared to historical controls. Methods: We designed a retrospective cohort study with the inclusion of patients in Alberta, Canada diagnosed with M0 CRPC between 2001-2020. Via chart review, we identified baseline characteristics, potential confounders, treatment details, and clinical outcomes. The primary outcome of interest was MFS. Secondary outcomes included: second progression-free survival (PFS2) and OS. Median survival times were measured using the Kaplan-Meier method and the log-rank test was used for comparison of outcomes based on ARPI exposure. Cox proportional hazard regression models were used to calculate hazard ratios (HR) accounting for impact of PSA doubling time (PSADT), use of osteoclast inhibiting agents, and presence of pelvic lymphadenopathy. Results: We identified 211 patients across multiple centres in Alberta with M0 CRPC, with 54 having received apalutamide (40/54), enzalutamide (7/54), or darolutamide (7/54). Median age at M0 CRPC diagnosis was 74 years; median PSADT was 4.4 months; and 19% of patients (40/211) had pelvic lymphadenopathy at diagnosis. Median MFS in patients treated with ARPIs was 47.5 months compared to 20.6 months in those not treated with ARPIs (HR, 0.23; 95% confidence interval [CI], 0.11-0.49; p < 0.001). Median PFS2 in ARPI treated patients was 66.3 months compared with 35.6 months (HR, 0.40; 95% CI, 0.18-0.87; p = 0.022). Median OS for patients treated with ARPI was not reached. Conclusions: Given the older age of men with advanced prostate cancer, real-world outcomes that include patients with comorbidities are important adjuncts to the interpretation of clinical trials exploring the benefit of novel therapeutics. Here, we demonstrate that in a real-world, unselected population of men with M0 CRPC, apalutamide, enzalutamide, and darolutamide seem to confer similar MFS and PFS2 benefits to those demonstrated in the SPARTAN, PROSPER, and ARAMIS studies. Real-world OS data remain immature and will be an important addition to these findings.

Clinical significance of translocation t(1;19) in childhood acute lymphoblastic leukemia in the context of contemporary therapies: a report from the Children's Cancer Group.

1998 ◽  
Vol 16 (2) ◽  
pp. 527-535 ◽  
Author(s):  
F M Uckun ◽  
M G Sensel ◽  
H N Sather ◽  
P S Gaynon ◽  
D C Arthur ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Free Survival ◽  
Cancer Group ◽  
Improved Outcomes ◽  
B Lineage ◽  
The Individual

PURPOSE The nonrandom translocation t(1;19) has been associated with poor outcome in pediatric B-lineage acute lymphoblastic leukemia (ALL). Because most patients treated by contemporary therapies now achieve improved outcomes, we have reassessed the prognostic significance of t(1;19). PATIENTS AND METHODS Cytogenetic data were accepted for 1,322 children (<21 years old) with newly diagnosed ALL enrolled between 1988 and 1994 on risk-adjusted studies of the Children's Cancer Group (CCG). Forty-seven patients (3.6%) were t(1;19) positive (+); 1,275 (96.4%) were t(1;19) negative (-). Clinical characteristics and treatment outcome were compared using standard methods. RESULTS Translocation (1;19)+ patients were more likely than t(1;19)- patients to be 10 years of age or greater (P < .001) or CD10+ CD19+ CD34- (P < .0001), or nonwhite (P = .02). Patients with a balanced t(1;19) were less likely to be hyperdiploid than patients with an unbalanced der(19)t(1;19). Event-free survival (EFS) was similar for the overall group of t(1;19)+ and t(1;19)- patients, with 4-year estimates of 69.5% (SD, 6.8%) and 74.8% (SD, 1.3%; P = .48), respectively. However, patients with unbalanced der(19)t(1;19) had significantly better outcomes than patients with balanced t(1;19): 4-year EFS were 80.6% (SD, 7.1%) and 41.7% (SD, 13.5%), respectively (P = .003). These differences were maintained within the individual studies analyses and after exclusion of t(1;19)+ patients whose cells were hyperdiploid with more than 50 chromosomes. CONCLUSION The overall group of t(1;19)+ patients, as well as the subgroup with an unbalanced der(19)+ (1;19) had outcomes similar to that of t(1;19)- patients, whereas patients with balanced t(1;19) had poorer outcomes. Thus, although the overall prognostic significance of t(1;19) has been obviated by contemporary risk-adjusted protocols, the balanced t(1;19) translocation remains an adverse prognostic factor.

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