Childhood cancer survivors who receive a mean heart radiation therapy (RT) dose of ≥ 5 Gy are at increased risk for heart failure (HF) by mid-life, warranting updated recommendations for cardiomyopathy surveillance.
A large European case-control study of the PanCareSurFup and ProCardio cohorts comprised 42,361 long-term childhood cancer survivors diagnosed between 1940 and 2009 across seven countries.
The most frequent cancer diagnoses were leukaemia (27%), lymphoma (15%), central nervous system tumours (18%) and sarcoma (12%).
The study, published in the Journal of Clinical Oncology [link], said the cumulative incidence of HF was 2.0% by 50 years of age.
“The cumulative incidence of HF was greater among those with cancer diagnosed from 1980 onward than among those diagnosed before,” it said.
“When compared with survivors with a mean heart RT dose of 0 Gy, a mean heart dose of < 5 Gy was not associated with HF risk (1.3; 95% CI, 0.8 to 2.0), the OR for 5 to <15 Gy was 5.5 (95% CI, 2.5 to 12.3), the OR for 15 to <35 Gy was 9.0 (95% CI, 4.6 to 17.6), and the OR for ≥ 35 Gy was 22.6 (95% CI, 4.9 to 102.8).”
The study also found that in survivors who received a maximum heart RT dose of 5 to <15 Gy, the OR of HF was significantly increased if ≥ 50% of the volume was exposed (OR, 5.6; 95% CI, 1.5 to 20.6).
“In survivors who received ≥15 Gy, the risk was already significantly increased if <50% of the heart was exposed.”
It also found the cumulative incidence of cardiac mortality because of HF was lower in the treatment period 1990-2008 compared with that in 1980-1990.
“As in the general population, this may be related to improvement in early diagnosis and treatment.”
The study did not identify any significantly increased risk of HF for survivors treated with 100 mg/m2 total cumulative anthracycline dose.
“When compared with survivors who did not receive anthracyclines, the OR associated with total cumulative anthracycline doses <100 mg/m2 did not reach statistical significance (2.3; 95% CI, 0.7 to 7.1), the OR for 100 to <250 mg/m2 was 5.8 (95% CI, 2.9 to 11.3), and the OR for ≥ 250 mg/m2 was 21.2 (95% CI, 11.4 to 39.2).”
Given the five-fold higher risk of HF in survivors who received a comparatively low mean heart RT dose of 5 to <15 Gy compared with survivors who did not receive RT in the heart region, the investigators said there were implications for follow-up.
“Therefore, we propose to include this measure in the current cardiomyopathy surveillance guideline and recommend echocardiographic follow-up for survivors treated with a mean heart RT dose of ≥5 Gy.”
Meanwhile, the results suggest reconsidering the current recommendation of surveillance for survivors treated with a total cumulative anthracycline dose <100 mg/m2.
The investigators concluded that their findings had implications for new treatment protocols for children with cancer and for cardiomyopathy surveillance guidelines.