Impact of a Genetic Evaluation Initiative to Increase Access to Genetic Services for Adolescent and Young Adults at a Tertiary Cancer Hospital

Abstract

Purpose: Adolescents and young adults (AYAs) with cancer are at increased risk for inherited cancer predisposition syndromes. Genetic counseling (GC) is important for accurate risk assessment, diagnosis, and management of inherited cancers. Numerous barriers prevent AYA access to genetic services. This study describes outcomes of a genetic evaluation initiative (GEI) regarding utilization of genetic services among AYAs.

Methods: To improve AYA access to GC, the AYA program at UT MD Anderson Cancer Center implemented GEI, a process for identifying and referring eligible patients for GC. We collected retrospective electronic medical record data between July 12, 2018 and July 12, 2019 to capture AYA's clinical characteristics, genetic referral, scheduled appointments, counseling, testing, and results.

Results: In total, 516 AYAs were referred to the AYA clinic during the study period with a median age of first cancer diagnosis of 17 years. One hundred sixty-six AYAs were identified who would benefit from genetic evaluation, 57 (34.3%) of whom had previously undergone counseling. One hundred nine patients were recommended for referral to GC, and 64.2% (70/109) were referred by the AYA team. To date, 58.6% (41/70) met with a genetic counselor and 75.6% (31/41) completed genetic testing, which yielded 1 pathogenic, 2 uncertain, and 29 benign results.

Conclusion: The GEI resulted in a 72.0% relative increase in the rate of GC utilization and represents a novel approach to increasing AYA patient access to cancer genetic services in this population.

Background

Approximately 70,000 adolescents and young adults (AYAs) ages 15–39 years are diagnosed with cancer annually in the United States, which is the leading cause of disease-related death in this population.¹ Cancers in AYAs often show characteristics of inherited cancer predisposition syndromes—for example, pediatric cancers occurring at unexpectedly older ages, or typically adult-onset cancers occurring at unexpectedly young ages.^2–4 Although the prevalence of cancer predisposition syndromes in the AYA population is not known, germline cancer predisposition mutations may be more prevalent in AYAs with cancer compared with older adults as mutational burden, environmental exposure, and lifestyle are less likely to be driving factors in the development of cancer at younger ages. Tumor biology differs significantly between young and older patients and thus approaches to genetic screening in other populations cannot necessarily be applied to AYAs.⁵ Identification of AYAs at risk for hereditary cancers is important to guide evidence-based management, to optimize long-term surveillance, and to reduce morbidity and mortality. Genetic counseling (GC) and/or identification of germline pathogenic variants (or lack thereof) also can help AYAs make informed decisions about life milestones that are highly relevant to young adults, such as family planning. However, childhood cancer patients often do not receive guideline-based genetic evaluation⁶ and genetic testing rates are lowest among the 18–34-year age group.⁷

Barriers to AYAs' access to GC exist at the institution, provider, and patient level. These barriers include the limited GC workforce, especially in the community setting, limited provider knowledge of AYA cancer genetics, and patient concerns such as consequences for future offspring and insurance discrimination. There are unique challenges to identifying AYAs who may benefit from genetic evaluation. First, collecting and updating family history information, which can determine who may be appropriate for counseling is difficult in the AYA population. AYAs have dynamic family histories, as parents, aunts, and uncles may develop cancer after the diagnosis in the patient due to their relatively young ages. Second, physicians may have concerns about how to talk to minors and young adults about genetic testing and parents may be uncomfortable discussing hereditary cancers with their children.⁸ Third, several cancers that often occur in AYAs lack established guidelines for referral to GC, which complicates the evaluation and determination of genetics referral.

The establishment of dedicated AYA oncology care programs^9,10 provides an opportunity to overcome many of the challenges associated with genetic evaluation of AYAs, to improve rates of appropriate referral for GC, and when indicated, genetic testing. We implemented the genetic evaluation initiative (GEI) program at The University of Texas MD Anderson Cancer Center (MDACC) to increase access to genetic services for AYAs at risk for cancer predisposition syndromes who are newly diagnosed with cancer and childhood cancer survivors. We describe outcomes of the GEI with regard to utilization of cancer genetics services (e.g., risk assessment and referral for GC, GC, and testing) among AYA patients seen in MDACC's AYA multidisciplinary clinic over the course of its first year.

Methods

MDACC's AYA multidisciplinary clinic provides comprehensive supportive care for AYAs with a current or prior cancer diagnosis to address personal, psychosocial, and medical needs that have been impacted by cancer. Patients, 15–39 years of age, who are newly diagnosed, undergoing treatment, or post-treatment are eligible for evaluation in the AYA program. Patients are referred for an initial consultation appointment in the AYA clinic by their primary MDACC physician, during which the following areas of concern are addressed: (1) oncofertility, (2) inherited predisposition to cancer, (3) psychosocial well-being, and (4) survivorship. The multidisciplinary team includes AYA-focused professionals, including physicians, nurses, nurse practitioners, educational/vocational counselors, genetic counselors, social workers, and dieticians. MDACC cares for more than 15,000 AYAs each year, and patients are treated for the large variety of diagnoses that impact AYAs. During the first year of the AYA Program's existence, departments including sarcoma, lymphoma, and pediatrics were more likely to refer patients to the AYA Program in comparison with other departments such as breast cancer, colorectal cancer, and radiation oncology.

Before their initial consultation, a genetic counselor (with expertise in pediatric and young adult cancer genetics) evaluates patients' clinical information (cancer type, age at diagnosis, and other pertinent health history) and family history to determine whether a referral for GC is recommended and confirms whether patients had already undergone GC or testing related to their personal or family history of cancer. Recommendations for GC referrals are based on National Comprehensive Cancer Network (NCCN) clinical practice guidelines¹¹ or consortium consensus statements regarding recommendations for counseling or testing in specific tumor types (e.g., DICER1 and associated conditions¹²). In the absence of guidelines or consensus statements, a literature review is conducted to determine if emerging research suggested GC for a specific tumor type. The small proportion of patients who underwent paired tumor normal sequencing also are reviewed; those who received GC or confirmatory testing for a possible germline finding are not recommended for a genetics referral. Most patients who were reviewed for this study had not undergone tumor normal testing because it was not standard care at the time of their diagnosis.

During the initial consultation, AYA medical providers discuss recommendations for GC referrals when indicated. Patients who consent to a genetics referral are scheduled to meet with a genetic counselor at a subsequent appointment; others my decline or defer referral.

Data collection

This study analyzed data from patients who were referred to the AYA multidisciplinary clinic between July 12, 2018 and July 12, 2019, and were followed until February 10, 2020. Data were retrospectively collected from the electronic medical record, including cancer type and age at diagnosis. When available, we collected documentation regarding GC and testing, specifically, whether a referral for GC was placed, whether a counseling appointment was scheduled, whether counseling and testing were completed, genetic testing results, and reasons for refusing GC or genetic testing. This study was approved by the MDACC Institutional Review Board with a waiver of informed consent for retrospective data collection.

Statistical analysis

The following GEI outcomes were evaluated: the proportion of patients recommended for GC who were not previously referred, proportion of patients for whom a referral was placed by an AYA provider, proportion of patients referred to counseling who met with the genetic counselor, and the proportion who completed genetic testing. Descriptive statistics were used to characterize the study population with respect to demographic and clinical characteristics. Two sample two-sided t-tests were used to compare mean, and chi-square analysis was used to compare proportions. To assess potential predictors of referral to GC (previously referred/referred through GEI), patients were compared on sociodemographic and clinical variables (age, gender, time since cancer diagnosis, and cancer type) using logistic regressions. R studio software version 3.5.1 was used for statistical analysis, and statistical significance was set at p < 0.05. In addition, the number of patients seen by GC and the specific cancer diagnoses were compared between the year before (July 12, 2017–July 12, 2018) and year following (July 12, 2018–July 12, 2019) initiation of the GEI.

Results

Demographic and clinical characteristics

During the study period, 516 AYA cancer patients were scheduled for initial consultations at the AYA clinic. Table 1 describes the demographic and clinical characteristics of the study population. Slightly fewer than half of the patients were female (47.7%) and approximately one third were Hispanic or Latino (29.3%) patients. Median age was 23 years (range, 15–39 years), with the median age of first cancer diagnosis at 17 years (range, 1 month–39 years). The most frequently diagnosed cancers were sarcoma (25.0%), lymphoma (18.8%), and leukemia (12.9%).

Table 1.

Demographic and Clinical Characteristics of Patients Seen at the Adolescent and Young Adult Clinic at MD Anderson Cancer Center from 2018 to 2019 (N = 516)

Variable	n	%
Sex (n = 516)
Female	246	47.7
Male	269	52.1
Current age
Median	23 years
Range	15–39
Age at cancer diagnosis
Median	17 years
Range	0.08–39
Race (n = 516)
White or Caucasian	327	63.4
Black or African American	44	8.5
Asian	21	4.1
Other	108	20.9
Unknown	16	3.1
Ethnicity (n = 516)
Hispanic or Latino	151	29.3
Not Hispanic or Latino	330	64.9
Unknown/declined	32	6.2
Cancer type (n = 516)
Sarcoma	129	25.0
Lymphoma	97	18.8
Leukemia	67	12.9
Head and neck	28	5.4
Germ cell tumor	24	4.7
Other	171	33.1

Identification and referral of AYA patients considered appropriate for GC

Figure 1 shows the number of patients identified as appropriate for referral to GC through the GEI, and subsequent outcomes. Of all patients who were scheduled for initial consultations at the AYA multidisciplinary clinic, the GEI identified 166 (32.2%) who were deemed appropriate for referral for GC; 57 of those (34.3%) had previously undergone GC. AYAs who were referred to GC through GEI had a longer time since cancer diagnoses compared with patients who had not previously been referred to GC (OR = 1.07, 95% confidence interval [CI]: 1.02–1.13, p = 0.009). There were no differences in age, gender, or cancer type. The remaining 109 had not been referred to GC, nor had they seen a genetic counselor. Through the GEI, it was recommended to the AYA clinic medical providers that these 109 patients be provided with a referral to GC.

FIG. 1.

Identification, referral, and completion of genetic counseling and testing among patients seen in the MD Anderson Cancer Center Adolescent and Young Adult Multidisciplinary Clinic from July 12, 2018 to July 12, 2019.

Of the 109 patients recommended for GC, 20 (18.3%) met NCCN guidelines for genetic testing, 8 (7.4%) were recommended based on their family history, 11 (10.1%) were based on a consortium consensus statement, and 64.2% (n = 70) were based on literature review for that specific cancer type by a genetic counselor. Eighty-four (77.1%) were seen for initial consultation at the AYA clinic and the remaining 25 (22.9%) did not attend their appointment. Of those seen in the AYA clinic, 70 (83.3%) were referred to GC, of the remaining patients (n = 14), 7 declined referral, 6 did not receive a referral from the AYA provider, or the reason was not specified in the electronic medical record (n = 1).

AYAs' utilization of GC and testing postreferral

Of the 71 patients referred to GC by an AYA medical provider, to date, 41 (58.6%) underwent GC; of those, 31 (75.6%) underwent genetic testing. Nineteen did not attend their scheduled GC appointments, and 10 had been scheduled but not yet seen at the time of study completion. Of the 41 AYAs with cancer who were seen for GC, 10 did not undergo genetic testing either because genetic testing was not recommended by the genetic counselor (n = 2), the patient had concerns due to insurance/cost (n = 1), the patient declined testing (n = 5), or for other reasons that were not documented (n = 2).

As a result of the GEI, 41 additional eligible AYAs with cancer were identified and seen for GC, who had not been referred for or seen for counseling before GEI implementation, bringing the total proportion of AYAs at risk for cancer predisposition syndromes who were seen for GC to 59.0% (98/166). This represented an absolute increase of 24.7%, and a 72.0% relative increase in receipt of appropriate GC as a result of GEI implementation.

AYAs' genetic testing outcomes

Thirty-one (75.6%) patients who were seen for counseling underwent one of the following types of genetic testing: targeted testing for a single gene (n = 14), testing for small gene panels of 2–10 genes (n = 12), or larger panels comprising of ≥11 genes (n = 4), or diepoxybutane assay + telomere (n = 1). One patient (3.2%) was found to have a pathogenic variant in MSH2, which diagnosed the patient with Lynch Syndrome, and two patients (6.4%) were found to have variants of uncertain significance in POLE and ATM. The remaining patients (90.3%) tested negative for a pathogenic germline gene variant (Supplementary Table S1).

Impact of the GEI on institution-wide GC for AYAs

Approximately 15,000 AYAs are seen at MDACC each year, including cancer patients as well as at-risk individuals. AYAs deemed appropriate for GC are referred to genetic counselors in one of 18 disease site-based clinics at MDACC, based on their presumptive hereditary cancer risk. On average, 687 AYAs undergo GC at MDACC each year. During the course of the year immediately before the GEI implementation (2017–2018), 677 AYA patients were seen for GC across MDACC and 52.7% (357/677) underwent genetic testing, which is significantly lower than the proportion of patients referred by the AYA clinic who received genetic testing (75.6%, p = 0.004) in the following year. In the year the GEI was implemented, the AYA program saw ∼3.4% of the total AYAs seen across the institution. The GEI directly resulted in the GC of an additional 6.0% (41/687) of the average AYAs who undergo GC at the institution. Patients seen in the AYA clinic included a larger representation of rare cancer types with most patients diagnosed with sarcoma (45%) followed by brain cancer (22%). In contrast, AYA patients with a breast cancer diagnosis comprise the largest proportion of those seen for GC at MDACC (45%), followed by colorectal cancer (8.1%). AYA patients from the general MDACC population had a median age of 31.5 years (range: 15–39) and were predominantly female (74.6%) and diagnosed with breast cancer (24.7%) and colon cancer (5%). Notably, patients with breast and colorectal cancer, which comprise the most common types of hereditary cancer were not seen in the AYA clinic during the study period, whereas breast and colon cancer together comprised the majority of cancer patients seen for GC in the general MDACC AYA population.

Discussion

Implementation of the novel GEI in a comprehensive cancer center's multidisciplinary AYA clinic successfully identified AYAs at risk for cancer predisposition syndromes and increased patient referral to and utilization of genetic services resulting in a 72.0% relative increase in receipt of GC. To our knowledge, this is the first study to quantify the added value of involving a genetic counselor within an AYA program to increase patient access to GC and testing. GEI was designed specifically to improve the identification of AYAs who were appropriate for GC as well as subsequent referral. Involvement of a genetic counselor in a multidisciplinary AYA clinic enabled consistent identification of AYAs at risk of hereditary cancer and helped facilitate timely access to counseling and testing. These findings may be useful for improving AYAs' access to genetic services at MDACC as well as at other institutions.

We speculate that the relative increase in utilization of GC services may be even higher at other institutions that adopt GEI. This study was conducted at a large academic institution with many resources to ensure that providers are trained to identify patients who may benefit from GC. This includes continuing medical education through lectures and conferences for providers to develop and increase their knowledge about genetics, NCCN guidelines, policies for follow-up when possible germline mutations are identified on tumor/normal testing, and a large number of specialized genetics clinics to identify cancer syndromes within certain cancer types. Despite this breadth of resources, GEI identified patients who would benefit from GC services, but had never been referred. Thus, we anticipate an even larger improvement in appropriate referral to GC if GEI is implemented at other hospitals that may have fewer resources to ensure appropriate referral to GC.

The GEI was particularly useful for identifying AYA GC candidates who were childhood survivors of or newly diagnosed with heterogeneous and rare cancers, which is a known barrier of access to GC.¹³ Rare cancers such as Hodgkin and non-Hodgkin lymphomas, thyroid, and bone and soft tissue sarcomas account for a large proportion of cancers in the AYA age group.¹⁴ Many of these rare cancer types lack established genetic risk assessment guidelines, which may limit oncologists' ability to identify patients at risk for cancer predisposition syndromes. Compared with common hereditary cancer types such as breast or colon cancer, which are typically diagnosed in adulthood, the genetics of rare cancers that typically affect the AYA age group are, to a large extent, not known. Yet, a hallmark of genetic cancer predisposition syndromes is their manifestation and diagnosis at younger ages, which suggests that many AYAs affected with cancer are likely to benefit from GC. Thus, specific knowledge of genetic cancer risk that commonly affects AYAs with cancer combined with a thorough genetic risk assessment for every AYA patient seen at the AYA clinic, was critical in identifying candidates for GC within GEI. Both pathogenic and benign genetic test results helped inform cancer risks of the AYAs as well as their family members.

Although most cancer centers, including MDACC, have well-established clinical referral processes, through which patients affected by common hereditary cancers are evaluated and referred to GC, many lack similar streamlined processes for genetic evaluation of rarer cancer types. Thus, the GEI within an AYA clinic, which serves a population disproportionately affected by rare cancer types, is well positioned to ensure access to GC. Although evidence regarding use of such GC models in the AYA setting is absent,¹⁵ in adult settings, similar GC models have improved patient access to GC and testing.^16–19

The GEI implemented in this study was also able to overcome some provider-level barriers that often limit patient access to genetic services by involving a genetic counselor to advise AYAs' medical providers of the need for a referral. Even for cancers with established risk assessment guidelines (e.g., melanoma), systematic barriers such as physician's lack of knowledge genetic testing and confidence to initiate genetic discussions^20,21 can limit patient access to GC. Keeping up to date with an ever-growing body of genetic literature and evidence guiding genetic evaluation and management of cancer patients presents a challenge for nongeneticist oncology providers. In this study we saw that over 64% of referrals made through the GEI were based on a literature review of specific cancer types, whereas only 25.6% were based on a patient or their family meeting NCCN guidelines. Thus, having a genetics specialist, who is able to keep up to date on emerging literature, review patients within this multidisciplinary clinic allowed for ease and timeliness in identification, referral, counseling, and testing. Additional approaches may have further improved the rate of GC uptake, including patient education resources describing the purpose and benefits of GC.

We recognize that appropriation of initiatives similar to GEI may not be feasible in smaller resource-limited clinical settings due to GC workforce limitation and the need to ensure optimal utilization of this limited resource. Although, including genetic counselors as part of the multidisciplinary team at the AYA clinic would be ideal, it is not feasible due to the shortage of genetic counselors nationwide. However GEI allowed for faster and more efficient use of the limited GC resources that were available, as we were able to evaluate hundreds of patients and only those who needed to meet with a genetic counselor were referred.

Newer service delivery models¹⁵ can further improve access to genetic health care by overcoming geographical barriers, allowing genetic counselors to see higher volume of patients, and supporting greater number of health care providers. Service delivery models such as telephone counseling²² and telegenetics²³ may be considered. Other options include group counseling for AYAs with similar conditions, which has the added benefit of facilitating social support among AYAs who have unique psychosocial needs compared with adults. Another option is tandem referral^24,25 where pretest counseling is conducted by another health care provider such as advanced practice nurses, followed by post-test counseling with a genetic counselor. While these strategies can improve access to GC, alternative strategies for identifying AYAs eligible for genetic evaluation also needs to be considered. One option is the use of online genetic risk assessment platforms^26,27 that identify patients with genetic risk factors with the goal of streamlining genetic appointments. However, the effectiveness of such tools to accurately assess genetic risk for rare cancers needs to be evaluated.

The improvement in GC referrals and uptake among AYA cancer patients observed in this study can likely be attributed to GEI rather than influences from external events or normal variation in practice. Although many of these AYA patients had been previously seen at MDACC for their cancer care, they had not received a referral to GC from their providers. To our knowledge, implementation of quality improvement efforts to increase AYA access to cancer genetics through AYA programs are limited and the GEI has potential to be implemented in other AYA programs that are in place across the nation. The number of AYA programs in cancer centers and community sites is increasing, and addressing AYA access to genetic services should be considered as a key component of new and established AYA programs. Further research is needed to better understand various clinical bottlenecks within the AYA referral process to develop interventions to overcome these barriers. The growth of AYA clinical programs and clinical guideline development has been an iterative process in the United States, and the activities of existing AYA programs such as this, are instrumental in informing each set of recommendations, guidelines, and criteria.

Study limitations include focus on a single AYA clinic in a comprehensive cancer center, which may limit generalizability to all oncology settings. Through retrospective data review of patients counseled from July 2017 to July 2018, we captured a predissemination cohort over a comparable period of time to observe baseline trends in the institution-wide use of genetics services. The observed relative frequency of different cancer types in our cohort may have been biased by the outreach activities performed at the AYA program's inception, whereby different oncology departments were approached at different times. During the study period, the AYA program did not see many AYAs with breast cancer or colorectal cancer, which comprise the largest proportion of patients seen for GC at MDACC. In addition, inclusion of patients age 15–39 represents a wide spectrum of cancer diagnoses, with differing cancer biology, that is, often directly related to age. With a median age of 23, the population in the current study was more representative of younger AYAs. Additional studies are needed to determine and address specific barriers to receipt of GC and testing among AYAs at risk for cancer predisposition.

In conclusion, we have demonstrated an improvement in AYA access to GC and genetic testing by implementing and integrating a genetic counselor within an AYA program at a large tertiary care cancer hospital. Implementation of GEI within the AYA program was feasible and successfully increased the use of accurate GC for rare cancer types over a 1-year period. Determination of hereditary cancer risk is critical for cancer decision making of index AYA cancer patients as well as young family members who may carry the same genetic mutation. It is imperative for AYA programs to continue to measure and report their programmatic outcomes to help the implementation of similar initiatives within AYA programs at other institutions as well as within other health care settings.

Author Disclosure Statement

M.R. and J.A.L. are codirectors of the AYA program at UT MD Anderson Cancer Center. J.C. is the genetic counselor who implemented the genetic evaluation initiative described in this article. S.M., B.A., D.B., A.Y., and S.K.P. have no conflicts of interest to declare. No competing financial interests exist for any authors.

Funding Information

This study was supported in part by the National Cancer Institute through Cancer Center Support Grant (CCSG) 5P30CA016672 (PI: P. Pisters); a Cancer Prevention Fellowship supported by the Cancer Prevention and Research Institute of Texas (CPRIT) grant award, RP170259 (to S.M.; PI: S. Chang and S. Shete).

Supplementary Material

Supplementary Table S1