School of Medicine and Health Sciences Poster Presentations

Title

Cardiac Dysfunction in Pediatric Sarcoma Survivors Exposed to Cardiotoxic Therapies

Document Type

Poster

Abstract Category

Cancer/Oncology

Keywords

Cardiac Dysfunction Pediatric Sarcoma Survivors

Publication Date

Spring 5-1-2019

Abstract

Background: Due to recent therapeutic advances, survival rates for childhood cancer now exceed 80%. Survivors, however, remain at increased risk for long-term treatment-related complications. After cancer recurrence and secondary malignancies, cardiac late effects have been a leading cause of premature morbidity and mortality among childhood cancer survivors. Due to their abundance of mitochondria, cardiomyocytes are particularly sensitive to the oxidative stress induced by anthracycline or chest-directed radiation exposure. High-dose anthracyclines are a key component of treatment protocols for children with sarcomas. The research aim in this study was to describe the prevalence of cardiac dysfunction in a large, single-institutional cohort of sarcoma survivors treated at Memorial Sloan Kettering (MSK) between 1999-2014. Materials and Methods: A retrospective review of echocardiograms and medical records of two-year sarcoma survivors (n= 123) seen at least once in the Pediatric Long-Term Follow-Up Program at MSK was performed. The primary outcome was evidence of cardiac dysfunction, as defined by Fractional Shortening (FS) <28%. Results: Six individuals (4.9%) had evidence of cardiac dysfunction, as defined by FS <28%. 2 of 6 received <250 mg/m2 doxorubicin, 3 of 6 received between 250-500 mg/m2 doxorubicin, and 1 of 6 received >500 mg/m2 doxorubicin. 1 of 6 had a history of chest-directed radiation. 2 of 6 had also received the cardiac protectant, dexrazoxane. Other non-echocardiogram based cardiac diagnoses reported include: atrial fibrillation (n=1), right bundle branch block (n=1), left bundle branch block (n=1). Conclusions: In this cohort of sarcoma survivors with a median duration of follow-up of 3.33 years, 5% of patients developed cardiac dysfunction after cancer therapy. Risk factors for cardiac dysfunction include younger age at treatment, exposure to chest-directed radiation, and higher cumulative dose of anthracycline. Lifelong cardiac screening with echocardiograms is indicated for sarcoma patients and other childhood cancer survivors exposed to anthracyclines and/or chest radiation. Treatment with novel cardioprotectants, such as dexrazoxane may be associated with lower rates of cardiac dysfunction in sarcoma survivors. Future analyses will evaluate time to cardiac dysfunction, prevalence of systolic and diastolic dysfunction, and evaluate potential risk modifiers, such as cardioprotectants (dexrazoxane), and/or cardiac medications (ACE inhibitors, beta blockers) among high-risk survivors of childhood cancer exposed to cardiotoxic therapies.

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Presented at Research Days 2019.

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Cardiac Dysfunction in Pediatric Sarcoma Survivors Exposed to Cardiotoxic Therapies

Background: Due to recent therapeutic advances, survival rates for childhood cancer now exceed 80%. Survivors, however, remain at increased risk for long-term treatment-related complications. After cancer recurrence and secondary malignancies, cardiac late effects have been a leading cause of premature morbidity and mortality among childhood cancer survivors. Due to their abundance of mitochondria, cardiomyocytes are particularly sensitive to the oxidative stress induced by anthracycline or chest-directed radiation exposure. High-dose anthracyclines are a key component of treatment protocols for children with sarcomas. The research aim in this study was to describe the prevalence of cardiac dysfunction in a large, single-institutional cohort of sarcoma survivors treated at Memorial Sloan Kettering (MSK) between 1999-2014. Materials and Methods: A retrospective review of echocardiograms and medical records of two-year sarcoma survivors (n= 123) seen at least once in the Pediatric Long-Term Follow-Up Program at MSK was performed. The primary outcome was evidence of cardiac dysfunction, as defined by Fractional Shortening (FS) <28%. Results: Six individuals (4.9%) had evidence of cardiac dysfunction, as defined by FS <28%. 2 of 6 received <250 mg/m2 doxorubicin, 3 of 6 received between 250-500 mg/m2 doxorubicin, and 1 of 6 received >500 mg/m2 doxorubicin. 1 of 6 had a history of chest-directed radiation. 2 of 6 had also received the cardiac protectant, dexrazoxane. Other non-echocardiogram based cardiac diagnoses reported include: atrial fibrillation (n=1), right bundle branch block (n=1), left bundle branch block (n=1). Conclusions: In this cohort of sarcoma survivors with a median duration of follow-up of 3.33 years, 5% of patients developed cardiac dysfunction after cancer therapy. Risk factors for cardiac dysfunction include younger age at treatment, exposure to chest-directed radiation, and higher cumulative dose of anthracycline. Lifelong cardiac screening with echocardiograms is indicated for sarcoma patients and other childhood cancer survivors exposed to anthracyclines and/or chest radiation. Treatment with novel cardioprotectants, such as dexrazoxane may be associated with lower rates of cardiac dysfunction in sarcoma survivors. Future analyses will evaluate time to cardiac dysfunction, prevalence of systolic and diastolic dysfunction, and evaluate potential risk modifiers, such as cardioprotectants (dexrazoxane), and/or cardiac medications (ACE inhibitors, beta blockers) among high-risk survivors of childhood cancer exposed to cardiotoxic therapies.