Recent employment trend of childhood cancer survivors in Japan: a cross-sectional survey

9591 Background: Bleomycin has been established as a pulmonary toxin, but the risk for toxicity in survivors of childhood cancer is poorly characterized. Methods: We conducted a cross-sectional study of lung function in survivors of childhood Hodgkin lymphoma and germ cell tumor treated with bleomycin at our institution between 1997 and 2010. We assessed their most recent post-therapy pulmonary function test (PFT). Spirometry and lung volumes were categorized as normal, restrictive, obstructive or mixed. Diffusing capacity of carbon monoxide (DLCO) was categorized as normal or abnormal. Results: 195 patients were treated with bleomycin. Ten died of non-pulmonary causes. Of 185 survivors, 143 (77%) had complete data available for analysis. Median cumulative bleomycin dose was 60U/m2 (IQR 30-60). Three patients (2%) had a history of acute bleomycin toxicity. PFTs were performed a median of 2.3 years (IQR 1.4-4.9) from completion of therapy. Spirometry was abnormal in 58 patients (41%); of whom 5 (9%) had respiratory symptoms. 42 (70%) had obstructive, 11 (18%) restrictive and 5 (9%) mixed ventilatory defects. Abnormalities were mild in 53 (91%), moderate in 3 (5%) and severe in 2 (4%). DLCO was abnormal in 27 patients, 26 (96%) of whom had mildly reduced DLCO and were asymptomatic. Univariate analysis did not demonstrate a significant association between gender, smoking, lung metastases, lung radiation, chemotherapy regimen, or autologous transplant and abnormal lung function. Disease relapse was associated with abnormal lung function (p=0.01). Smoking (p=0.04) and relapse (p=0.03) were associated with abnormal DLCO. The odds ratio of developing abnormal spirometry for each 1unit/m2 increase in bleomycin was 1.01 (95% CI 1.00-1.02, p=0.07). Conclusions: Childhood cancer survivors treated with bleomycin frequently have evidence of asymptomatic abnormalities on PFT. The current recommendation for pulmonary function testing in childhood cancer survivors appears justified.

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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 (Preprint)

10.2196/preprints.27898 ◽

2021 ◽

Author(s):

Oliver Zolk ◽

Annika von dem Knesebeck ◽

Norbert Graf ◽

Thorsten Simon ◽

Barbara Hero ◽

...

Keyword(s):

Cohort Study ◽

Health Status ◽

Cancer Survivors ◽

Childhood Cancer ◽

Late Effects ◽

Genetic Risk ◽

Cardiac Toxicity ◽

Childhood Cancer Survivors ◽

Cross Sectional ◽

Study Participants

BACKGROUND Cardiac toxicity is the most common non-malignant cause of death in childhood cancer survivors attributed to treatment-related consequences. Identifying patients at risk of developing late cardiac toxicity is therefore crucial to improving treatment outcomes. Genetic markers have been proposed to be used together with clinical risk factors to predict the individual risk of cardiac toxicity from cancer therapies such as doxorubicin. OBJECTIVE The primary aim is to replicate the previously described associations of doxorubicin-induced cardiotoxicity with RARG rs2229774, SLC28A3 rs7853758 and UGT1A6 rs17863783 variants and to evaluate the predictive value of the multimarker genetic test. The secondary aim is to evaluate the prevalence of cardiovascular dysfunction in childhood cancer survivors and to replicate the association of doxorubicin-related cardiotoxicity with other candidate genes. METHODS This is the pharmacogenetic sub-study of the research project Structural Optimization for Children with Cancer after Anthracycline Therapy (LESS-Anthra). We invited 2158 survivors of childhood neuroblasoma or nephroblastoma who were 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 health status and cardiovascular diagnoses of the study participants were recorded using a questionnaire completed by the cardiologist. Digital echocardographic data were centrally evaluated to determine the contractile function parameters. Medical data on tumor diagnosis and treatment protocol were taken from the study documentation. Survivors were screened for variants in several candidate genes by TaqMan genotyping. RESULTS This study included 657 survivors treated with doxorubicin for childhood cancer, resulting in the largest German cohort assembled for investigation of cardiovascular late effects to date. Data analyses are yet to be completed. CONCLUSIONS The study will define the genetic risk related to three marker genes proposed for risk assessment in a pharmacogenetic guideline. Moreover, the results of this study will show the prevalence of cardiovascular dysfunction in survivors of pediatric neuroblastoma or nephroblastoma treated with doxorubicin. The results will help to improve primary treatment and follow-up care to reduce cardiovascular late effects in the growing population of childhood cancer survivors. CLINICALTRIAL German clinical trials register ID: DRKS00015084

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METABOLIC SYNDROME PARAMETERS, DETERMINANTS, AND BIOMARKERS IN ADULT SURVIVORS OF CHILDHOOD CANCER: PROTOCOL OF THE DUTCH CHILDHOOD CANCER SURVIVOR STUDY METABOLIC SYNDROME (DUTCH LATER METS STUDY) (Preprint)

10.2196/preprints.21256 ◽

2020 ◽

Author(s):

Vincent Pluimakers ◽

Marta Fiocco ◽

Jenneke van Atteveld ◽

Monique Hobbelink ◽

Dorine Bresters ◽

...

Keyword(s):

Risk Factors ◽

Metabolic Syndrome ◽

Cancer Survivors ◽

Childhood Cancer ◽

Previous Treatment ◽

Adult Survivors ◽

Childhood Cancer Survivors ◽

Snp Analysis ◽

Cross Sectional ◽

Survivors Of Childhood Cancer

BACKGROUND Potential late effects of treatment for childhood cancer include adiposity, insulin resistance, dyslipidemia and hypertension. These risk factors cluster together as metabolic syndrome (MetS) and increase the risk for development of diabetes mellitus and cardio- and cerebrovascular disease. Knowledge on risk factors, timely diagnosis and preventive strategies is of importance to prevent cardio- and cerebrovascular complications and improve quality of life. Currently, no studies in national cohorts on prevalence and determinants of MetS in childhood cancer survivors including biomarkers and genetic predisposition are available. OBJECTIVE The objectives of the Dutch LATER METS study are to assess 1) the prevalence and risk factors of MetS and its separate components, and 2) the potential value of additional biomarkers, in the national cohort of adult long-term survivors of childhood cancer. METHODS This is a cross-sectional study, based on recruitment of all survivors treated in the Netherlands between 1963 and 2002. MetS will be classified according to the definitions of the National Cholesterol Education Program (NCEP-ATP III) as well as the Joint Interim Statement (JIS), and compared to reference data. Dual-energy X-ray absorptiometry (DXA) scans were performed to assess body composition in more detail. The effect of patient characteristics, previous treatment, and genetic variation on the risk of MetS will be assessed. The diagnostic and predictive value of novel biomarkers will be tested. RESULTS Patient accrual started in 2016 and lasted until April 2020. A total of 2380 survivors has participated, in seven pediatric oncology hospitals. From July 2020, biomarker testing, SNP analysis and data analysis will be performed. CONCLUSIONS The Dutch LATER METS study will provide knowledge on clinical and genetic determinants of MetS, and the diagnostic value of biomarkers, in childhood cancer survivors. The results of this study will be used to optimize surveillance guidelines for MetS in survivors, based on enhanced risk stratification and screening strategies. This will improve diagnosis of MetS, and prevent complications. CLINICALTRIAL Registered at toetsingonline.nl, NL32117.018.10

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High impact physical activity and bone health of lower extremities in childhood cancer survivors: A cross-sectional study of SURfit

Yearbook of Paediatric Endocrinology ◽

10.1530/ey.17.9.14 ◽

2020 ◽

Author(s):

Zurcher SJ ◽

Jung R ◽

Monnerat S ◽

Schindera C ◽

Eser P ◽

...

Keyword(s):

Physical Activity ◽

Cancer Survivors ◽

Childhood Cancer ◽

Bone Health ◽

Lower Extremities ◽

Childhood Cancer Survivors ◽

Cross Sectional Study ◽

High Impact ◽

Sectional Study ◽

Cross Sectional

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Predictors for participation in DNA self-sampling of childhood cancer survivors in Switzerland

10.1101/2021.05.25.21257796 ◽

2021 ◽

Author(s):

Nicolas Waespe ◽

Sven Strebel ◽

Denis Marino ◽

Veneranda Mattiello ◽

Fanny Muet ◽

...

Keyword(s):

Cancer Survivors ◽

Childhood Cancer ◽

Age Groups ◽

Childhood Cancer Survivors ◽

Cross Sectional Study ◽

Cancer Predisposition ◽

Second Primary ◽

Cross Sectional ◽

Cancer Predisposition Syndrome ◽

Foreign Nationality

Research on germline genetic variants relies on a sufficient number of eligible participants which is difficult to achieve for rare diseases such as childhood cancer. With self-collection kits using saliva or buccal swabs, participants can contribute genetic samples conveniently from their home. We identified determinants of participation in DNA self-collection in this cross-sectional study. We invited 928 childhood cancer survivors in Switzerland with a median age of 26.5 years (interquartile range 18.8-36.5), of which 463 (50%) participated. Foreign nationality (odds ratio [OR] 0.5, 95%-confidence interval [CI] 0.4-0.7), survivors aged 30-39 years at study versus other age groups (OR 0.5, CI 0.4-0.8), and those with a known cancer predisposition syndrome (OR 0.5, CI 0.3-1.0) participated less. Survivors with a second primary neoplasm (OR 1.9, CI 1.0-3.8) or those living in a French or Italian speaking region (OR 1.3, 1.0-1.8) tended to participate more. We showed that half of survivors participate in germline DNA self-sampling relying completely on mailing of sample kits. Foreign nationality, age 30-39 years, and cancer predisposition syndromes were associated with less participation. More targeted recruitment strategies may be advocated for these subgroups. To increase participation in DNA self-sampling, understanding and perceptions of survivors need to be better understood.

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