Families' experiences accessing care after genomic sequencing in the pediatric cancer context: "It's just been a big juggle".

Access to genomic sequencing (GS) and resulting recommendations have not been well described in pediatric oncology. GS results may provide a cancer predisposition syndrome (CPS) diagnosis that warrants screening and specialist visits beyond cancer treatment, including testing or surveillance for family members. The Texas KidsCanSeq (KCS) Study evaluated implementation of GS in a diverse pediatric oncology population. We conducted semi-structured interviews (n = 20) to explore experiences of KCS patients' families around learning about a CPS diagnosis and following up on recommended care. We used qualitative content analysis to develop themes and subthemes across families' descriptions of their experiences accessing care and to understand which factors presented barriers and/or facilitators. We found participants had difficulty differentiating which follow-up care recommendations were made for their child's current cancer treatment versus the CPS. In families' access to follow-up care for CPS, organizational factors were crucial: travel time and distance were common hardships, while coordination of care to streamline multiple appointments with different providers helped facilitate CPS care. Financial factors also impacted families' access to CPS-related follow-up care: having financial assistance and insurance were facilitators for families, while costs and lack of insurance posed as barriers for patients who lost coverage during transitions from pediatric to adult care, and for adult family members who had no coverage. Factors related to beliefs and perceptions, specifically perceiving the risk as less salient to them and feeling overwhelmed with the patient's cancer care, presented barriers to follow-up care primarily for family members. Regarding social factors, competing life priorities made it difficult for families to access follow-up care, though having community support alleviated these barriers. We suggest interventions to improve coordination of cancer treatment and CPS-related care and adherence to surveillance protocols for families as children age, such as care navigators and integrating longitudinal genetic counseling into hereditary cancer centers.

Circulating tumor DNA sequencing of pediatric solid and brain tumor patients: An institutional feasibility study.

The potential of circulating tumor DNA (ctDNA) analysis to serve as a real-time "liquid biopsy" for children with central nervous system (CNS) and non-CNS solid tumors remains to be fully elucidated. We conducted a study to investigate the feasibility and potential clinical utility of ctDNA sequencing in pediatric patients enrolled on an institutional clinical genomics trial. A total of 240 patients had tumor DNA profiling performed during the study period. Plasma samples were collected at study enrollment from 217 patients and then longitudinally from a subset of patients. Successful cell-free DNA extraction and quantification occurred in 216 of 217 (99.5%) of these initial samples. Twenty-four patients were identified whose tumors harbored 30 unique variants that were potentially detectable on a commercially-available ctDNA panel. Twenty of these 30 mutations (67%) were successfully detected by next-generation sequencing in the ctDNA from at least one plasma sample. The rate of ctDNA mutation detection was higher in patients with non-CNS solid tumors (7/9, 78%) compared to those with CNS tumors (9/15, 60%). A higher ctDNA mutation detection rate was also observed in patients with metastatic disease (9/10, 90%) compared to non-metastatic disease (7/14, 50%), although tumor-specific variants were detected in a few patients in the absence of radiographic evidence of disease. This study illustrates the feasibility of incorporating longitudinal ctDNA analysis into the management of relapsed or refractory patients with childhood CNS or non-CNS solid tumors.

Inflammatory Myofibroblastic Tumor of the Orbit in an 8-Month Old.

Inflammatory myofibroblastic tumor is a mesenchymal neoplasm, commonly seen in the lung and abdominopelvic region of children. The authors present an 8-month-old female with a 2-month history of left-sided proptosis. Examination was significant for left-sided proptosis, a left exotropia and hypotropia, left supraduction and adduction deficits, and left optic disc elevation. MRI imaging revealed an extraconal left superomedial orbital mass with globe displacement and proptosis. Left anterior orbitotomy with excisional biopsy showed a solid mass composed of an infiltrative proliferation of bland spindle cells in a variably myxoid background with associated perivascular lymphoplasmacytic infiltration. Immunohistochemistry was positive for ALK-1 and CD34 and demonstrated focal positivity for S100. Fluorescence in-situ hybridization showed an additional copy of the 3'ALK gene (46%) in interphase cells examined. Next generation targeted sequencing found a DCTN1/ALK fusion. Findings were consistent with inflammatory myofibroblastic tumor. To the authors' knowledge, this is one of the largest primary orbital inflammatory myofibroblastic tumors in the youngest reported patient.

Project GIVE: using a virtual genetics service platform to reduce health inequities and improve access to genomic care in an underserved region of Texas.

BACKGROUND: The utilization of genomic information to improve health outcomes is progressively becoming more common in clinical practice. Nonetheless, disparities persist in accessing genetic services among ethnic minorities, individuals with low socioeconomic status, and other vulnerable populations. The Rio Grande Valley (RGV) at the Texas-Mexico border is predominantly Hispanic/Latino with a high poverty rate and very limited access to genetic services. Funded by the National Center for Advancing Translational Sciences, Project GIVE (Genetic Inclusion by Virtual Evaluation) was launched in 2022 to reduce the time to diagnosis and increase provider knowledge of genomics in this region, with the goal of improving pediatric health outcomes. We describe our experience of establishing a virtual pediatric genomic service in this region to expeditiously identify, recruit, and evaluate pediatric patients with undiagnosed diseases. METHODS: We have utilized an innovative electronic health record (EHR) agnostic virtual telehealth and educational platform called Consultagene to receive referrals from healthcare providers in the RGV. Using this portal, genetic services, including virtual evaluation and genome sequencing (GS), are being delivered to children with rare diseases. The study has also integrated effective methods to involve and educate community providers through in-person meetings and Continuing Professional Education (CPE) events. RESULTS: The recruitment efforts have proven highly successful with the utilization of Consultagene in this medically underserved region. The project's ongoing engagement efforts with local healthcare providers have resulted in progressively more referrals to the study over time, thus improving inclusion and access to genomic care in the RGV. Additionally, the curated CPE content has been well received by healthcare providers in the region. CONCLUSIONS: Project GIVE study has allowed advanced genetic evaluation and delivery of GS through the virtual Consultagene portal, effectively circumventing the recognized socioeconomic and logistical barriers to accessing genetic services within this border community.

Comparing the Diagnostic Yield of Germline Exome Versus Panel Sequencing in the Diverse Population of the Texas KidsCanSeq Pediatric Cancer Study.

PURPOSE: To evaluate the relative diagnostic yield of clinical germline genomic tests in a diverse pediatric cancer population. PATIENTS AND METHODS: The KidsCanSeq study enrolled pediatric cancer patients across six sites in Texas. Germline analysis included both exome sequencing and a therapy-focused pediatric cancer gene panel. The results were categorized by participants demographics, the presence of pathogenic or likely pathogenic (P/LP) variants, and variants of uncertain significance (VUS) in cancer predisposition genes (CPGs). Pediatric actionable CPGs were defined as those with cancer surveillance recommendations during childhood. RESULTS: Cancer P/LP variants were reported by at least one platform in 103 of 578 (17.8%) participants of which 76 were dominant cancer genes (13.1%) with no significant differences by self-described race or Hispanic ethnicity. However, the proportion of participants with VUS was greater in Asian and African American participants (P = .0029). Diagnostic yield was 16.6% for exome versus 8.5% for panel (P < .0001) with 42 participants with concordant germline results. Exome-only results included P/LP variants in 30 different CPGs in 54 participants, whereas panel-only results included seven participants with a copy number or structural P/LP variants in CPGs. There was no significant difference in diagnostic yield limited to pediatric actionable CPGs (P = .6171). CONCLUSION: Approximately 18% of a diverse pediatric cancer population had germline diagnostic findings with 50% of P/LP variants reported by only one platform because of CPGs not on the targeted panel and copy number variants (CNVs)/rearrangements not reported by exome. Although diagnostic yields were similar in this diverse population, increases in VUS results were observed in Asian and African American populations. Given the clinical significance of CNVs/rearrangements in this cohort, detection is critical to optimize germline analysis of pediatric cancer populations.

Preferences for survivorship education and delivery among Latino and non-Latino childhood cancer survivors and caregivers.

PURPOSE: To assess survivor and parent perceptions of the long-term survivor visit and preferences regarding accessing health information, survivorship education, and support networks in rural and metropolitan regions of Texas. METHODS: Leveraging the multi-institutional Survivorship and Access to Care for Latinos to Understand Disparities (SALUD) cohort, we administered a 26-item bilingual survey to adult survivors of childhood cancer and parents of younger survivors. Characteristics and responses were compared between survivors vs. parents and Latinos vs. non-Latinos using a t test or Fisher exact test. Odds ratios for the outcomes of interest were calculated with 95% confidence intervals. RESULTS: We received 138 responses from 59 survivors and 79 parents of survivors treated at three Texas pediatric cancer hospitals/clinics. Parents were more likely than survivors to seek survivorship information from other survivors or parents of survivors (OR=6.32, 95% CI 1.78, 22.47), and non-Latinos preferred social media as an educational resource (OR=3.70, CI 1.58, 8.68). Survivors, particularly Latino survivors, preferred short videos as a mode of survivorship education delivery. Highest topic priorities for survivorship education were 'risk for second cancers' and 'diet, nutrition, and exercise.' All parents and survivors who rated survivor physical and mental health as 'fair' or 'poor' identified as Latino. CONCLUSIONS: These results highlight differences in perceived health status between Latino and non-Latino survivors and support the development of adapted survivorship education content to address the specific needs of Latino survivors. Implications for Cancer Survivors Results of this study suggest a need for survivorship educational materials in multiple formats and that are tailored to the style, content, language preferences, and health literacy status of the target population.

Reducing Time to Diagnosis of Rare Genetic Diseases in a Medically Underserved Hispanic Population- Lessons Learned for Meaningful Engagement.

Background: The utilization of genomic information to improve health outcomes is progressively becoming more common in clinical practice. Nonetheless, disparities persist in accessing genetic services among ethnic minorities, individuals with low socioeconomic status, and other vulnerable populations. The Rio Grande Valley at the Texas-Mexico border is predominantly Hispanic with a high poverty rate and an increased prevalence of birth defects, with very limited access to genetics services. The cost of a diagnosis is often times out of reach for these underserved families. Funded by the National Center for Advancing Translational Sciences (NCATS), Project GIVE (Genetic Inclusion by Virtual Evaluation) was launched in 2022 to shorten the time to diagnosis and alleviate healthcare inequities in this region, with the goal of improving pediatric health outcomes. Methods: Utilizing Consultagene, an innovative electronic health record (EHR) agnostic virtual telehealth and educational platform, we designed the study to recruit 100 children with rare diseases over a period of two years from this region, through peer-to-peer consultation and referral. Conclusions: Project GIVE study has allowed advanced genetic evaluation and delivery of genome sequencing through the virtual portal, effectively circumventing the recognized socioeconomic and other barriers within this population. This paper explores the successful community engagement process and implementation of an alternate genomics evaluation platform and testing approach, aiming to reduce the diagnostic journey for individuals with rare diseases residing in a medically underserved region.