St. Jude Children's Research Hospital, Memphis, TN
Matthew J. Ehrhardt , Qi Liu , John L. Jefferies , Daniel A. Mulrooney , Yadav Sapkota , Jason Goldberg , Stephanie B Dixon , John Thomas Lucas , Kirsten K. Ness , Deo Kumar Srivastava , Wojciech Mazur , Juan Carlos Plana Gomez , Leslie L. Robison , Yutaka Yasui , Melissa M. Hudson , Gregory T. Armstrong
Background: Among survivors exposed to anthracycline or chest radiation (RT) who have an ejection fraction (EF) of ≥50%, the utility of GLS and NT-proBNP to identify survivors who are at highest risk for future CM is unknown. Methods: Survivors participating in the St. Jude Lifetime Cohort, ≥5 years from cancer diagnosis and at risk for CM per the International Guideline Harmonization Group (IGHG), underwent baseline surveillance echocardiography. A baseline GLS and NT-proBNP was also performed for survivors with an EF ≥50%. Multivariable Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of CM (graded per modified Common Terminology Criteria for Adverse Events v4.0) based on abnormal baseline GLS (≥ -18) and/or NT-proBNP (>age-sex-specific 97.5th percentiles) adjusted for age at baseline assessment, age at diagnosis, sex, race, hypertension, diabetes, obesity, and IGHG risk group (Table footnote). Results: Among 1598 at-risk survivors (median age 35.1, range 9.4-68.8 years), all had GLS and 1110 NT-proBNP at baseline. 165 (10.3%) developed CM ≥ grade 2 at a median follow-up of 5.2 (0.7-10.0) years. IGHG moderate- and high-risk survivors exposed to anthracyclines were at increased risk of CM at follow-up if both baseline GLS and NT-proBNP were abnormal (HR=3.4, 95% CI: 1.9-5.8; Table) or GLS was abnormal and NT-proBNP not assessed (HR=3.8, 95% CI: 2.0-7.2), or when GLS was normal and NT-proBNP was abnormal (HR=1.9, 95% CI: 1.1-3.4). Abnormal GLS and/or NT-proBNP were not associated with increased risk of CM in IGHG low-risk survivors or in those defined as moderate- to high-risk due to chest RT only. Conclusions: Among long-term survivors of childhood cancer exposed to >100 mg/m2 anthracycline, abnormal GLS and NT-proBNP identified those survivors at increased risk of future CM despite an EF ≥50% on surveillance echocardiography. Conditional surveillance strategies utilizing GLS and NT-proBNP may benefit moderate- to high-risk survivors.
Any Anthracycline + Chest RTb (N=289) or Anthracyclinec Only (n=605) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
IGHG Low-Riska(n=512) | Chest RTb Only (n=192) | IGHG Moderate- and High-Risk | |||||||||
GLS | NT-proBNP | HR | 95% CI | p | HR | 95% CI | p | HR | 95% CI | p | |
Cardiomyopathy, n (%) | 23 (4.5%) | 25 (13.0%) | 117 (13.1%) | ||||||||
Variables | |||||||||||
N | + | N | 1.0 | 1.0 | 1.0 | ||||||
A | + | N | 1.1 | 0.3 - 3.5 | 0.89 | 0.8 | 0.3 - 2.1 | 0.65 | 1.1 | 0.6 - 2.0 | 0.69 |
N | + | A | 0.0 | 0.0 - 1.6 | 0.98 | 0.9 | 0.3 - 2.6 | 0.87 | 1.9 | 1.1 - 3.4 | 0.02 |
A | + | A | 0.0 | 0.0 - 1.8 | 0.99 | 1.1 | 0.4 - 2.6 | 0.89 | 3.4 | 1.9 - 5.8 | <0.001 |
N | + | NA | 1.2 | 0.5 - 3.3 | 0.67 | 1.5 | 0.2 - 11.6 | 0.68 | 1.7 | 0.9 - 3.1 | 0.11 |
A | + | NA | 1.0 | 0.2 - 4.8 | 0.97 | 1.1 | 0.2 - 8.0 | 0.94 | 3.8 | 2.0 - 7.2 | <0.001 |
N=normal; A=abnormal; NA=not assessed.
Adjusted for race, sex, age, age at cancer diagnosis, hypertension, diabetes, obesity, and IGHG risk group.
aanthracycline <100 mg/m2 and RT <15 Gy; b≥15 Gy; c≥100 mg/m2.
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