Qualitative Study Report on the Experience of Extensive Germline Sequencing in Children with Cancer Aged 12-18

Background Introduction

With the development of genetic sequencing technology, germline DNA sequencing has gradually become a routine practice in pediatric cancer care. Recent studies estimate that about 10% of children with cancer have genetic susceptibility. As sequencing technology advances and more genetic susceptibility syndromes are identified, the range of genes that can be tested and the number of patients have expanded. This means that, technically, routine sequencing can be performed on all pediatric cancer patients, not just those at high risk of carrying specific susceptibility genes. Furthermore, there is a trend to perform germline sequencing early in the cancer diagnosis process. However, cancer susceptibility testing in children remains a topic of ongoing ethical debate. These debates involve what information should be provided in the informed consent process, the appropriate timing of consent, how to involve children in decision-making, and whether re-consent is needed when children reach the legal age.

In this context, the authors conducted this study to explore the experiences and needs of adolescents recently diagnosed with cancer regarding extensive germline genetic sequencing. They aimed to understand how these adolescents and their families view and experience this routine sequencing.

Paper Source

The paper was completed by the following authors and institutions: Sebastian B. B. Bon, Roel H. P. Wouters, Jette J. Bakhuizen, Marjolijn C. J. Jongmans, Marry M. van den Heuvel-Eibrink, and Martha A. Grootenhuis from the Princess Máxima Center for Pediatric Oncology. The paper was published in the European Journal of Human Genetics (2024), Volume 32, pages 567-575. It was received on October 6, 2023, revised on January 29, 2024, accepted on February 5, 2024, and published online on February 27, 2024.

Research Methods

Research Background

This study was based on the PREDICT sequencing study, which tested 143 genes related to pediatric cancer. The gene panel and selection criteria can be found in Supplementary File 1. Participants in the PREDICT study were cancer patients diagnosed at the Princess Máxima Center for Pediatric Oncology (age <19 years) between June 2020 and August 2022. Pathogenic or likely pathogenic variant results were communicated to patients and their families. A phased inclusion approach was used for patients with hematological malignancies, central nervous system tumors, and solid tumors. The PREDICT study did not include tumor DNA sequencing.

From December 2021, the REFLECT study, in conjunction with the PREDICT study, offered questionnaire research to all family members (parents of children of all ages and patients aged 12-18) and interview research to patients aged 12-18. Interviews were conducted between informed consent and disclosure of germline genetic sequencing results.

Collection and Analysis of Interview Data

Eligible PREDICT sequencing study participants (aged 12 to 18) could participate in the REFLECT interview study. Exclusion criteria included: insufficient Dutch language proficiency, confirmed cancer susceptibility gene, or refusal of interview due to cancer recurrence or stem cell transplantation.

Interviews were scheduled at a time and place convenient for the adolescents, using a semi-structured interview guide. Interview content included: adolescents’ motivations and perceived burdens of participating in sequencing, evaluation of the consultation process and provided materials, and views on future re-analysis and re-consent. Interviews lasted an average of 20 minutes (range: 14-34 minutes) and were audio-recorded and transcribed verbatim.

The study used inductive thematic analysis, coding interviews through NVivo software. The initial three interviews were independently coded by two authors, with differences resolved through discussion. Subsequent interviews were initially coded by one author and systematically reviewed by another. Through an iterative process, new codes were recoded when they emerged, ultimately forming a code tree and identifying themes. All authors reviewed and discussed the code tree until consensus was reached.

Research Results

The study interviewed 21 adolescents awaiting germline genetic sequencing results, aged 12 to 18, with 10 males and 11 females among the interviewees. Through analysis of these interview data, the following six major themes were distilled:

1. Adolescents show a casual attitude towards sequencing: Interviewees had a casual attitude towards genetic sequencing, viewing it as a normal part of cancer treatment. Most participants considered the possibility of finding susceptibility to be low.

2. Adolescents emphasize autonomy in consultation and consent: The vast majority of adolescents believed that they should decide on sequencing themselves, as it concerns their life, body, and DNA.

3. Adolescents and parents jointly participate in decision-making: Although adolescents emphasized autonomy, the decision to participate in sequencing was usually the result of discussions with parents.

4. Adolescents view genetic information as valuable knowledge: Adolescents considered genetic information as an important part of “being informed” and believed that understanding genetic risks was helpful for themselves, siblings, and family members.

5. Adolescents prefer visualized and concise consultation materials: Interviewees expressed dissatisfaction with existing lengthy letter information, preferring brief and visually appealing infographics.

6. Adolescents want to continue playing a role in future decisions: Most adolescents believed they should have the opportunity for re-consent in the future and be notified before re-analyzing data when new genes are discovered.

Conclusion

This study reveals adolescents’ positive attitudes towards participating in germline genetic sequencing and their strong desire to be involved in decision-making. The findings suggest that as gene sequencing technology becomes more widely applied, effectively communicating immediate and long-term impacts during consultation is crucial to helping adolescents make informed decisions. Future consultations should focus more on visual expression and information delivery that meets adolescents’ needs to enhance their autonomy in genetic sequencing. This study provides important insights for the increasingly common application of germline sequencing in pediatric cancer care, ensuring that adolescents’ perspectives are incorporated into relevant decision-making processes.

Research Significance

This study provides a comprehensive understanding of the attitudes and needs of pediatric cancer patients experiencing germline genetic sequencing. The exploration of technical and ethical issues in this research not only provides valuable experience for the design and implementation of scientific research but also offers specific suggestions on how to effectively conduct genetic sequencing consultations for adolescents in medical practice. It has important implications for the formulation and improvement of relevant policies in the future.