Pediatric Oncology Study Research Articles

ICatalog: An open-source, collaborative platform for precision oncology studies.

10020 Background: Genomic profiling of patient (pt) tumors using next-generation sequencing (NGS) has become an integral part of precision oncology (PO). To address the need for a streamlined, interoperable approach to clinical and NGS data management, interpretation, and reporting for a multi-institution pediatric PO study we developed iCatalog (iCat), a clinical decision support system for a multi-institution pediatric PO study. Methods: iCat was developed by the University of Chicago (UChicago) and Dana-Farber Cancer Institute to create clinical interpretation reports for the iCat2/Genomic Assessment Informs Novel Therapy Consortium (GAIN) study. It is a web-based application using the Python Django framework using open-source software and runs on virtual machines (VM) behind a secure firewall. iCat manages user and administrative permissions according to role and site. It securely stores, manages, and integrates genomic and clinical information as well as internal and external genomic knowledge on a patient level. Data types available during interpretation and report generation include pt demographics, specimen-level information such as diagnosis from pathology reports, and molecular data. iCat can host molecular data from different NGS test types. These data are entered through web interfaces and API calls. Genomic knowledge accessible in iCat is a combination of information brought in from external resources and gene and variant-level pediatric-specific curations completed in iCat by curators. Editable study-specific patient reports are generated for each test. Results: As of January 10, 2024, iCat has generated reports for 902 tests and stores information for an additional 217 tests for the 742 pts enrolled in the GAIN study. Of the 217 tests, 25 tests have reports in progress and 192 tests had reports generated manually before iCat was developed. Genomic data are from 11 different test types and clinical data are from patients with 92 rare pediatric solid tumor diagnoses. A total of 108 pts have received iCat clinical interpretation reports integrating genomic data from more than one NGS test type. The knowledge base contains pediatric-specific research-team authored curations for 561 genes, 2114 unique SNVs, 268 unique CNVs, and 227 unique structural variants. Test-specific, variant-level therapeutic recommendations have been made on 666 reports for 502 pts. Diagnostic or hereditary risk associations have been made on 729 reports for 537 pts. Conclusions: iCat is an academically developed open-source platform for PO studies that integrates clinical and genomic data, supports gene and variant interpretation, and facilitates the generation of an individualized genomic report with relevant clinical information for treating physicians. We developed and tested iCat for a pediatric precision oncology study and propose it as a customizable, collaborative platform for future precision oncology research.

Abstract 824: Comparing experiences of Spanish and non-English/non-Spanish speaking parents of children with cancer

Abstract Introduction: Children with cancer whose parents speak languages other than English (LOE) experience disparities including underrepresentation on clinical trials and decreased access to resources. Few studies in pediatric oncology have investigated the communication experiences of families who speak LOE, particularly for languages other than Spanish. The primary objective of this study was to characterize the experiences of parents of children with cancer who speak LOE. Methods: Parents of children recently diagnosed with cancer who spoke LOE were enrolled concurrently in two cohorts, Spanish speaking and non-English/non-Spanish speaking. Semi-structured interviews were conducted about parent perceptions of medical care, communication and support from the medical team within 3 months of a new cancer diagnosis and 6-12 months post-diagnosis. Inductive content analysis was performed, with iterative transcript review and memo-writing informing the development of codes. Code frequency, temporal duration and distribution across language subtype were calculated and reported as descriptive statistics. Analysis was organized in MAXQDA, a mixed-methods data analysis software. Results: Of the 28 parents enrolled, 20 spoke Spanish and 8 spoke other languages including Dari, Nepali, Karan, Cantonese, Chuukese and French. All parents completed first interviews and 14 have completed second interviews to date. All parents described challenges with interpretation, but difficulties were reported more often by non-Spanish speakers: 67% of non-Spanish speakers encountered interpreters who spoke a different dialect (vs. 35% of Spanish speakers), 33% had interactions where no interpreter was available via any modality (vs. 0%), and 75% of their children were asked to interpret by the medical team (vs. 12%). Additionally, non-Spanish speakers lacked access to written educational materials or hospital documents in their language and they were unable to build rapport with interpreters, whereas Spanish speakers described regular access to these resources. Spanish speakers also frequently reported incorrect interpretation that was recognized by providers who understood some Spanish. This was never reported by non-Spanish speakers as no medical team members spoke their languages. Conclusion: Nearly 40% of the United States population speaks a language other than English or Spanish at home, yet their needs are significantly underrecognized and understudied. Our findings demonstrated that challenges related to interpretation are pervasive, and non-English/non-Spanish speakers may face greater difficulties. Overall, parents who speak LOE report receiving disparate care and deficient resources. An urgent need exists to provide equitable communication and resources, particularly for non-Spanish speakers who report significant obstacles in receipt of high-quality pediatric cancer care. Citation Format: Melanie Stall, Naomi Winick, Erica Kaye. Comparing experiences of Spanish and non-English/non-Spanish speaking parents of children with cancer [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 824.

Abstract 823: Parent-endorsed potential interventions to improve language disparities in pediatric cancer

Abstract Introduction: Children with cancer whose parents speak languages other than English (LOE) experience disparities including underrepresentation on clinical trials, decreased access to resources and inadequate interpretative services. Few studies in pediatric oncology have investigated the communication experiences of families who speak LOE, and rarely have studies sought parental recommendations for improvement. In this study, we aimed to characterize the experiences of parents of children with cancer who speak LOE and identify stakeholder-driven interventions to improve deficiencies. Methods: We enrolled parents of children with cancer who spoke any LOE and conducted semi-structured interviews about perceptions of medical care, communication and support from the medical team within 3 months of a new cancer diagnosis and 6-12 months post-diagnosis. Inductive content analysis was performed, with iterative transcript review and memo-writing informing the development of codes. Code frequency, temporal duration and distribution across language subtype were calculated and reported as descriptive statistics. Analysis was organized in MAXQDA, a mixed-methods data analysis software. Results: Twenty-eight parents, representing 7 different languages, were enrolled. All parents completed first interviews and 14 have completed second interviews to date. Parents described frequent problems with interpretation and felt their child’s care would be improved if they spoke English. Parents made suggestions on how to improve their experience and understanding of their child’s medical care (Table 1). Conclusion: Challenges related to language interpretation are pervasive and parents who speak LOE believe their child’s cancer care would be improved if they spoke English. Parents identified preferred communication practices and specific interventions that may be useful in promoting understanding of their child’s medical care and overall enhance supportive resources. Parent-endorsed communication practices and potential interventions to improve language disparities Preferred communication practices Use simple terms Limit conversations between providers when no interpreter present Speak to English and non-English speakers equally Always automatically use professional interpreters Take your time Repeat Demonstrate Rephrase Use drawings Point Ask for preferred language Be specific and detailed Speak slowly Use short phrases Allow time for interpretation Requested resources in preferred language Educational videos Written educational materials Translated hospital documents List of supportive resources List of financial resources List of reliable websites Language matched parent buddy support system Side by side instructions in English and preferred language System-level changes Increased in-person interpreter staffing Staff education on approach to LOE encounters Patient advocate to review medications and check labels Interpreter use at all points of contact Provision of language concordant providers Citation Format: Melanie Stall, Naomi Winick, Erica Kaye. Parent-endorsed potential interventions to improve language disparities in pediatric cancer [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 823.

Involved-site Radiotherapy Delineation Dilemmas in the Treatment of Adult Hodgkin Lymphoma: Turkish Society for Radiation Oncology Hematological Oncology, Pediatric Oncology and TBI Study Group Case-based Questionnaire Review (TROD 03-005)

AimsThe International Lymphoma Radiation Oncology Group (ILROG) defined involved-site radiotherapy (ISRT) guidelines. These rules offer a certain variability that allows for autonomous decision-making in diverse clinical settings. However, this flexibility also gives rise to conflicts about the selection of treatment fields in the daily decision-making process. The aim of this study was to show the extent of interobserver variability when ILROG-ISRT recommendations were used in different clinical scenarios. Materials and methodsThe 10-question survey used in our study consisted of two parts (part A and part B) and was prepared by four senior radiation oncologists experienced in the haemato-oncology field. The results were presented by stratifying according to clinical experience (<10 years, ≥10 years). Binomial tests (one-sided) were conducted to assess whether answers for each group and the whole group reached a consensus. ResultsTwenty-six radiation oncologists, 13 of whom had less than 10 years of experience and 13 seniors, participated in the survey. Eighty per cent of respondents thought ILROG did not bring sufficient solutions for all clinical scenarios but offered solutions in some cases. In different case-based scenarios, the consensus among the respondents decreased down to 38%. Senior radiation oncologists were found to have more doubts about the adequacy of current guidelines. ConclusionsILROG guidelines allow for a high degree of variability in real-life clinical scenarios and different interpretation of the recommendations may lead to increased toxicity and recurrences. Therefore, there is a need for refinement in ISRT delineation strategies. On behalf of the Turkish Society for Radiation Oncology Hematological Oncology, Pediatric Oncology and TBI Study Group, we are planning to carry out further educational contouring sessions to detect the interobserver variability in real-life contouring cases.

Information fraction estimation: Strategies for a phase 3 non-inferiority maximum duration design with time to event outcome.

There is considerable debate surrounding the choice of methods to estimate information fraction for futility monitoring in a randomized non-inferiority maximum duration trial. This question was motivated by a pediatric oncology study that aimed to establish non-inferiority for two primary outcomes. While non-inferiority was determined for one outcome, the futility monitoring of the other outcome failed to stop the trial early, despite accumulating evidence of inferiority. For a one-sided trial design for which the intervention is inferior to the standard therapy, futility monitoring should provide the opportunity to terminate the trial early. Our research focuses on the Total Control Only (TCO) method, which is defined as a ratio of observed events to total events exclusively within the standard treatment regimen. We investigate its properties in stopping a trial early in favor of inferiority. Simulation results comparing the TCO method with alternative methods, one based on the assumption of an inferior treatment effect (TH0), and the other based on a specified hypothesis of a non-inferior treatment effect (THA), were provided under various pediatric oncology trial design settings. The TCO method is the only method that provides unbiased information fraction estimates regardless of the hypothesis assumptions and exhibits a good power and a comparable type I error rate at each interim analysis compared to other methods. Although none of the methods is uniformly superior on all criteria, the TCO method possesses favorable characteristics, making it a compelling choice for estimating the information fraction when the aim is to reduce cancer treatment-related adverse outcomes.

Social determinants of cognitive outcomes in survivors of pediatric brain tumors treated with conformal radiation therapy.

Social determinants of health including parental occupation, household income, and neighborhood environment are predictors of cognitive outcomes among healthy and ill children; however, few pediatric oncology studies have investigated this relationship. This study utilized the Economic Hardship Index (EHI) to measure neighborhood-level social and economic conditions to predict cognitive outcomes among children treated for brain tumors (BT) with conformal radiation therapy (RT). Two hundred and forty-one children treated on a prospective, longitudinal, phase II trial of conformal photon RT (54-59.4 Gy) for ependymoma, low-grade glioma, or craniopharyngioma (52% female, 79% white, age at RT = 7.76 ± 4.98 years) completed serial cognitive assessments (intelligence quotient [IQ], reading, math, and adaptive functioning) for ten years. Six US census tract-level EHI scores were calculated for an overall EHI score: unemployment, dependency, education, income, crowded housing, and poverty. Established socioeconomic status (SES) measures from the extant literature were also derived. Correlations and non-parametric tests revealed EHI variables share modest variance with other SES measures. Income, unemployment, and poverty overlapped most with individual SES measures. Linear mixed models, accounting for sex, age at RT, and tumor location, revealed EHI variables predicted all cognitive variables at baseline and change in IQ and math over time, with EHI overall and poverty most consistent predictors. Higher economic hardship was associated with lower cognitive scores. Neighborhood-level measures of socioeconomic conditions can help inform understanding of long-term cognitive and academic outcomes in survivors of pediatric BT. Future investigation of poverty's driving forces and the impact of economic hardship on children with other catastrophic diseases is needed.

Changing incentives to ACCELERATE drug development for paediatric cancer.

More effective incentives are needed to motivate paediatric oncology drug development, uncoupling it from dependency on adult drug development. Although the current European and North-American legislations aim to promote drug development for paediatrics and rare diseases, children and adolescents with cancer have not benefited as expected from these initiatives and cancer remains the first cause of death by disease in children older than one. Drug development for childhood cancer remains dependent on adult cancer indications and their potential market. The balance between the investment needed to execute a Paediatric Investigation Plan (PIP) in Europe and an initial Paediatric Study Plan (iPSP) in the US, coupled with the potential financial reward has not been sufficiently attractive to incite the pharmaceutical industry to develop drugs for rare indications such as childhood cancer. We propose changes in the timing and nature of the rewards within the European Paediatric Medicine Regulation (PMR) and Regulation on Orphan Medicinal Products (both currently under review), which would drive earlier initiation of paediatric oncology studies and provide incentives for drug development specifically for childhood indications. We suggest modifying the PMR to ensure mechanism-of-action driven mandatory PIP and reorganization of incentives to a stepwise and incremental approach. Interim and final deliverables should be defined within a PIP or iPSP, each attracting a reward on completion. A crucial change would be the introduction of the interim deliverable requiring production of paediatric data that inform the go/no-go decisions on whether to take a drug forward to paediatric efficacy trials. Additionally, to address the critical gap in the current framework where there is a complete lack of incentives to promote paediatric-specific cancer drug development, we propose the introduction of early rewards in the Orphan Regulation, with a variant on the US-Creating Hope Act and its priority review vouchers.

Development and refinement of Rel@x:A training in hypnosis-derived communication for pediatric nurses to prevent procedural pain.

Studies in pediatric oncology have shown that hypnosis effectively reduces patients' pain and distress during painful procedures. This remains underutilized in the healthcare system due to the staff cost and availability of hypnotherapists. To develop the use of hypnosis-derived communication, we aimed to train nurses to use hypnosis-derived communication while they perform painful procedures. This study aimed to (1) develop a brief training in hypnosis-derived communication for pediatric nurses named Rel@x, (2) pretest the training with experienced pediatric oncology nurses, and (3) refine the training based on nurses' suggestions. The Rel@x training consists of two 4-h sessions: one related to relational aspects and another one presenting one of two selected hypnotic communication techniques ("pleasant place" or "magic glove"). Rel@x makes use of manuals, cue card reminders, visual aids, videos, and an e-learning platform. To refine Rel@x, a complete training cycle was conducted with seven female pediatric oncology nurses. A mixed method study with an evaluation questionnaire and a post-training focus group interview was conducted. Quantitative data showed that nurses overall positively rated the training program: relevance and acceptability (median average of 5.4/6); use of hypnotic communication (median average of 5.2/6); expected effects (median average of 5.4/6); program implementation (5.6/6). Two general themes emerged from the qualitative data: perceptions of hypnotic communication and the evaluation of the Rel@x training program. Based on nurses' suggestions, Rel@x was refined by adding more practical components, more time for practice, more time between the two sessions and additional tools (cue card reminders, keywords, virtual e-learning recap module). The use of hypnosis-derived communication during painful procedures and the Rel@x training were viewed favorably amongst pediatric nurses. Rel@x offers a complete training in hypnosis-derived communication for pediatric nurses. This training fosters the optimal use of hypnosis-derived communication during care and may significantly reduce children's procedural pain and distress.

Pathology of Wilms' tumour in International Society of Paediatric Oncology (SIOP) and Children's oncology group (COG) renal tumour studies: Similarities and differences

Excellent outcomes for patients with Wilms' tumour (WT), &gt;90% for all stages together, have been achieved through researching WT in multicentre and multinational trials and studies in the last 50 years, led by two major groups—the International Society of Paediatric Oncology (SIOP) and the Children's Oncology Group (COG) (previously the National Wilms' Tumour Study Group). Despite the two groups having different approaches, the survival outcomes are remarkably similar. In general, in the SIOP approach, which is followed in Europe and most other countries around the world, patients are first treated with preoperative chemotherapy; this is followed by surgery and, if necessary, postoperative chemotherapy and radiotherapy. In the COG approach, which is mainly followed in North America, patients are treated with upfront surgery, followed, if necessary, by postoperative chemotherapy and radiotherapy. In both groups, postoperative treatment primarily depends on tumour histological classification and stage, although, in recent studies, other prognostic factors have also been included (tumour volume, response to preoperative chemotherapy, and molecular markers). Owing to separate initial treatments, there are differences in histological assessment and subtyping of WT, and, more importantly, in staging criteria. In this review, we discuss the similarities and differences between the two groups in order to help pathologists who are dealing with WT to understand and follow the pathological protocol that is appropriate for a particular case, because, in many centres, both approaches may be followed, depending on individual case/patient circumstances.

Five-Year Follow-up After Multimodal Treatment Incorporating HDR Brachytherapy for Bladder Prostate Rhabdomyosarcoma in Children

Five-Year Follow-up After Multimodal Treatment Incorporating HDR Brachytherapy for Bladder Prostate Rhabdomyosarcoma in Children

Utilizing Multilingual Methods and Rapid Analysis for Global Qualitative Research During a Pandemic

Historically, qualitative research has complemented quantitative biologic and epidemiologic studies to provide a more complete understanding of pandemics. The COVID-19 pandemic has generated unique and novel challenges for qualitative researchers, who have embraced creative solutions including virtual focus groups and rapid analyses to continue their work. We present our experience conducting a multilingual global qualitative study of healthcare resilience among teams of pediatric oncology professionals during the COVID-19 pandemic. We provide an in-depth description of our methodology and an analysis of factors we believe contributed to our study’s success including our use of technology, engagement of a large multilingual team, global partnerships, and framework-based rapid analysis. We hope these techniques may be useful to qualitative researchers conducting studies during the current pandemic, as well as for all pediatric oncology studies including multiple languages or geographically disparate subjects.

Racial and ethnic disparities in communication study enrollment for young people with cancer: A descriptive analysis of the literature

ObjectiveWe aimed to evaluate the racial and ethnic diversity of study participants in recent pediatric cancer communication literature. MethodsWe systematically searched for communication studies in pediatric oncology published between January 2018 and September 2020, limiting analysis to US studies. We considered race and ethnicity as separate categories in our analysis. Two authors screened studies and abstracted characteristics of race and ethnicity reporting and enrollment. ResultsOf 98 articles included in this analysis, many studies failed to report participants’ race (21/98) and ethnicity (40/98). Most studies ascertained race and ethnicity by self-report (51/98); 25 studies did not describe how they ascertained race and ethnicity. White participants were overrepresented in studies relative to the US population (median 80% in studies vs 72% in 2020 US census). Racial and ethnic minorities were underrepresented (Black: 7% vs 14%; Asian: 4% vs 7%; Pacific Islander: 0% vs 0.5%; Native American: 0.5% vs 3%; Hispanic 8% vs 19%). ConclusionCommunication literature in pediatric oncology underrepresents all racial and ethnic minority populations and is inconsistent in the reporting of race and ethnicity. Practice implicationsFuture work should follow best practices to ensure this literature adequately represents the experiences of all families in pediatric oncology.

Recruitment principles and strategies for supportive care research in pediatric oncology

BackgroundVariations in clinical practice contribute to negative outcomes for children with cancer. Research in this area is imperative to standardise practice, yet such research is challenging to undertake, and a significant proportion of studies fail. A common reason for failure is poor recruitment, yet little information is available to support researchers and clinicians planning such research.MethodsOur primary aim was to describe the recruitment strategies and outcomes in a tertiary children’s hospital across multiple observational supportive care studies. Secondary aims were to establish principles to improve both recruitment strategies and the reporting of recruitment. We undertook a retrospective descriptive analysis of the recruitment logs and data from three studies in pediatric oncology. The mean time to recruit one participant was calculated. Common reasons for not approaching eligible participants and reasons potential participants declined are described.ResultsOf the 235 potential candidates across all studies, 186 (79%) were approached and of these 125 (67%) provided consent, with 117 (63%) completing baseline measures. We estimated recruitment per participant required an average 98 min of experienced research nurse time. Four factors are described that influence recruitment and six principles are outlined to maximise recruitment and the generalisability of research findings.ConclusionsWe highlight the recruitment experiences across three different projects in children’s cancer supportive care research and provide a roadmap for other researchers planning to undertake clinical research in pediatrics.

Clinical Characteristics and Treatment Outcomes of Childhood Acute Promyelocytic Leukemia in Korea: A Nationwide Multicenter Retrospective Study by Korean Pediatric Oncology Study Group.

PurposeAcute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea.Materials and MethodsSeventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively.ResultsOf 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×109/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×109/L than in those with initial WBC ≥ 10×109/L (p=0.020).ConclusionThis study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.

NURS-11. MARIJUANA, HEMP, AND THE CHILD WITH CANCER: PATIENT, PARENT, AND CLINICIAN EDUCATION

Many pediatric oncology patients report medical marijuana (MMJ) and hemp-based CBD use. Eleven states and Washington, DC have legalized marijuana for recreational use for adults greater than 21. Medical marijuana is legalized in 33 states. Additionally, due to the bipartisan Farm Bill passed in December of 2018, hemp is federally legal. Marijuana has medical legalization in 23 countries worldwide. Clinical trials in adults have examined MMJ for cancer-related symptoms. New research is emerging on MMJ in anticancer therapy, MMJ receptors on tumor cells, and the potential role for MMJ as an immunomodulator. Few pediatric oncology studies have evaluated MMJ. We describe the initial findings of a prospective observational study of MMJ on the quality of life (QOL) in pediatric brain tumor patients. Specific aims included (1) MMJ’s association with symptoms (nausea, anxiety, pain, fatigue, and cognitive problems) and (2) MMJ’s impact on family dynamics. The legality of hemp plus the increasing use of MMJ raises concerns with pharmacological interactions with CBD and the medications routinely administered to children with cancer. Nurses are the frontline for discussions with patients about MMJ and must be aware of the emerging field of MMJ in pediatric cancer. Additionally, nurses can influence patient care protocols and processes for alternative therapy administration enabling an open dialogue between providers, parents, and patients regarding treatments, symptoms, adverse effects, and drug interactions. Education about how to have conversations about important facets to cover and consider is crucial to patient safety and increased quality of life.

Preoperative Wilms tumor rupture in children.

According to the guidelines of International Society of Pediatric Oncology (SIOP) and National Wilms Tumor Study (NWTS), Wilms tumor with preoperative rupture should be classified as at least stage III. Few clinical reports can be found about preoperative Wilms tumor rupture. The purpose of this study was to investigate our experience on the diagnosis, treatment and prognosis of preoperative Wilms tumor rupture. Patients with Wilms tumor who underwent treatment according to the NWTS or SIOP protocol from January 2008 to September 2017 in Beijing Children's Hospital were reviewed retrospectively. The clinical signs of preoperative tumor rupture were acute abdominal pain, and/or fall of hemoglobin. The radiologic signs of preoperative tumor rupture are as follows: (1) retroperitoneal and/or intraperitoneal effusion; (2) acute hemorrhage located in the sub-capsular and/or perirenal space; (3) tumor fracture communicating with peritoneal effusion; (4) bloody ascites. Patients with clinical and radiologic signs of preoperative tumor rupture were selected. Patients having radiologic signs without clinical symptoms were also selected. The clinical data, treatments and outcomes were analyzed. Meanwhile, patients without preoperative Wilms tumor rupture during the same period were collected and analyzed. 565 Patients with Wilms tumor were registered in our hospital. Of these patients, 45 patients were diagnosed with preoperative ruptured Wilms tumor. All preoperative rupture were confirmed at surgery. Spontaneous tumor rupture occurred in 41 patients, the other 4 patients had traumatic history. Of the 45 patients, 41 were classified as stage III, 3 patients with pulmonary metastases were classified as stage IV, and one patient with bilateral tumors were classified as stage V. Of these patients with preoperative tumor rupture at stage III, 30 patients had clinical and radiologic signs of tumor rupture, the other 11 patients had radiologic signs without clinical symptoms. Among the 41 patients at stage III, 13 patients had immediate surgery without preoperative chemotherapy (immediate group), and 28 patients had delayed surgery after preoperative chemotherapy (delayed group). In immediate group, 12 patients had localized rupture, 1 patient underwent emergency surgery because of continuous bleeding. In delayed group, 4 had inferior vena cava tumor embolus (1 thrombus extended to inferior vena cava behind the liver, three thrombi got to the right atrium), 4 crossed the midline with large tumors, 20 had extensive rupture without localization. In immediate group, tumor recurrence and metastasis developed in 2 patients, and no death occurred. In the delayed group, tumor recurrence and metastasis developed in 8 patients, and 7 patients died. During the same period, 41 patients were classified as stage III without preoperative rupture. In the non-ruptured group, tumor recurrence and metastasis developed in 3 patients, and 4 patients died. The median survival time in the ruptured group (both immediate group and delayed group) and non-ruptured group were (85.1 ± 7.5) and (110.3 ± 5.6) months, and the 3-year cumulative survival rates were 75.1% and 89.6%, respectively. The overall survival rate between the ruptured and non-ruptured groups showed no statistic difference (P = 0.256). However, there was significant difference in recurrence or metastasis rate between the ruptured and non-ruptured groups (24.4% vs 7.3%; P = 0.031). Contrast-enhanced computed tomography (CT) and ultrasonography (US) are of major value in the diagnosis of preoperative tumor rupture,and immediate surgery or delayed surgery are available therapeutic methods. The treatment plan was based on patients' general conditions, tumor size, position and impairment degree of tumor rupture, extent of invasion and experience of a multidisciplinary team (including surgeon and anesthesiologists). In our experience, for ruptured preoperative tumor diagnosed with stage III, the criteria for immediate surgery are as follows: tumor not acrossing the midline, tumor without inferior vena cava thrombus, localized rupture, being capable of complete resection. Selection criteria for delayed surgery after preoperative chemotherapy are as follows: large tumors, long inferior vena cava tumor thrombus, tumors infiltrating to surrounding organs, unlocalized rupture, tumors can not being resected completely. Additionally, patients with preoperative Wilms tumor rupture had an increased risk of postoperative recurrence or metastasis.

The pediatric precision oncology study INFORM: Clinical outcome and benefit for molecular subgroups.

LBA10503 Background: Several pediatric precision oncology programs have identified molecular actionable variants. However, the clinical benefit is largely unknown. We here report a target prioritization algorithm and associated clinical outcome. Methods: INFORM is a prospective, non-interventional, multi-center, multi-national, and feasibility registry collecting clinical and molecular data. Patients with refractory/relapsed/progressive malignant disease, including primary diagnosis high-risk entities, can be enrolled. Fresh frozen tumor material (incl. germline DNA) was subjected to WES, lcWGS, RNA-Seq, RNA expression array and DNA-methylation. A weekly interdisciplinary molecular board reviewed and prioritized alterations based on a 7- step scale from ‘very high’ to ‘very low’, depending on the type of alteration and its entity specific relevance (described by Worst et al. Eur J Cancer 2016). Results: To date, more than 1300 patients were enrolled. 525 patients finished follow-up and were included in this analysis. They were enrolled in 72 centers in 8 countries. The median age was 12.0 (range 0 - 40) years. Average turnaround time from submission to report was 25.4 days. Median PFS and OS were 116 (95% CI 105 – 135) and 289 (95% CI 250 – 335) days. The distribution of the highest priority target per patient was: very high 8.0%, high 14.8%, moderate 20.3%, intermediate 23.6%, borderline 14.4%, low 2.5%, very low 1.0% and no actionable target 15.4%. 149 patients received targeted treatment on the basis of identified targets, of which 20 had a very high priority target (mostly ALK, BRAF and NRAS mutations and MET and NTRK-fusions) with a median PFS of 204.5 (95% CI 91.0 – 628.0) compared to 114 (95% CI 103 – 133) days in all other 505 patients (p = 0.0095). OS did not show clinically relevant differences. Explorative analysis of the time to progression (TTP) ratio (before compared to after enrollment) showed that patients treated according to a very high priority target had a higher TTP ratio (1.0) compared to all other patients (0.7). Possible predisposition syndromes were identified in 7.8% of patients, half of which were newly diagnosed. Methylation analysis provided a diagnosis refinement in 8% of CNS tumors. Conclusions: Pediatric precision oncology in a real world, multi-national setting is feasible. The prioritization algorithm identifies subgroups benefitting from molecularly matched targeted treatment. Still, for the patients without a very high priority target further layers of molecular and functional data should be incorporated in future programs.

Implementing a pediatric oncology nursing multisite trial

The Parent Educational Discharge Support Strategies (PEDSS) nursing study includes 16 magnet pediatric oncology institutions across the United States and one in Saudi Arabia, evaluating a nurse-led parent educational discharge support strategy for families experiencing a child newly diagnosed with cancer. During the first 3 months of the study, a research implementation survey was administered electronically to each site principal investigator to evaluate facilitators and barriers in the research process for this multisite nurse-led pediatric oncology study. Facilitators included nursing leadership support and commitment from the nursing staff. Common barriers reported were the Institutional Review Board process, the consent process, the timing of the intervention, data collection, as well as nursing time for the study. Results from the survey suggest nurse-led research teams were motivated and felt the intervention was easy to deliver. Nursing practice is enhanced when nurses participate in research and generate evidence regarding best practices within pediatric oncology nursing care. Nursing research endeavors focusing on collaborative approaches for implementation can lead to successful nursing studies with careful planning, training and administrative support.

Impact of Ethnicity on Toxicities Associated with Dose Escalating Methotrexate in Pediatric Patients with Acute Lymphoblastic Leukemia

Background: Epidemiologic studies in pediatric oncology have demonstrated disparities in Acute Lymphoblastic Leukemia (ALL) outcomes and survival for various ethnic minorities including Hispanic patients. While differences between outcomes and survival of different racial/ethnic groups in pediatric ALL is well documented, the impact of race/ethnicity on the incidence of methotrexate related toxicities in this population has not been fully described. Methotrexate, a mainstay of pediatric ALL regimens, has the potential to cause a variety of toxicities including myelosuppression, hepatic injury, acute kidney injury (AKI), mucositis, and central nervous system (CNS) injury. Recent literature suggests that Hispanic ethnicity may be associated with an increased risk of methotrexate toxicity, specifically neurotoxicity (Giordano (2017)). This project evaluated ethnicity associated with the incidence of methotrexate toxicities that could lead to dose reduction or delays in therapy such as grade 3 or 4 myelosuppression, hepatic injury, nephrotoxicity, and mucositis in patients receiving dose escalating methotrexate. Methods: A single-center, retrospective chart review was conducted at a 224 bed pediatric hospital. Patients were eligible for inclusion if they had a diagnosis of ALL and received intravenous (IV) dose escalating methotrexate between August 1, 2011 and March 31, 2019. Electronic medical records were used to identify eligible patients using medication identification numbers cross referenced with diagnosis codes. Toxicity data was collected to evaluate interruption in dose escalation of IV methotrexate due to grade 3 or 4 liver dysfunction, nephrotoxicity, mucositis, neutropenia, or thrombocytopenia. The primary outcome was percentage of doses which resulted in a dose-limiting toxicity. A two-sample t-test was performed for the primary outcome between Hispanic white and non-Hispanic white patients. Results: Of the 64 patients initially identified, 60 patients were included for final analysis. Two patients were excluded due to a diagnosis of Acute Biphenotypic Leukemia, one patient did not receive IV methotrexate per protocol due to delay in therapy and was subsequently ineligible, and one patient did not receive dose escalating methotrexate per protocol for unspecified reasons. A total of 460 doses were given to 60 patients. The sample size consisted of 22 non-Hispanic white, 21 Hispanic white, 9 Black, 3 Hispanic black, 1 Asian, 1 multi-racial, and 3 patients with unspecified ethnicity. The percentage of patients who experienced at least one toxicity was 58.3% (35 patients). The most common grade 3 or 4 toxicity experienced per dose was thrombocytopenia (6.5%), followed by neutropenia (6.3%), mucositis (1.3%), liver dysfunction (0.22%), and no patient experienced nephrotoxicity. When comparing the rate of toxicity between Hispanic and non-Hispanic patients, Hispanic patients experienced toxicity at a rate of 17.4% per dose compared to non-Hispanic patients at 12.2% per dose, although this was not a statistical significant difference (p = 0.61). Hispanic white and non-Hispanic white patients received the same amount of doses at 165 doses of IV methotrexate. Hispanic white patients experienced a toxicity rate of 19.4% per dose compared to 12.1% per dose in the non-Hispanic white patients. Hispanic white patients experience more thrombocytopenia, where as non-Hispanic white patients experienced more neutropenia. Although not statistically significant possibly due to small sample size, Hispanic ethnicity was associated with higher rates of methotrexate toxicities. Understanding the impact of methotrexate toxicity in respect to ethnicity is important to improving treatment outcomes for pediatric patients with ALL. More robust studies with a larger sample size are warranted to explore the potential impact of ethnicity on tolerability of this regimen. Disclosures No relevant conflicts of interest to declare.

Flow cytometric detection of leukemic blasts in cerebrospinal fluid predicts risk of relapse in childhood acute lymphoblastic leukemia: a Nordic Society of Pediatric Hematology and Oncology study

Central nervous system (CNS) involvement by cytospin is associated with increased risk of relapse in childhood acute lymphoblastic leukemia. We investigated if flow cytometric analysis of cerebrospinal fluid (CSF) at diagnosis improves the prediction of relapse. This prospective cohort study included patients (1.0-17.9 years) treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. CSF flow cytometry samples were obtained at 17 centers, preserved with Transfix®, and analyzed at a central laboratory. One-hundred and seventy-one (25.4%) of 673 patients were positive by flow cytometry (CNSflow+). The 4-year cumulative incidence of relapse was higher for patients with cytospin positivity (CNScyto+) (17.1% vs. 7.5%), CNSflow+ (16.5% vs. 5.6%), and cytospin and/or flow positivity (CNScomb+) (16.7% vs. 5.1%). In Cox regression analysis stratified by immunophenotype and minimal residual disease day 29 and adjusted by sex, predictors of relapse were age (hazard ratio [HR] 1.1, 95% CI 1.1-1.2, P < 0.001), white blood cell count at diagnosis (HR 1.4, 95% CI 1.1-1.6, P < 0.001), and CNScomb+ (HR 2.2, 95% CI 1.0-4.7, P = 0.042). Flow cytometric analysis of CSF improves detection of CNS leukemia, distinguishes patients with high and low risk of relapse, and may improve future risk stratification and CNS-directed therapy.