P693Cardiac biomarkers for the detection of anthracycline cardiotoxicity in childhood cancer - a meta-analysis

Abstract Introduction Heart failure is the most concerning cardiovascular side effect of anthracycline chemotherapy. Pediatric cancer patients and survivors of childhood cancer are particularly vulnerable to cancer therapy-related cardiotoxicity. Cardiac biomarkers may be beneficial for screening and diagnosis of anthracycline-related heart failure in pediatric cancer patients and survivors of childhood cancer but systematic data is not yet available. Purpose To evaluate (N-terminal pro) brain natriuretic peptide (BNP/NT-proBNP) and cardiac troponin for screening and prediction of cancer therapy-related cardiotoxicity in pediatric cancer patients and survivors of childhood cancer. Methods Cochrane, PubMed, Web of Science, and Wiley Library were screened for studies investigating cardiac troponin or BNP/NT-proBNP in pediatric cancer patients receiving anthracycline therapy or survivors of childhood cancer. The primary endpoint was left ventricular (LV) dysfunction as defined by decreased ejection fraction (EF) or fractional shortening (FS). The study was registered at the International prospective register of systematic reviews (PROSPERO) (CRD42018106616). Results A total of 1643 subjects from 27 studies were included. BNP/NT-proBNP levels were higher in patients post-treatment compared to control subjects or pre-treatment values (standardized mean difference = 1.0; 95% CI: 0.6–1.4; n=239). The risk for left ventricular (LV) dysfunction was increased in patients with elevated BNP/NT-proBNP (OR=5.5; 95% CI: 2.0–15.2; n=357). This was demonstrated for acute cardiotoxicity (OR=22.3; 95% CI: 3.3–151.1; n=88) and in survivors of childhood cancer (OR=3.2; 95% CI: 1.0–10.0; n=269). Sensitivity for the prediction of acute or subacute LV dysfunction was 28.9% and specificity was at 91.7%. The frequency of troponin elevations was increased after anthracycline therapy (OR=3.6; 95% CI: 2.0–6.5; n=305) but troponin was not associated with LV dysfunction (OR=0.2; 95% CI: −0.2 to 0.5; n=273). Conclusion BNP/NT-proBNP is elevated in pediatric patients receiving anthracycline chemotherapy and serves as a marker for the prediction of cardiotoxicity and screening for late cardiotoxicity in survivors of childhood cancer. So far, there is no systematic evidence on a benefit of cardiac troponin for the detection of anthracycline cardiotoxicity in children. Standardized recommendations on the role of cardiac biomarkers are needed for the optimal detection of anthracycline cardiotoxicity in childhood cancer patients. Acknowledgement/Funding IFORES research grant of the Medical Faculty, University Duisburg-Essen, Essen, Germany

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The Utility of Verbal Therapy for Pediatric Cancer Patients and Survivors: Expressive Writing, Video Narratives, and Bibliotherapy Exercises

Frontiers in Pediatrics ◽

10.3389/fped.2021.579003 ◽

2021 ◽

Vol 9 ◽

Author(s):

Jill K. Jones ◽

John F. Evans ◽

Raymond C. Barfield

Keyword(s):

Quality Of Life ◽

Childhood Cancer ◽

Cancer Patients ◽

Pediatric Cancer ◽

Expressive Writing ◽

Pediatric Cancer Patients ◽

Stressful Experience ◽

Cancer Experience ◽

Survivors Of Childhood Cancer

Childhood cancer is a stressful experience. No pediatric patient, however, should be made to feel as if their concerns and feelings about their cancer experience must be bottled up inside. Importantly, talking and writing about one's illness has myriad implications for young cancer patients and survivors. The most salient of these may include increased understanding of one's condition as well as improved physical and cognitive symptoms (e.g., lowered depression, decreased anxiety, and an enhanced quality of life overall). This literature review explores three promising avenues for verbal therapy in the pediatric oncology setting: expressive writing, video narratives, and bibliotherapy exercises. Several recent studies, covering verbal therapy methods from illness blogging to book interventions, are referenced and discussed. Ultimately, we conclude that expressive writing, video narratives, and bibliotherapy exercises are valuable, feasible, inexpensive, and acceptable tools for patients and survivors of childhood cancer to facilitate self-expression—and to find meaning in the uncertainty and anxiety that cancer inherently fosters. We recommend that future studies investigate this theme so that we may improve quality of life and mental health for pediatric cancer patients and survivors worldwide.

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P1568Cardiac biomarkers for the prediction of cardiotoxicity in cancer patients: a meta-analysis

European Heart Journal ◽

10.1093/eurheartj/ehz748.0328 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Cited By ~ 3

Author(s):

L Michel ◽

R I Mincu ◽

A A Mahabadi ◽

F Al-Rashid ◽

T Rassaf ◽

...

Keyword(s):

Cancer Therapy ◽

Cancer Patients ◽

Cardiac Troponin ◽

Meta Analysis ◽

High Dose Chemotherapy ◽

Left Ventricular ◽

Inhibitor Therapy ◽

Cardiac Biomarkers ◽

High Dose ◽

Β Blocker

Abstract Background Cancer therapy-related heart failure is the most concerning cardiac adverse event in patients undergoing cancer therapy. Valid diagnostic measures are fundamental for a timely diagnosis but systematic data on the use of diagnostic parameters in this collective is sparse. Cardiac biomarkers may be beneficial for diagnosis and screening of cancer therapy-related heart failure. Purpose Systematic data for cardiac biomarkers in cancer therapy-related cardiotoxicity is urgently needed to establish guideline recommendations. We therefore conducted the present systematic review and meta-analysis to assess cardiac troponin and (N-terminal pro) brain natriuretic peptide (BNP/NT-proBNP) in the prediction of left ventricular (LV) systolic dysfunction in cancer patients. Methods Cochrane, PubMed, Web of Science, and Wiley Library were screened for studies investigating cardiac troponin or BNP/NT-proBNP in cancer patients receiving cytotoxic chemotherapy with and without anthracyclines, human epidermal growth factor receptor 2 (HER2) inhibitor therapy and radiotherapy. Reduced LV ejection fraction (LVEF) was defined as primary endpoint. Results A total of 5772 patients from 58 studies were included. Chemotherapy and HER2 inhibitor therapy was associated with an elevation of troponin levels above the 99th percentile (odds ratio (OR) = 14.3; 95% confidence interval (CI): 6.9–29.5). Patients treated with anthracyclines and high-dose chemotherapy had the highest rates of troponin elevation (OR = 17.5; 95% CI: 10.1–30.2 for anthracyclines; OR = 75.1; 95% CI: 4.4–1296.9 for high-dose chemotherapy, respectively). The risk for LVEF impairment was increased in troponin positive patients compared to troponin negative patients under high-dose regimens (OR = 97.9; 95% CI: 52.1–183.8) and anthracyclines with and without concomitant HER2 inhibitors (OR = 7.0; 95% CI: 1.4–34.1 and OR = 10.5; 95% CI: 2.0–54.3). Cardiac troponin below the 99th percentile had a negative predictive value of 94% for the prediction of cardiotoxicity. Absolute plasma BNP/NT-proBNP was increased in patients with LV dysfunction (standardized mean difference = 0.6; 95% CI = 0.0–1.2) but pathologically increased BNP/NT-proBNP did not predict decreased LVEF (OR = 2.0; 95% CI: 0.9–7.2). Preventive β-blocker therapy and angiotensin converting enzyme (ACE) inhibitor therapy was associated with decreased troponin elevation compared to control (OR = 2.9; 95% CI: 1.1–7.3; Figure 4). The effect was more pronounced in ACE inhibitor-treated patients compared to β-blocker-treated patients (Chi2 = 4.4; p=0.04; I2 = 77.4%). Conclusion Elevated troponin levels predict left ventricular dysfunction in cancer patients and a decrease in troponin may indicate response to cardioprotective therapy in cancer therapy-related cardiotoxicity. Cardiac troponin qualifies as a screening test to identify patients at high risk for manifest cardiotoxicity who require referral to cardio-oncology units. Acknowledgement/Funding IFORES research grant of the Medical Faculty, University Duisburg-Essen, Essen, Germany

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Bullying in pediatric cancer patients in a third level hospital in Mexico city

Journal of Neurology & Stroke ◽

10.15406/jnsk.2021.11.00445 ◽

2021 ◽

Vol 11 (1) ◽

pp. 7-10

Author(s):

Indira Judith Arreguín-González ◽

Farina Esther Arreguín-González ◽

Andrea López-Soule ◽

Delfino Eduardo Ordaz-Velázquez ◽

Juan Miguel Salgado-Ramírez

Keyword(s):

Cancer Survivors ◽

Childhood Cancer ◽

Cancer Patients ◽

Mexico City ◽

Pediatric Cancer ◽

Childhood Cancer Survivors ◽

Patients Âgés ◽

Pediatric Cancer Patients ◽

Being Bullied ◽

Level Hospital

Aim: Determine if childhood cancer patients suffer bullying and identify its causes Compare what patients say about bullying, when they are alone versus presence of their parents. Method: We studied 47 childhood cancer patients ages varied between 5 and 17 years old. With previous parental authorization we applied a questionnaire called “That´s how we hang out at school” in two moments, first one in presence of their parents, and the second one without them. Results: Scholar childhood cancer survivors suffer bullying in 89.4%, in contrast with 25.8% of children without cancer suffered bullying according to literature. Secquelae and alopecia were the main causes for bullying, also teacher´s and Student´s lack of knowledge thinking that cancer is contagious. We also observed that children accepted being bullied in presence of the doctor, but not in front of their parents. Conclusion: Childhood cancer patients are more harassed than children without cancer due to secqueale, atipya or consumption that they present, also, fear of contagion enhances harassment and lack of teacher´s intervention. Children deny being bullied in front of their parents, but accept it without them.

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Mutational Consequences of Chemotherapy in Hematopoietic Stem and Progenitor Cells of Pediatric Cancer Patients

Blood ◽

10.1182/blood-2021-148471 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2154-2154

Author(s):

Eline J.M. Bertrums ◽

Axel Rosendahl-Huber ◽

Jurrian de Kanter ◽

Anais C.N. van Leeuwen ◽

Flavia Peci ◽

...

Keyword(s):

Cancer Treatment ◽

Childhood Cancer ◽

Cancer Patients ◽

Pediatric Cancer ◽

Post Treatment ◽

Chemotherapeutic Drugs ◽

Induced Mutations ◽

Hematopoietic Stem ◽

Pediatric Cancer Patients

Abstract Background Childhood cancer survivors are confronted with a variety of chronic health conditions as a consequence of their life saving therapy. Chemotherapy is the cornerstone of childhood cancer treatment, which consists of combinations of various drugs administered over multiple years. Most chemotherapeutic drugs act by fatally damaging the DNA or blocking the replication thereof. Although high-intensity chemotherapy efficiently eradicates tumor cells, the impact on the genomes of normal, that is noncancerous, cells remains unknown. Mutagenicity of cancer treatment on normal hematopoietic cells may contribute to the development of chronic health conditions later in life, such as therapy-related acute myeloid leukemia (t-AML). Here, we characterized the mutational consequences of chemotherapy in the genomes of hematopoietic stem and progenitor cells (HSPCs) of children treated for cancer. Methods This study was approved by the Biobank and Data Access Committee of the Princess Máxima Center for Pediatric Oncology and all samples were obtained via the in-house biobank. We performed whole-genome sequencing (WGS) on multiple single HSPCs from all patients as well as the t-AML if available. In case of t-AML patients, samples were taken before t-AML treatment. Data on mutation accumulation in HSPCs of healthy individuals from 0-63 years of age was previously acquired. To distinguish the effects of different chemotherapies, we developed an in vitro approach using cord blood HSPCs to experimentally define the mutational consequences of individual chemotherapeutic drugs in primary human cells. Results Our cohort consisted of 22 pediatric cancer patients of which we obtained bone marrow aspirates and/or peripheral blood from timepoints pre- and post-treatment for their first cancer. We included 17 t-AML patients with varying first cancer diagnoses and five acute lymphoblastic leukemia (ALL) patients who did not develop t-AML. Patient characteristics and therapy information is described in Table 1. We compared the mutational burden of pre- and post-treatment HSPCs of the childhood cancer patients to those of healthy treatment-naïve individuals. HSPCs at time of first diagnosis of childhood cancer patients displayed a mutation burden similar to HSPCs of healthy individuals. In contrast, post-treatment HSPCs showed a significantly higher increase in mutation number over time than expected by normal ageing. We used mutational signature analysis to pinpoint the causes of this increased mutation burden in post-treatment HSPCs. Surprisingly, in most of these HSPCs the additive mutational effect could be attributed to clock-like processes, active during normal aging. Only few chemotherapeutic drugs showed direct mutagenic effects, such as platinum drugs and thiopurines. Whereas cisplatin-induced mutations could be observed in all cells exposed to this drug, thiopurine-induced mutations were present in a subset of the exposed HSPCs. These differences in thiopurine-induced mutagenesis across multiple exposed HSPCs could even be observed within individual patients. In one patient, the HSPCs containing the thiopurine-signature shared the oncogenic MLL-rearrangement with the t-AML blasts and had shorter telomeres compared to the HSPCs without this signature. This finding indicates that these cells have undergone more cell divisions, suggesting that thiopurine-induced mutagenesis requires DNA replication. We also identified novel therapy-associated mutational signatures. One of these signatures was observed in multiple patients who received a hematopoietic stem cell transplantation, as part of their cancer treatment, after which they displayed a viral reactivation for which they were treated. By WGS of in vitro exposed cord blood HSPCs, we demonstrated that this signature is caused by the antiviral drug ganciclovir, which is commonly used to treat cytomegalovirus infections. The second signature was present in HSPCs of a patient who received a combination of thiotepa and treosulfan. Conclusions Enhanced mutation accumulation after pediatric cancer treatment is caused by both direct and indirect mechanisms. The variance in mutagenic effects of (chemo)therapies on healthy HSPCs may influence the risk an individual patient has to develop t-AML and could, in future, play a role in t-AML risk assessment of pediatric cancer survivors and the development of new treatment regimens. Figure 1 Figure 1. Disclosures Zwaan: Sanofi: Consultancy.

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Bullying in pediatric cancer patients in a third level hospital in Mexico city

Journal of Neurology & Stroke ◽

10.15406/jnsk.2020.11.00445 ◽

2020 ◽

Vol 11 (1) ◽

pp. 7-10

Author(s):

Indira Judith Arreguín-González ◽

Farina Esther Arreguín-González ◽

Andrea López-Soule ◽

Delfino Eduardo Ordaz-Velázquez ◽

Juan Miguel Salgado-Ramírez

Keyword(s):

Cancer Survivors ◽

Childhood Cancer ◽

Cancer Patients ◽

Mexico City ◽

Pediatric Cancer ◽

Childhood Cancer Survivors ◽

Patients Âgés ◽

Pediatric Cancer Patients ◽

Being Bullied ◽

Level Hospital

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Cardiac radiation dose in pediatric cancer patients is associated with tricuspid regurgitation and decreased left ventricular wall thickness

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2004.07.016 ◽

2004 ◽

Vol 60 (1) ◽

pp. S248-S249

Author(s):

E.R. Hale ◽

L.S. Constine ◽

M.J. Adams ◽

C.A. French ◽

S.R. Lipsitz ◽

...

Keyword(s):

Radiation Dose ◽

Cancer Patients ◽

Wall Thickness ◽

Pediatric Cancer ◽

Tricuspid Regurgitation ◽

Left Ventricular ◽

Ventricular Wall ◽

Left Ventricular Wall Thickness ◽

Pediatric Cancer Patients ◽

Ventricular Wall Thickness

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The landscape of cardiovascular care in pediatric cancer patients and survivors: a survey by the ACC Pediatric Cardio-Oncology Work Group

Cardio-Oncology ◽

10.1186/s40959-019-0051-8 ◽

2019 ◽

Vol 5 (1) ◽

Cited By ~ 2

Author(s):

Thomas D. Ryan ◽

William L. Border ◽

Carissa Baker-Smith ◽

Ana Barac ◽

Matthew J. Bock ◽

...

Keyword(s):

Childhood Cancer ◽

Cancer Patients ◽

Pediatric Cancer ◽

Work Group ◽

Care Delivery ◽

Evaluation Process ◽

Cardiac Risk Factor ◽

Lv Function ◽

Pediatric Cancer Patients ◽

Cardiovascular Care

Abstract Objective To enhance the understanding of cardiovascular care delivery in childhood cancer patients and survivors. Study design A 20-question survey was created by the Pediatric Cardio-oncology Work Group of the American College of Cardiology (ACC) Cardio-oncology Section to assess the care, management, and surveillance tools utilized to manage pediatric/young adult cardio-oncology patients. The survey distribution was a collaborative effort between Cardio-oncology Section and membership of the Adult Congenital and Pediatric Cardiology Section (ACPC) of the ACC. Results Sixty-five individuals, all self-identified as physicians, responded to the survey. Most respondents (n = 58,89%) indicated childhood cancer patients are regularly screened prior to and during cancer therapy at their centers, predominantly by electrocardiogram (75%), standard echocardiogram (58%) and advanced echocardiogram (50%) (i.e. strain, stress echo). Evaluation by a cardiologist prior to/during therapy was reported by only 8(12%) respondents, as compared to post-therapy which was reported by 28 (43%, p < 0.01). The most common indications for referral to cardiology at pediatric centers were abnormal test results (n = 31,48%) and history of chemotherapy exposure (n = 27,42%). Of note, during post-treatment counseling, common cardiovascular risk-factors like blood pressure (31,48%), lipid control (22,34%), obesity & smoking (30,46%) and diet/exercise/weight loss (30,46%) were addressed by fewer respondents than was LV function (72%). Conclusions The survey data demonstrates that pediatric cancer patients are being screened by EKG and/or imaging prior to/during therapy at most centers. Our data, however, highlight the potential for greater involvement of a cardiovascular specialist for pre-treatment evaluation process, and for more systematic cardiac risk factor counseling in posttreatment cancer survivors.

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