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

Abstract Background Research on germline genetic variants relies on enough eligible participants which is difficult to achieve for rare diseases such as childhood cancer. With self-collection kits, participants can contribute genetic samples conveniently from their home. Demographic and clinical factors were identified previously that influenced participation in mailed self-collection. People with pre-existing heritable diagnoses might participate differently in germline DNA collection which might render sampling biased in this group. In this nationwide cross-sectional study, we analysed predictive factors of participation in DNA self-collection including heritable diagnoses. Methods We identified childhood cancer survivors from the Swiss Childhood Cancer Registry for invitation to germline DNA self-sampling in September 2019. Participants received saliva sampling kits by postal mail at their home, were asked to fill them, sign an informed consent, and send them back by mail. Two reminders were sent to non-participants by mail. We compared demographic, clinical, and treatment information of participants with non-participants using univariable and multivariable logistic regression models. Results We invited 928 childhood cancer survivors in Switzerland with a median age of 26.5 years (interquartile range 19-37), of which 463 (50%) participated. After the initial send out of the sampling kit, 291 (63%) had participated, while reminder letters led to 172 additional participants (37%). 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 survivors with a known cancer predisposition syndrome (OR 0.5; CI 0.3-1.0) were less likely to participate in germline DNA collection. 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; CI 1.0-1.8) tended to participate more. Conclusions We showed that half of childhood cancer survivors participated in germline DNA self-sampling relying completely on mailing of sample kits. Written reminders increased the response by about one third. More targeted recruitment strategies may be advocated for people of foreign nationality, aged 30-39 years, and those with cancer predisposition syndromes. Perceptions of genetic research and potential barriers to participation of survivors need to be better understood. Trial registration Biobank: https://directory.bbmri-eric.eu/#/collection/bbmri-eric:ID:CH_HopitauxUniversitairesGeneve:collection:CH_BaHOP Research project: Clinicaltrials.gov: NCT04702321.

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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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Utility of a Cancer Predisposition Screening Tool for Predicting Subsequent Malignant Neoplasms in Childhood Cancer Survivors

Journal of Clinical Oncology ◽

10.1200/jco.21.00018 ◽

2021 ◽

pp. JCO.21.00018

Author(s):

Noelle Cullinan ◽

Ian Schiller ◽

Giancarlo Di Giuseppe ◽

Mohammed Mamun ◽

Lara Reichman ◽

...

Keyword(s):

Cancer Survivors ◽

Childhood Cancer ◽

Conditional Logistic Regression ◽

Childhood Cancer Survivors ◽

Cancer Predisposition ◽

Malignant Neoplasms ◽

Primary Cancer ◽

Primary Malignancy ◽

Control Approach ◽

Cancer Predisposition Syndrome

PURPOSE Childhood cancer survivors (CCS) are at risk of developing subsequent malignant neoplasms (SMNs) resulting from exposure to prior therapies. CCS with underlying cancer predisposition syndromes are at additional genetic risk of SMN development. The McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) tool identifies children with cancer at increased likelihood of having a cancer predisposition syndrome, guiding clinicians through a series of Yes or No questions that generate a recommendation for or against genetic evaluation. We evaluated MIPOGG's ability to predict SMN development in CCS. METHODS Using the provincial cancer registry (Ontario, Canada), and adopting a nested case-control approach, we identified CCS diagnosed and/or treated for a primary malignancy before age 18 years (1986-2015). CCS who developed an SMN (cases) were matched, by primary cancer and year of diagnosis, with CCS who did not develop an SMN (controls) over the same period (1:5 ratio). Potential predictors for SMN development (chemotherapy, radiation, and MIPOGG output) were applied retrospectively using clinical data pertaining to the first malignancy. Conditional logistic regression models estimated hazard ratios and 95% CIs associated with each covariate, alone and in combination, for SMN development. RESULTS Of 13,367 children with a primary cancer, 317 (2.4%) developed an SMN and were matched to 1,569 controls. A MIPOGG output recommending evaluation was significantly associated with SMN development (hazard ratio 1.53; 95% CI, 1.06 to 2.19) in a multivariable model that included primary cancer therapy exposures. MIPOGG was predictive of SMN development, showing value in nonhematologic malignancies and in CCS not exposed to radiation. CONCLUSION MIPOGG has additional value for SMN prediction beyond treatment exposures and may be beneficial in decision making for enhanced individualized SMN surveillance strategies for CCS.

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Absolute Risk Prediction of Second Primary Thyroid Cancer Among 5-Year Survivors of Childhood Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2012.41.8996 ◽

2013 ◽

Vol 31 (1) ◽

pp. 119-127 ◽

Cited By ~ 33

Author(s):

Stephanie A. Kovalchik ◽

Cécile M. Ronckers ◽

Lene H.S. Veiga ◽

Alice J. Sigurdson ◽

Peter D. Inskip ◽

...

Keyword(s):

Thyroid Cancer ◽

Cancer Survivors ◽

Childhood Cancer ◽

Thyroid Nodule ◽

Absolute Risk ◽

Childhood Cancer Survivors ◽

Second Primary ◽

Cancer Type ◽

Risk Models ◽

Treatment Information

Purpose We developed three absolute risk models for second primary thyroid cancer to assist with long-term clinical monitoring of childhood cancer survivors. Patients and Methods We used data from the Childhood Cancer Survivor Study (CCSS) and two nested case-control studies (Nordic CCSS; Late Effects Study Group). Model M1 included self-reported risk factors, model M2 added basic radiation and chemotherapy treatment information abstracted from medical records, and model M3 refined M2 by incorporating reconstructed radiation absorbed dose to the thyroid. All models were validated in an independent cohort of French childhood cancer survivors. Results M1 included birth year, initial cancer type, age at diagnosis, sex, and past thyroid nodule diagnosis. M2 added radiation (yes/no), radiation to the neck (yes/no), and alkylating agent (yes/no). Past thyroid nodule was consistently the strongest risk factor (M1 relative risk [RR], 10.8; M2 RR, 6.8; M3 RR, 8.2). In the validation cohort, 20-year absolute risk predictions for second primary thyroid cancer ranged from 0.04% to 7.4% for M2. Expected events agreed well with observed events for each model, indicating good calibration. All models had good discriminatory ability (M1 area under the receiver operating characteristics curve [AUC], 0.71; 95% CI, 0.64 to 0.77; M2 AUC, 0.80; 95% CI, 0.73 to 0.86; M3 AUC, 0.75; 95% CI, 0.69 to 0.82). Conclusion We developed and validated three absolute risk models for second primary thyroid cancer. Model M2, with basic prior treatment information, could be useful for monitoring thyroid cancer risk in childhood cancer survivors.

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Young Survivors at KSA: registry for standardised assessment of long-term and late-onset health events in survivors of childhood and adolescent cancer—a study protocol

BMJ Open ◽

10.1136/bmjopen-2021-053749 ◽

2021 ◽

Vol 11 (12) ◽

pp. e053749

Author(s):

Maria Otth ◽

Daniel Drozdov ◽

Claudia Hügli ◽

Katrin Scheinemann

Keyword(s):

Cancer Survivors ◽

Childhood Cancer ◽

Late Effects ◽

Late Onset ◽

Childhood Cancer Survivors ◽

Adolescent Cancer ◽

Link Type ◽

Open Access Journals ◽

Young Survivors ◽

Scientific Meetings

IntroductionA high proportion of survivors of childhood and adolescent cancer experience chronic medical conditions — late effects. Most studies on late effects have a retrospective or questionnaire-based design, which leads to unavoidable limitations such as missing data or different severity coding and grading of late effects. We, therefore, need prospective data, including standardised severity coding and grading. ‘Young Survivors at KSA’ aims to close this gap by assessing frequency, severity, risk factors and longitudinal changes of late effects in childhood cancer survivors prospectively and in a standardised way.Methods and analysisWithin the ‘Young Survivors at KSA’ registry, we collect data from regular follow-up visits in a comprehensive database prospectively and repeatedly from start of the study and retrospectively at most until January 2016. We classify and grade the severity of late effects according to the Common Terminology Criteria for Adverse Events version 4.0 modified by Hudson et al. The outcome variables correspond to results from risk-stratified organ examinations, performed according to the Children’s Oncology Group guidelines version 5.0 and the recommendations by the International Guideline Harmonization Group. We collect the exposure variables from the patients’ medical history, including detailed information on cancer diagnosis and treatment. We analyse the data in an exposure-driven and organ system-driven approach. We start recruitment with patients treated at the Kantonsspital Aarau, Switzerland. However, our design allows the inclusion of additional national centres later.Ethics and dissemination‘Young Survivors at KSA’ is approved by the Ethikkommission Nordwest- und Zentralschweiz, reference number AO_2020–00012. The results of this study will be presented at scientific meetings, including meetings with childhood cancer survivors and published in peer-reviewed and if possible open access journals. New insights gained from the study will be used directly in clinical practice.Trial registration numberClinicalTrials.gov NCT04811794; https://clinicaltrials.gov/ct2/show/study/NCT04811794

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