Parental Preferences Surrounding Timing and Content of Consent Conversations for Clinical Germline Genetic Testing Following a Child's New Cancer Diagnosis

PURPOSE

Clinical genomic testing is increasingly being used to direct pediatric cancer care. Many centers are interested in offering testing of tumors and paired germline tissues at or near the time of cancer diagnosis. We conducted this study to better understand parent preferences surrounding timing and content of consent conversations for clinical germline genetic testing of their children with cancer as a part of real-time cancer care.

PATIENTS AND METHODS

A seven-question survey developed by the Division of Cancer Predisposition and collaborators at St Jude Children's Research Hospital (St Jude) was distributed to members of the St Jude Patient Family Advisory Council, which included parents of childhood cancer survivors and bereaved parents whose children with cancer had died. Parents were asked to provide free text comments after each question. Qualitative methods were used to derive codes from parent comments, and survey results were depicted using descriptive statistics.

RESULTS

The survey was completed by 172 parents. Ninety-three (54%) endorsed an approach for consent conversations ≥ 1 month after cancer diagnosis, whereas 58 (34%) endorsed an approach at 1-2 weeks and 21 (12%) at 1-2 days. Needing time to adjust to a new or relapsed cancer diagnosis and feeling overwhelmed were frequent themes; however, parents acknowledged the urgency and importance of testing. Parents desired testing of as many cancer-related genes as possible, with clinical utility the most important factor for proceeding with testing. Most parents (75%) desired germline results to be disclosed in person, preferably by a genetic counselor.

CONCLUSION

Parents described urgency and benefits associated with germline testing, but desired flexibility in timing to allow for initial adjustment after their child's cancer diagnosis.

INTRODUCTION

Comprehensive germline testing using next-generation sequencing (NGS) technologies is expanding in pediatric oncology from research-based to clinical testing. Such testing has enhanced our understanding of the molecular drivers of childhood cancer and the prevalence and spectrum of underlying cancer-predisposing genetic variants. Several prior studies have explored parent views on pretest counseling for germline genetic testing, the consenting and decision-making process, and parent attitudes, understanding, and preferences regarding which results are to be returned or not returned. Overwhelmingly, parents endorse participation for their children in germline testing and desire the return of results that are deemed clinically actionable and of uncertain significance.^1-5 However, many of these prior studies focused on germline testing in the context of research and not as standard clinical care at the time of cancer diagnosis.

CONTEXT

• Key Objective

• Clinical genomic testing of tumor and paired germline tissues is increasingly offered at the time of cancer diagnosis. Clinicians should understand parental preferences surrounding timing and content of consent conversations for clinical germline genetic testing of their children with newly diagnosed cancer.

• Knowledge Generated

• Fifty-four percent of the parents surveyed endorsed an approach for consent conversations ≥ 1 month after cancer diagnosis, whereas 34% endorsed an approach at 1-2 weeks, and 12% at 1-2 days. Needing time to adjust to a new or relapsed cancer diagnosis and feeling overwhelmed were frequent themes; however, parents acknowledged the urgency and importance of testing.

• Relevance

• Parents understand the urgency and benefits of germline testing; however, consent conversations should be flexible in allowing for initial adjustment after the child's cancer diagnosis.

In these studies, parents describe an urgency in consenting to testing and express hope that the findings may benefit their child, as well as their other children with cancer.⁴ Accordingly, most parents' consent to germline testing for their children. Nevertheless, 12%-30% decline testing, with common reasons for declining including feeling overwhelmed with their child's cancer diagnosis, the anticipated psychologic impact of results, time commitment/logistics (ie, blood draw and study-specific factors), privacy, and lack of interest.⁶ One prior study used a questionnaire to solicit parent attitudes regarding integration of genetic counseling and testing in the pediatric oncology setting.³ Parents expressed an interest in genetic counseling and germline testing, but uncertainty was also reported. Howard Sharp et al⁷ recently assessed demographic and clinical characteristics associated with declining to participate in pediatric oncology–focused NGS testing as part of a research study. Race/ethnicity significantly differentiated study refusal, with parents of Black children more likely to decline, compared with parents of non-Hispanic and Hispanic White children. Common reasons for declining included feeling overwhelmed (23%) and fear of insurance discrimination (17%).

Over the past decade, it has become apparent that germline testing of children with cancer can add clinical value by identifying an underlying genetic predisposition, which may inform cancer treatment and enable tumor surveillance and risk-reducing interventions.^8-12 Furthermore, advances in NGS technologies and interpretation of results have allowed for more efficient and less costly testing. As a result, germline testing is evolving to include more genes and is being offered more frequently as clinical care. Despite these factors, studies assessing the optimal timing and content of consent conversations for children with cancer and parent preferences surrounding the disclosure of germline results in the real-time clinical scenario are scant, as is the number of parents surveyed.

At our institution, clinical germline testing is routinely offered to all new patients with cancer, generally several weeks to months after cancer diagnosis, with pretest counseling provided by an experienced team of pediatric cancer genetic counselors. However, given the impact of genomic information on clinical management, plans are underway to offer comprehensive tumor and paired germline testing earlier in the trajectory of care. In preparation for this new process, our aim was to explore parent preferences regarding the timing of approach for discussion of clinical germline testing, the extent of testing, the topics to be covered in germline consent conversations, and process of result disclosure. The overall goal was to enhance the consenting process for expanded germline genetic testing at the time of a child's cancer diagnosis and initiation of treatment.

PATIENTS AND METHODS

Study Population

The Patient Family Advisory Council (PFAC) is a leadership council, consisting of parents and staff who meet monthly, serving as an organized and effective voice representing patients and families at St Jude Children's Research Hospital (St Jude) through a centralized forum.¹³ The council is composed of two parent cohorts: parents of childhood cancer survivors, referred to as the family voice, and bereaved parents, referred to as the legacy voice. Meetings allow staff to present institutional initiatives to patient and caregivers and gain important feedback to implement and/or optimize these initiatives.

A seven-question survey was developed to ask members of the PFAC their perspectives regarding the timing of germline genetic testing for their children with cancer, the extent of germline genes tested, perceptions of benefits and risks, topics of discussion necessary during the consent process, and preferences surrounding disclosure of test results. After each question, parents were offered an opportunity to provide additional comments. This quality improvement project was approved by the institutional review board as nonhuman subject research.

Data Analysis

Survey results were scored as percentages. Parent comments were transcribed verbatim. Three study team members with experience in qualitative methods used grounded theory and constant comparative method for inductive semantic content analysis¹⁴ using MAXQDA software version 2020 plus (MAXQDA, Berlin, Germany). Codes were derived from parent comments associated with each question. The study team members had 100% agreement for all codes assigned to the responses during content analysis. Each parent comment was coded individually, and the frequency of each code in the parent response was counted.

RESULTS

The survey was distributed to 619 members of the PFAC and returned by 172 members (28% return rate), of which 135 parents were members of the family voice and 37 parents were members of the legacy voice. The patient demographics for the responding parents are depicted in Table 1. Both the legacy and family voice parents were predominately White and > 50% had a male child with cancer. Brain tumor (37%) was the most common cancer diagnosis of legacy voice children, and leukemia/lymphoma was the most common cancer diagnosis of family voice children. The legacy voice parents were on average 7.7 years from their child's cancer diagnosis and on average 4.9 years from their child's death, whereas the family voice parents were on average 4.5 years from their child's cancer diagnosis. When parents were asked if they recalled consenting to germline genetic testing for their child, 46 (27%) reported that their child had undergone germline genetic testing, 44 (26%) reported that their child did not have testing, and 76 (44%) were unsure. Thirteen parents did not answer the question.

TABLE 1.

Patient Demographics

Question 1: When Is the Best Time to Approach Patients and Their Caregivers to Discuss Germline Genetic Testing?

Parents were provided preferences regarding timing of discussion surrounding germline testing. Preferences for testing included within the first 2 days, within the first 2 weeks, or after 1-2 month. Most parents (93; 54%) endorsed discussion and testing after 1 month or more from their child's cancer diagnosis, followed by within the first 2 weeks (58; 34%) and within the first 2 days (21; 12%). More legacy voice parents (21; 57%) endorsed testing within the first 2 days and 2 weeks compared with the family voice parents (58; 43%); however, these differences were not statistically different. For both groups, most parents desired time to process the cancer diagnosis before being approached for conversations about germline genetic testing. Table 2 describes the timing preference codes and several representative associated quotes.

TABLE 2.

Parent Comments on Timing of Germline Testing

Question 2: Which of the Following Germline Genetic Tests Would You Prefer for Your Child? No Testing at All, Testing of a Few Genes Related to My Child's Cancer, Testing of Several Genes Related to My Child's Cancer and Other Cancers, or Testing of All Possible Cancer-Related Genes

Most parents (139; 81%) endorsed germline testing of as many cancer-related genes as possible, whereas 21 (12%) endorsed testing of genes specifically related to their child's cancer and 9 (5%) endorsed testing of one or a few cancer-related genes. Only three (2%) parents endorsed no testing.

Notable quotes from parents:

Testing as many genes as possible:

I feel it's better to have as much information as possible, to help with treatment decisions.

I have concerns about future health coverage because of the results of this testing.

The more we know may provide comfort, while others may not want to know anything.

His diagnosis was a death sentence, but if there was a chance that he could make it—I would have wanted him tested for everything.

Testing only a few genes:

I would want answers, but I also wouldn't want potentially unnecessary worries.

Question 3: What Would You Have Preferred for Your Child? Testing of a Limited Number of Genes With Option to Expand to More Genes if the Results Are Negative or Unclear, or Initial Testing of Many Genes

When given a choice to begin with limited versus expanded germline testing at the time of diagnosis, 110 (64%) parents endorsed expanded testing, whereas 39 (23%) endorsed testing of a limited panel with expansion if the initial results were negative. Twenty-three parents (13%) were not sure of which type of testing to pursue for their child with cancer.

Question 4: How Important It Is for You to Discuss the Following Topics With Your Health Care Provider or Genetic Counselor Before Consenting to Germline Genetic Testing for Your Child?

Parents were given topics associated with germline testing and asked to rank them according to their perceived importance of discussing with a health care provider or genetic counselor before consenting to germline testing for their child (options: not important, a little important, neutral, important, and very important). The ranking of importance is listed in Figure 1. Most parents (169; 98%) ranked the impact of germline results on the child's cancer care now and in the future as an essential topic for discussion. This was followed by understanding the risks and benefits of germline testing for their child or other family members (166; 97%), the types of germline results and their implications (159; 92%), and concerns about insurance (154; 90%).

FIG 1.

Parent ranking of topics most important when considering germline testing: (A) family voice and (B) legacy voice.

Question 5: What Factors Might Affect Your Decision for Germline Genetic Testing for Your Child?

Parents described the clinical utility of testing as the most important factor affecting their decision to proceed with germline testing, specifically the potential for testing to change the treatment plan and clinical outcome (Table 3). Another common factor affecting their decision included having enough time to process their child's diagnosis. The parents described the need to understand and process the child's diagnosis, treatment plan, and prognosis before initiating the discussion of germline genetic testing. Parents also described wanting information that could explain the reason for their child's cancer and inform lifestyle changes on the basis of germline test results. Parents desire thoughtfulness from the clinical staff when being approached for testing, specifically asking for consideration of the family's emotional well-being at the time. Finally, parents described concerns that testing would label their child and present difficulties in obtaining health insurance coverage in the future.

TABLE 3.

Factors That Would Affect When You Would Feel Most Comfortable Proceeding With Germline Testing for Your Child

Question 6: How Would You Like to Receive Germline Testing Results?

Options for receiving germline test results, including a paper document, an app on the phone, a webpage on the internet, and an in-person meeting with genetics professional, with 117 (68%) parents preferring an in-person meeting with genetics professional. Additional comments included the importance of an in-person meeting if positive results are to be disclosed and the importance of being provided a paper copy of their child's germline report.

Question 7: Additional Thoughts or Comments

Comments and thoughts that parents shared emphasized concepts of empowerment, parental worry/guilt, and giving time to process. Notable quotes from parents:

We participated 1 month after arrival, had established a routine, and were in a mindset to comprehend new information. In-person meetings to discuss testing and results are important.

We learned of a genetic mutation in our family 8 years after my son's diagnosis. If that testing had been done earlier, we could have potentially found my second son's tumor sooner.

The more we know about the changes in the genome, the closer we'll be to finding a cure. The importance of this testing needs to be addressed within the first few weeks.

Parents feel guilty and worry about something they had done to cause their child's diagnosis, so I don't believe the results would be a deterrent of doing the test. The more information the caregiver has, the better!

DISCUSSION

In this study, one of the largest to date, we sought to elicit the preferences of parents for obtaining informed consent for clinical germline testing for their children with cancer, including the timing, extent of testing, and topics of importance during the consenting process. Time for adjustment and feeling overwhelmed after the initial cancer diagnosis was a frequent theme; however, parents acknowledged the potential importance and urgency of testing. That said, most parents (54%) preferred consent conversations within the first 1-2 months and 2 months after their child's cancer diagnosis. Of interest, bereaved parents were more likely to endorse testing within the first 2 days after diagnosis. These parents expressed hope that findings may have changed their child's clinical outcome. For these parents, thoughts of finding the cause or treatment options for their child's cancer more likely outweighed potential concerns.¹⁵ Parents expressed the desire for the clinical team to consider the emotional stability of the child and family before approaching for consent. Most parents endorsed the testing of as many genes as possible in hopes of gaining knowledge of their child's diagnosis and informing subsequent care.

Our results are in line with and build upon those previously published. In one prior report, parents described being overwhelmed at the time of their child's cancer diagnosis, unable to concentrate and vulnerable to saying yes to nearly everything being asked of them.¹⁶ These same parents preferred a two-phase consent process in which consent is first obtained to collect diagnostic tissue, and a discussion and consent for sequencing follows several weeks later. Our previous work also supports a two-phase consent process as being favorable in providing the needed education, improving parental understanding, and providing sufficient time for decision making.¹⁷ Another study, again using a multistep process, approached parents 2-28 days after their child's cancer diagnosis.² Among interviewed parents, the majority did not object to being approached for counseling during the first 4 weeks after diagnosis. However, a few did feel the timing was too early and welcomed the flexibility given by the counseling team. Given the competing procedures and activities at the time of a new cancer diagnosis, it is essential that providers carefully consider how best to carry out these conversations to ensure families understand the testing process and potential results.

Comprehensive germline genetic testing has only recently been incorporated into clinical care; therefore, it is not surprising that almost half of the parents we surveyed were unsure if their child had undergone testing. It is possible that such testing was not offered or, alternatively, that it was completed but the results were forgotten because of the abundance of information parents are given at the time of their child's cancer diagnosis. Notably, one third of surveyed parents preferred a staged approach or were unsure about their preferred testing strategy. To enhance parental understanding, a genetic counselor should be available to discuss the germline testing process, germline test results, and the downstream implications. Indeed, most parents endorsed the involvement of a genetic counselor during the consent process and disclosure of results. Druker et al¹⁸ recommends that genetic counseling be initiated at the time of a child's cancer diagnosis; therefore, if testing is indicated, it may be completed immediately. Consent for germline testing represents an important and ongoing dialogue, not a single event.⁵

As NGS testing moves into practice, the clinical and research testing pathways are often intermingled and carried out earlier in a child's cancer trajectory. The patient and family may not be referred to a genetic counselor until after the testing is completed and positive findings or variants of unknown significance are identified. Although this process may enable a more rapid initial workflow for the oncology team, there is potential for misconceptions by patients and families and surprise when these results are returned. There is also the risk that patients may not follow through with subsequent counseling, which could lead to missed opportunities for tumor surveillance or genetic counseling and testing of other family members. In one recent study, almost one quarter of patients failed to follow through after their child had undergone paired tumor/normal NGS testing.¹⁹ For patients with positive germline findings, it is recommended that the genetic counseling interaction continue into the patient's survivorship trajectory, to facilitate long-term adaptation to a genetic diagnosis, and enable connection to available resources, testing of at-risk family members, and reproductive counseling.¹⁸ Similarly, patients with variants of unknown significance should be followed prospectively for understanding of potential clinical implications and possible reclassification of the results to benign or pathogenic.

Despite the large number of parents surveyed, there are several limitations to this study. As a retrospective survey, many of these parents may never have been offered germline testing for their children. Alternatively, testing might have been offered but the details forgotten, or its impacts changed with time since testing. Therefore, some responses to questions may be hypothetical. Prospective studies are warranted to validate and/or refine these findings among parents who have consented to germline testing in a real-time clinical setting.

Genomic sequencing of children with cancer has not been found to be ethically disruptive in leaving the parents or physicians unprepared in clinical decision making.²⁰ However, several considerations should be made when approaching a child with a newly diagnosed or relapsed cancer and their family for consent for germline testing. We describe most parents as wanting to be proactive, desiring testing, and wanting extensive testing to better understand their child's cancer and the familial implications. However, clinicians should consider the patient's circumstances and the current physical and emotional well-being of the family. The family should be informed, with an understanding of potential or lack of clinical utility. They should be allowed the time needed to discuss testing with family members, friends, and/or members of the medical team, and to have their concerns heard and questions answered. Ideally, all children with cancer should undergo a formal genetics evaluation to elucidate possible underlying predisposition; however, in situations where this is not feasible, at least those undergoing germline testing with positive findings or variants of unknown significance should be referred to a genetic counselor for discussion of the findings and continued follow-up.

AUTHOR CONTRIBUTIONS

Conception and design: Belinda N. Mandrell, Liza Marie Johnson, Roya Mostafavi, Katianne M. Howard Sharp, Kim E. Nichols

Financial support: Belinda N. Mandrell

Administrative support: Belinda N. Mandrell

Provision of study materials or patients: Belinda N. Mandrell

Collection and assembly of data: Belinda N. Mandrell, Liza Marie Johnson, Jami Gattuso, Jamie L. Maciaszek

Data analysis and interpretation: Belinda N. Mandrell, Mary Caples, Jami Gattuso, Jamie L. Maciaszek, Katianne M. Howard Sharp, Kim E. Nichols

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center.

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