Pediatric Cancer Treatment Research Articles

Child and Caregiver Perspectives on COVID-19 During Pediatric Cancer Treatment: A Mixed Methods Approach

Child and Caregiver Perspectives on COVID-19 During Pediatric Cancer Treatment: A Mixed Methods Approach

Metronomic Chemotherapy for Pediatric Refractory Solid Tumors: A Retrospective Single-Center Study.

Metronomic chemotherapy (MC) is based on chronic administration of chemotherapeutic agents at minimally toxic doses without prolonged drug-free breaks, that inhibits tumor angiogenesis and induces tumor dormancy. This study aimed to determine the efficacy of MC for pediatric refractory solid tumors. We retrospectively analyzed the data of pediatric patients with relapsed/refractory solid tumors who received treatment, including low-dose continuous administration of anticancer drugs, at our institute. Of the 18 patients, the disease statuses at the initiation of MC were complete remission (n=2), partial remission/stable disease (n=5), and progressive disease (n=11). The overall survival rate was 61% at 12 months and 34% at 24 months, and the progression-free survival rate was 21% at 12 and 24 months. Although only 5 of the 18 patients showed certain tumor regression or maintained remission, tumors that stabilized, maintained remission/stable disease, and showed certain advantages in terms of overall survival rate, even if limited to progressive disease. Approximately half of the patients demonstrated temporal tumor stabilization and improved survival time. Overall, previous reports and the present study support the conclusion that MC has the potential to play an important role in pediatric cancer treatment during the advanced stage.

Factors influencing caregiver decisions to use complementary and integrative therapies in pediatric oncology settings: Findings from a qualitative analysis

PurposeComplementary and integrative medicine (CIM) therapies (i.e., non-conventional Western medicine interventions) may reduce side-effects associated with pediatric oncology treatment. CIM therapies may also improve caregiver psychological and physical health that is exacerbated during pediatric cancer treatment. Despite known benefits, these therapies are not widely used within pediatric oncology populations in the United States. To guide and promote CIM use among this population, the aim of this project was to qualitatively explore factors that contribute to caregivers' decision to include CIM use in their own and child's care. MethodsTwenty caregivers of children (ages 0.5–14 years) being treated for cancer participated in this study. Each completed a demographic form and the CIM use questionnaire. Qualitative interviews followed by a card sort task were used to assess barriers and facilitators of uptake for caregivers and their child with cancer. ResultsA number of predisposing (e.g., child age, beliefs) and needs factors (e.g., potential to treatment-related side-effects) provide insight into caregivers’ decisions to use CIM for their child. Analyses also revealed the importance of enabling factors (e.g., resources) for caregiver use. Caregivers also reported benefiting from additional information about risk/benefit analysis of these therapies, and current research for CIM use in caregivers and children being treated for cancer. ConclusionChildren may benefit from individually tailored complementary and integrative medicine consultations that explore patient history and specific needs factors to improve preference concordant care and uptake. Caregivers may benefit from support that improves enabling factors associated with care (e.g., improved accessibility).

Unraveling the Landscape of Pediatric Glioblastoma Biomarkers: A Comprehensive Review of Enhancing Diagnostics and Therapeutic Insights.

Glioblastoma, the most common and aggressive form of primary brain tumor, poses significant challenges to patients, caregivers, and clinicians alike. Pediatric glioblastoma is a rare and aggressive brain tumor that presents unique challenges in treatment. It differs from its adult counterpart in terms of genetic and molecular characteristics. Its incidence is relatively low, but the prognosis remains grim due to its aggressive behavior. Diagnosis relies on imaging techniques and histopathological analysis. The rarity of the disease underscores the need for effective treatment strategies. In recent years, the quest to understand and manage pediatric glioblastoma has seen a significant shift towards unraveling the intricate landscape of biomarkers. Surgery remains a cornerstone of glioblastoma management, aiming to resect as much of the tumor as possible. Glioblastoma's infiltrative nature presents challenges in achieving a complete surgical resection. This comprehensive review delves into the realm of pediatric glioblastoma biomarkers, shedding light on their potential to not only revolutionize diagnostics but also shape therapeutic strategies. From personalized treatment selection to the development of targeted therapies, the potential impact of these biomarkers on clinical outcomes is undeniable. Moreover, this review underscores the substantial implications of biomarker-driven approaches for therapeutic interventions. All advancements in targeted therapies and immunotherapy hold promise for the treatment of pediatric glioblastoma. The genetic profiling of tumors allows for personalized approaches, potentially improving treatment efficacy. The ethical dilemmas surrounding pediatric cancer treatment, particularly balancing potential benefits with risks, are complex. Ongoing clinical trials and preclinical research suggest exciting avenues for future interventions.

Abstract 4814: Pediatric radiation treatment adherence in LMIC

Abstract Background: Radiation therapy plays a significant role in the treatment of pediatric cancer. However, there have been documented challenges and difficulties encountered by patients while accessing care for cancer and it has been postulated that travel distance contributes to treatment breaks and abandonment. Objectives: The objective of this study was to determine the prevalence of treatment breaks, assess the travel burden of patients receiving radiotherapy for pediatric cancers at a high-volume center in Nigeria and to determine the impact of travel burden on treatment breaks and treatment completion. Materials and Methods: A retrospective cross-sectional study design was utilized. Data was extracted from the electronic medical records of all pediatric patients referred to the center for radiation therapy between June 2019 and June 2023. Data was analyzed using Microsoft Excel and the results were presented in descriptive statistics. Association between data were analyzed using chi-square test with the level of significance (p) set at <0.05. Results: A total of 210 pediatric cancer patients were enrolled with an average age of 10.9 years. Children aged 0-14 years accounted for 69.05% while 30.95% were between the age of 15 and 19 years. Brain tumors were the most predominant diagnosis, representing 28.10% of cases. Treatment intent was predominantly radical or curative (81.69%). 61.43% (129) of the patient population came from the within the state with an average travel distance of 19.3 km. Of all the 210 patients, 44.29% of patients did not commence RT. The reasons for this were mostly financial constraints but were not explored in this study. Of those who did commence RT, 54.70% had breaks, and 45.30% did not have breaks. Also, 75.21% of patients completed their treatment; however, 24.79% were unable to complete their treatment. Travel distances varied, with the average distance to the treatment center being 165.3 km and the median at 28.5 km. The study categorized travel distance into quartiles: short (0-16 km), medium (>16 km to 28.5 km), long (>28.5 km to 302 km), and very long (>302 km to 1387 km). Chi-square test did not reveal a significant association between travel distance and treatment completion (p=0.57), nor between travel distance and treatment breaks (p=0.20). Conclusion: These findings highlight the complex interplay of demographic factors, disease profiles, and socioeconomic barriers affecting treatment continuity and completion among pediatric oncology patients in a resource-limited setting. These findings suggest that in this low - resource context, other variables such as socioeconomic status and financial barriers may play a more pivotal role than travel distance in treatment commencement, adherence and completion. As such, more detailed investigation of the obstacles through a comprehensive and targeted strategy could lead to more favorable outcomes in pediatric cancer radiation therapy adherence. Citation Format: Adedayo Joseph, Adeseye Akinsete, Ugonna Fakile, Chidiebere Agbakwuru, Lensa Keno, Omolola O. Adisa, Aishat Oladipo, Oluwafunmilayo Fagbemide, Muhammad Habeebu, Wilfred Ngwa. Pediatric radiation treatment adherence in LMIC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4814.

Abstract 1084: Preclinical testing of a cell adhesion molecule 1 (CADM1) targeting antibody-drug conjugate in osteosarcoma and other pediatric solid tumor models

Abstract Introduction: Survival outcomes of osteosarcoma have remained stagnant for decades, emphasizing the urgent need to identify new cell surface targets and develop novel therapies. Antibody-drug conjugates (ADCs), known for their targeted delivery of cytotoxic agents to specific targets, present an attractive therapeutic class for potential use in osteosarcoma. Methods: We previously identified Cell Adhesion Molecule 1 (CADM1) is highly expressed on the cell surface in osteosarcoma using an integrated proteomic and transcriptomic surfaceome profiling approach. As a proof of concept, a humanized CADM1 antibody (clone PTA021-A1) was conjugated with Tesirine (SG3249), a pyrrolobenzodiazepine (PBD) dimer payload. The antitumor activity of this CADM1 ADC was validated in vivo in 8 osteosarcoma patient-derived xenografts (PDXs). CADM1 is also highly expressed in other pediatric solid malignancies such as neuroblastoma and Wilms tumor. The CADM1 ADC was tested in vitro in neuroblastoma and Wilms tumor models. Negative controls included a CD19 targeting ADC with the same payloads and CADM1 negative Ewing sarcoma models. Results: The expression of the CADM1 was validated by flow cytometry in osteosarcoma, neuroblastoma, and Wilms tumor cell lines, and by immunohistochemistry (IHC) in osteosarcoma patient samples and PDX models. In vivo testing of CADM1 ADC in 8 osteosarcoma PDX models showed that the ADC was well-tolerated and significantly prolonged progressive-free survival in all osteosarcoma models. Complete response (CR) and maintained CR was observed in 3 models. In vitro testing for neuroblastoma and Wilms tumor is ongoing, and preliminary data suggest promising antitumor activities. Conclusions: CADM1 is highly expressed in osteosarcoma and other pediatric solid tumors. CADM1 ADC demonstrated promising antitumor in vitro and in vivo activity in osteosarcoma, and initial in vitro studies in neuroblastoma and Wilms tumor show similarly promising responses. These data support the need for further studies assessing the potential of a CADM1 ADC as a novel agent for the treatment of pediatric solid cancers. Citation Format: Zhongting Zhang, Yifei Wang, Wendong Zhang, Xiangjun Tian, Qi Wang, Rossana N Lazcano Segura, Michael Roth, Jonathan Gill, Douglas Harrison, Zhaohui Xu, Yianhua Yi, Sylvester Jusu, Giuseppe Longo, Xin Zhou, Jing Wang, Richard Gorlick. Preclinical testing of a cell adhesion molecule 1 (CADM1) targeting antibody-drug conjugate in osteosarcoma and other pediatric solid tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1084.

Increasing pediatric radiation oncology capacity in sub-saharan Africa using technology: a pilot of a pediatric radiation oncology virtual training course

BackgroundThe shortage of skilled healthcare professionals in pediatric oncology and the limited access to training programs remain significant challenges in Nigeria and sub-Saharan Africa. The the Pediatric Radiation Oncology (Virtual) Course, ‘PedROC’ project aims to contribute to improving pediatric cancer outcomes in Nigeria by increasing the capacity of radiation oncology professionals. To address the gap in access to pediatric radiation oncology professional development, the PedROC project was created, harnessing technology to improve radiation oncology training via a curriculum delivered through web-conferencing. This study aimed to evaluate the effectiveness of the PedROC pilot in enhancing the capacity, confidence, and skill of radiation oncologists in decision-making, prescribing, and treatment planning of radiotherapy for children diagnosed with cancer.MethodsA multidisciplinary faculty of specialists in radiation oncology, pediatric oncology, oncology nursing, radiation therapy technology, and medical physics collaborated to identify the key learning needs in pediatric radiation oncology in the country. The team collaborated to develop a comprehensive curriculum covering the most common pediatric cancers in sub-Saharan Africa for the training program. The training course was conducted over two days, delivering twenty-four half-hour sessions for a total of 12 h, from July 31 to August 01, 2021.ResultsAnalysis of pre and post - training surveys showed a significant increase in self-reported confidence measures across all domains among radiation oncologists. The program successfully improved participants’ knowledge and confidence levels in managing common pediatric cancers using radiotherapy, particularly addressing radiotherapy-specific issues such as appropriate dose, target volume delineation, treatment planning, dose constraints, and plan evaluation.ConclusionThe PedROC pilot showed the efficacy of this model in enhancing the capacity and confidence of radiation oncology professionals involved in the treatment of pediatric cancer. The findings indicate that technology holds significant potential to increase pediatric radiation oncology capacity in Africa, ensuring improved access to proper treatment and ultimately improving pediatric cancer outcomes.

Quality of life of caregivers at the end of their child's pediatric cancer treatment: cancer-specific worry and material hardship.

Emerging research suggests that completion of pediatric cancer treatment can be challenging for caregivers given shifting roles and responsibilities. Lower caregiver quality of life (QOL) has been associated with cancer-related variables, higher cancer caregiving strain, and more household material hardship during pediatric cancer treatment. Caregiver QOL at the end of treatment has not been fully investigated but has implications for child and family well-being. Using a psycho-oncology framework, this study aimed to understand the cumulative burden of household material hardship and cancer-related factors on caregiver QOL at the end of treatment. Caregivers (N = 143) of children (Mage=10.51 years) within 1 year of ending active cancer treatment completed self-report questionnaires assessing their QOL, cancer-specific worry, and material hardship (e.g., housing, insurance). Total months of active cancer treatment were extracted from the medical record. Hierarchical linear regression was used to test the relative effects of length of treatment, material hardship, and cancer-specific worry on caregiver QOL. Cancer-specific worry was significantly associated with and accounted for significant variance in caregiver QOL, above and beyond the length of treatment and material hardship. Caregivers who endorsed more cancer-specific worry had poorer QOL. Material hardship was also significantly associated with caregivers' QOL, but length of treatment was not. Caregivers with sufficient resources and less worry about cancer have higher QOL. Findings highlight the importance of end-of-treatment screening of caregivers' subjective cancer-specific worry in addition to material hardship, irrespective of their cancer-related stressors, for ongoing psychosocial support.

An Update on Emergent Nano-Therapeutic Strategies against Pediatric Brain Tumors.

Pediatric brain tumors are the major cause of pediatric cancer mortality. They comprise a diverse group of tumors with different developmental origins, genetic profiles, therapeutic options, and outcomes. Despite many technological advancements, the treatment of pediatric brain cancers has remained a challenge. Treatment options for pediatric brain cancers have been ineffective due to non-specificity, inability to cross the blood-brain barrier, and causing off-target side effects. In recent years, nanotechnological advancements in the medical field have proven to be effective in curing challenging cancers like brain tumors. Moreover, nanoparticles have emerged successfully, particularly in carrying larger payloads, as well as their stability, safety, and efficacy monitoring. In the present review, we will emphasize pediatric brain cancers, barriers to treating these cancers, and novel treatment options.

“Being a Good Parent” During Times of Illness as Defined by Chinese Children With Cancer, Their Parents, and Providers

Background Identifying the definition of “being a good parent” facilitates the understanding of parents’ personal beliefs and deeds regarding their ill child. Objective The aim of this study was to explore the concept of “being a good parent to my ill child” during pediatric cancer treatment from the perspective of Chinese children, parents, and providers. Methods A descriptive qualitative study was conducted with 6 children, 18 parents, 5 doctors, 19 nurses, and 3 social workers by semistructured interviews at 3 Chinese hospitals. Results Except for “letting the Lord lead,” 7 themes from the original conceptual model were validated, for example, “being there for my child” (n = 51, 100.0%); “doing right by my child” (n = 38, 74.5%), “being an advocate for my child” (n = 27, 52.9%), “conveying love to my child” (n = 26, 51.0%), “making my child healthy” (n = 18, 35.3%), “being a good life example” (n = 13, 25.5%), and “not allowing suffering” (n = 13, 25.5%). A new theme, “rebuilding myself” (n = 39, 76.5%), emerged in the Chinese context. “Being a good parent to my ill child” is perceived differently among stakeholders. Healthcare professionals’ facilitation to fulfill the concept included “recognizing the individualized good-parent definition,” “providing best available care” and “establishing a supportive environment.” Conclusion “Being a good parent to my ill child” is meaningfully expressed by Chinese parents and recognized by children and providers during pediatric cancer treatment. Implications for Practice It is important to support parents in conveying their internal good parent definition and sharing it with stakeholders. Attention should be paid to related cultural influencers, a supportive family-friendly environment, and shared decision making involving the child’s voice.

Every Move Counts to Improve Bone Health at Clinical Sites in Young Pediatric Cancer Survivors: The iBoneFIT Project.

We aimed to examine the associations of 24-hour movement behaviors (moderate-to-vigorous physical activity [MVPA], light physical activity [LPA], sedentary behavior [SB] and sleep) with age-, sex- and race-specific areal bone mineral density (aBMD) Z-score parameters at clinical sites in young pediatric cancer survivors. This cross-sectional multicenter study was carried out within the iBoneFIT framework in which 116 young pediatric cancer survivors (12.1 ± 3.3 years old; 42% female) were recruited. We obtained anthropometric and body composition data (i.e., body mass, stature, body mass index and region-specific lean mass), time spent in movement behaviors over at least seven consecutive 24-hour periods (wGT3x-BT accelerometer, ActiGraph) and aBMD Z-score parameters (age-, sex- and race-specific total at the body, total hip, femoral neck and lumbar spine). Survivors were classified according to somatic maturity (pre or peri/post-pubertal depending on the estimated years from peak height velocity). The adjusted models' coefficients were used to predict the effect of reallocating time proportionally across behaviors on the outcomes. In pre-pubertal young pediatric cancer survivors, reallocating time to MVPA from LPA, SB and sleep was significantly associated with higher aBMD at total body (B = 1.765, P = .005), total hip (B = 1.709, P = .003) and lumbar spine (B = 2.093, P = .001). In peri/post-pubertal survivors, reallocating time to LPA from MVPA, SB and sleep was significantly associated with higher aBMD at all sites (B = 2.090 to 2.609, P = .003 to .038). Reallocating time to SB from MVPA or LPA was significantly associated with lower aBMD at most sites in pre-pubertal and peri/post-pubertal survivors, respectively. Finally, reallocating time to sleep from MVPA, LPA and SB was significantly associated with lower aBMD at total body (B = -2.572, P = .036) and total hip (B = -3.371, P = .015). These findings suggest that every move counts and underline the benefits of increasing MVPA or LPA, when low MVPA levels are present, for bone regeneration following pediatric cancer treatment completion.

Serum anti-Müllerian hormone is lower in patients with multiple radioiodine dose for treatment of pediatric thyroid cancer.

Treatment of patients with pediatric differentiated thyroid cancer (DTC) often involves radioiodine (RAI), which is associated with increased risks of short- and long-term adverse outcomes. The impact of RAI treatment on the female reproductive system remains uncertain. Anti-Müllerian hormone (AMH) is a marker of ovarian reserve and is related to fertility. The aim was to analyze the association between RAI and serum AMH level in women treated with RAI. We evaluated women with pediatric DTC treated with RAI at the age of ≤19 years. Serum AMH was measured. The study included 47 patients with a mean age of 25.1 years (12.4-50.8) at AMH measurement and follow-up of 11.8 ± 8.4 years. The mean RAI administered was 235 mCi (30-1150). Sixteen (34%) received multiple RAI doses (471 ± 215 mCi). Mean AMH level was 2.49 ng/mL (0.01-7.81); the level was 1.57 ng/mL (0.01-7.81) after multiple RAI doses and 2.99 ng/mL (0.01-6.63) after a single RAI dose (P = 0.01). Patients who received a cumulative RAI lower than 200 mCi had higher AMH levels (2.23 ng/mL, 0.39-7.81) than those who received more (1.0 ng/mL, 0.01-6.63; P = 0.02). In patients with similar cumulative RAI activities, administration of multiple RAI doses was significantly and independently associated with AMH level lower than the reference range for age (HR: 5.9, 1.55-52.2, P = 0.014) after age adjustments. Levels of AMH were lower after multiple RAI doses, especially after a cumulative RAI dose above 200 mCi. More studies are needed to clarify the impact of RAI on fertility considering its cumulative activity and treatment strategy.

Current and future therapy for BRAF-mutant pediatric glioma

Current and future therapy for BRAF-mutant pediatric glioma Professor Peter J. Houghton from the Greehey Children’s Cancer Research Institute discusses new approaches to pediatric cancer treatment specifically for BRAF-mutant pediatric glioma. Low-grade glioma (LGG) is the most frequently diagnosed brain tumor in children, and although five and ten-year survival is quite high, this does not reveal the toxicity of current therapies. Conventional treatment includes intensive chemo-radiation therapy that can lead to cognitive decline, malignant transformation, and other life-debilitating or -threatening sequelae. (1) The 15-year incidence of adverse outcomes such as blindness, hearing loss, obesity, and hormonal imbalance is 18%, 22%, 53%, and approximately 25%, respectively. Among survivors assessed for intellectual function, 34% had an intelligence quotient (IQ) below average. Treatment-resistant progressive disease is the most common cause of death. (2)

A Benzarone Derivative Inhibits EYA to Suppress Tumor Growth in SHH Medulloblastoma.

Development of a benzarone derivative that inhibits EYA1 and impedes the growth of SHH medulloblastoma provides an avenue for improving treatment of this malignant pediatric brain cancer.

The influence of pediatric cancer treatment on taste perception and food hedonics: a systematic review.

Children with cancer are at risk of poor nutritional status during treatment and into survivorship. Objectively measured taste perception and self-reported food hedonics are 2 factors that may influence food intake. This 2-armed systematic review examined whether chemotherapy and radiotherapy affect (1) taste perception and (2) hedonic experiences of children and survivors of childhood cancer. A 2-armed systematic literature search was conducted in the Medline, CINAHL, Embase, and PsychInfo database until June 2022. The effects of cancer treatment on objective taste perception or food hedonics (ie, food liking or aversion and appetite) were examined. Peer-reviewed articles published in English of studies that included children (aged <18 years) or survivors of childhood cancer (any age) were reviewed. Risk of bias was determined using the Evidence Analysis Library by the Academy of Nutrition and Dietetics. A total of 1417 articles in the taste search arm and 3862 articles in the hedonics search arm were identified. Of these, 9 and 4 articles were eligible for review, respectively. Cancer treatment had highly variable effects on taste perception during treatment and into survivorship. Learned food aversions were experienced by children receiving chemotherapy treatment and liking of meats and salty foods by children with cancer was affected. The impact of treatment on appetite varied. Cancer treatment did not uniformly affect taste perception. Food liking may be negatively affected, and learned food aversions may develop during cancer treatment. To establish the clinical relevance of childhood cancer treatment on taste perception and food hedonics, more research is required. PROSPERO registration no.CRD42020207127.

Parents’ emotion socialization beliefs over the first four months of children’s cancer treatment: a pilot longitudinal study

ABSTRACT In this pilot study, we longitudinally investigated parents’ coaching and dismissing emotion socialization (ES) belief changes over the first four months of children’s cancer treatment. Children were 1–18 years old, M(SD) = 7.66(5.26), at enrollment. We also investigated whether parents’ negative emotion intensity or reactivity moderated changes. We collected data at chemotherapy commencement, one month later, and four months later. We used hierarchical linear models to investigate study aims. Parents reported decreased emotion coaching beliefs over time but did not change their emotion dismissing beliefs. Parents’ perceptions of their own emotional intensity and reactivity were unrelated to ES beliefs or ES belief changes. These findings could inform future intervention efforts to decrease children’s adjustment difficulties and/or promote resilience during pediatric cancer treatment. Our findings also shed light on mechanisms of ES belief change because the intensity and reactivity of parents’ own negative emotions did not explain significant variance in their beliefs about their child’s ability to manage emotions during early cancer treatment.

Caregiver condition management and family functioning after pediatric cancer treatment: Moderation by race and ethnicity.

End of pediatric cancer treatment requires family adjustment. Caregivers who struggle to incorporate the child's condition into family life have poorer family outcomes. To better understand factors that contribute to successful transition off active childhood cancer treatment, we sought to examine caregiver perceived management ability of the youth's condition and family functioning as predictors of caregiver distress, evaluate family functioning as a mediator between perceived ability and distress, and explore race and ethnicity as a moderator between perceived ability and family functioning. Caregivers (N=141) completed measures assessing family management (condition management ability; CMA), family functioning, and distress as part of a clinical education and screening program within 1year of the end of treatment. Bias-corrected bootstrap regression analyses examined mediation and moderated mediation models with patient race and ethnicity as the moderator. The overall mediation model was statistically significant for CMA→family functioning→distress. Race and ethnicity moderated the relationship between CMA and family functioning, but the full model was not significant. CMA was related to family functioning for caregivers of non-Hispanic white youth, but not caregivers of Hispanic youth. Family functioning was related to distress for all caregivers. Family functioning serves as an initial intervention target to reduce caregiver distress. Caregiver perceived management ability of their child's condition is a meaningful predictor of family functioning and distress for caregivers of non-Hispanic white youth, yet CMA may be limited as a screener of family management patterns for diverse populations, and other family management dimension may be more applicable.

Abstract A165: FGFR alterations in pediatric cancers: Opportunity for targeted therapy

Abstract Introduction: The Fibroblast Growth Factor Receptor (FGFR) family consists of four members, FGFR1–4, and is involved in regulating cell proliferation, survival, and differentiation. FGFR alterations, such as fusions, mutations and amplification, have been found in multiple adult cancers, for which several FGFR inhibitors are in clinical development. Although cancer is a leading cause of death in children, the understanding of genetic causes of pediatric cancers is urgently lacking and the progress in developing targeted therapy in children significantly lags that in adults. This study aimed to uncover the FGFR alterations in pediatric cancers and provide preclinical rationale for FGFR inhibitors as potential therapy in children with cancer.  Methods: The prevalence of FGFR alterations in pediatric cancers such as neuroblastoma (NB) , gliomas and sarcomas was calculated based on systematic queries of multiple cancer databases that house real-world molecular profiling data. A pan-FGFR inhibitor, BGJ398, was used as a tool compound for FGFR inhibition. Effect of BGJ398 on cell proliferation was tested by Incucyte in a panel of 12 NB cell lines. Cell migration, survival and signaling pathway modulation were carried out in a subset of NB lines. Results: The overall rates of genomic alterations (fusions, mutations and amplification) of FGFR1, 2, 3 and 4 in pediatric cancers are 0.5%, 0.1%, 1.1% and 0.8%, respectively, with pediatric gliomas exhibiting higher rates in all subtypes. Although FGFR genomic alterations are rare (&amp;lt;0.1%) in neuroblastoma and rhabdoid sarcoma, overexpression of FGFR1-4 is observed in subsets of these tumors. In pediatric glioma, FGFR1, 2, 3 and 4 alterations are found in 1%, 1.6%, 2.1% and 0.9% tumor samples, respectively, and the mutation profile substantially differs from that of adult glioma. Dose-dependent inhibition of cell proliferation and migration, as well as induction of cell death, were achieved with BGJ398 treatment in a panel of NB cells, accompanied by inhibition of MAPK pathway and induction of apoptosis. Conclusions: Adult and pediatric cancers share common mechanisms of FGFR activation, but differ in overall alteration rates and in relative abundance of specific aberrations. Preliminary preclinical data indicates the therapeutic potential of FGFR inhibitors in the treatment of certain pediatric cancers. Citation Format: Ivan Li, Yuchen Huo, Gary Li, Peter Zage. FGFR alterations in pediatric cancers: Opportunity for targeted therapy [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A165.

14 The Impact of Socioeconomic Status (SES) on Phonemic Fluency in Patients with Pediatric Brain Tumor (PBT)

Objective:Phonemic fluency, an important cognitive skill for everyday functioning, has been shown to decline in comparison to same-aged peers following pediatric cancer diagnosis and treatment, despite intact semantic fluency. More generally, socioeconomic status (SES) has recently been shown to be one of the strongest predictors of neuropsychological outcomes among pediatric oncology patients, with lower SES predicting worse intellectual and academic functioning. However, the association between SES and phonemic fluency within this population has yet to be explored. The main objective of this project was to determine whether SES (specifically estimated household income) significantly predicts phonemic fluency performance among patients with PBT, and it was hypothesized that higher SES would be associated with better phonemic fluency outcomes.Participants and Methods:136 participants with PBT ages 7-20 (x=14.15 years, SD=3.87), were administered phonemic fluency trials (either from the NEPSY - Second Edition or Delis-Kaplan Executive Function System, with no significant differences in performance between measures). The sample was 58.8% male and half Latino (50.0%), followed by Caucasian (30.1%), Asian American (7.4%), Black (6.6%), and Other (5.9%) ethnicity. All patients identified English as their primary and preferred language regardless of predominant household language, reducing the potential confounding impact of language. Given documented associations between PBT and lower intelligence following diagnosis and treatment, estimated intellectual functioning was included in the first block of hierarchical regression to isolate and further elucidate the potential contributing influence of SES on phonemic fluency. Median household income for specific neighborhoods was used as a proxy for SES, while Wechsler Matrix Reasoning (MR) was used as an estimate of general intellectual functioning given the high correlation between MR and full scale IQ.Results:Consistent with prior literature, phonemic fluency was lower than normative age expectations [t(135)=-3.653, p=.0002], though still within the average range clinically (x=8.93). As hypothesized, SES was positively correlated with phonemic fluency [r(136)=.219, p=.005]. Furthermore, SES significantly predicted phonemic fluency performance above and beyond estimated intelligence, accounting for a significant increase in variance (p=.020). Post-hoc analyses also revealed poorer phonemic fluency among participants with infratentorial brain tumors as compared to supratentorial brain tumors after controlling for SES, t(108)=-1.748, p=.042.Conclusions:Consistent with the known impact of SES on neuropsychological late effects among patients with pediatric cancer, phonemic fluency was positively correlated with SES among participants with PBT above and beyond estimated intelligence, suggesting the distinct role of SES on rapid verbal retrieval within this population. This has important implications for identifying patients at higher risk, helping to ensure timely provision of services and supports. Poorer phonemic fluency was also noted among patients with infratentorial (vs. supratentorial) brain tumors after controlling for SES, which may influence studies combining tumor location as the vast majority of PBTs are infratentorial. This supports prior literature demonstrating the need for increased cerebellar activation during phonemic (vs. semantic) retrieval. Additional research is needed to further explore these findings.

12 Differential Processing Efficiency Skills in Survivors of Pediatric Primary CNS Cancer and Cancers of non-CNS Origin

Objective:Pediatric cancer and cancer-related treatments may disrupt brain development and place survivors at risk for long term problems with cognitive functions. Processing efficiency has been operationalized as a nuanced cognitive skill that reflects both processing speed (PS) and working memory (WM) abilities and is sensitive to neurobiological disruption. Pediatric cancer survivors are at risk for processing efficiency deficits; however, a thorough characterization of processing efficiency skills across pediatric primary central nervous system (CNS) tumor and non-CNS cancer survivors has not yet been reported.Participants and Methods:Participants were selected from a mixed retrospective clinical database of pediatric cancer survivors (Total n=160; primary CNS tumor n=33; Non-CNS n=127). Univariate analyses were conducted to examine differences in processing efficiency mean scores (t-tests) and percent impairment (scores &gt;1 SD below mean; chi-squared tests) between the total sample and normative sample, and across groups (CNS vs. Non-CNS). Multiple linear regressions were utilized to evaluate the relationships between additional risk factors, including biological sex, age at diagnosis, time since treatment, and socioeconomic status, and processing efficiency outcomes.Results:The total sample obtained lower scores on WM (M=90.83, SD=13.35) and PS (M=88.86, SD=14.38) measures than normative samples (M=100, SD=15), p &lt; 0.001. Greater percentage of pediatric cancer survivors demonstrated impairment across all processing efficiency measures (24.8-38.1%) than normative samples (15.9%), p &lt; 0.001. Regarding group differences, the CNS group obtained lower mean WM (M=84.85, SD =11.77) and PS (M=80, SD=14.18) scores than the Non-CNS group (WM M=92.39, SD=13.32; PS M=91.16, SD=13.56), p &lt; 0.001. Rates of impairment between groups only differed for PS scores, with 63.6% of the CNS group and 31.5% of the non-CNS group demonstrating impairment, p &lt; 0.001. Primary CNS tumor cancer type and male biological sex emerged as the only significant risk factors that predicted processing efficiency skills, with male sex predicting lower scores on PS (ß=8.91 p&lt;.001) and semantic fluency (ß=7.59, p=.007).Conclusions:These findings indicate that both pediatric primary CNS tumor and non-CNS cancer survivors exhibit substantial weaknesses in processing efficiency skills after treatment. While both groups demonstrated deficits compared to normative samples, the CNS group was more susceptible to PS impairments than non-CNS group. A basic initial study of the relationships between risk factors and processing efficiency skills revealed that primary CNS cancer was a predictor of lower performance on working memory and processing speed measures, while male biological sex was a significant risk factor for worse performance on processing speed and semantic fluency measures. Continued focus on the construct of processing efficiency in pediatric cancer survivors is warranted. Applying a standardized approach to assessing and communicating this nuanced cognitive skill could contribute to advancing both clinical practice and outcomes research of pediatric cancer survivors.