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A population-based multistate model for diffuse large B-cell lymphoma-specific mortality in older patients.

ABSTRACT: BACKGROUND:Despite effective therapies, outcomes for diffuse large B-cell lymphoma (DLCBL) remain heterogeneous in older individuals due to comorbid diseases and variations in disease biology. METHODS:Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, the authors conducted a multistate survival analysis of 11,780 patients with DLBCL who were aged ?65 years at the time of diagnosis (2002-2009). Cox proportional hazards models were used to specify the impact of prognostic factors on overall survival and cause-specific deaths, and the Aalen-Johansen estimator was used to project the course of DLBCL over time with or without standard therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). RESULTS:Advanced age (hazard ratio [HR] for ages 71-75 years: 1.25; HR for ages 76-80 years: 1.46; HR for ages 81-85 years: 1.88; and HR for age ?86 years: 2.26), DLBCL stage (HR for Ann Arbor stage II: 1.28; HR for stage III: 1.54; and HR for stage IV: 1.95), Charlson Comorbidity Index (CCI) ?1 (HR for CCI of 1, 1.15; and HR for CCI >1, 1.37), and not being married (HR, 1.12) were associated with an increased risk of DLBCL-specific death. Being female (HR, 0.91) and of higher socioeconomic status (HR, 0.91) were associated with a lower risk of DLBCL-related mortality after therapy. For patients treated with R-CHOP (3610 patients), the risk of death due to DLBCL was 14.0% and 18.6%, respectively, at 2 and 5 years of treatment and plateaued afterward, confirming a 5-year "cure" point while receiving R-CHOP among older patients. CONCLUSIONS:Conducting a survival analysis over a large data set, the current study evaluated competing risks for death within a multistate modeling framework, and identified age, sex, and CCI as risk factors for DLBCL-specific and other causes of death.

SUBMITTER: Caglayan C

PROVIDER: S-EPMC6509004 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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A population-based multistate model for diffuse large B-cell lymphoma-specific mortality in older patients.

Çağlayan Çağlar Ç Goldstein Jordan S JS Ayer Turgay T Rai Ashish A Flowers Christopher R CR

Cancer 20190201 11

<h4>Background</h4>Despite effective therapies, outcomes for diffuse large B-cell lymphoma (DLCBL) remain heterogeneous in older individuals due to comorbid diseases and variations in disease biology.<h4>Methods</h4>Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, the authors conducted a multistate survival analysis of 11,780 patients with DLBCL who were aged ≥65 years at the time of diagnosis (2002-2009). Cox proportional hazards models were used to specify the im ...[more]

PMID: 30707765

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Project description:BackgroundWe modeled the clinical course of a cohort of diffuse large B-cell lymphoma (DLBCL) patients with no prior cardiovascular diseases (CVDs) using a multistate modeling framework.Patients and methodsData on 2600 patients with DLBCL diagnosed between 2000 and 2018 and had received chemotherapy with or without radiotherapy were obtained from a population-wide electronic health database of Hong Kong. We used the Markov illness-death model to quantify the impact of doxorubicin and various risk factors (therapeutic exposure, demographic, comorbidities, cardiovascular risk factors, and lifestyle factors which included smoking) on the clinical course of DLBCL (transitions into incident CVD, lymphoma death, and other causes of death).ResultsA total of 613 (23.6%) and 230 (8.8%) of 2600 subjects died of lymphoma and developed incident CVD, respectively. Median follow-up was 7.0 years (interquartile range 3.8-10.8 years). Older ages [hazard ratio (HR) for >75 versus ≤60 years 1.88; 95% confidence interval (CI) 1.25-2.82 and HR for 61-75 versus ≤60 years 1.60; 95% CI 1.12-2.30], hypertension (HR 4.92; 95% CI 2.61-9.26), diabetes (HR 1.43; 95% CI 1.09-1.87), and baseline use of aspirin (HR 5.30; 95% CI 3.93-7.16) were associated with an increased risk of incident CVD. In a subgroup of anticipated higher-risk patients (aged 61-75 years, smoked, had diabetes, and received doxorubicin), we found that they remained on average 7.9 (95% CI 7.2-8.8) years in the DLBCL state and 0.1 (95% CI 0.0-0.4) years in the CVD state, if they could be followed up for 10 years. The brief time in the CVD state is consistent with the high chance of death in patients who developed CVD. Other causes of death have overtaken DLBCL-related death after about 5 years.ConclusionsIn this Asian population-based cohort, we found that incident CVDs can occur soon after DLBCL treatment and continued to occur throughout survivorship. Clinicians are advised to balance the risks and benefits of treatment choices to minimize the risk of CVD.

Project description:BackgroundThe molecular diversity exhibited by diffuse large B-cell lymphoma (DLBCL) is a significant obstacle facing current precision therapies. However, scoring using the International Prognostic Index (IPI) is inadequate when fully predicting the development of DLBCL. Reprogramming lipid metabolism is crucial for DLBCL carcinogenesis and expansion, while a predictive approach derived from lipid metabolism-associated genes (LMAGs) has not yet been recognized for DLBCL.MethodsGene expression profiles of DLBCL were generated using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The LASSO Cox regression was used to construct an effective predictive risk-scoring model for DLBCL patients. The Kaplan-Meier survival assessment was employed to compare a given risk score with the IPI score and its impact on the survival of DLBCL patients. Functional enrichment examination was performed utilizing the KEGG pathway. After identifying hub genes via single-sample GSEA (ssGSEA), immunohistochemical staining and immunofluorescence were performed on lymph node samples from control and DLBCL patients to confirm these identified genes.ResultsSixteen lipid metabolism- and survival-associated genes were identified to construct a prognostic risk-scoring approach. This model demonstrated robust performance over various datasets and emerged as an autonomous risk factor for predicting the development of DLBCL patients. The risk score could significantly distinguish the development of DLBCL patients from the low-risk and elevated-risk IPI classes. Results from the inhibitory immune-related pathways and lower immune scores suggested an immunosuppressive phenotype within the elevated-risk group. Three hub genes, MECR, ARSK, and RAN, were identified to be negatively correlated with activated CD8 T cells and natural killer T cells in the elevated-risk score class. Ultimately, it was determined that these three genes were expressed by lymphoma cells but not by T cells in clinical samples from DLBCL patients.ConclusionThe risk level model derived from 16 lipid metabolism-associated genes represents a prognostic biomarker for DLBCL that is novel, robust, and may have an immunosuppressive role. It can compensate for the limitations of the IPI score in predicting overall survival and has potential clinical application value.

Dataset Information

A population-based multistate model for diffuse large B-cell lymphoma-specific mortality in older patients.

Publications

A population-based multistate model for diffuse large B-cell lymphoma-specific mortality in older patients.

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