Anthracycline induced cardiac toxicity in pediatric Ewing sarcoma: A longitudinal study

Brown, Tanya; Vijarnsorn, Chodchanok; Potts, Jim; Milner, Ruth; Sandor, George G.S.; Fryer, Christopher

doi:10.1002/pbc.24404

Cited by 39 publications

(37 citation statements)

References 43 publications

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“…After 300-450 mg/m 2 of doxorubicin, the incidence of cardiomyopathy is significant [12][13][14][15][16] with systolic dysfunction in more than 25% of patients beyond 15 years. [15] Many long-term survivors are still young (40-50 years old) and at risk for cardiac deterioration over the ensuing decades.…”

Section: Introductionmentioning

confidence: 99%

Intensified Chemotherapy With Dexrazoxane Cardioprotection in Newly Diagnosed Nonmetastatic Osteosarcoma: A Report From the Children's Oncology Group

Schwartz

Wexler

Krailo

et al. 2015

Pediatric Blood & Cancer

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Background Although chemotherapy has improved outcome of osteosarcoma, 30–40% of patients succumb to this disease. Survivors experience substantial morbidity and mortality from anthracycline-induced cardiotoxicity. We hypothesized that the cardioprotectant dexrazoxane would 1) support escalation of the cumulative doxorubicin dose (600 mg/m2) and 2) not interfere with the cytotoxicity of chemotherapy measured by necrosis grading in comparison to historical control data.9 Procedure Children and adolescents with non-metastatic osteosarcoma were treated with MAP (methotrexate, doxorubicin, cisplatin) or MAPI (MAP/ifosfamide). Dexrazoxane was administered with all doxorubicin doses. Cardioprotection was assessed by measuring left ventricular fractional shortening. Interference with chemotherapy-induced cytotoxicity was determined by measuring tumor necrosis after induction chemotherapy. Feasibility of intensifying therapy with either high cumulative-dose doxorubicin or high-dose ifosfamide/etoposide was evaluated for ‘standard responders’ (SR, <98% tumor necrosis at definitive surgery). Results Dexrazoxane did not compromise response to induction chemotherapy. With doxorubicin (450–600 mg/m2) and dexrazoxane, grade 1 or 2 left ventricular dysfunction occurred in 5 patients; 4/5 had transient effects. Left ventricular fractional shortening z-scores (FSZ) showed minimal reductions (0.0170 ±0.009/week) over 78 weeks. Two patients (<1%) had secondary leukemia, one as a first event, a similar rate to what has been observed in prior trials. Intensification with high-dose ifosfamide/etoposide was also feasible. Conclusions Dexrazoxane cardioprotection was safely administered. It did not impair tumor response or increase the risk of secondary malignancy. Dexrazoxane allowed for therapeutic intensification, increasing the cumulative doxorubicin dose in SR to induction chemotherapy. These findings support the use of dexrazoxane in children and adolescents with osteosarcoma.

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Section: Introductionmentioning

confidence: 99%

Intensified Chemotherapy With Dexrazoxane Cardioprotection in Newly Diagnosed Nonmetastatic Osteosarcoma: A Report From the Children's Oncology Group

Schwartz

Wexler

Krailo

et al. 2015

Pediatric Blood & Cancer

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“…n Anthracycline-induced cardiac toxicity Anthracyclines are a class of cytotoxic drug used to treat many cancers and are associated with cardiotoxicity (anthracycline-induced cardiotoxicity). In pediatric Ewing sarcoma patients, age was identified as a risk factor (p < 0.004), with young age associated with a higher incidence of cardiotoxicity [49].…”

Section: Pediatric Oncology and Hematologymentioning

confidence: 99%

Pediatric Perspective on Pharmacogenomics

et al. 2013

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The advances in high-throughput genomic technologies have improved the understanding of disease pathophysiology and have allowed a better characterization of drug response and toxicity based on individual genetic make up. Pharmacogenomics is being recognized as a valid approach used to identify patients who are more likely to respond to medication, or those in whom there is a high probability of developing severe adverse drug reactions. An increasing number of pharmacogenomic studies are being published, most include only adults. A few studies have shown the impact of pharmacogenomics in pediatrics, highlighting a key difference between children and adults, which is the contribution of developmental changes to therapeutic responses across different age groups. This review focuses on pharmacogenomic research in pediatrics, providing examples from common pediatric conditions and emphasizing their developmental context.

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“…However, months to years later, they experience debilitating functional impairments. [97, 98, 100, 103–106] , [107] There is a window of time between exposure to cancer therapy and future morbidity, which could be used for corrective actions. Unfortunately, once cancer survivors present with clinical symptoms, it is often too late for health-preserving interventions.…”

Section: Detect Chemotherapy-induced Tissue Injuriesmentioning

confidence: 99%

How PET/MR Can Add Value for Children with Cancer

Daldrup-Link

2017

Curr Radiol Rep

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Purpose To review how PET/MR technology could add value for pediatric cancer patients. Recent Findings Since many primary tumors in children are evaluated with MRI and metastases are detected with PET/CT, integrated PET/MR can be a time-efficient and convenient solution for pediatric cancer staging. 18F-FDG PET/MR can assess primary tumors and the whole body in one imaging session, avoid repetitive anesthesia and reduce radiation exposure compared to 18F-FDG PET/CT. This article lists 10 action points, which might improve the clinical value of PET/MR for children with cancer. However, even if PET/MR proves valuable, it cannot enter mainstream applications if it is not accessible to the majority of pediatric cancer patients. Therefore, innovations are needed to make PET/MR scanners affordable and increase patient throughput. Summary PET/MR offers opportunities for more efficient, accurate and safe diagnoses of pediatric cancer patients. The impact on patient management and outcomes has to be substantiated by large-scale prospective clinical trials.

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Anthracycline induced cardiac toxicity in pediatric Ewing sarcoma: A longitudinal study

Abstract: The high incidence of cardiotoxicity associated with higher administered anthracycline dose, young age, bolus infusion, and EF decline warrants evaluation in a larger cohort.

Cited by 39 publications

References 43 publications

Intensified Chemotherapy With Dexrazoxane Cardioprotection in Newly Diagnosed Nonmetastatic Osteosarcoma: A Report From the Children's Oncology Group

Intensified Chemotherapy With Dexrazoxane Cardioprotection in Newly Diagnosed Nonmetastatic Osteosarcoma: A Report From the Children's Oncology Group

Pediatric Perspective on Pharmacogenomics

How PET/MR Can Add Value for Children with Cancer

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