Parental Perspectives on the Use of Tumor Molecular Profiling and Germline Genetic Testing During their Children’s Cancer Treatment

Abstract

Purpose

Tumor molecular profiling (TMP) with germline genetic testing (GGT) is becoming standard practice in pediatric cancer care. Yet, little is known about parents’ understanding of these practices, or testing’s psychosocial risks and benefits. This study characterized parental knowledge, attitudes, and beliefs about TMP and GGT.

Method

A cross-sectional, mixed-methods study was conducted among N=75 parents of children with cancer. Parents completed a survey on cancer-related knowledge, attitudes toward GGT, psychological stress, communication, and decision-making. A subset (N=31, 41%) then completed interviews about TMP and GGT that were content-coded and interpreted in light of survey findings.

Results

Correlative analyses indicated that parents’ greater understanding of cancer and genetics was associated with favorable attitudes toward GGT (r=0.34), preferences for more information about GGT results (r=0.56) and reduced decisional regret about GGT (r=−0.61). Families who communicated less openly held more favorable views on GGT (r=−0.38) and preferred more information about GGT (r=−0.39), but had children who were more anxious (r=−0.36). Parents who were more anxious (r=0.40) and who favored GGT (r=0.41) also had children who were more anxious (all p’s <0.05). Thematically, most parents recalled their children’s test results (94%), but recollection of testing type was suboptimal (58% for TMP, 61% for GGT). Nearly 70% believed it would be helpful to speak to other families for psychosocial support; additional potential resources included healthcare providers (31%) and websites (23%).

Conclusion

When children with cancer undergo TMP and/or GGT, their parents would benefit psychoeducational resources to improve outcomes.

Introduction

There are approximately 16,000 children diagnosed with cancer annually in the US.¹ For many, and especially those with refractory or relapsed disease, treatment can be informed by the identification of specific, targetable genomic changes in their tumors.^2,3 Using tumor molecular profiling (TMP) in this manner can offer insight into broader biological pathways involved in tumor development and prognosis, and alter children’s cancer treatment while minimizing treatment-associated toxicity. This has the potential to push cure rates beyond the current 5-year survival of 85%.^1,4 It is further estimated that up to 18% of children with cancers have an underlying hereditary predisposition that may be identified through germline genetic testing (GGT), which may be conducted independently or in conjunction with TMP.^5,6 While TMP informs treatment decisions for the current cancer, GGT has broader implications for cancer control and surveillance, reproductive planning, and family risk assessment.^7,8 The implementation of TMP and GGT in pediatric oncology varies considerably across institutions and studies; while TMP is increasingly employed to inform targeted therapies, GGT is not always performed in parallel. Integrated approaches can identify germline pathogenic variants in a significant subset of patients, even though nearly half of whom would not have met traditional criteria for genetic testing. This highlights the potential benefits of combined testing strategies in identifying hereditary cancer predispositions that might otherwise remain undetected.

But as TMP and GGT are being increasingly adopted in pediatric oncology practice, it is important to understand the potential medical and psychosocial benefits and harms that they pose to young patients, their parents, and families. TMP allows pediatric oncologists to molecularly characterize their patients’ cancer diagnoses, allowing for more accurate risk stratification, identification of specific genomic alterations amenable to precision medicine therapeutics, and inform choices regarding clinical trial eligibility.⁹ However, only a small subset of pediatric cancers have specific targetable variants found for which there are drugs. Moreover, germline variants can be incidentally discovered and with implications for biological relatives. This includes relatives younger than the age at which cancer screening and/or prevention options are available. Thus, TMP testing poses several risks, including detecting a profile without immediate therapeutic action or an incidental discovery of a hereditary cancer predisposition. These findings may engender psychologic distress for children with cancer and their families.^10,11

GGT can similarly allow at-risk patients to participate in specific risk-reduction and early detection strategies to mitigate cancer risk when available, thereby offering patients and their families additional insight into their future disease onset.^12,13 However, there may be psychosocial consequences of doing so. Children with cancer may learn of their susceptibility to adult-onset cancers that have no clear prevention or clinically actionable solutions before adulthood, potentially leading to medical uncertainty and anxiety. Additionally, when patients have a poor prognosis or continue follow-up/surveillance as a result of their current cancer diagnosis, this too may add to their mental burden.^14,15

Traditionally, patient education and counseling has been included prior to somatic or germline testing to facilitate informed decision making.^16,17 Before TMP and GGT, eliciting patients’ preferences for genetic information, including learning about incidental and secondary findings (i.e., germline pathogenic variants unrelated to their current diagnosis), and a plan for the return of results, is important. The American College of Medical Genetics and Genomics recommends that reportable secondary findings include pathogenic variants in 97 genes, including 30 genes in which pathogenic variants are related to cancer/neoplastic syndromes.¹⁸ Unfortunately, there is wide variation in the education and counseling practices implemented in pediatric oncology settings, and not all centers have access to providers with genetics expertise.¹⁹ Moreover, parents may have difficulty opting-out of receiving their children’s genetic testing results if they do not wish to learn them.²⁰

Given the complexity of TMP and GGT and its implications for children’s cancer and risk management, as well as that of their family members, important questions have been asked about the psychosocial sequelae of their genetic testing.²¹ For example, children with cancer and their parents tend to perceive and respond differently to germline sequencing. Some adolescents with cancer report indifference, while others perceive its results as a prominent aspect of their cancer journey.²² Parents, however, more uniformly report experiencing significant distress and guilt when testing reveals an underlying hereditary predisposition affecting their children.^23,24 In particular, parents without a partner, with a greater understanding of the molecular underpinnings of cancer risk, and those who were worried at the outset about their children’s genetic testing were more anxiety-prone to their children’s positive results.²³ Given that parents may have a better understanding of GGT and the consequences of its findings than their children, they could be vulnerable to psychological stress when receiving and interpreting germline results, including implications for their family’s health.

Findings like these highlight the need to further investigate parental perspectives on TMP and GGT when their children have cancer. Therefore, a key research question emerges: what do parents know, think, and feel about somatic and germline testing in the context of their children’s cancer treatment? Given the multifaceted nature of this question, it is beneficial to engage more than one mode of data collection to understand the full scope of these parents’ lived experiences.²⁵ The present study leveraged a sequential explanatory design in mixed-methods research to investigate this topic. The advantage of applying mixed-methods research is that it combines both qualitative and quantitative approaches to yield a more comprehensive and insightful understanding into the phenomena by integrating and thematically linking both sources of information. Findings derived from this methodology could help determine parents’ psychoeducational counseling needs, and guide interventions among providers who work with children undergoing treatment for cancer and their families.

Methods

Study Design

This study employed a sequential explanatory mixed-methods design. It involved two stages: an initial quantitative stage followed by a qualitative stage to help explain and elaborate on quantitative findings. This approach permitted the research team to identify patterns or relationships using conventional statistics, and then explore possible underlying reasons or contextual factors through in-depth qualitative inquiry. Importantly, the integration of these two approaches occurred during an interpretive phase. This yielded a fuller understanding of the research question by connecting numeric trends with participants’ voiced experiences.

Participants

Participants were English-speaking adult parents who self-nominated as being the primary caretaker of a child with cancer. Their children were diagnosed with a pediatric malignancy prior to the age of 18 years for which they underwent TMP at least 12 months prior to study enrollment; 83% of participants’ children also received GGT. Children originated from one of three comprehensive cancer centers with a pediatric oncology program with expertise in using TMP and GGT with their patients, either as part of clinical research and/or practice. In one center, TMP and GGT were routinely offered. In the other two centers, TMP and GGT were offered based on clinical need. These three centers also varied in program size; all were members of the Children’s Oncology Group and had in-house access to specialized cancer genetic counseling. At two of the three centers, all participants who underwent GGT were seen by genetic counseling (pre- and/or post-test) and at the third, such counseling was available by parental request.

Participants were identified using a combination of methods, including patient lists of the treating providers and reviews of children’s electronic health records by clinical research coordinators. Potential participants were initially contacted by email/mail and/or telephone about the purpose of the study and to inquire if they were interested in participating. Interested participants were then screened, completed an online informed consent form, and were asked to take a multidimensional quantitative survey: >80% of those offered the opportunity chose to do so, and there were no differences in study uptake based on participants’ demographic characteristics (i.e., parent age, gender, race; all p’s>0.05). Upon conclusion of the survey, participants were asked whether they would be willing to participate in a telephone interview with a research staff member to elaborate on their perspectives about pediatric TMP and/or GGT (>70% consent). Only one parent was enrolled per child, and no children were related (i.e., siblings with cancer). Participants received modest reimbursements for their time. The protocol was reviewed and approved by all three centers’ Institutional Review Boards.

Quantitative Survey

Sociodemographic and Clinical Characteristics:

Participants self-reported their age, gender, race, ethnicity, education level, and marital status. Participants also reported their children’s cancer characteristics, which were verified through health records by study staff.²⁶

Parent-Child Communication:

The openness subscale of the Parent-Adolescent Communication (PAC) scale was used to assess the extent to which participants tend to speak with their children openly about family issues. The 10 items were summed together to form a total score with good reliability (α=.92); higher scores indicated more open, less problematic parent-child communication.²⁷

Perceived Cancer Causes:

Perceptions about the roles of genes and health behavior in cancer development and their importance in cancer control were assessed with two task-specific items (1=not at all/not at all important, 7=completely/very important). Higher scores corresponded to greater understanding of the roles that genes and health behaviors play in cancer development and control.²⁸

Genetic Knowledge:

Participants’ knowledge about cancer genetics was assessed using a single True/False item identified from the research literature on how adults with cancer and their blood relatives experienced germline genomic sequencing: “Sometimes we find a gene change we know nothing about.”²⁶

Preferences for the Return of Genetic Test Results:

Participants’ preferences for the return of GGT results were assessed using a 4-item scale adapted from the research literature, asking whether or not a participant would want a certain type of germline result returned to them. Higher scores indicated stronger preferences for more genetic information, with high internal consistency (α=.78).²⁶

Attitudes Toward Pediatric Genetic Testing:

Participants’ attitudes toward GGT in children were assessed using an adaptation of the Pediatric Testing Attitudes Scale (P-TAS). The P-TAS is a 12-item measure about testing children for cancer germline gene mutations using a 5-point Likert scale from “strongly disagree” to “strongly agree” and its internal consistency reliability was strong (α=.89). A higher P-TAS score suggests more prominent views favoring GGT.²⁹

Psychological Stress:

Participants self-reported the psychological stress of both themselves and their children using the short-form of the Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety scale (α=.93 self-report, α=.95 parent proxy report for their children). Responses are provided on a 5-point Likert ranging from “never” to “always”: higher scores indicated greater levels of psychological stress.³⁰

Decision Regret:

Decision regret and satisfaction were assessed by 2 items adapted from the Decision Regret Scale and the Satisfaction with Decision Scale regarding the use of GGT during children’s cancer treatment, and the adequacy of the information provided to reach an informed choice about such testing.^31,32 When summed, higher scores indicated more decisional regret and less satisfaction (r=.71, p<.05).

Qualitative Interview

An in-depth interview guide (see Appendix) was developed by the study team and administered over the telephone to ask participants about their and their children’s perspectives about pediatric TMP and GGT. Domains of inquiry included: 1) recall of pediatric TMP and GGT completion and results (knowledge); 2) timing of testing in relationship to their children’s cancer diagnosis and treatment (attitude, belief); 3) their interactions with the children’s healthcare providers (i.e., oncologists, genetic counselors) about testing (knowledge, attitude, belief); 4) communication about testing and talking with children and other relatives about the results (knowledge, attitude, belief), and; 5) resources for making testing decisions and need for psychoeducational support (knowledge, attitude, belief). For resources, suggestions were elicited in both an open- and closed-ended manner. All interviews were digitally recorded and verbatim transcribed (duration M=29:6 minutes; SD=7:2 minutes; Longest=45:2 minutes; Shortest=12.5 minutes). Data were content-analyzed, as described below, and interpreted in light of survey findings and consistent with the study’s frame.

Data Analysis

For the survey data, descriptive statistics were used to characterize the sociodemographic and clinical characteristics of the sample (Table 1). Summary statistics for each measure were computed, along with internal consistency reliability. Bivariate correlation analyses for continuous variables then examined associations between and among the constructs of interest (Table 2). Following well-established methods for content coding and analysis in social science research,³³ interview data were read, coded, and analyzed by the study team (including M.R.Y and K.P.T.) using a study-specific codebook that was developed iteratively: inter-coder reliability across the codes was high (Cohen’s kappa >80%).^25,34 Coders identified, categorized, and defined responses expressed by parents in reference to cognitive, affective, and emotional components of children’s cancer, TMP, and GGT. Coders jointly reviewed responses and developed codes and definitions, then applied codes to each parent response individually. This process resulted in 15 discrete codes. Any differences were resolved by consensus conversations with the senior coder to reach 100% agreement, and all coding decisions and processes were documented. The study accounted for multiple occurrences of a code within one parental response by counting the number of parents endorsing each code and tallied the frequency of each code (i.e., individual code frequency/total code frequency; Table 3). Multiple codes with overlapping meanings were consolidated in superordinate categories. However, these codes were also retained to contextualize parental reflections. The study team (including its clinicians and researchers with expertise in psychosocial aspects of cancer genomics) conversed about these findings in an interpretive manner to better characterize their meaning and reviewed corresponding survey responses. Illustrative quotes are provided and indicate the characteristics of parents and children. Unless otherwise specified, the developmental stage at which the child was genetically tested is given.

Table 1.

Participant Demographics

	Survey (N=75)				Interview (N=31)
Parent	M	SD	n	%	M	SD	n	%
Age*	43.2	5.8	37		43.1	6.1	21
Gender
Female			48	64.0			18	58.1
Male			27	36.0			13	41.9
Race
White			60	82.2			29	93.5
Non-White			13	17.8			2	6.5
Ethnicity
Hispanic/Latine			13	18.3			3	9.7
Non-Hispanic			58	81.7			28	90.3
Highest level of education
Less than bachelor’s			28	39.4			10	32.3
Bachelor’s or above			43	60.6			21	67.7
Marital status
Partnered			59	83.1			23	82.1
Not partnered			14	19.7			5	17.9
Genetic knowledge (Correct)			56	78.9
Child
Age at cancer diagnosis*	7.8	6.2	74		6.6	6.2	31
Years since diagnosis*	3.7	3.0	37		4.2	3.2	24
Cancer type*
Brain/CNS tumor			16	28.2			4	13.8
Non-CNS tumor			55	77.5			25	86.2
Germline Genetic Testing Performed
Yes			62	82.7			25	80.6
No			13	17.3			6	19.4
Pathogenic Variant Found
Yes			29	20.4			15	48.4
No			46	79.6			16	52.6

^*Missing age data for n=38 surveyed participants. Data do not sum to 100% due to missing information.

Table 2.

Bivariate Associations from Quantitative Survey (N=75)

Variable	1	2	3	4	5	6	7	8
1. Parent-child communication*  (M=43.9; SD= 5.8; Range=10–50)	1	−0.05	0.38 p=0.02	−0.39 p=0.02	−0.38 p=0.04	−0.36 p=0.02	0.01	0.28
2. Perceived cancer causes*  (M=10.8; SD=2.4; Range=2–14)		1	0.08	0.27 p=0.05	0.34 p=0.02	0.26	0.27	−0.49 p=0.04
3. Genetic knowledge*  (0=False/incorrect, 1=True/correct)			1	0.08	0.09	−0.33 p=0.04	−0.25 p=0.07	−0.29 p=0.02
4. Preferences for return of results*  (M=11.1; SD=1.5; Range=4–12)				1	0.28 p=0.05	−0.11	0.03	−0.17
5. Attitudes toward pediatric GGT*  (M=45.6; SD= 9.2; Range=12–60)					1	0.41 p=0.008	0.13	−0.61 p=0.02
6. Child anxiety**  (M=14.8; SD=6.2; Range=8–40)						1	0.40 p=0.02	0.09
7. Parent anxiety**  (M=9.4; SD=3.9; Range=4–20)							1	−0.09
8. Decision regret**  (M=2.7; SD=1.1; Range=2–6)								1

^*Favorable/better outcome;

^**Poorer outcome.

Table 3.

Content Analysis from Qualitative Interviews (N=31)

	Transcript Frequency/Percentage of Total (N/%)	Frequency of Coded Responses in Transcripts (N)	Percentage of Coded Responses in Transcripts (%)*
Recollection of TMP Testing	26/84%
Yes		18	58%
No/Uncertain		8	26%
Recollection of Germline Testing	23/74%
Yes		19	61%
No/Uncertain		4	13%
Recollection of Receiving Results	31/100%
Yes		29	94%
No		2	6%
Testing Offered at Right Time	25/81%
Yes		22	71%
No		3	10%
Time to Decide about Testing	9/29%
Days or as soon as possible		4	13%
Weeks		2	6%
Month or more		3	10%
Interacted with Oncologist	31/100%
Yes		31	100%
No		0	0%
Interacted with Genetic Counselor	31/100%
Yes		21	68%
No/Maybe		10	32%
Communicated with Family	31/100%
Yes		29	94%
No		2	6%
Discussed Treatment with Children	28/90%
Depends on age and maturity		24	77%
Both parents and children should be involved in discussions about treatment		1	3%
Parents only should be involved in discussions about treatment		3	10%
Speak with Other Families	29/94%
Yes		21	68%
No/Maybe		8	26%
Resources Cited as Helpful**	(select all that apply)
Talking with a physician or healthcare provider		21	31%
Website with online learning modules		16	23%
Connecting with someone who has gone through a similar experience		9	13%
Pamphlet or guidebook		8	12%
Information and support through social media posted by an expert		8	12%
Instructional video		6	9%

^*Data represent the proportion of coded responses for that sentiment across all N=31 transcripts.

^**Percentages do not sum to 100% due to the option to select multiple responses.

For the integrative step, the study team utilized both sets of data during interpretation. Specifically, qualitative findings were used to clarify, extend, and explicate the quantitative results. This included comparing and contrasting survey findings with those generated within and among key informant interviews. Regarding the qualitative findings, and as described by Ahmed and colleagues,³⁵ this investigation adhered to a number of measures to enhance the rigor and reproducibility of the qualitative and mixed-methods approaches. Specifically, it followed the Consolidated Criteria for Reporting Qualitative Research (COREQ)--a framework used to investigate, evaluate, and strengthen the presentation of qualitative research methodology, and widely regarded as a standard in the field.

Results

As displayed in Table 1, most of the N=75 participants in the study sample were partnered, non-Hispanic white, female, college-educated, and in their early forties. The average age of their children at cancer diagnosis was almost eight years-old, and most children had solid, non-central nervous system (non-CNS) tumors. The vast majority of children (83%) were tested within 30 days of the child’s cancer diagnosis. Among the approximately 49% of cases where parents self-reported the child’s age at diagnosis and current age, the average amount of time between those two dates was 3.7 years (SD=3.0): most children were 12.5 years-old at the time of survey. As confirmed by health records, 83% of participants’ children underwent GGT and 20% carried pathogenic variants in a cancer-causing gene.

Survey Findings

The correlation matrix in Table 2 shows bivariate associations among the study’s continuous variables. A clustering of themes that underlay participants’ perspectives on pediatric genetic testing emerged, beginning with their understanding of cancer, its causes, and genetics. A total of 79% of participants responded to the knowledge item correctly about cancer genetics: those who did had greater open communication with their children (r=0.38, p=0.02), were less anxious themselves (r=−0.25, p=0.07) as were their children (r=−0.33, p=0.04), and regretted their GGT decision less (r=−0.29, p=0.02). Further, participants who responded to the knowledge item correctly about cancer’s causes held more favorable attitudes toward pediatric GGT (r=0.34, p=0.02); these parents also experienced less decisional regret about their child’s GGT (r=−0.49, p=0.04). Participants’ attitudes toward pediatric GGT and decisional regret were inversely associated: those with more favorable views about testing experienced less regret (r=−0.61, p=0.02).

Another theme across the bivariate associations was the level of detail that participants wished to receive from GGT for their children. Participants who preferred to learn a greater variety of results from GGT tended to know more about cancer causation (r=0.27, p=0.05). These same participants who wanted to learn more from the results also held more favorable attitudes toward pediatric GGT (r=0.28, p=0.05). On a single survey item administered to the subset of participants whose children underwent GGT (N=23, 31%) which inquired about cascade testing among relatives (i.e., those who had genetic testing as a result of the child’s GGT), 74% (N=17) indicated they had communicated with their child’s relatives about the results and discussed plans to be tested in the future.

Finally, results revealed relationships between family communication and anxiety. Within families who communicated less openly, participants held more favorable attitudes toward pediatric GGT (r=−0.38, p=0.04) and preferred to receive more results from this type of testing (r=−0.39, p=0.02). Families with less open communication styles also tended to be raising more anxious children, as reported by their parents (r=−0.36, p=0.02). Regarding parent-reported child anxiety, greater anxiety among children was reported by participants who were also more anxious (r=0.40, p=0.02) and those with more favorable attitudes toward pediatric GGT (r=0.41, p=0.008).

Key Informant Interview Findings

To further explore the themes that emerged from the survey, qualitative data were collected and are illustrated by quotations. Several themes were reiterated by participants when asked to elaborate upon their experiences with their children’s TMP and GGT (Table 3). First, participants explained their recollection of TMP, as well as whether they believed it was offered at the right time. Next, they were asked about their communication with their child’s healthcare providers and attitudes and beliefs about sharing the details of genetic testing with relatives (e.g., in preparation for cascade genetic testing). Participants also commented on resources that would support informed decision-making about GGT.

Recollection of and Attitudes and Beliefs About Genetic Testing:

Although all participants in this study had children who received TMP with or without GGT, not all participants recalled these tests accurately. For example, only 58% of participants recalled their children receiving TMP. Additionally, although 81% of participants’ children received GGT (as confirmed by record review), only 61% recalled their children doing so. Regardless of whether or not participants recalled the type of genetic testing their children underwent (TMP or GGT), 94% recalled receiving a genetic test result for their children, and a majority (71%) believed such testing was offered at the right time during pediatric cancer treatment:

I would say we were offered it [TMP] very early on, and I think that’s exactly when it should be offered…as early as possible.

Non-Hispanic white father to a school-aged child

Having even up to a week or so to think about it [TMP], to talk to people about it, to talk to their oncology team about it [and] decide if that’s something they want to do or not [is helpful]. But I understand from going and talking about tumor sequencing, there’s also a time limit.

Non-Hispanic white mother to a school-aged child

Communication:

By way of background, all participants (100%) recalled interacting with a pediatric oncologist about their child’s treatment for cancer, including discussing genetic testing. A majority (68%) also recalled interacting with a genetic counselor. Most participants (94%) indicated that they informed one or more first- or second-degree family members about their child’s TMP and/or GGT results, including cascade genetic testing for inherited cancer risk among the cases where this would have been applicable.

Regarding conversations about children’s treatment with the medical team, including use and outcomes of genetic testing, a majority (77%) expressed that those who were older and/or more mature should be included. Conversely, only 10% felt these conversations should take place among parents without affected children present, independent of children’s ages or maturity levels:

Any conversation [with the oncologist]…with myself and my husband also was with my son…As much as I thought that might be overwhelming, I think it’s good [to include children in conversations about germline genetic testing].

Non-Hispanic white mother to a teen

I think the parents have a role to play in deciding what and how to share what they’re learning with their child…depending also on the age of the child. Some of the things that we were told during our…germline testing…were very hard to interpret…You wouldn’t want…a small child to overhear that stuff and come to their own conclusions about what’s going on.

Non-Hispanic white father to a toddler

Psychoeducational Support:

Considering sources of support, a majority of participants (68%) indicated an openness and/or desire to speak with families in similar situations, noting this would be helpful in acquiring information regarding implications of TMP and/or GGT for their children’s cancer treatment and family’s overall cancer risk:

I think the best thing for any cancer family is to connect with other cancer families, whether it be about genetic testing, whether it be about anything like this, it always is helpful…No one understands this journey like another family. If [another parent] had said to me in the beginning of this process, ‘You should do the genetic testing…I would have mentioned it to my doctors. I didn’t even know there was anything like this.

Non-Hispanic white mother to a school-aged child

Regarding other desired sources of information and support about TMP and GGT in the context of children’s cancer treatment and inherited risk, the most commonly cited resources were consultations with healthcare providers (31%) and use of websites with online learning modules (23%). Peer support was reflected in an additional 13% of coded responses, print materials and social media posts in 12%, and video resources in 9%.

Discussion

This mixed-methods study evaluated parents’ knowledge, attitudes, and beliefs about TMP and GGT for their children with cancer. Parents who answered a cancer genetics knowledge item correctly had more open communication with their children, and did not tend to experience adverse psychological distress. At the same time, parents who were more aware of cancer’s genetic and behavioral causes desired more information about their children’s results and were optimistic about its potential to guide treatment and manage risk. Being more cognizant could reflect these parents’ preferences for information about genetic testing and their interest in shared decision-making with their child’s oncologist. Whether or not all parents would want to be actively engaged in treatment decision-making remains to be seen. Differences in parents’ decision making styles could be due to ways of coping with medical information,³⁶ as well as the timing of consent for testing.¹⁹ A paper by Walser and colleagues underscores the importance of using plain language during the informed consent process to facilitate parents’ understanding about genomic sequencing³⁷; Yu and colleagues have outlined multiple strategies that providers can use toward that end.³⁸ Behavioral studies conducted in Australia by Gereis and colleagues³⁹ and McGill and colleagues⁴⁰ document the challenges some families have in understanding childhood cancer precision medicine research and clinical care, including TMP and GGT. It is possible that parental anxiety factored into how they considered TMP/GGT results. As noted in the literature, parental anxiety is commonly associated with the diagnosis of cancer in children and when informed by genomic sequencing results and genetic testing. In a paper by Sharp and colleagues, negative emotions were more commonly seen in parents of children with pathogenic variant results than among those with variants of uncertain significance.⁴¹

The complex relationships between genetic knowledge, preferences and values regarding testing, and parent-child communication style suggest that parents weigh the implications of TMP and/or GGT results with the psychosocial well-being of their children in mind. Survey data suggest that families with elevated anxiety were less comfortable discussing their thoughts, feelings, and experiences in an open, honest, and supportive manner; qualitative data point to additional factors, such as the age and/or maturity level of the child. It is important to respect the autonomy of older adolescents and young adults who may want to be more involved in the decision-making process related to testing.²² As these children reach the age of majority, one must also consider when they should be offered access to their results even if their parents are not supportive of them doing so.²² These and other communication-related decisions are especially important when considering children’s worry levels during their treatment for cancer. Further research should explore the directionality of the associations with family anxiety and parental attitudes toward pediatric genetic testing in the context of children’s cancer treatment--where genetic education and counseling is essential.⁴²

Decision-making regarding TMP and GGT can be supported by psychoeducational resources so that families understand their implications. These resources are especially important given parents’ inconsistent recall of GGT findings.²⁴ In this sample, there was a discrepancy between parents’ recall of their children’s testing and the accuracy of the information. Although some parents could not readily distinguish between TMP and GGT testing types, most were able to correctly recall receiving their children’s results; the vast majority identified learning this news from a member of their children’s healthcare team. Parents’ challenges in recalling and distinguishing between somatic (i.e., TMP) and germline (i.e., GGT) test results, and their actionable implications, suggests room for improvement in the preparation of these parents for their children’s testing.⁴³ Typically, patient education would take place during pre- and post-test genetic counseling, but it is increasingly being offered without interactions with genetics specialists.³⁸ Whether or not it is best to pair GGT with TMP for all children undergoing treatment for cancer has not yet been established. Data from this study suggest that if it were to become the standard of care, better tools to facilitate families’ decision-making and comprehension are sorely needed.

These results also emphasize the importance of preserving parents’ choice to selectively receive the results of their children’s TMP and GGT to allow for communication of result implications to their children and relatives at the time that is best for them. Given these parents are already navigating their child’s cancer treatment and its impact on their prognosis and quality of life, TMP and GGT results pose the risk of further contributing to an overload of information during an already demanding and psychologically stressful time. For example, if TMP and GGT results were to indicate a cancer predisposition with adult-onset cancer risk, then parents would need to decide if, when, and how to relay this information to others. If parents were given the option of when and to what extent they would like their child to participate in TMP and GGT, or when they would like to receive TMP and GGT results, then this would preserve those choices. Data from some parents who were interviewed raised questions about the timing of the introduction of GGT relative to TMP. For example, does GGT need to be included within the discussion surrounding the child’s diagnosis and/or treatment for cancer, or can it be deferred until the family and pediatric oncology team have the opportunity to engage in more in-depth conversations? However, most families endorsed the appropriateness of the timing. Data from Mandrell and colleagues would suggest that parents identify with the benefits of GGT but also appreciate flexibility in when such testing would be performed to give parents more time to adjust to the child’s cancer journey.^19,44

When a pathogenic variant is identified, it is also important to keep in mind that, for some families, speaking with potentially at-risk relatives about children’s cancer and genetic testing could be important so that relatives’ own cancer risks are managed. Both survey and interview data suggest that once genetic test results are returned (either TMP or GGT), a majority of parents informed their family members about some aspect of it. Among these cases, their data consistently aligned toward cascade genetic testing intentions among relatives. Thus, providers should remain sensitive to the psychosocial burdens posed for parents and at-risk relatives, and likely depending on the child’s prognosis. However, the process of engaging at-risk relatives (including the children’s siblings) is complicated. They may not be open to these discussions or, in the case of second-degree relatives, have resources to receive appropriate counseling. It is not known if at-risk relatives (including the children’s siblings) would be ready to engage in testing. In a recent study, after 18 months of follow-up, an average of two relatives per family of children with cancer undergoing GGT had received cascade genetic testing.⁴⁵

The study highlights the need for genetic education and counseling protocols to help meet the needs of parents, children, and at-risk relatives in the same way in which adult oncology patients and their families have benefitted. Our quantitative and qualitative data suggest a range of resources these parents may take advantage of to meet their needs for information and support, including genetic counseling. Beyond this approach, parents were receptive to other resource modalities, including patient-provider networking, online modules, and peer support.

Limitations

This study has several limitations including its modest sample size, homogeneity of participants’ demographic characteristics, and voluntary response bias that can affect the generalizability of its findings. Most participants were female, White, college-educated, and in a partnered relationship. Any conclusions drawn should be limited to those with similar backgrounds to those studied here. Future research with more representative study samples would be beneficial. Also, some participants had children who were tested as part of a clinical research protocol and others were not. Differences in the extent of informed consent for research versus clinical care could be present, which might affect parental understanding and their responses to the present study.³⁷ Moreover, this work relied on self-report data obtained from parents about themselves and their children. Although reliable and valid, self-report behavior rating scales were used in the quantitative stage. It is possible that parents’ perceptions of their children’s behavior were influenced by parents’ perceptions of their own well-being. Further, the use of a single-item assessment of knowledge may not have captured the depth of this construct, although when considered in light of other knowledge-related domains of inquiry assessed by the study the strength of these findings is enhanced. Additionally, we did not compare and contrast the perspectives of parents of children with different types of cancer and/or GGT results (i.e., positive, negative, variants of uncertain significance). Parents of children with newly-diagnosed disease may also differ from those of children who relapsed. The varying lengths of time between children’s cancer diagnosis, genetic testing, and enrollment in this study were also uncontrolled. A larger, clinically selective, and more diverse sample of children with cancer would be necessary for these to be addressed with adequate statistical power.

Conclusions

There is a swift pace of discovery of germline variants in children undergoing TMP and treatment for cancer.^7,46 This has the potential to improve clinical outcomes by providing information relevant to therapeutic planning and implementing cancer prevention for at-risk individuals. Clinical decision-making about genetic testing must be undertaken with a multidisciplinary team, including the child (when age appropriate) and family. To realize the full potential of both somatic and germline testing integrated within pediatric oncology, there is a gap in our understanding of the outcomes of testing, including implications for those at risk. At the same time, research and clinical efforts regarding patient education and counseling must keep up with these discoveries or a lag may develop between translational breakthroughs and patients’ and families’ understanding of their implications for cancer management.⁴⁷ The outcomes of this study suggest a disparity between the information and support the parents in these circumstances receive and could benefit from, including ways to strengthen their understanding of TMP and GGT results and to reduce its psychological burden.