Cardiac Function in 5-Year Survivors of Childhood Cancer

Pal, Helena J. van der; Dalen, Elvira C. van; Hauptmann, Michael; Kok, Wouter E.; Caron, Huib N.; Bos, Cor van den; Oldenburger, Foppe; Koning, Caro C.E.; Leeuwen, Flora E. van; Kremer, Leontien C. M.

doi:10.1001/archinternmed.2010.233

Cited by 156 publications

(97 citation statements)

References 41 publications

(48 reference statements)

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“…These findings suggest that there is no safe dose of anthracyclines. Even doses as low as 100 mg/m 2 have been associated with reduced cardiac function [14,16,17]. …”

Section: Cardiotoxicity Risk Factorsmentioning

confidence: 99%

Cardiotoxicity and Cardioprotection in Childhood Cancer

Lipshultz¹,

Sambatakos

Maguire

et al. 2014

Acta Haematol

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Children diagnosed with cancer are now living longer as a result of advances in treatment. However, some commonly used anticancer drugs, although effective in curing cancer, can also cause adverse late effects. The cardiotoxic effects of anthracycline chemotherapy, such as doxorubicin, and radiation can cause persistent and progressive cardiovascular damage, emphasizing a need for effective prevention and treatment to reduce or avoid cardiotoxicity. Examples of risk factors for cardiotoxicity in children include higher anthracycline cumulative dose, higher dose of radiation, younger age at diagnosis, female sex, trisomy 21 and black race. However, not all who are exposed to toxic treatments experience cardiotoxicity, suggesting the possibility of a genetic predisposition. Cardioprotective strategies under investigation include the use of dexrazoxane, which provides short- and long-term cardioprotection in children treated with doxorubicin without interfering with oncological efficacy, the use of less toxic anthracycline derivatives and nutritional supplements. Evidence-based monitoring and screening are needed to identify early signs of cardiotoxicity that have been validated as surrogates of subsequent clinically significant cardiovascular disease before the occurrence of cardiac damage, in patients who may be at higher risk.

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“…These findings suggest that there is no safe dose of anthracyclines. Even doses as low as 100 mg/m 2 have been associated with reduced cardiac function [14,16,17]. …”

Section: Cardiotoxicity Risk Factorsmentioning

confidence: 99%

Cardiotoxicity and Cardioprotection in Childhood Cancer

Lipshultz¹,

Sambatakos

Maguire

et al. 2014

Acta Haematol

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“…Doksorubisin mencegah sintesis ribonucleic acid (RNA) dan deoxyribonucleic acid (DNA) melalui proses interkalasi. [3][4][5][6][7] Toksisitas terhadap jantung dilaporkan paling banyak karena penggunaan doksorubisin. Kardiotoksisitas merupakan salah satu komplikasi jangka panjang yang serius pada terapi kanker atau keganasan.…”

unclassified

Fungsi Sistolik dan Diastolik Jantung pada Pasien Anak dengan Osteosarkoma yang Mendapat Terapi Doksorubisin Di RS Cipto Mangunkusumo

Handojo

Sjakti

Yanuarso

et al. 2016

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Latar belakang. Doksorubisin merupakan obat golongan antrasiklin yang penting dan efektif pada pengobatan tumor padat pada anak. Doksorubisin mencegah sintesis RNA dan DNA melalui proses interkalasi. Kardiotoksisitas dilaporkan paling banyak karena penggunaan doksorubisin tersebut sehingga penggunaannya masih terbatas.Tujuan. Mengetahui fungsi jantung pada anak dengan osteosarkoma setelah mendapat terapi doksorubisin di RSCM.Metode. Studi deskriptif potong lintang dilakukan di RSCM, Divisi Hematologi-Onkologi IKA dan Sub Bagian Onkologi Orthopedik dan Traumatologi, dengan menelusuri catatan registrasi dan rekam medis pasien anak dengan osteosarkoma sejak 1 Januari 2005 sampai dengan 31 Desember 2012.Hasil. Terdapat 25 subjek penelitian, 21 di antaranya selesai menjalani kemoterapi dan mendapat total dosis kumulatif doksorubisin dengan rentang 300 mg/m2 sampai 675 mg/m2. Fungsi sistolik LV mengalami penurunan rerata fraksi ejeksi 3,3% dan pemendekan 2,5% setelah mendapat doksorubisin. Fungsi diastolik LV mengalami penurunan rerata rasio E/A 17,6%. Sembilan dari 18 pasien yang selesai menjalani kemoterapi dan mendapat total dosis kumulatif doksorubisin 375 mg/m2 mengalami gangguan fungsi diastolik tidak disertai gangguan fungsi sistolik. Kardiomiopati dilatasi ditemukan pada satu pasien setelah mendapat dosis kumulatif doksorubisin 300 mg/m2 dan satu pasien setelah mendapat dosis 675 mg/m2. Pasien berusia ≥10 tahun dan berjenis kelamin perempuan lebih banyak mengalami penurunan fungsi sistolik dan diastolik LV setelah mendapat doksorubisin.Kesimpulan. Fungsi sistolik dan diastolik LV menurun setelah pasien mendapat terapi doksorubisin dengan dosis kumulatif 300 mg/m2. Penurunan fungsi diastolik mendahului penurunan fungsi sistolik LV. Dosis, usia, dan jenis kelamin perempuan dapat menjadi faktor risiko penurunan fungsi jantung setelah pemberian doksorubisin.

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“…In addition, exercise testing of childhood cancer survivors has demonstrated a below-predicted exercise capacity (22,63). The risk for cardiovascular disease was found to be high and was attributed to anthracycline treatment years earlier (2,27,49,54,65). Anthracycline use, mostly doxorubicin (DOX), daunorubicin, and epirubicin, remains common, and it is estimated that about one-half of childhood cancer survivors will have received anthracyclines.…”

mentioning

confidence: 99%

Cardiac response to doxorubicin and dexrazoxane in intact and ovariectomized young female rats at rest and after swim training

Calvé¹,

Haddad²,

Barama³

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Calvé A, Haddad R, Barama SN, Meilleur M, Sebag IA, Chalifour LE. Cardiac response to doxorubicin and dexrazoxane in intact and ovariectomized young female rats at rest and after swim training. Am J Physiol Heart Circ Physiol 302: H2048 -H2057, 2012. First published March 23, 2012; doi:10.1152/ajpheart.01069.2011The impact of cancer therapies on adult cardiac function is becoming a concern as more children survive their initial cancer. Cardiovascular disease is now a significant problem to adult survivors of childhood cancer. Specifically, doxorubicin (DOX) may be particularly harmful in young girls. The objective of this study was to characterize DOX damage and determine the ability of dexrazoxane (DEX) to reduce DOX-mediated cardiac damage in sedentary and swim-trained female rats. Female Sprague-Dawley rats were left intact or ovariectomized (OVX) at weaning then injected with DEX (60 mg/kg) before DOX (3 mg/kg), DOX alone, or PBS. Rats were separated into sedentary and swim cohorts. Body weight was reduced in DOX:DEX-but not PBSor DOX-treated rats. Echocardiographic parameters were similar in sedentary rats. Swim training revealed greater concentric remodeling in DOX-treated rats and reduced fractional shortening in DOX:DEXtreated rats. Calsequestrin 2 was reduced with DOX and increased with DOX:DEX postswim. Sarco(endo)plasmic reticulum Ca 2ϩ -ATPase 2a was reduced and calsequestrin 2 reduced further by swim training only in intact rats. OVX rats were heavier and developed eccentric remodeling post-swim with DOX and eccentric hypertrophy with DOX:DEX. Changes in SERCA2a and calsequestrin 2 expression were not observed. Ovariectomized DOX-and DOX:DEXtreated rats stopped growing during swim training. DEX coinjection did not relieve DOX-mediated cardiotoxicity in intact or hormonedeficient rats. DOX-mediated reductions in growth, cardiac function, and expression of calcium homeostasis proteins were exacerbated by swim. DEX coadministration did not substantially relieve DOXmediated cardiotoxicity in young female rats. Ovarian hormones reduce DOX-induced cardiotoxicity.echocardiography; Sprague-Dawley rat; ovariectomy; sarco(endo) plasmic reticulum Ca 2ϩ -ATPase 2a; calsequestrin 2IT IS WELL RECOGNIZED THAT increasing numbers of children now survive childhood cancer because of treatment improvements. However, almost two-thirds of childhood cancer survivors have at least one chronic illness and close to one-third had severe or life-threatening conditions when only in their midtwenties (9, 44, 61). In addition, exercise testing of childhood cancer survivors has demonstrated a below-predicted exercise capacity (22, 63). The risk for cardiovascular disease was found to be high and was attributed to anthracycline treatment years earlier (2,27,49,54,65). Anthracycline use, mostly doxorubicin (DOX), daunorubicin, and epirubicin, remains common, and it is estimated that about one-half of childhood cancer survivors will have received anthracyclines. Evidence suggests that young females may have a greater incidence of DOX...

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Cardiac Function in 5-Year Survivors of Childhood Cancer

Cited by 156 publications

References 41 publications

Cardiotoxicity and Cardioprotection in Childhood Cancer

Cardiotoxicity and Cardioprotection in Childhood Cancer

Fungsi Sistolik dan Diastolik Jantung pada Pasien Anak dengan Osteosarkoma yang Mendapat Terapi Doksorubisin Di RS Cipto Mangunkusumo

Cardiac response to doxorubicin and dexrazoxane in intact and ovariectomized young female rats at rest and after swim training

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