Cardiovascular magnetic resonance for early detection of late cardiotoxicity in asymptomatic survivors of hodgkin and non-hodgkin lymphoma

Abstract

Funding Acknowledgements Type of funding sources: None. Background Long-term survivors of Hodgkin (HL) and non-Hodgkin (NHL) lymphomas experience late adverse effects of mediastinal radiotherapy and/or anthracycline containing chemotherapy, which lead to premature cardiovascular morbidity and mortality. It is unknown whether early stages of myocardial dysfunction and heart failure in these survivors can be detected by cardiovascular magnetic resonance imaging (CMR). Purpose To identify early sensitive markers for the detection of subclinical late cardiotoxicity using CMR in asymptomatic survivors of HL and (primary mediastinal large B-cell lymphoma) NHL. Methods For this prospective observational study, we included 80 HL or selected NHL survivors, who have been free of disease for ≥5 years and were treated with mediastinal radiotherapy (RT) with/without chemotherapy. Patients with known cardiac disease were excluded. Included patients were compared to 40 age- and sex matched healthy controls. CMR included 1) cine imaging for assessment of left ventricular (LV) and right ventricular (RV) dimensions, systolic function and strain; 2) 2-dimensional late gadolinium enhancement (LGE) imaging; 3) T2 mapping and 4) pre- and post-contrast T1 mapping (MOLLI) for assessment of native T1 values and extracellular volume (ECV). Results Of the 80 patients, 78 (98%) had a history of HL and 2 (2%) of NHL with a mean age of 47 ± 11 years (46% male). All patients were treated with mediastinal RT which was combined with anthracycline containing chemotherapy in 68 (85%) patients. The median interval between diagnosis and CMR was 20 [14 – 26] years. Differences in CMR characteristics between patients and healthy controls are shown in the table. LV end-systolic volume was statistically significantly higher, but LV ejection fraction and mass were significantly lower in patients compared to healthy controls. RV volumes were significantly lower in patients, but RV ejection fraction was preserved. Strain parameters of the LV, i.e. global longitudinal strain, global circumferential strain and global radial strain, were slightly but significantly reduced in patients. No significant differences were found in myocardial T2 times and ECV; however, native myocardial T1 time was significantly higher in patients compared to healthy controls. LGE was detected in 25% of the patients and in the majority of patients with LGE this was classified as hinge point fibrosis. Conclusion Asymptomatic survivors of HL and NHL are not exempt of late cardiotoxicity, which can be detected by subtle changes in LV myocardial function, strain and native T1 value with CMR. Furthermore, late gadolinium enhancement was present in 25% of the patients. Further longitudinal studies are needed to assess the implication of these changes in relation to clinical outcome.

Quantitative assessment of radiotherapy-induced myocardial damage using MRI: A systematic review

“…Global analysis of ECV [47] and short follow-up times (less than 2 years) [52], [62] did not show any changes post-RT. However, segmental analysis (i.e., by the American Heart Association (AHA) model) of ECV at high-dose regions over short follow-up times (0.5 year) [54] and global analysis over longer followups in concurrent treatments (greater than 67.6 months) [60] demonstrated an increase of ECV signal.…”

“…In 3/11 patients with esophageal cancer, LV systolic volume increased at 3-5 months following neoadjuvant chemoradiotherapy [57]. An increase of LV end-systolic volume was also noted in 80 HL and NHL patients who were treated by mediastinal RT with/without chemotherapy at 20 years compared to healthy control (p=0.01) [47].…”

“…No signi cant reduction of LVEF was noted at 6 months in the whole cohort ( Recent RT-induced MCT studies showed no signi cant changes of LVEF and/or relations between LVEF and dose mostly due to short follow-ups [51], [52], low dose of radiation to the heart [44], small sample size [49], and uncertainty in the exact cumulative dose for longer follow-up studies. However, studies with longer follow-up (20 years and more) showed a decrease in LVEF [46], [47]. Also, studies that were conducted on patients treated with older RT techniques such as anterior-mantle-eld, in which overdosage is expected in anterior parts of the irradiated volume, showed declines in LVEF following RT [46].…”

“…Discussion on cardiac chamber dimensions Over short follow-ups, cardiac chambers dimensions did not change and/or were recovered after therapy completion [44], [56], potentially due to compensatory features of the heart. Changes in cardiac chamber dimension were mostly noted over longer follow-up times [47], when damages are less likely to be reversible, and in concurrent treatments (e.g., epirubicin-based chemotherapy followed by RT) [52], in which cardiotoxic drugs enhance the probability of cardiac dysfunction. Finally, a relationship between radiation dose and LV end-diastolic volume was noted in pediatric cancer patients [55], who are shown to be more susceptible to radiation damage compared to adult patients [20].…”

“…In 31 patients with Hodgkin's disease who were treated with mediastinal RT, LVEF dropped below 55% in 23% of patients at 24 years post-RT treatment [46]. Also, long-term survivors of Hodgkin's lymphoma (HL) and non-HL (NHL) who were treated with mediastinal RT in combination with chemotherapy (85% of the cohort) demonstrated lower LVEF compared to healthy controls (53±5% vs 60±5%, p<0.001) at a median of 20 years post-treatment [47]. Finally, in a small study with ten patients with different thoracic malignancies, LVEF dropped below 50% in only one patient midtreatment and in two patients at the end of therapy (all patients' LVEF were above 50% at baseline) [48].…”