Cardiovascular Disease After Hodgkin Lymphoma Treatment

Abstract

IMPORTANCE Hodgkin lymphoma (HL) survivors are at increased risk of cardiovascular diseases. It is unclear, however, how long the increased risk persists and what the risk factors are for various cardiovascular diseases. OBJECTIVES To examine relative and absolute excess risk up to 40 years since HL treatment compared with cardiovascular disease incidence in the general population and to study treatment-related risk factors for different cardiovascular diseases. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study included 2524 Dutch patients diagnosed as having HL at younger than 51 years (median age, 27.3 years) who had been treated from January 1, 1965, through December 31, 1995, and had survived for 5 years since their diagnosis. EXPOSURES Treatment for HL, including prescribed mediastinal radiotherapy dose and anthracycline dose. MAIN OUTCOMES AND MEASURES Data were collected from medical records and general practitioners. Cardiovascular events, including coronary heart disease (CHD), valvular heart disease (VHD), and cardiomyopathy and congestive heart failure (HF), were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS After a median follow-up of 20 years, we identified 1713 cardiovascular events in 797 patients. After 35 years or more, patients still had a 4-to 6-fold increased standardized incidence ratio of CHD or HF compared with the general population, corresponding to 857 excess events per 10 000 person-years. Highest relative risks were seen in patients treated before 25 years of age, but substantial absolute excess risks were also observed for patients treated at older ages. Within the cohort, the 40-year cumulative incidence of cardiovascular diseases was 50% (95% CI, 47%-52%). Fifty-one percent of patients with a cardiovascular disease developed multiple events. For patients treated before 25 years of age, cumulative incidences at 60 years or older were 20%, 31%, and 11% for CHD, VHD, and HF as first events, respectively. Mediastinal radiotherapy increased the risks of CHD (hazard ratio [HR], 2.7; 95% CI, 2.0-3.7), VHD (HR, 6.6; 95% CI, 4.0-10.8), and HF (HR, 2.7; 95% CI, 1.6-4.8), and anthracycline-containing chemotherapy increased the risks of VHD (HR, 1.5; 95% CI, 1.1-2.1) and HF (HR, 3.0; 95% CI, 1.9-4.7) as first events compared with patients not treated with mediastinal radiotherapy or anthracyclines, respectively. Joint effects of mediastinal radiotherapy, anthracyclines, and smoking appeared to be additive. CONCLUSIONS AND RELEVANCE Throughout their lives, HL survivors treated at adolescence or adulthood are at high risk for various cardiovascular diseases. Physicians and patients should be aware of this persistently increased risk.

Long-term risk of second malignancy and cardiovascular disease after Hodgkin lymphoma treatment

“…Several studies suggest that anthracycline-containing chemotherapy further increases the radiotherapy-related risk of VHD and HF by two-to threefold compared with radiotherapy alone. 11,51,53 This effect was additive in a recent report 11 and more than additive in another study. Three recent case-control studies addressed the shape of the radiation dose-response curve for CHD and VHD after HL treatment.…”

“…After 35 years of follow up, HL survivors still had a four-to sixfold increased SIR of CHD or HF compared with the general population, corresponding to 81 865 excess events of CHD and HF per 10 000 person-years. 11 Within the cohort, 40-year cumulative incidence of CVD was 50%. In patients treated before 25 years of age, the highest RRs were seen (for CHD and VHD, as well as HF), but substantial AERs were also observed for patients treated at older ages.…”

“…[6][7][8] Common late effects include second and subsequent malignant neoplasms (SMNs), several cardiovascular diseases (CVDs), thyroid dysfunction, subfertility, premature menopause, and fatigue. [7][8][9][10][11][12][13][14][15][16][17] In addition to this wide range of physical late effects, many HL survivors face psychosocial problems that may or may not be linked to specific treatments, but significantly reduce their quality of life. These include impaired memory and concentration, depression and anxiety, sexual problems, and problems with employment and insurances.…”

Long-term hospitalisation rates among 5-year survivors of Hodgkin lymphoma in adolescence or young adulthood: A nationwide cohort study

“…Several studies of cause‐specific mortality in survivors of Hodgkin lymphoma diagnosed in childhood or early adult life have been carried out,19, 20, 21 and the risk of hospitalisation among survivors of all types of cancer diagnosed in adolescence and young adulthood has been studied in other populations 22, 23, 24, 25. Other studies specifically of survivors of Hodgkin lymphoma diagnosed in young adulthood have usually reported on specific risks of second cancers11, 26, 27, 28, 29, 30, 31, 32, 33 or cardiovascular diseases 12, 34, 35, 36. The results of our study are in agreement with their findings.…”

2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines

“…Choroba serca związana z napromienianiem u pacjentów z chłoniakiem typowo ujawnia się 15-20 lat po początkowym leczeniu, a młodsi pacjenci są bardziej podatni na jej wystąpienie niż osoby starsze [137]. Wśród chorych, którzy przebyli chłoniaka Hodgkina, ryzyko CAD jest zwiększone 4-7-krotnie w porów-naniu z populacją ogólną, a skumulowana zapadalność na CVD po 40 latach od leczenia wynosi nawet 50% [138]. Na podstawie tych danych wydaje się właściwe, aby dokonywać systematycznej przesiewowej oceny w kierunku chorób serca u pacjentów po radioterapii, rozpoczynając ją 10-15 lat po początkowym leczeniu nowotworu i kontynuując do końca życia.…”