scholarly journals Heterogeneous Definitions of Secondary Acute Myeloid Leukemia (AML) Yield Distinct Outcomes in Response to First-Line Treatment with Hypomethylating Agents (HMA) and Venetoclax (Ven)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1216-1216
Author(s):  
Irena Tan ◽  
Matthew Schwede ◽  
Paul Phan ◽  
Raymond Yin ◽  
Tian Y Zhang ◽  
...  
Keyword(s):  
Real World ◽  
Proportional Hazards ◽  
De Novo ◽  
Hematologic Malignancy ◽  
Cox Proportional Hazards ◽  
Secondary Mutation ◽  
Mutation Profile ◽  
Significant Difference ◽  
De Novo Aml

Abstract Background: The combination of HMA and venetoclax is now standard of care for patients with AML who are not candidates for intensive chemotherapy. Elderly patients are more likely to have secondary AML (sAML), although the presence of an antecedent hematologic malignancy is often not apparent by history. Lindsley et al (Blood, 2015) showed that a somatic mutation in SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 is >95% specific for sAML and associated with worse outcomes. While outcomes with HMA/ven in patients meeting standard criteria for sAML have recently been reported (Pullarkat, ASCO 2021), we set out to conduct a real-world analysis of sAML patients receiving HMA/ven, including those with a secondary mutation profile (SMP) as described by Lindsley et al. We hypothesized that-when treated with HMA/ven-outcomes of patients with SMP may be most similar to those with de novo AML. Methods: Patients diagnosed with AML at Stanford Cancer Institute from 4/2017-3/2021 and treated with front-line HMA/ven were retrospectively reviewed. These included patients previously treated with HMA monotherapy for an antecedent hematologic malignancy and those who had previously received ≤ 3 cycles of HMA monotherapy for AML. Responses were classified per the modified International Working Group response criteria. Overall survival (OS) was assessed for all patients, and for patients who had a complete response (CR) or CR with incomplete hematologic recovery (CRi), duration of response (DoR) was also assessed. Statistical analyses were performed in R using the logrank test, with hazard ratios (HR) computed using the Cox proportional hazards model. For multivariate analyses, p-values for a specific variable were calculated using Cox proportional hazards regression. Results: 82 patients met criteria for inclusion; 78 had valid response assessments and 49 (62.8%) had achieved a CR or CRi at first response assessment. Median age was 72 years, with 3 patients younger than 60. 62 patients were male, median ECOG performance status (PS) was 1, median Charlson Comorbidity Index (CCI) was 6, median time to death or end of follow-up from the start of treatment was 366 days, and 58% of patients had adverse risk AML per ELN guidelines. Fig 1a demonstrates demographics for de novo, sAML (excluding SMP), and patients with SMP AML. 13 patients met criteria for AML-MRC, 23 patients had prior history of antecedent hematologic malignancy (18 with MDS or CMML, 5 with MDS/MPN overlap or MPN), 12 had tAML, and 20 patients possessed a SMP and did not meet criteria for the other three categories of sAML. 14 patients with de novo AML were characterized by the absence of any of the above factors. Patients with de novo AML were less likely to have adverse risk disease (29% vs. 64% in others) and had lower CCI scores (mean 5.1 vs. 6.2) but had no significant differences in age, gender, follow-up time, or PS. There was no statistically significant difference in rates of CR/CRi between the different subgroups or the different types of sAML; 69% of patients with de novo AML, 79% of SMP patients, and 57% of patients with other types of sAML achieved a CR or CRi. However, SMP patients had response durations and OS patterns similar to patients with de novo AML (Fig 1b and 1c), and when grouped with de novo patients, both DoR (HR = 3.5, p = 0.047, Fig 1d) and OS (HR = 2.1, p = 0.042, Fig 1e) were significantly longer than those of the sAML patients. Neither DoR nor OS were significantly longer when the SMP patients were grouped with sAML patients (respectively: HR = 3.3, p = 0.22, Fig 1f; HR = 1.5, p = 0.37, Fig 1g). In multivariate Cox proportional regression adjusting for age, ELN risk category, CCI, and PS, worse OS for sAML patients was maintained relative to the SMP and de novo patients (HR 2.9, p = 0.036), although the difference in DoR was no longer significant (HR 4.4, p= 0.10). Conclusions: Patients meeting standard definitions of sAML had worse outcomes than those with de novo AML when treated with HMA/ven in a retrospective, real-world analysis. Although a secondary mutation profile as described by Lindsley et al may be helpful in identifying patients with sAML, when treated with HMA/ven, patients with this profile have outcomes that align more closely with those of patients with de novo AML. Figure 1 Figure 1. Disclosures Mannis: Astex, Forty Seven Inc/Gilead, Glycomimetics, and Jazz Pharmaceuticals: Research Funding; AbbVie, Agios, Astellas Pharma, Bristol Myers Squibb, Genentech, MacroGenics, Pfizer, and Stemline: Consultancy.

The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis

2021 ◽  
pp. 1-9
Author(s):  
Leonard Naymagon ◽  
Douglas Tremblay ◽  
John Mascarenhas
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Significant Difference ◽  
The Impact

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank <i>p</i> = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, <i>p</i> = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.

Abstract 15567: Residual Cholesterol and Cardiovascular Events in Patients With Coronary Artery Disease Under Different Glucose Metabolism Status

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jian-jun Li ◽  
Yexuan Cao ◽  
Hui-Wen Zhang ◽  
Jing-Lu Jin ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Glucose Metabolism ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Significant Difference ◽  
Artery Disease

Introduction: The atherogenicity of residual cholesterol (RC) has been underlined by recent guidelines, which was linked to coronary artery disease (CAD), especially for patients with diabetes mellitus (DM). Hypothesis: This study aimed to examine the prognostic value of plasma RC, clinically presented as triglyceride-rich lipoprotein-cholesterol (TRL-C) or remnant-like lipoprotein particles-cholesterol (RLP-C), in CAD patients with different glucose metabolism status. Methods: Fasting plasma TRL-C and RLP-C levels were directly calculated or measured in 4331 patients with CAD. Patients were followed for incident MACEs for up to 8.6 years and categorized according to both glucose metabolism status [DM, pre-DM, normal glycaemia regulation (NGR)] and RC levels. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals. Results: During a mean follow-up of 5.1 years, 541 (12.5%) MACEs occurred. The risk for MACEs was significantly higher in patients with elevated RC levels after adjustment for potential confounders. No significant difference in MACEs was observed between pre-DM and NGR groups (p>0.05). When stratified by status of glucose metabolism and RC levels, highest levels of RLP-C, calculated and measured TRL-C were significant and independent predictors of developing MACEs in pre-DM (HR: 2.10, 1.98, 1.92, respectively; all p<0.05) and DM (HR: 2.25, 2.00, 2.16, respectively; all p<0.05). Conclusions: In this large cohort study with long-term follow-up, data firstly demonstrated that higher RC levels were significantly associated with the worse prognosis in DM and pre-DM patients with CAD, suggesting RC might be a target for patients with impaired glucose metabolism.

No difference in reoperation rates for nonunions (operative nonunions) in posterior cervical fusions stopping at C7 versus T1/2: a cohort of 875 patients

2021 ◽  
pp. 1-7
Keyword(s):  
Proportional Hazards ◽  
Smoking Status ◽  
Incidence Rates ◽  
Cox Proportional Hazards ◽  
Adjacent Segment ◽  
Spine Registry ◽  
Age At Surgery ◽  
Significant Difference ◽  
Reoperation Rates

OBJECTIVE The challenges of posterior cervical fusions (PCFs) at the cervicothoracic junction (CTJ) are widely known, including the development of adjacent-segment disease by stopping fusions at C7. One solution has been to cross the CTJ (T1/T2) rather than stopping at C7. This approach may have undue consequences, including increased reoperations for symptomatic nonunion (operative nonunion). The authors sought to investigate if there is a difference in operative nonunion in PCFs that stop at C7 versus T1/T2. METHODS A retrospective analysis identified patients from the authors’ spine registry (Kaiser Permanente) who underwent PCFs with caudal fusion levels at C7 and T1/T2. Demographics, diagnoses, operative times, lengths of stay, and reoperations were extracted from the registry. Operative nonunion was adjudicated via chart review. Patients were followed until validated operative nonunion, membership termination, death, or end of study (March 31, 2020). Descriptive statistics and 2-year crude incidence rates and 95% confidence intervals for operative nonunion for PCFs stopping at C7 or T1/T2 were reported. Time-dependent crude and adjusted multivariable Cox proportional hazards models were used to evaluate operative nonunion rates. RESULTS The authors identified 875 patients with PCFs (beginning at C3, C4, C5, or C6) stopping at either C7 (n = 470) or T1/T2 (n = 405) with a mean follow-up time of 4.6 ± 3.3 years and a mean time to operative nonunion of 0.9 ± 0.6 years. There were 17 operative nonunions, and, after adjustment for age at surgery and smoking status, the cumulative incidence rates were similar between constructs stopping at C7 and those that extended to T1/T2 (C7: 1.91% [95% CI 0.88%–3.60%]; T1/T2: 1.98% [95% CI 0.86%–3.85%]). In the crude model and model adjusted for age at surgery and smoking status, no difference in risk for constructs extended to T1/T2 compared to those stopping at C7 was found (adjusted HR 1.09 [95% CI 0.42–2.84], p = 0.86). CONCLUSIONS In one of the largest cohort of patients with PCFs stopping at C7 or T1/T2 with an average follow-up of > 4 years, the authors found no statistically significant difference in reoperation rates for symptomatic nonunion (operative nonunion). This finding shows that there is no added risk of operative nonunion by extending PCFs to T1/T2 or stopping at C7.

Association of circulating tumor cells (CTC) with survival outcomes in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) in a real-world cohort.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 59-59
Author(s):  
Umang Swami ◽  
Taylor Ryan McFarland ◽  
Benjamin Haaland ◽  
Adam Kessel ◽  
Roberto Nussenzveig ◽  
...  
Keyword(s):  
Real World ◽  
Proportional Hazards ◽  
De Novo ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Eligibility Criteria ◽  
Free Survival ◽  
Cox Proportional Hazards Models ◽  
Risk Of Progression ◽  
The Relationship

59 Background: In mCSPC, baseline CTC counts have been shown to correlate with PSA responses and progression free survival (PFS) in small studies in the context of androgen deprivation therapy (ADT) without modern intensification with docetaxel or novel hormonal therapy. Similar correlation of CTC count with PSA responses and PFS was recently reported from an ongoing phase 3 trial in mCSPC setting (SWOG1216) without reporting the association in the context of ADT intensification. Furthermore, none of these studies correlated CTCs with overall survival (OS). Herein we evaluated whether CTCs were associated with outcomes including OS in a real world mCPSC population treated with intensified as well as non-intensified ADT. Methods: Eligibility criteria: new mCSPC receiving ADT with or without intensification and enumeration of baseline CTCs by FDA cleared Cell Search CTC assay. The relationship between CTC counts (categorized as: 0, 1-4, and ≥5/7.5 ml) and both PFS and OS was assessed in the context of Cox proportional hazards models, both unadjusted and adjusted for age, Gleason, PSA at ADT initiation, de novo vs. non-de novo status, and ADT intensification vs. non-intensification therapy. Results: Overall 99 pts were identified. Baseline characteristics are summarized in Table. In unadjusted analyses, CTC counts of ≥5 as compared to 0 were strongly associated with inferior PFS (hazard ratio [HR] 3.38, 95% CI 1.85-6.18; p < 0.001) and OS (HR 4.44 95% CI 1.63-12.10; p = 0.004). In multivariate analyses, CTC counts of ≥5 as compared to 0 continued to be associated with inferior PFS (HR 5.49, 95% CI 2.64-11.43; p < 0.001) and OS (HR 4.00, 95% CI 1.31-12.23; p = 0.015). Within the ADT intensification subgroup also, high CTC counts were associated with poor PFS and OS. For PFS, the univariate HR for CTC ≥5 vs. 0 was 4.87 (95% CI 1.66-14.30; p = 0.004) and multivariate HR for CTC ≥5 vs. 0 was 7.43 (95% CI 1.92-28.82; p = 0.004). For OS, the univariate HR for CTC ≥5 vs. 0 was 15.88 (95% CI 1.93-130.58; p = 0.010) and multivariate HR for CTC ≥5 vs. 0 was 24.86 (95% CI 2.03-304.45; p = 0.012). Conclusions: To best of our knowledge this is the first study to show that high baseline CTC counts are strongly associated with inferior PFS as well as OS in pts with newly diagnosed mCSPC, even in those who received intensified ADT therapy. Identifying these pts at highest risk of progression and death can help with counselling and prognostication in clinics as well as design and enrollment in future clinical trials. [Table: see text]

scholarly journals The Significance of Follow-Up Serum Uric Acid Levels in Predicting All-Cause Mortality and Cardiovascular Mortality in Peritoneal Dialysis Patients

2021 ◽  
Author(s):  
Pingping Ren ◽  
Qilong Zhang ◽  
Yixuan Pan ◽  
Yi Liu ◽  
Chenglin Li ◽  
...  
Keyword(s):  
Uric Acid ◽  
Peritoneal Dialysis ◽  
Serum Uric Acid ◽  
Cardiovascular Mortality ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Kaplan Meier ◽  
Significant Difference ◽  
All Cause Mortality

Abstract Background: Studies on the correlation between serum uric acid (SUA) and all-cause mortality in peritoneal dialysis (PD) patients were mainly based on the results of baseline SUA. We aimed to analyze the change of SUA level post PD, and the correlation between follow-up SUA and prognosis in PD patients. Methods: All patients who received PD catheterization and maintaining PD in our center from March 2, 2001 to March 8, 2017 were screened. Kaplan-Meier and Cox proportional-hazards regression models were used to analyze the effect of SUA levels on the risks of death. We graded SUA levels at baseline, 6 months, 12 months, 18 months and 24 months post PD by mean of SUA plus or minus a standard deviation as cut-off values, and compared all-cause and cardiovascular mortality among patients with different SUA grades. Results: A total of 1402 patients were included, 763 males (54.42%) and 639 females (45.58%). Their average age at PD start was 49.50±14.20 years. The SUA levels were 7.97±1.79mg/dl at baseline, 7.12±1.48mg/dl at 6 months, 7.05±1.33mg/dl at 12 months, 7.01±1.30mg/dl at 18 months, and 6.93±1.26mg/dl at 24 months. During median follow-up time of 31 (18, 49) months, 173 (12.34%) all-cause deaths occurred, including 68 (4.85%) cardiovascular deaths. There were no significant differences on all-cause mortality among groups with graded SUA levels at baseline, 12 months, 18 months and 24 months during follow-up or on cardiovascular mortality among groups with graded SUA levels at baseline, 6 months, 12 months, 18 months and 24 months during follow-up. At 6 months post PD，Kaplan Meier analysis showed there was significant difference on all-cause mortality among graded SUA levels (c2=11.315, P=0.010), and the all-cause mortality was lowest in grade of 5.65mg/dl≤SUA<7.13mg/dl. Conclusion: SUA level decreased during follow up post PD. At 6 months post PD, a grade of 5.65mg/dl≤SUA<7.13mg/dl was appropriate for better patients’ survival.

scholarly journals Docetaxel vs. Novel Hormonal Agent for Upfront Management of De Novo Metastatic Hormone-Sensitive Prostate Cancer: A Comprehensive Report of a Single-Center Experience

2021 ◽  
Author(s):  
Sunny Guin ◽  
Bobby K. Liaw ◽  
Tomi Jun ◽  
Kristin Ayers ◽  
Bonny Patel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Value ◽  
Proportional Hazards ◽  
De Novo ◽  
Standard Of Care ◽  
Cox Proportional Hazards ◽  
Post Treatment ◽  
Real World Data ◽  
Significant Difference ◽  
Hormone Sensitive

Abstract Background: Upfront docetaxel or novel hormonal agents (NHA) such as abiraterone and enzalutamide have become the standard of care for metastatic hormone sensitive prostate cancer (mHSPC). However, data comparing the efficacy of docetaxel and NHAs in this setting are limited.Patients and Methods: This was a retrospective cohort study of patients with de novo mHSPC treated with upfront docetaxel or an NHA between January 1, 2014 and April 30, 2019 within the Mount Sinai Health System. Clinical data were extracted from the medical record. The primary outcome was failure-free survival (FFS), defined as the time to next treatment. The primary predictor was treatment with docetaxel or NHA. FFS was compared between the two groups using the Kaplan Meier method and multivariable Cox proportional hazards models. We additionally assessed the prognostic value of post-treatment PSA.Results: We identified 94 de novo mHSPC patients; 52 and 42 treated with upfront docetaxel and NHAs, respectively. NHAs were associated with significantly longer FFS compared to docetaxel (20.7 vs. 10.1 months, p=0.023). In a multivariable model adjusting for demographics and clinical factors, docetaxel was independently associated with worse FFS compared to NHAs (HR 1.96, 95% CI 1.12−3.45, p=0.019). High metastasis burden patients had a significantly longer FFS with NHAs than docetaxel (25.12 vs. 9.63 months, p=0.014), while there was no significant difference in FFS among low metastasis burden patients (NHA 20.71 vs. Docetaxel 26.5 months, p=0.9). Regardless of treatment, lower post-treatment PSA levels were associated with improved FFS (58.95 vs. 11.57 vs. 9.4 months for PSA ≤0.2, 0.2-0.4, >0.4ng/ml, respectively; p<0.001) Conclusion: Comparative analysis of real-world data demonstrated longer FFS in de novo mHSPC treated with NHA compared to docetaxel. In addition, the depth of PSA response following combination treatment may hold prognostic value for mHSPC outcomes.

P6355The behavior of atrial fibrillation in patients with heart failure hospitalization

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Fukunaga ◽  
K Hirose ◽  
A Isotani ◽  
T Morinaga ◽  
K Ando
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Cardiovascular Disease ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Significant Difference ◽  
The Impact

Abstract Background Relationship between atrial fibrillation (AF) and heart failure (HF) is often compared with proverbial question of which came first, the chicken or the egg. Some patients showing AF at the HF admission result in restoration of sinus rhythm (SR) at discharge. It is not well elucidated that the restoration into SR during hospitalization can render the preventive effect for rehospitalization. Purpose To investigate the impact of restoration into SR during hospitalization for readmission rate of the HF patients showing AF. Methods We enrolled consecutive 640 HF patients hospitalized from January 2015 to December 2015. Patients data were retrospectively investigated from medical record. Patients showing atrial fibrillation on admission but unrecognized ever were defined as “incident AF”; patients with AF diagnosed before admission were defined as “prevalent AF”. Primary endpoint was a composite of death from cardiovascular disease or hospitalization for worsening heart failure. Secondary endpoints were death from cardiovascular disease, unplanned hospitalization related to heart failure, and any hospitalization. Results During mean follow up of 19 months, 139 patients (22%) were categorized as incident AF and 145 patients (23%) were categorized as prevalent AF. Among 239 patients showing AF on admission, 44 patients were discharged in SR (39 patients in incident AF and 5 patients in prevalent AF). Among incident AF patients, the primary composite end point occurred in significantly fewer in those who discharged in SR (19% vs. 42% at 1-year; 23% vs. 53% at 2-year follow-up, p=0.005). To compare the risk factors related to readmission due to HF with the cox proportional-hazards model, AF only during hospitalization [Hazard Ratio (HR)=0.37, p<0.01] and prevalent AF (HR=1.67, p=0.04) was significantly associated. There was no significant difference depending on LVEF. Conclusion Newly diagnosed AF with restoration to SR during hospitalization was a good marker to forecast future prognosis.

Association of mean arterial pressure with all-cause and cardiovascular mortality in young adults

2020 ◽  
Vol 96 (1138) ◽  
pp. 455-460 ◽  
Author(s):  
Shuo Sun ◽  
Kenneth Lo ◽  
Lin Liu ◽  
Jiayi Huang ◽  
Ying Qing Feng ◽  
...  
Keyword(s):  
Young Adults ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Cardiovascular Mortality ◽  
Proportional Hazards ◽  
Continuous Variable ◽  
Cox Proportional Hazards ◽  
Significant Difference ◽  
Cvd Mortality

BackgroundMean arterial pressure (MAP) is a predictor of all-cause and cardiovascular disease (CVD) mortality in middle-aged population and elderly, but less evidence has been shown in young adults.ObjectivesWe examined the associations of MAP with all-cause and CVD mortality in young adults aged between 18 and 40 years.MethodsData were from the National Health and Nutrition Examination Survey (1999–2006) and participants were followed up to 31 December 2015. MAP was categorised by quartiles. Multivariable Cox proportional hazards models and Kaplan-Meier survival curves were performed to estimate the association between MAP, all-cause and CVD mortality.ResultsThere were a total of 8356 (4598 women (55.03%)) participants with the mean age of 26.63±7.01 years, of which 265 (3.17%) and 10 (0.12%) cases of all-cause and cardiovascular mortality occurred during a median follow-up duration of 152.96±30.45 months, respectively. There was no significant difference in the survival rate by MAP quartiles (p=0.058). When MAP was treated as a continuous variable, the multivariable adjusted HRs for all-cause and CVD mortality were 1.00 (95% CI 0.96 to 1.04; p=0.910) and 0.94 (95% CI 0.77 to 1.14; p=0.529), respectively. When using the lowest quartile (Q1) as referent, the adjusted HRs for all-cause mortality from Q2 to Q4 were 1.16 (95% CI 0.56 to 2.42), 1.06 (95% CI 0.48 to 2.32) and 0.91 (95% CI 0.37 to 2.24; p for tend was 0.749) after adjusting for potential confounders.ConclusionThere was no significant association of MAP with all-cause and CVD mortality in young adults with a relatively short follow-up time.

Real-world outcomes in recurrent versus de novo metastatic pancreatic adenocarcinoma.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 387-387
Author(s):  
Laura Miotke ◽  
Christopher Duane Nevala-Plagemann ◽  
Jian Ying ◽  
Vaia Florou ◽  
Benjamin Haaland ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Proportional Hazards ◽  
De Novo ◽  
Recurrent Disease ◽  
Smoking Status ◽  
Single Agent ◽  
Clinic Visit ◽  
Cox Proportional Hazards ◽  
Ductal Adenocarcinoma ◽  
Significant Difference

387 Background: Optimal management of patients with recurrent pancreatic ductal adenocarcinoma (PDAC) is unknown. In the clinical trials that established a survival benefit with combination chemotherapy compared to single agent gemcitabine, patients with recurrent PDAC were either excluded (PRODIGE-4) or severely underrepresented (MPACT). In this study, we evaluated clinical outcomes of recurrent PDAC patients who receive systemic therapy and compared outcomes to patients with de novo advanced PDAC. Methods: Patients diagnosed with advanced PDAC between 2014 and October of 2019 were included using the nationwide Flatiron Health EHR-derived de-identified database. Patients without a clinic visit or initiation of treatment within 90 days of diagnosis were excluded. Patients were characterized as either de novo or recurrent PDAC based on stage at diagnosis and history of surgery. Patients with recurrent PDAC were further stratified based on time to recurrent disease. Overall survival (OS) was summarized within groups via Kaplan-Meier survival estimates, and compared between groups in the context of univariable and multivariable Cox proportional hazards models. The covariates adjusted for were gender, age, race, ECOG, smoking status, primary site, CA199, albumin, lymphocytes, neutrophils and monocytes. Results: We included 5170 patients with advanced PDAC, of which 1101 (21.3%) met criteria for recurrent disease. Patients with recurrent PDAC were more likely to have tumors in the head of the pancreas (71% vs 40%, p < 0.001) and had lower median CA19-9 (92.8 vs 617, p < 0.001), compared to the de novo PDAC patients. Median OS for the recurrent group was 10.8 m (95% CI = 9.9-11.7) vs. 7.3 m (95% CI = 7.0-7.7) in the de novo group (p < 0.001, both univariate and multivariable adjusted analyses). The most common first line palliative chemotherapy in patients with recurrent disease was Nab-paclitaxel plus gemcitabine (41%) or FOLFIRINOX (21%). Patients who recurred within six months of surgery (28%) had an OS of 10.0 m (95% CI = 8.7 -11) vs. 11.6 m (95% CI 10-12, p = 0.256) in those who recurred greater than six months from surgery. Conclusions: Our data suggest that patients with recurrent disease have significantly better survival outcomes compared to patients with de novo metastatic disease. We did not observe a significant difference in survival of patients who recurred within 6 months of resection compared to those who recurred greater than six months after surgery. These data support the inclusion of patients with recurrent PDAC in clinical trials, including those who develop recurrent disease within 6 months of surgery, with appropriate stratification for these variables.

P6360Prognostic value of polypharmacy in patients with heart failure

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R Fujita ◽  
K Takabayashi ◽  
K Iwatsu ◽  
K Matsumura ◽  
T Ikeda ◽  
...  
Keyword(s):  
Heart Failure ◽  
Hospital Readmission ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Medication Schedule ◽  
Significant Difference ◽  
Patients With Heart Failure ◽  
Clinical Background ◽  
The Impact

Abstract Background Polypharmacy creates an increased patient's burden by drug-drug interactions and poor adherence. However, there are very few studies available evaluating the association of polypharmacy with hospital readmission in patients with heart failure (HF). Purpose The aim of this study was to investigate the impact of polypharmacy on hospital readmission for HF. Methods We enrolled 1253 patients who were hospitalized with acute heart failure (AHF) or acute exacerbation of chronic heart failure in the Kitakawachi Clinical Background and Outcome of Heart Failure Registry (KICKOFF Registry) from April 2015 to July 2018 (age 78.1±11.5 years, male 51.4%). Our Registry is a prospective multicenter community-based cohort study of HF patients in Japan. The inclusion criteria for the registry was a diagnosis of HF during hospitalization according to the Framingham criteria, and there were no exclusion criteria. From data at discharge, we collected data on clinical characteristics, medication schedule, and social backgrounds. We defined polypharmacy as the use of seven or more medications. The primary end point was HF rehospitalization within 1 year after discharge. Cox proportional hazards regression analysis was used to describe the association between polypharmacy and 1-year HF rehospitalization, controlling for potential confounding factors. Results In this study, the prevalence of polypharmacy was 59.7% of all patients. Patients with polypharmacy were more likely to have comorbidities such as hypertension, dyslipidemia, diabetes, chronic kidney disease, coronary artery disease and dementia. They also had lower EF (50.9±0.64 vs 53.6±0.80, p<0.01), compared to patients without polypharmacy. There was no significant difference in age, gender and BMI, compared to patients without polypharmacy. During the follow-up period, a total of 278 patients (24.9%) were readmitted for HF. In Kaplan-Meier analyses, hospital readmission for HF during 1-year follow-up was significantly higher in patients with polypharmacy (p<0.01) (figure). After adjusting for gender, age, EF, and the other co-morbidities, polypharmacy was independently associated with higher risk of rehospitalization for HF (hazard ratio 1.28, 95% confidence interval, 1.07–1.52, p<0.01). Conclusion Polypharmacy is an independent predictor of hospital readmission for HF. Our study suggests the need for developing an effective strategy to choose the appropriate drugs in patients with HF. Acknowledgement/Funding Nakajima Steel Pipe

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