Abstract
Simple SummaryThe multidisciplinary team of Fondazione Italiana Linfomi researchers conducted a systematic review of the literature (PubMed, EMBASE, Cochrane database) regarding incidence, comparison between systemic therapies and radiotherapy (RT) (old versus modern techniques), and the better monitoring of long-term classical Hodgkin lymphoma and diffuse large B-cell lymphoma survivors on late cardiological sequelae. The research focused on patients treated in adulthood and with first- or second-line antineoplastic therapies, including autologous stem cell transplant. Our purpose was to provide an overall and updated picture of the incidence of the phenomenon, the risk factors, and the updated early detection and follow-up strategies.Cardiotoxicity represents the most frequent cause with higher morbidity and mortality among long-term sequelae affecting classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) patients. The multidisciplinary team of Fondazione Italiana Linfomi (FIL) researchers, with the methodological guide of Istituto di Ricerche Farmacologiche “Mario Negri”, conducted a systematic review of the literature (PubMed, EMBASE, Cochrane database) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in order to analyze the following aspects of cHL and DLBCL survivorship: (i) incidence of cardiovascular disease (CVD); (ii) risk of long-term CVD with the use of less cardiotoxic therapies (reduced-field radiotherapy and liposomal doxorubicin); and (iii) preferable cardiovascular monitoring for left ventricular (LV) dysfunction, coronary heart disease (CHD) and valvular disease (VHD). After the screening of 659 abstracts and related 113 full-text papers, 23 publications were eligible for data extraction and included in the final sample. There was an increased risk for CVD in cHL survivors of 3.6 for myocardial infarction and 4.9 for congestive heart failure (CHF) in comparison to the general population; the risk increased over the years of follow-up. In addition, DLBCL patients presented a 29% increased risk for CHF. New radiotherapy techniques suggested reduced risk of late CVD, but only dosimetric studies were available. The optimal monitoring of LV function by 2D-STE echocardiography should be structured according to individual CV risk, mainly considering as risk factors a cumulative doxorubicine dose >250 mg per square meter (m2) and mediastinal radiotherapy >30 Gy, age at treatment <25 years and age at evaluation >60 years, evaluating LV ejection fraction, global longitudinal strain, and global circumferential strain. The evaluation for asymptomatic CHD should be offered starting from the 10th year after mediastinal RT, considering ECG, stress echo, or coronary artery calcium (CAC) score. Given the suggested increased risks of cardiovascular outcomes in lymphoma survivors compared to the general population, tailored screening and prevention programs may be warranted to offset the future burden of disease.
Highlights
Cardiotoxicity is the most frequent cause of morbidity and mortality occurring in lymphoma survivors after second cancers [1,2,3]
P: patient population in long-term survivors of classical Hodgkin lymphoma (cHL) or diffuse large B-cell lymphoma (DLBCL) (>5 years free of disease and treatment), with age >18 years at diagnosis; I: chemotherapy or chemotherapy + standard dose radiotherapy; C1: homogeneous population for age and sex untreated; What is the incidence of cardiovascular disease (CVD) in long-term survivors of cHL or DLBCL after first-line treatment?
What is the incidence of CVD in long-term survivors of cHL or DLBCL after the firstor second-line treatment?
Summary
Cardiotoxicity is the most frequent cause of morbidity and mortality occurring in lymphoma survivors after second cancers [1,2,3]. Numerous studies on the long-term followup of classical Hodgkin lymphoma (cHL) patients have shown that cardiovascular disease (CVD) can occur more than 20 years after treatment. CVD is defined as coronary heart disease (CHD), which included myocardial infarction (MI), percutaneous coronary intervention, coronary artery bypass graft surgery, or >75% stenosis on coronary angiogram or autopsy, cardiomyopathy, valvular heart disease (VHD), or pericardial disease. Patients treated at a young age may present severe comorbidities that affect their quality of life and overall survival [1]. Causes of cardiovascular long-term toxicity are well recognized in dose-dependent, anthracycline-including chemotherapy and mediastinal radiotherapy.
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