An initial health economic evaluation of pharmacogenomic testing in patients treated for childhood cancer with anthracyclines

Dionne, François; Aminkeng, Folefac; Bhavsar, Amit P.; Groeneweg, Gabriella; Smith, Anne H. W.; Visscher, Henk; Rassekh, Shahrad R.; Ross, Colin J.D.; Carleton, Bruce

doi:10.1002/pbc.26887

Cited by 9 publications

(9 citation statements)

References 37 publications

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“…Using actual data from the Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Converting-Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial (PARADIGM-HF), Packer coauthored a letter with Claggett et al 2 that derived actuarial estimates of age-specific expected survival times and found that PARADIGM-HF-eligible patients aged 55 years have a projected life expectancy of 11.6 years while receiving enalapril and 12.9 years with sacubitril/valsartan, a difference of 1.3 years. 2 Similar survival estimates were reported for PARADIGM-HF-eligible patients aged 65 years (10 years for enalapril vs 11.4 years for sacubitril/valsartan). 2 These survivals are clearly at or over the 10-year duration that Packer states is "irrelevant" for patients after heart failure.…”

Section: Conflict Of Interestsupporting

confidence: 70%

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Potential of Oncocardiology

2017

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Section: Conflict Of Interestsupporting

confidence: 70%

“…Interestingly, RARG (rs2229774) was shown to increase the transcription of topoisomerase IIβ. 2 Thus, patients who developed anthracycline-induced cardiotoxicity are predicted to have higher topoisomerase IIβ expression. This is consistent with the new paradigm described in our review.…”

Section: Jennifer Cautela MD Nathalie Lalevee Phd Franck Thuny Md Phdmentioning

confidence: 99%

Potential of Oncocardiology

2017

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“…All other patients should be considered at moderate genetic risk. An initial health economic evaluation of pharmacogenomic testing in patients treated for childhood cancer with anthracyclines suggests that information gained from the pharmacogenomic test could reduce mortality by approximately 17% and reduce costs by about 6% [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular Health Status And Genetic Risk In Survivors of Childhood Neuroblastoma and Nephroblastoma Treated With Doxorubicin: Protocol of the Pharmacogenetic Part of the LESS-Anthra Cross-Sectional Cohort Study

Zolk¹,

Knesebeck²,

Graf³

et al. 2022

JMIR Res Protoc

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Background In childhood cancer survivors (survival of 5 years or more after diagnosis), cardiac toxicity is the most common nonmalignant cause of death attributed to treatment-related consequences. Identifying patients at risk of developing late cardiac toxicity is therefore crucial to improving treatment outcomes. The use of genetic markers has been proposed, together with clinical risk factors, to predict individual risk of cardiac toxicity from cancer therapies, such as doxorubicin. Objective The primary aim of this study is to evaluate the value of multimarker genetic testing for RARG rs2229774, UGT1A6 rs17863783, and SLC28A3 rs7853758 for predicting doxorubicin-induced cardiotoxicity. The secondary aim is to replicate previously described associations of candidate genetic markers with doxorubicin-induced cardiotoxicity. Moreover, we will evaluate the prevalence of cardiovascular dysfunction in childhood cancer survivors after neuroblastoma or nephroblastoma. Methods This is the pharmacogenetic substudy of the research project Structural Optimization for Children With Cancer After Anthracycline Therapy (LESS-Anthra). We invited 2158 survivors of childhood neuroblastoma or nephroblastoma treated with doxorubicin according to the trial protocols of SIOP 9/GPOH, SIOP 93-01/GPOH, SIOP 2001/GPOH, NB 90, NB 97, or NB 2004 to participate in this prospective cross-sectional cohort study. The study participants underwent a cardiological examination and were asked to provide a blood or saliva sample for genotyping. The study participants' health statuses and cardiovascular diagnoses were recorded using a questionnaire completed by the cardiologist. Digital echocardiographic data were centrally evaluated to determine the contractile function parameters. Medical data on the tumor diagnosis and treatment protocol were taken from the study documentation. Survivors were screened for variants of several candidate genes by TaqMan genotyping. Results This study includes 657 survivors treated with doxorubicin for childhood cancer, the largest German cohort assembled to date to investigate cardiovascular late effects. Data analyses are yet to be completed. Conclusions This study will define the genetic risk related to 3 marker genes proposed in a pharmacogenetic guideline for risk assessment. Moreover, the results of this study will show the prevalence of cardiovascular dysfunction in survivors of pediatric neuroblastoma or nephroblastoma who were treated with doxorubicin. The results will help to improve primary treatment and follow-up care, thus reducing cardiovascular late effects in the growing population of childhood cancer survivors. Trial Registration German Clinical Trials Register DRKS00015084; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00015084 International Registered Report Identifier (IRRID) DERR1-10.2196/27898

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“…This was comparable to PPV of 34.4% and NPV 90.9% obtained in other studies 9,19,41 . With current care, the estimated average lifetime cost of DIC is $8,667 per treated patient 42 . Our test will reduce DIC related life cost and deaths in 33% of patients who carry the risk variants.…”

Section: Discussionmentioning

confidence: 99%

Cardiotoxicity and pharmacogenetics of doxorubicin in black Zimbabwean breast cancer patients

Nyangwara

Mazhindu

Chikwambi

et al. 2022

Preprint

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AIMS Doxorubicin-induced cardiotoxicity (DIC) is a significant cause of mortality in cancer care. This study was conducted to establish the frequency of DIC in Zimbabwean breast cancer patients on doxorubicin and to test the DIC predictive power of genetic biomarkers. METHODS A cohort of 50 Zimbabwean breast cancer patients treated with doxorubicin were followed up for 12 months with serial echocardiography and genotyped for UGTA1A6*4, SLC28A3 and RARG. 11% of the patients experienced DIC. RESULTS The frequency of SLC28A3 (rs7853758), UGT1A6*4 (rs17863783) and RARG (rs2229774) was 60.7%, 17.9% and 14.3% respectively. No association between DIC and the three variants was observed. CONCLUSIONS This is the first study on the prevalence of DIC and associated genetic biomarker predictive evaluation in Zimbabwean breast cancer patients. The genetic frequencies observed in our study was different to that reported in other populations. A larger sample size with a longer follow up time will be necessary in future studies.

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An initial health economic evaluation of pharmacogenomic testing in patients treated for childhood cancer with anthracyclines

Cited by 9 publications

References 37 publications

Potential of Oncocardiology

Potential of Oncocardiology

Cardiovascular Health Status And Genetic Risk In Survivors of Childhood Neuroblastoma and Nephroblastoma Treated With Doxorubicin: Protocol of the Pharmacogenetic Part of the LESS-Anthra Cross-Sectional Cohort Study

Cardiotoxicity and pharmacogenetics of doxorubicin in black Zimbabwean breast cancer patients

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