Dexrazoxane and heart function among long-term childhood cancer survivors: A Children’s Oncology Group study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10513-10513
Author(s):  
Eric Jessen Chow ◽  
Sanjeev Aggarwal ◽  
David R Doody ◽  
Richard Aplenc ◽  
Saro Armenian ◽  
...  

10513 Background: Dexrazoxane (DRZ) has cardioprotective effects among doxorubicin (DOX) treated childhood cancer survivors up to 5 years after therapy. However, longer-term data are lacking. Methods: P9404, P9425, P9426, and DFCI 95-01 were randomized trials of acute lymphoblastic leukemia and Hodgkin lymphoma, where patients were randomly assigned to DOX±DRZ. P9754 enrolled osteosarcoma patients who all received DOX+DRZ. In all studies, DRZ was given as an intravenous bolus before DOX (10:1mg ratio). DOX doses ranged from 100-600 mg/m2 across these 5 trials. A subset of COG institutions prospectively assessed cardiac function in long-term survivors from these trials, plus a matched group of osteosarcoma survivors treated with DOX alone. Echocardiograms (left ventricular [LV] Biplane ejection fraction [EF], shortening fraction [SF]) and blood biomarkers (b-type natriuretic peptides [BNP], N-terminal [NT] proBNP) were all analyzed centrally, with DRZ status masked. Lower LV function was defined as EF<50% or SF<30%. T-test, rank-sum, and multivariate regression adjusted for sex, cancer diagnosis age, current age, DOX dose, and chest radiotherapy were used to examine differences and associations by DRZ status. Results: Among 173 participants assessed (52% DRZ+; 54% male; mean DOX 294±96 mg/m2) 17.6±2.4y since cancer diagnosis, DRZ+ participants were slightly younger (27.8 vs 29.6y, p=0.02), but baseline characteristics otherwise did not differ significantly by DRZ status. DRZ status was associated with higher FS (34.7±3.6% vs 33.4±4.3%, p=0.04) and EF (63.4±5.4% vs 61.4±5.5%, p=0.01), and lower BNP (median 10.4 pg/mL [IQR 6.0-18.0] vs 13.0 [IQR 6.0-28.2], p=0.03) and NT-proBNP (median 30.8 pg/mL [IQR 18.9-58.2] vs 47.1 [IQR 23.0-83.1], p<0.01). In stratified analyses, the cardioprotective effects associated with DRZ tended to be more pronounced in females (vs males) and those who received DOX ≥300 mg/m2 (vs <300mg/m2). Results from multivariate models were similar: DRZ was associated with higher SF (1.4% [95% CI 0.2, 2.6]) and EF (2.7% [95% CI 0.8, 4.6]), and reduced BNP (-4.0 pg/mL [95% CI -7.6, -0.4]) and NT-proBNP (-20.7 pg/mL [95% CI -33.5, -7.9]). Overall, DRZ was associated with a reduced risk of having lower LV function (odds ratio 0.27 [95% CI 0.08-0.96]). Conclusions: After >17y, childhood cancer survivors treated with DOX+DRZ had better LV systolic function and less myocardial wall stress compared with those treated with DOX alone. DRZ may preferentially benefit females and those treated with greater DOX doses.

2016 ◽  
Vol 68 (Suppl. 3) ◽  
pp. 10-14 ◽  
Author(s):  
Saro H. Armenian

While the increased rates of survival in childhood cancers have increased progressively in recent decades, many childhood cancer survivors will have at least one chronic health condition within 40 years of age. In this regard, cardiovascular complications have emerged as a leading cause of long-term morbidity and mortality in long-term survivors of childhood cancer, likely due to exposure to anthracycline chemotherapy, and outcomes in patients with anthracycline-related cardiomyopathy remain poor. Some progress has been made in understanding the mechanisms at the basis of anthracycline-related cardiomyopathy, which appear to involve generation of reactive oxygen species, leading to mitochondrial dysfunction, followed by myocyte apoptosis and maladaptive left ventricular remodeling. Even if several guidelines currently exist for monitoring cancer patients treated with cardiotoxic therapies who are at high risk for heart failure, much work remains to be done in finding reliable markers for screening for cardiac dysfunction. Studies from our group have identified alterations in L-carnitine in cancer survivors. While additional investigations are needed, preliminary studies suggest a role for carnitine in primary prevention (during treatment) and secondary prevention (to improve function after treatment).


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e23070-e23070
Author(s):  
Wendy Bottinor ◽  
Justin Godown ◽  
Gary Coburn ◽  
Jonathan Soslow ◽  
Scott C. Borinstein

e23070 Background: In patients receiving active chemotherapy, myocardial strain has prognostic utility for risk of subsequent cardiomyopathy. We hypothesized a decrement in strain in early off-treatment childhood cancer survivors (CCS) is prognostic for developing cardiomyopathy. Methods: Retrospective analysis was performed in 22 CCS. Global longitudinal strain (GLS) and global circumferential strain (GCS) were assessed at baseline and on the first end-of-treatment study with adequate imaging quality. Parametric methods assessed the association between changes in GLS/GCS and cardiovascular outcomes. Results: All CCS had normal echocardiograms at baseline and on the first end-of-treatment study . On long-term follow up 5/22 developed echocardiographic abnormalities defined as either left ventricular ejection fraction < 55% (n = 4) and/or left ventricular mass Z score < -2.0 (n = 4). Mean age at diagnosis was (mean ± SEM) 13.0 ± 1.3 and 10.7 ± 1.2, p = 0.37 for those without and with long-term abnormalities respectively. Patients who developed long-term echocardiographic abnormalities had a greater decrement in GCS between baseline and fist end-of-treatment echocardiograms (-6.9 ± 0.9% vs -0.7 ± 1.2%, p = 0.011) and a trend towards greater decrement in GLS (-1.5 ± 1.3% vs 1.2 ± 0.7%, p = 0.069). In early off-therapy CCS an absolute change in GCS of 7% was associated with subsequent cardiovascular dysfunction within 10 years. Conclusions: Change in GCS of 7% or greater from baseline to first end-of-treatment echocardiogram may identify CCS at risk for cardiomyopathy on long-term follow up and offer a window for early intervention. Strain imaging may provide an early method of identifying CCS at higher risk for developing cardiomyopathy on long-term follow up. These survivors may benefit from increased surveillance or early intervention with cardioprotective therapies.


PLoS ONE ◽  
2020 ◽  
Vol 15 (5) ◽  
pp. e0232708
Author(s):  
Nina Streefkerk ◽  
Wim J. E. Tissing ◽  
Joke C. Korevaar ◽  
Eline van Dulmen-den Broeder ◽  
Dorine Bresters ◽  
...  

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Maria Otth ◽  
Patrick Wechsler ◽  
Sibylle Denzler ◽  
Henrik Koehler ◽  
Katrin Scheinemann

Abstract Background The successful transition of childhood cancer survivors (CCSs) from pediatric to adult long-term follow-up care is a critical phase, and determining the right time point can be challenging. We assessed the feasibility of the use of existing transition readiness tools in the context of the Swiss health care system, assessed partly transition readiness in Swiss CCSs, and compared our findings with Canadian CCSs for which these tools were originally developed. Methods We officially translated the Cancer Worry Scale (CWS) and Self-Management Skill Scale (SMSS) into German and integrated them into this cross-sectional study. We included CCSs attending the long-term follow-up (LTFU) clinic in the Division of Oncology-Hematology, Department of Pediatrics, Kantonsspital Aarau. We used descriptive statistics to describe transition readiness. Results We randomly recruited 50 CCSs aged ≥18 years at participation. The CCSs had a median CWS score of 62 (interquartile range 55–71), indicating a moderate level of cancer-related worry. Despite high self-management skills, some answers showed a dependency of CCSs on their parents. Our experience shows that the CWS and SMSS are easy for Swiss CCSs to use, understand, and complete. The interpretation of the results must take differences in health care systems between countries into account. Conclusions The translated CWS and SMSS are appropriate additional measures to assess transition readiness in CCSs. These scales can be used longitudinally to find the individual time point for transition and the completion by CCSs enables the health care team to individualize the transition process and to support the CCSs according to their individual needs.


2014 ◽  
Vol 62 (2) ◽  
pp. 322-328 ◽  
Author(s):  
Morven C. Brown ◽  
Gillian A. Levitt ◽  
Eva Frey ◽  
Edit Bárdi ◽  
Riccardo Haupt ◽  
...  

2004 ◽  
Vol 13 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Sigrid Pemberger ◽  
Reinhold Jagsch ◽  
Eva Frey ◽  
Rosemarie Felder-Puig ◽  
Helmut Gadner ◽  
...  

Author(s):  
L. M. E. van Erp ◽  
H. Maurice-Stam ◽  
L. C. M. Kremer ◽  
W. J. E. Tissing ◽  
H. J. H. van der Pal ◽  
...  

Abstract Purpose This study aimed to increase our understanding of the psychosocial well-being of young adult childhood cancer survivors (YACCS) as well as the positive and negative impacts of cancer. Methods YACCS (aged 18–30, diagnosed ≤ 18, time since diagnosis ≥ 5 years) cross-sectionally filled out the “Pediatric Quality of Life Inventory Young Adults” (PedsQL-YA), “Hospital Anxiety and Depression Scale” (HADS), and “Checklist Individual Strengths” (CIS-20R) to measure fatigue and survivor-specific “Impact of Cancer - Childhood Survivors” (IOC-CS), which measures the long-term impact of childhood cancer in several domains. Descriptive statistics (IOC-CS), logistic regression (HADS, CIS-20R), and ANOVA (PedsQL-YA, HADS, CIS-20R) were performed. Associations between positive and negative impacts of childhood cancer and psychosocial outcomes were examined with linear regression analyses. Results YACCS (N = 151, 61.6% female, mean age 24.1 ± 3.6, mean time since diagnosis 13.6 ± 3.8) reported lower HRQOL (− .4 ≤ d ≤ − .5, p ≤ .001) and more anxiety (d = .4, p ≤ .001), depression (d = .4, p ≤ .01), and fatigue (.3 ≤ d ≤ .5, p ≤ .001) than young adults from the general Dutch population. They were at an increased risk of experiencing (sub)clinical anxiety (OR = 1.8, p = .017). YACCS reported more impact on scales representing a positive rather than negative impact of CC. Various domains of impact of childhood cancer were related to psychosocial outcomes, especially “Life Challenges” (HRQOL β = − .18, anxiety β = .36, depression β = .29) and “Body & Health” (HRQOL β = .27, anxiety β = − .25, depression β = − .26, fatigue β = − .47). Conclusion YACCS are vulnerable to psychosocial difficulties, but they also experience positive long-term impacts of childhood cancer. Positive and negative impacts of childhood cancer were associated with psychosocial outcomes in YACCS. Screening of psychosocial outcomes and offering targeted interventions are necessary to optimize psychosocial long-term follow-up care for YACCS.


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