Anthracycline treatment, cardiovascular risk factors and the cumulative incidence of cardiovascular disease in a cohort of newly diagnosed lymphoma patients from the modern treatment era

Boddicker, Nicholas; Larson, Melissa C.; Castellino, Alessia; Herrmann, Joerg; Inwards, David J.; Thanarajasingam, Gita; Maurer, Mathew S.; Allmer, Cristine; Witzig, Thomas E.; Nowakowski, Grzegorz S.; Habermann, Thomas M.; Villarraga, Hector R.; Slager, Susan L.; Cerhan, James R.; Thompson, Carrie A.

doi:10.1002/ajh.26230

Cited by 8 publications

(7 citation statements)

References 44 publications

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“…Interestingly, radiation therapy to the chest and mediastinum did not emerge as an independent risk factor for CHF. Consistent with our study, a prospective cohort study of patients with newly diagnosed lymphoma found that patients had increased risk of cardiovascular disease, especially CHF, at 10 years, but receipt of radiation therapy was not associated with this outcome and this was also found in the study by Salz et al using a Danish registry cohort. However, not all chest radiation affects the heart to the same degree.…”

Section: Discussionmentioning

confidence: 99%

Association of Anthracycline With Heart Failure in Patients Treated for Breast Cancer or Lymphoma, 1985-2010

et al. 2023

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ImportanceAnthracyclines increase the risk for congestive heart failure (CHF); however, long-term cumulative incidence and risk factors for CHF after anthracycline therapy are not well defined in population-based studies.ObjectiveTo compare the long-term cumulative incidence of CHF in patients with breast cancer or lymphoma treated with anthracycline therapy compared with healthy controls from the same community.Design, Setting, and ParticipantsThis retrospective population-based case-control study included data from the Rochester Epidemiology Project. Participants included residents of Olmsted County, Minnesota, diagnosed with breast cancer or lymphoma from January 1985 through December 2010 matched for age, sex, and comorbidities with healthy controls, with a final ratio of 1 case to 1.5 controls. Statistical analysis was performed between July 2017 and February 2022.ExposuresCancer treatment and CHF risk factors.Main Outcomes and MeasuresThe main outcome was new-onset CHF, as defined by the modified Framingham criteria. Cox proportional hazards regression was used to estimate hazard ratios (HRs) to compare the risk of CHF in participants with cancer vs controls, adjusted for age, sex, diabetes, hypertension, hyperlipidemia, coronary artery disease, obesity, and smoking history.ResultsA total of 2196 individuals were included, with 812 patients with cancer and 1384 participants without cancer. The mean (SD) age was 52.62 (14.56) years and 1704 participants (78%) were female. Median (IQR) follow-up was 8.6 (5.2-13.4) years in the case group vs 12.5 (8.7-17.5) years in the control group. Overall, patients with cancer had higher risk of CHF compared with the control cohort even after adjusting for age, sex, diabetes, hypertension, coronary artery disease, hyperlipidemia, obesity, and smoking status (HR, 2.86 [95% CI, 1.90-4.32]; P &lt; .001). After adjusting for the same variables, CHF risk was greater for patients with cancer receiving anthracycline (HR, 3.25 [95% CI, 2.11-5.00]; P &lt; .001) and was attenuated and lost statistical significance for patients with cancer not receiving anthracyclines (HR, 1.78 [95% CI, 0.83-3.81]; P = .14). Higher cumulative incidence for patients treated with anthracyclines vs comparator cohort was observed at 1 year (1.81% vs 0.09%), 5 years (2.91% vs 0.79%), 10 years (5.36% vs 1.74%), 15 years (7.42% vs 3.18%), and 20 years (10.75% vs 4.98%) (P &lt; .001). There were no significant differences in risk of CHF for patients receiving anthracycline at a dose of less than 180 mg/m2 compared with those at a dose of 180 to 250 mg/m2 (HR, 0.54 [95% CI, 0.19-1.51]) or at a dose of more than 250 mg/m2 (HR, 1.23 [95% CI, 0.52-2.91]). At diagnosis, age was an independent risk factor associated with CHF (HR per 10 years, 2.77 [95% CI, 1.99-3.86]; P &lt; .001).Conclusions and RelevanceIn this retrospective population-based case-control study, anthracyclines were associated with an increased risk of CHF early during follow-up, and the increased risk persisted over time. The cumulative incidence of CHF in patients with breast cancer or lymphoma treated with anthracyclines at 15 years was more than 2-fold that of the control group.

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Section: Discussionmentioning

confidence: 99%

Association of Anthracycline With Heart Failure in Patients Treated for Breast Cancer or Lymphoma, 1985-2010

et al. 2023

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“…We focused on validating disease endpoints and second‐primary cancers, while other health outcomes were self‐reported. However, with our access to medical records, LEO can validate other endpoints later, such as in the MER for cardiovascular disease 36 …”

Section: Discussionmentioning

confidence: 99%

“…36 While the LEO cohort has age, sex, racial/ethnic and geographic diversity, patients older than 80 years were underrepresented in the cohort relative to SEER data, as were Asian/Pacific Islanders. All LEO recruitment centers are academic medical centers with strong lymphoma clinical practices, and thus LEO will not be fully representative of community patients, although many participants enrolled at LEO centers are managed in the community.…”

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The Lymphoma Epidemiology of Outcomes cohort study: Design, baseline characteristics, and early outcomes

Cerhan,

Maurer,

Link

et al. 2024

American J Hematol

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To address the current and long‐term unmet health needs of the growing population of non‐Hodgkin lymphoma (NHL) patients, we established the Lymphoma Epidemiology of Outcomes (LEO) cohort study (NCT02736357; https://leocohort.org/). A total of 7735 newly diagnosed patients aged 18 years and older with NHL were prospectively enrolled from 7/1/2015 to 5/31/2020 at 8 academic centers in the United States. The median age at diagnosis was 62 years (range, 18–99). Participants came from 49 US states and included 538 Black/African‐Americans (AA), 822 Hispanics (regardless of race), 3386 women, 716 age <40 years, and 1513 rural residents. At study baseline, we abstracted clinical, pathology, and treatment data; banked serum/plasma (N = 5883, 76.0%) and germline DNA (N = 5465, 70.7%); constructed tissue microarrays for four major NHL subtypes (N = 1189); and collected quality of life (N = 5281, 68.3%) and epidemiologic risk factor (N = 4489, 58.0%) data. Through August 2022, there were 1492 deaths. Compared to population‐based SEER data (2015–2019), LEO participants had a similar distribution of gender, AA race, Hispanic ethnicity, and NHL subtype, while LEO was underrepresented for patients who were Asian and aged 80 years and above. Observed overall survival rates for LEO at 1 and 2 years were similar to population‐based SEER rates for indolent B‐cell (follicular and marginal zone) and T‐cell lymphomas, but were 10%–15% higher than SEER rates for aggressive B‐cell subtypes (diffuse large B‐cell and mantle cell). The LEO cohort is a robust and comprehensive national resource to address the role of clinical, tumor, host genetic, epidemiologic, and other biologic factors in NHL prognosis and survivorship.

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“…Anthracycline-induced cardiotoxicity is a growing challenge for public health, due to the ageing population with an increasing prevalence of cardiovascular risk factors and the widespread use of anthracyclines in lymphoma therapy, with high response rates and improved overall survival 14 . Our study reports incidence and risk factors for cardiotoxicity in a cohort of 200 lymphoma patients undergoing rst-line treatment with anthracyclines.…”

Section: Discussionmentioning

confidence: 99%

Predictors of Anthracycline-inducedcardiotoxicity in Lymphoma Patients: A Retrospective Cohort Study

LOPEZ-GARCIA,

MACIA,

GOMEZ-TALAVERA

et al. 2023

Preprint

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Background: Anthracycline-induced cardiotoxicity (CT) is a growing concern for public health, with a growing incidence due to improved survival rates for patients with hematological malignancies due to diagnostic and therapeutic advances. Identification of patients at risk for anthracycline-induced CT is vital to develop preventive strategies. Methods: A single-center retrospective cohort study was conducted between 1 January 2017 and 15 February 2023. Medical records of patients with lymphoma treated with first-line anthracyclines were reviewed. Demographic data, cardiovascular risk factors, biomarkers of myocardial damage and echocardiographic information were collected. Results: A total of 200 patients were included. The incidence of CT was 17.4 % (35/200). Patients with CT were older than those without CT, with a mean age of 65.17 years vs 56.77 (p = 0.008). Dyslipidemia (DL) (31.4% vs 13.4% p = 0.017) and previous cardiovascular disease (40% vs 13.3%, p< 0.001) were more frequent in the group who developed an event. Mean baseline NT-proBNP levels in the subgroup with cardiovascular events were 388.73 kg /L ± 101.02, and 251.518 kg /L ± 26.22 in those who did not (p = 0.004). Differences in Troponin I levels were identified during and after treatment without exceeding the laboratory’s upper reference limit. Patients were followed for a median of 51.83 months (0.76-73.49). The presence of a CT event had a negative impact on overall mortality from any cause (HR = 2.23 (95% CI 1.08-2.93), p = 0.031). Conclusions: Early identification of risk factors is crucial to manage patients at risk for anthracycline-induced cardiotoxicity.

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Anthracycline treatment, cardiovascular risk factors and the cumulative incidence of cardiovascular disease in a cohort of newly diagnosed lymphoma patients from the modern treatment era

Cited by 8 publications

References 44 publications

Association of Anthracycline With Heart Failure in Patients Treated for Breast Cancer or Lymphoma, 1985-2010

Association of Anthracycline With Heart Failure in Patients Treated for Breast Cancer or Lymphoma, 1985-2010

The Lymphoma Epidemiology of Outcomes cohort study: Design, baseline characteristics, and early outcomes

Predictors of Anthracycline-inducedcardiotoxicity in Lymphoma Patients: A Retrospective Cohort Study

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