A competing-risks nomogram and recursive partitioning analysis for cause-specific mortality in patients with esophageal neuroendocrine carcinoma

2019 ◽  
Vol 32 (11) ◽  
Author(s):  
G Zhang ◽  
B Wu ◽  
X Wang ◽  
J Li

SUMMARY The objective of this study is to estimate the probability of cause-specific mortality using a competing-risks nomogram and recursive partitioning analysis in a large population-based cohort of patients with esophageal neuroendocrine carcinoma. The surveillance, epidemiology and end results database was used to identify 162 patients diagnosed with esophageal neuroendocrine carcinoma from 1998 to 2014. We estimated a cumulative incidence function for cause-specific mortality. A nomogram was constructed by using a proportional subdistribution hazard model, validated using bootstrap cross-validation, and evaluated with a decision curve analysis to assess its clinical utility. Finally, we performed risk stratification using a recursive partitioning analysis to divide patients with esophageal neuroendocrine carcinoma into clinically useful prognostic groups. Tumor location, distant metastasis, surgery, radiotherapy, and chemotherapy were significantly associated with cause-specific mortality. The calibration plots demonstrated good concordance between the predicted and actual outcomes. The discrimination performance of a Fine–Gray model was evaluated by using the c-index, which was 0.723 for cause-specific mortality. The decision curve analysis ranged from 0.268 to 0.968 for the threshold probability at which the risk model provided net clinical benefits relative to hypothetical all-screening and no-screening scenarios. The risk groups stratified by a recursive partitioning analysis allowed significant distinction between cumulative incidence curves. We determined the probability of cause-specific mortality in patients with esophageal neuroendocrine carcinoma and developed a nomogram and recursive partitioning analysis stratification system based on a competing-risks model. The nomogram and recursive partitioning analysis appear to be suitable for risk stratification of cause-specific mortality in patients with esophageal neuroendocrine carcinoma and will help clinicians to identify patients at increased risk of cause-specific mortality to guide treatment and surveillance decisions.

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-9
Author(s):  
John L Vaughn ◽  
Laura C Pinheiro ◽  
Adam J Olszewski ◽  
Narendranath Epperla

Introduction: Splenic marginal zone lymphoma (SMZL) is an indolent B-cell non-Hodgkin lymphoma that usually presents in elderly patients with splenomegaly, lymphocytosis, and cytopenias (either due to hypersplenism or autoimmune phenomena). Treatment of SMZL has advanced over the past decade including identification of better tolerable chemotherapy regimens (such as rituximab and bendamustine) and the advent of novel agents (such as ibrutinib and lenalidomide). We sought to determine whether advances in treatment and supportive care over the past decade have translated to decreased lymphoma-specific mortality among patients with SMZL. Method: We used the population-based Surveillance, Epidemiology, and End Results (SEER)-18 database. We included adult patients with SMZL diagnosed between 2000-2017 who were 18-84 years old at the time of diagnosis. We excluded patients with a history of malignancy prior to SMZL, those with missing survival times and those with central nervous system involvement. Patients were divided into two cohorts based on period of diagnosis (era-1: 2000-2008, and era-2: 2009-2017). Five-year relative survival (RS) was estimated using the Pohar-Perme method. Differences between RS distributions was tested with a log-rank-type test. The risk of SMZL-specific death was estimated by calculating the cumulative incidence function (CIF). The difference between CIF distributions was tested with the Pepe-Mori test. The competing risks of SMZL-specific death and death from other causes were modeled using Fine and Gray regression. All tests of differences were performed at a two-sided alpha of 0.05. Results: We included 1,548 patients with SMZL. Table 1 shows the baseline characteristics. The median age at diagnosis was 66 years (IQR = 57-74) years. Most patients were non-Hispanic White (81%) with advanced stage at diagnosis (stage III-IV, 70%). Five-year RS was 84% (95% CI = 80-87%) during era-1 and 89% (95% CI = 85-92%) during era-2 (p = 0.21. The CIF distributions for SMZL-specific death and death from other causes are shown in Figure 1A and Figure 1B, respectively (Pepe-Mori p = 0.02). In our multivariable competing risks model, the period of diagnosis, age, and stage at diagnosis were significant predictors of SMZL-specific death (Table 2). Patients in era-2 had significantly lower risk of SMZL-specific death [subhazard ratio (SHR) = 0.30, 95% CI = 0.22-0.41), while the cumulative incidence of mortality significantly increased with age (SHR = 1.39 per decade, 95% CI = 1.24-1.56) and advanced stage (SHR = 1.55, 95% CI= 1.04-2.13). Conclusion: There has been a significant reduction in the risk of SMZL-specific death for patients with SMZL in the most recent era possibly due to advances in therapy. This reduction in mortality persists even after accounting for competing risks of mortality from other causes. Disclosures Olszewski: Spectrum Pharmaceuticals: Research Funding; Adaptive Biotechnologies: Research Funding; TG Therapeutics: Research Funding; Genentech, Inc.: Research Funding. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria.


2019 ◽  
Vol 48 (6) ◽  
pp. 1897-1905 ◽  
Author(s):  
Alyssa N Troeschel ◽  
Yuan Liu ◽  
Lindsay J Collin ◽  
Patrick T Bradshaw ◽  
Kevin C Ward ◽  
...  

Abstract Background Breast cancer (BC) survivors are at increased risk of cardiovascular disease (CVD) due to shared risk factors with BC and cardiotoxic treatment effects. We aim to investigate racial differences in mortality due to CVD and BC among women diagnosed with invasive BC. Methods Data from 407 587 non-Hispanic Black (NHB) and White (NHW) women diagnosed with malignant BC (1990–2014) were obtained from the Surveillance, Epidemiology, and End Results database. Cumulative incidence of mortality due to CVD and BC was calculated by race and age (years). Cox models were used to obtain hazard ratios (HR) and 95% confidence intervals (95%CI) for the association of race/ethnicity with cause-specific mortality. Results The 20-year cumulative incidence of CVD-related mortality was higher among younger NHBs than NHWs (e.g. age 55–69: 13.3% vs 8.9%, respectively). NHBs had higher incidence of BC-specific mortality than NHWs, regardless of age. There was a monotonic reduction in CVD-related mortality disparities with increasing age (age <55: HR = 3.71, 95%CI: 3.29, 4.19; age 55–68: HR = 2.31, 95%CI: 2.15, 2.49; age 69+: HR = 1.24, 95%CI: 1.19, 1.30). The hazard of BC-specific mortality among NHBs was approximately twice that of NHWs (e.g. age <55: HR = 1.98, 95%CI: 1.92, 2.04). Conclusions There are substantial differences in mortality due to CVD and BC between NHB and NHW women diagnosed with invasive BC. Racial differences were greatest among younger women for CVD-related mortality and similar across age groups for BC-specific mortality. Future studies should identify pathways through which race/ethnicity affects cause-specific mortality, to inform efforts towards reducing disparities.


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