Rhabdomyosarcoma (RMS) is an aggressive soft tissue sarcoma derived from embryonic mesenchymal tissue. RMS can be found anywhere in the body, including the head and neck, extremities, pelvis, and genitourinary tract. PerinealRMS is a rare and aggressive form of RMS. Patients often have a delayed presentation following onset of symptoms and frequently present with regional lymph node involvement and/or distant metastases. Primary tumor site is an important prognostic factor for RMS, with the perineal region being considered an unfavorable location. We present a case of Perineal RMS in a 6-year-old boy who later developed an invasive inguinal lymph node recurrence. UROLOGY 200: e63-e66, 2025. (c) 2025 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Approximately 20 In this Review, the authors provide a comprehensive historical overview of the advancements in the understanding of biology and genetics of paediatric renal non-Wilms tumours, and discuss how this information can be used to develop new targeted therapies for these rare cancers.

The objective of this study is to report the long‐term timing and patterns of relapse for children enrolled in Children's Oncology Group AREN0534, a multicenter phase III clinical trial conducted from 2009 to 2015. Participants included children with bilateral Wilms tumor (BWT) or unilateral WT with genetic predisposition to develop BWT followed for up to 10 years. Smoothed hazard (risk) functions for event‐free survival (EFS) were plotted so that the timing of events could be visualized, both overall and within pre‐specified groups. Two hundred and twenty‐two children (190 BWT and 32 unilateral WT with BWT predisposition) were followed for a median of 8.6 years. Fifty events were reported, of which 48 were relapse/progression. The overall 8‐year EFS was 75% (95% confidence interval: 69%–83%). The highest risk for an EFS event was immediately after diagnosis with a declining rate over 2 years. A second peak of events was observed around 4 years after diagnosis, and a small number of events were reported until the end of the follow‐up period. In subset analyses, later increases in risk were more commonly observed in patients with female sex, anaplastic histology, negative lymph nodes or margins, and favorable histology Wilms tumor patients with post‐chemotherapy intermediate risk. Among relapses that occurred after 2 years, most were to the kidney. These patterns suggest that late events may be second primary tumors occurring more commonly in females, although more investigation is required. Clinicians may consider observation of patients with BWT beyond 4 years from diagnosis.

BACKGROUND: To review race and ethnic group enrollment and outcomes for Wilms tumor (WT) across all 4 risk-assigned therapeutic trials from the current era Children’s Oncology Group Renal Tumor Biology and Risk Stratification Protocol, AREN03B2. STUDY DESIGN: For patients with WT enrolled in AREN03B2 (2006 to 2019), disease and biologic features, therapeutic study-specific enrollment, and event-free (EFS) and overall (OS) 4-year survival were compared between institutionally reported race and ethnic groups. RESULTS: Among 5,146 patients with WT, no statistically significant differences were detected between race and ethnic groups regarding subsequent risk-assigned therapeutic study enrollment, disease stage, histology, biologic factors, or overall EFS or OS, except the following variables: Black children were older and had larger tumors at enrollment, whereas Hispanic children had lower rates of diffuse anaplasia WT and loss of heterozygosity at 1p. The only significant difference in EFS or OS between race and ethnic groups was observed among the few children treated for diffuse anaplasia WT with regimen UH-1 and -2 on high-risk protocol, AREN0321. On this therapeutic arm only, Black children showed worse EFS (hazard ratio = 3.18) and OS (hazard ratio = 3.42). However, this finding was not replicated for patients treated with regimen UH-1 and -2 under AREN03B2 but not on AREN0321. CONCLUSIONS: Race and ethnic group enrollment appeared constant across AREN03B2 risk-assigned therapeutic trials. EFS and OS on these therapeutic trials when analyzed together were comparable regarding race and ethnicity. Black children may have experienced worse stage-specific survival when treated with regimen UH-1 and -2 on AREN0321, but this survival gap was not confirmed when analyzing additional high-risk AREN03B2 patients.

INTRODUCTION:The COVID-19 pandemic onset had a global debilitating impact on individuals and on burgeoning careers. In 2021, the Children's Oncology Group Young Investigators Committee, Young SIOP (International Society of Paediatric Oncology) Network, and Young SIOPE (European Society for Paediatric Oncology) co-sponsored a survey to explore the impacts of the first year of the pandemic on early-career pediatric oncology professionals with respect to working practices, productivity, professional and career development, personal wellbeing, and changing childcare needs. METHODS:The survey comprised demographic, multiple-choice, and free-text questions, and was distributed via email and social media with English, French, and Spanish versions available. Descriptive statistics and chi-square tests were used to compare quantitative data by self-designated gender and country of origin. Qualitative data were described using content analysis. RESULTS:Professionals (N = 499, 26.3% male, 77.2% MDs) in 48 countries (77.6% high income) responded in English (79.4%), Spanish (12.4%), and French (8.2%). Respondents had difficulty obtaining and keeping jobs (26.9%), worsened overall academic productivity (50.7%, with higher rates among bench scientists, p < 0.01), and decreased career opportunities (40.9%). Childcare challenges impacted 56.7% of respondents and was felt more negatively among women (p = 0.008) and in high-income settings (p < 0.0001). Qualitative data (n = 300) highlighted these differences were often attributable to diminished professional/personal boundaries and impacted their personal wellbeing. CONCLUSION:The COVID-19 pandemic significantly impacted early-career academic and clinical professionals working in pediatric oncology, with unique challenges noted among those with childcare responsibilities. Career disruptions that resulted from the pandemic should be considered and mitigated by governing bodies and hiring institutions.

Neuroblastoma is the most common extracranial solid tumor diagnosed in children. This inaugural version of the NCCN Guidelines for Neuroblastoma provides recommendations for the diagnosis, risk classification, and treatment of neuroblastoma. The information in these guidelines was developed by the NCCN Neuroblastoma Panel, a multidisciplinary group of representatives with expertise in neuroblastoma, consisting of pediatric oncologists, radiologists, pathologists, surgeons, and radiation oncologists from NCCN Member Institutions. The evidence-based and consensus recommendations contained in the NCCN Guidelines are intended to guide clinicians in selecting the most appropriate treatments for their patients with this clinically heterogeneous disease.

ObjectiveTo describe United States (US) pediatric oncologists’ experiences with treatment refusal or abandonment, exploring types and frequency of decision-making conflicts, and their impact.Study designWe conducted exploratory qualitative interviews of pediatric oncologists (n = 30) with experience caring for a pediatric patient who refused or abandoned curative treatment. Interviewees were recruited using convenience and nominated expert sampling, soliciting experiences from diverse geographic locations and institution sizes across the US. We analyzed transcripts using applied thematic analysis to identify and refine meaningful domains.ResultsMany oncologists reported multiple experiences with refusal and abandonment. Most anticipated case frequency would increase due to misinformation, particularly on the internet. Interviewees described cases of treatment refusal and abandonment, but also a wider variety of cases than previously described in existing publications, including cases involving: non-adherence; negotiations for different treatments; negotiations for complementary and alternative medicine; delayed treatment initiation; and refusal of a component of recommended therapy. Cases often involved multiple stages or types of conflicts. Recurring patient/family behaviors emerged: clear opposition to treatment from the outset; hesitancy about treatment despite initiating therapy; and psychosocial circumstances becoming an obstacle to treatment completion. Oncologists revealed substantial professional and personal repercussions of these cases.ConclusionOncologist interviews highlight a broad range of conflicts, yielding a taxonomy of treatment refusal, non-adherence and abandonment (TRNA) that accounts for the heterogeneity of situations described. Cases’ complexity and interrelatedness points to a functional model of TRNA that includes families’ behaviors. This preliminary taxonomy and model warrant further research and examination to refine the model and generate strategies to prevent and mitigate TRNA.

Objectives: Although parotid gland malignancies are uncommon, they nevertheless represent a cause of morbidity and mortality in the pediatric population. Few studies have sought to identify disparities related to their presentation, treatment, and survival. There is a need to understand these variations to improve care for historically underrepresented groups. Study design: Retrospective Cohort Study. Setting: Surveillance, Epidemiology, and End Results (SEER) Program Database. Methods: Analysis of pediatric patients with parotid gland malignancies between 2000 and 2019. Race and ethnicity were classified as Non-Hispanic White, Non-Hispanic Black, Asian, and Hispanic for multivariable analysis. Outcomes included tumor size and stage at diagnosis, survival, and need for facial nerve sacrifice. Kaplan-Meier analysis was used to analyze survival. Multivariable logistic regression was conducted to identify predictors of outcomes. Results: 149 patients met the criteria for inclusion. Stratified by race/ethnicity, Non-Hispanic Black (Median 23 mm, IQR 15-33), Asian (30 mm, 14-32), and Hispanic (23 mm, 20-28) patients had larger tumors at presentation than Non-Hispanic White patients (18 mm, 12-25, p = 0.017). Disease-specific survival differed by timeto-treatment (log-rank, p = 0.01) and overall survival differed by income (p < 0.001). On multivariable analysis, Hispanic patients were more likely to experience facial nerve sacrifice (OR 3.71, 95%CI 1.25-11.6, p = 0.020), and Non-Hispanic Black (OR 3.37, 0.95-11.6, = 0.053) and Asian (OR 5.67, 1.46-22.2, p = 0.011) patients presented with larger tumors compared to Non-Hispanic White patients. Conclusions: Variations in presentation and treatment exist across race and ethnicity in pediatric parotid cancer. Identifying these disparities may help improve access and outcomes for underserved patient populations. Level of evidence: III.

Neuroblastoma is the most common extracranial solid tumor diagnosed in children. This inaugural version of the NCCN Guidelines for Neuroblastoma provides recommendations for the diagnosis, risk classification, and treatment of neuroblastoma. The information in these guidelines was developed by the NCCN Neuroblastoma Panel, a multidisciplinary group of representatives with expertise in neuroblastoma, consisting of pediatric oncologists, radiologists, pathologists, surgeons, and radiation oncologists from NCCN Member Institutions. The evidence-based and consensus recommendations contained in the NCCN Guidelines are intended to guide clinicians in selecting the most appropriate treatments for their patients with this clinically heterogeneous disease.

BackgroundPatients with stage IV favorable histology Wilms tumor (FHWT) with extrapulmonary metastases (EPM) constitute a small subset of patients with FHWT. Because of their rarity and heterogeneity, optimal FHWT treatment is not well understood. Children's Oncology Group protocol AREN0533 assigned patients with FHWT and EPM to intensified chemotherapy, regimen M, after initial DD-4A chemotherapy. To improve understanding of prognostic factors and best therapies, experiences of patients with EPM on AREN0533, as well as on protocols AREN03B2 and NWTS-5, were reviewed.MethodsCombined outcomes for patients with EPM from NWTS-5, AREN0533, and AREN03B2 were determined. Those treated on AREN0533 were compared with those treated on NWTS-5. Prognostic factors were explored in the pooled cohort.ResultsForty-seven patients with FHWT with EPM enrolled on AREN0533, 37 enrolled on NWTS-5, and 64 were followed only on AREN03B2. The pooled cohort of all 148 patients demonstrated a 4-year event-free survival (EFS) of 77.3% (95% CI, 70.8-84.4) and 4-year overall survival of 88.9% (95% CI, 83.9-94.2). Four-year EFS of patients with EPM treated on AREN0533 was 76.0% (95% CI, 64.6-89.4) vs 64.9% (95% CI, 51.7-82.2) on NWTS-5; hazard ratio, 0.64, p = .26; no difference in overall survival was observed. Increasing linear age and slow incomplete lung response were associated with worse EFS in a pooled cohort.ConclusionsOutcomes for patients with EPM are among the lowest for children with FHWT. Further trials with standardized surgical and radiation treatment to metastatic sites, and prospectively collected biologic and treatment details are needed.Clinical trial registrationClinical Trials.gov identifiers: NCT00379340, NCT00898365, and NCT00002611. Pooled outcomes across three studies of patients with favorable histology Wilms tumor and extrapulmonary metastases revealed 4-year event-free survival of 77.3% and overall survival of 88.9%, with no statistical differences seen between patients on AREN0533 compared with those on NWTS-5. Missing details on local management of metastatic sites informs a critical need for better data capture in future studies to optimize local control strategies and chemotherapy regimens for this higher-risk favorable histology Wilms tumor patient group.

PURPOSEAlthough the International Neuroblastoma Risk Group Data Commons (INRGdc) has enabled seminal large cohort studies, the research is limited by the lack of real-world, electronic health record (EHR) treatment data. To address this limitation, we evaluated the feasibility of extracting treatment data directly from EHRs using the REDCap Clinical Data Interoperability Services (CDIS) module for future submission to the INRGdc.METHODSPatients enrolled on the Children's Oncology Group neuroblastoma biology study ANBL00B1 (ClinicalTrials.gov identifier: NCT00904241) who received care at the University of Chicago (UChicago) or the Vanderbilt University Medical Center (VUMC) after the go-live dates for the Fast Healthcare Interoperability Resources (FHIR)-compliant EHRs were identified. Antineoplastic drug orders were extracted using the CDIS module. To validate the CDIS output, antineoplastic agents extracted through FHIR were compared with those queried through EHR relational databases (UChicago's Clinical Research Data Warehouse and VUMC's Epic Clarity database) and manual chart review.RESULTSThe analytic cohort consisted of 41 patients at UChicago and 32 VUMC patients. Antineoplastic drug orders were identified in the extracted EHR records of 39 (95.1%) UChicago patients and 26 (81.3%) VUMC patients. Manual chart review confirmed that patients with missing (n = 8) or discontinued (n = 1) orders in the CDIS output did not receive antineoplastic agents during the timeframe of the study. More than 99% of the antineoplastic drug orders in the EHR relational databases were identified in the corresponding CDIS output.CONCLUSIONOur results demonstrate the feasibility of extracting EHR treatment data with high fidelity using HL7-FHIR via REDCap CDIS for future submission to the INRGdc. A path to unlocking high-quality EHR treatment data for neuroblastoma research using REDCap CDIS.

OBJECTIVES:To characterize the spectrum of legal options considered in cases of treatment refusal, nonadherence, and abandonment (TRNA); clinicians' thought processes regarding legal intervention; and perceived consequences of legal involvement. METHODS:We conducted in-depth, semistructured interviews with 30 pediatric oncologists between May and September of 2019 regarding experiences with TRNA. The interview guide covered types of conflicts encountered; factors and strategies considered in response; effects of TRNA cases, personally and professionally; the role of ethical frameworks and legal requirements; and resources needed to manage TRNA cases. Interviews were transcribed and coded iteratively using thematic analysis. RESULTS:Participants represented a range of institutional sizes, geographic locations, and years in practice. Twenty-five of 30 interviewees discussed legal consideration with regard to TRNA. Most participants first engaged the legal system through child protective service agencies. They considered patient age, treatment efficacy, quality of life (burden of treatment), and prognosis; family resources and social context; and preservation of therapeutic relationships and possible consequences of reporting. Experiences and outcomes of legal involvement varied. CONCLUSIONS:Clinicians struggle with the tension between obligations to report medical neglect and fears that reporting may result in more harm than benefit to the child in question. We urgently need more dialog between health care professionals and child protective services and legal professionals. Stakeholders from both groups would benefit from a greater understanding of the other's thought processes; clarity regarding the relevant facts; and mutual progress toward creative, evidence-based solutions to working out these complex challenges.

Chyloperitoneum is an uncommon diagnosis in peritoneal dialysis (PD) patients. While admitted for emesis and feeding intolerance, a 16-month-old male on PD developed milky-colored dialysate with increased triglycerides, indicating chyloperitoneum. In adult PD patients, chyloperitoneum can indicate potentially life-threatening pathologies including malignancies and liver or heart disease. By contrast, pediatric patients on PD with chyloperitoneum had recently undergone PD catheter or gastrostomy tube placement with presumed disruption of abdominal lymphatics. Slowing lymph flow through dietary manipulation and rarely, temporary withholding of PD, resolved chyloperitoneum. We report a toddler on PD with chyloperitoneum in whom abdominal investigation showed multifocal hepatoblastoma. Chemotherapy and a medium chain triglycerides (MCTs)-based diet led to prompt resolution of chyloperitoneum. Intrabdominal malignancy in this patient illustrates the importance of a prompt, thorough evaluation of chyloperitoneum to allow definitive therapy if required.

INTRODUCTION:The purpose of this study is to examine the outcomes in children with anaplastic bilateral Wilms tumor (BWT) from study AREN0534 in order to define potential prognostic factors and areas to target in future clinical trials.METHODS:Demographic and clinical data from AREN0534 study patients with anaplasia (focal anaplasia [FA], or diffuse anaplasia [DA]) were compared. Event-free survival (EFS) and overall survival (OS) were reported using Kaplan-Meier estimation with 95% confidence bands, and differences in outcomes between FA and DA compared using log-rank tests. The impact of margin status was analyzed.RESULTS:Twenty-seven children who enrolled on AREN0534 had evidence of anaplasia (17 DA, 10 FA) in at least one kidney and were included in this analysis. Twenty-six (96%) had BWT. Nineteen percent had anaplastic histology in both kidneys (four of 17 DA, and one of 10 FA). Forty-six percent with BWT had bilateral nephron-sparing surgery (NSS); one child who went off protocol therapy, eventually required bilateral completion nephrectomies. Median follow-up for EFS and OS was 8.6 and 8.7 years from enrollment. Four- and 8-year EFS was 53% [95% confidence interval (CI): 34%-83%] for DA; 4-year EFS was 80% [95% CI: 59%-100%], and 8-year EFS 70% [95% CI: 47%-100%] for FA. Three out of 10 children with FA and eight out of 17 children with DA had events. EFS did not differ statistically by margin status (p = .79; HR = 0.88). Among the six children who died (five DA, one FA), all experienced prior relapse or progression within 18 months.CONCLUSION:Events in children with DA/FA in the setting of BWT occurred early. Caution should be taken about interpreting the impact of margin status outcomes in the context of contemporary multimodal therapy. Future targeted investigations in children with BWT and DA/FA are needed.

Being a parent is hard, particularly parenting adolescents, who need to be given choices and allowed the space to learn how to make choices for themselves, even when those choices result in negative consequences. This essay explores how Steven Sondheim and James Lapine's 1987 musical Into the Woods provides relatable stories of the challenges of being a parent, the challenges of parenting adolescents, and just how messy parents and families can be despite everyone trying their best. The stories of Little Red Riding Hood, Rapunzel, Jack, and Cinderella show us various stages, trajectories, and occasional tragedies of adolescents' emerging autonomy, while the Baker's and the Witch's struggles becoming and being parents encapsulate how disorderly and untidy parenting often is. Pediatricians and clinical bioethicists, who are often in a position to scrutinize the choices of parents and teens, should remember that parents and adolescents are almost always motivated by good intentions and doing the best that they can. Perhaps the best we can do is accompany them on their journey "into the woods."

To describe strategies that pediatric oncologists utilize to persuade families to initiate or continue chemotherapy after refusing treatment, we examined transcripts from interviews of oncologists with relevant experience. We identified three cases in which the pediatric oncologists' approaches led to voluntary acceptance of recommended treatment without legal intervention. Strategies used include direct communication with alternative medicine providers, time-limited trial of alternative therapy, and praying with the family. While we cannot conclude whether these approaches could be generalized to other cases, they offer ideas for pediatric oncologists to consider when facing the decision to seek judicial involvement or discontinue persuasive efforts.

Pediatric Blood & CancerEarly View e30393 LETTER TO THE EDITOR A case of high-risk neuroblastoma in a child with CLOVES syndrome Marina Girgis, Marina Girgis orcid.org/0009-0004-6091-9710 Departments of Internal Medicine and Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USASearch for more papers by this authorDaniel J. Benedetti, Corresponding Author Daniel J. Benedetti [email protected] orcid.org/0000-0003-1524-3518 Department of Pediatrics, Division of Pediatric Hematology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, USA Correspondence Daniel J. Benedetti, Department of Pediatrics, Division of Hematology/Oncology, Vanderbilt University Medical Center, 397 Preston Research Bldg, 2200 Pierce Ave, Nashville, TN 37232, USA. Email: [email protected]Search for more papers by this author Marina Girgis, Marina Girgis orcid.org/0009-0004-6091-9710 Departments of Internal Medicine and Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USASearch for more papers by this authorDaniel J. Benedetti, Corresponding Author Daniel J. Benedetti [email protected] orcid.org/0000-0003-1524-3518 Department of Pediatrics, Division of Pediatric Hematology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, USA Correspondence Daniel J. Benedetti, Department of Pediatrics, Division of Hematology/Oncology, Vanderbilt University Medical Center, 397 Preston Research Bldg, 2200 Pierce Ave, Nashville, TN 37232, USA. Email: [email protected]Search for more papers by this author First published: 24 April 2023 https://doi.org/10.1002/pbc.30393Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. REFERENCES 1Mirzaa G, Graham JM Jr, Keppler-Noreuil K. PIK3CA-related overgrowth spectrum. In: Adam MP , Everman DB , Mirzaa GM , eds. GeneReviews. University of Washington, Seattle; 1993. 2Kurek KC, Luks VL, Ayturk UM, et al. Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome. Am J Hum Genet. 2012; 90(6): 1108- 1115. 3Madsen RR, Vanhaesebroeck B, Semple RK. Cancer-associated PIK3CA mutations in overgrowth disorders. Trends Mol Med. 2018; 24(10): 856- 870. 4Martinez-Lopez A, Blasco-Morente G, Perez-Lopez I, et al. CLOVES syndrome: review of a PIK3CA-related overgrowth spectrum (PROS). Clin Genet. 2017; 91(1): 14- 21. 5Kandoth C, McLellan MD, Vandin F, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013; 502(7471): 333- 339. 6Stachler MD, Rinehart EM, Garcia E, Lindeman NI. PIK3CA mutations are common in many tumor types and are often associated with other driver mutations. Appl Immunohistochem Mol Morphol. 2016; 24(5): 313- 319. 7Samuels Y, Waldman T. Oncogenic mutations of PIK3CA in human cancers. Curr Top Microbiol Immunol. 2010; 347: 21- 41. 8Thorpe LM, Yuzugullu H, Zhao JJ. PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting. Nat Rev Cancer. 2015; 15(1): 7- 24. 9Kostopoulou ON, Holzhauser S, Lange BKA, et al. Analyses of FGFR3 and PIK3CA mutations in neuroblastomas and the effects of the corresponding inhibitors on neuroblastoma cell lines. Int J Oncol. 2019; 55(6): 1372- 1384. 10Peterman CM, Fevurly RD, Alomari AI, et al. Sonographic screening for Wilms tumor in children with CLOVES syndrome. Pediatr Blood Cancer. 2017; 64(12):e26684. 11Blatt J, Finger M, Price V, Crary SE, Pandya A, Adams DM. Cancer risk in Klippel–Trenaunay syndrome. Lymphat Res Biol. 2019; 17(6): 630- 636. 12Matthay KK, Shulkin B, Ladenstein R, et al. Criteria for evaluation of disease extent by (123)I-metaiodobenzylguanidine scans in neuroblastoma: a report for the International Neuroblastoma Risk Group (INRG) Task Force. Br J Cancer. 2010; 102(9): 1319- 1326. 13MacFarland SP, Zelley K, Surrey LF, et al. Pediatric somatic tumor sequencing identifies underlying cancer predisposition. JCO Precis Oncol. 2019; 3:PO1900062. 14Zhang J, Walsh MF, Wu G, et al. Germline mutations in predisposition genes in pediatric cancer. N Engl J Med. 2015; 373(24): 2336- 2346. 15Grobner SN, Worst BC, Weischenfeldt J, et al. The landscape of genomic alterations across childhood cancers. Nature. 2018; 555(7696): 321- 327. 16Newman S, Nakitandwe J, Kesserwan CA, et al. Genomes for kids: the scope of pathogenic mutations in pediatric cancer revealed by comprehensive DNA and RNA sequencing. Cancer Discov. 2021; 11(12): 3008- 3027. 17Mussa A, Duffy KA, Carli D, et al. The effectiveness of Wilms tumor screening in Beckwith–Wiedemann spectrum. J Cancer Res Clin Oncol. 2019; 145(12): 3115- 3123. 18Mills JR, Moyer AM, Kipp BR, Poplawski AB, Messiaen LM, Babovic-Vuksanovic D. Unilateral vestibular schwannoma and meningiomas in a patient with PIK3CA-related segmental overgrowth: co-occurrence of mosaicism for 2 rare disorders. Clin Genet. 2018; 93(1): 187- 190. 19Brodeur GM, Nichols KE, Plon SE, Schiffman JD, Malkin D. Pediatric cancer predisposition and surveillance: an overview, and a tribute to Alfred G. Knudson Jr. Clin Cancer Res. 2017; 23(11): e1- e5. https://doi.org/10.1158/1078-0432.CCR-17-0702 20Griff JR, Duffy KA, Kalish JM. Characterization and childhood tumor risk assessment of genetic and epigenetic syndromes associated with lateralized overgrowth. Front Pediatr. 2020; 8:613260. 21Crepin J-C, Carmignac V, Kuentz P, et al. Low risk of embryonic cancer in PIK3CA-related overgrowth spectrum: impact on screening recommendations. Paper presented at: Proceedings of International Society for the Study of Vascular Anomalies; 2018: P160. 22Kamihara J, Bourdeaut F, Foulkes WD, et al. Retinoblastoma and neuroblastoma predisposition and surveillance. Clin Cancer Res. 2017; 23(13): e98- e106. 23Venot Q, Blanc T, Rabia SH, et al. Targeted therapy in patients with PIK3CA-related overgrowth syndrome. Nature. 2018; 558(7711): 540- 546. 24Andre F, Ciruelos E, Rubovszky G, et al. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med. 2019; 380(20): 1929- 1940. 25Dam V, Morgan BT, Mazanek P, Hogarty MD. Mutations in PIK3CA are infrequent in neuroblastoma. BMC Cancer. 2006; 6: 177. Early ViewOnline Version of Record before inclusion in an issuee30393 ReferencesRelatedInformation

BackgroundOn the fifth National Wilms Tumor Study, treatment for clear cell sarcoma of the kidney (CCSK) included combined vincristine, doxorubicin, cyclophosphamide, and etoposide (regimen I) plus radiation therapy (RT), yielding 5-year event-free survival (EFS) rates of 100%, 88%, 73%, and 29% for patients who had with stage I, II, III, and IV disease, respectively. In the Children's Oncology Group study AREN0321 of risk-adapted therapy, RT was omitted for stage I disease if lymph nodes were sampled, and carboplatin was added for stage IV disease (regimen UH-1). Patients who had stage II/III disease received regimen I with RT.MethodsFour-year EFS was analyzed for patients enrolled on AREN0321 and on those enrolled on AREN03B2 who received AREN0321 stage-appropriate chemotherapy.ResultsEighty-two patients with CCSK enrolled on AREN0321, 50 enrolled on AREN03B2 only. The 4-year EFS rate was 82.7% (95% confidence interval [CI], 74.8%-91.4%) for AREN0321 and 89.6% (95% CI, 81.3%-98.7%) for AREN03B2 only (p = .28). When combining studies, the 4-year EFS rates for patients who had stage I (n = 10), II (n = 47), III (n = 65), and IV (n = 10) disease were 90% (95% CI, 73.2%-100.0%), 93.4% (95% CI, 86.4%-100.0%), 82.8% (95% CI, 74.1%-92.6%), and 58.3% (95% CI, 34%-100.0%), respectively. There were no local recurrences among seven patients with stage I disease who were treated without RT. One stage I recurrence occurred in the brain, which was the most common site of relapse overall. Among patients with local stage III tumors, neither initial procedure type, margin status, nor lymph node involvement were prognostic.ConclusionsPatients with stage I CCSK had excellent outcomes without local recurrences when treated without RT. Patients with stage IV disease appeared to benefit from a carboplatin-containing regimen, although their outcomes remained unsatisfactory. Further research is needed to improve outcomes for patients with advanced-stage disease (ClinicalTrials.gov identifiers NCT00335556 and NCT00898365). The results of this study indicated that treatment of clear cell sarcoma of the kidney can be risk-adapted based on disease stage, radiotherapy should be omitted for patients with stage I disease if lymph nodes are sampled, and patients with stage IV disease appear to benefit from a carboplatin-containing regimen. With treatment according to the Children's Oncology Group AREN0321 study, most relapses occurred within 3 years, and the most common sites of recurrence were in the central nervous system.