Granberg, Candace F.

ABSTRACT The local treatment of bladder and prostate rhabdomyosarcoma is a multidisciplinary decision, incorporating elements of patient age, tumor size and location, nodal involvement, and access to local expertise and technology. The relative absence of long‐term bladder and bowel function outcome data complicates discussions, particularly given improved survival rates and development of new surgical and radiotherapy techniques. These INSTRuCT guidelines, a collaboration of the Children's Oncology Group, Soft Tissue Sarcoma Committee, European Pediatric Soft Tissue Sarcoma Study Group, and the Cooperative Weichteilsarkom Studiengruppe, reflect international expert consensus and are intended to inform practice, generate discussion, and highlight areas of future inquiry.

Introduction: Congenital preauricular lesions, including skin tags, accessory tragi, and pits, have long been associated with renal anomalies due to their shared embryologic origin. Despite the common practice of recommending routine renal ultrasound screening for these patients, the necessity of this protocol has not been conclusively validated. Methods: A retrospective review was conducted at a single institution from 1996 to 2025. A total of 109 patients presenting with congenital preauricular lesions were identified. Data extracted included demographics, comorbidities, syndromic status, hearing assessments, external ear abnormalities, and renal imaging findings. Statistical analyses (chi-square, Fisher's exact test, and one-sample proportion z-tests) were employed to evaluate the prevalence of renal anomalies compared to the general population and explore associations with other clinical factors. Results: Of the 109 patients with congenital preauricular lesions, 69 underwent renal imaging, and 34.8% (24/69) were found to have abnormal findings, significantly higher ( P = .0011) than the estimated 1.5% prevalence among the general US population. Hydronephrosis was the most frequent abnormality, while no significant differences emerged across syndromic versus nonsyndromic patients, external ear anomalies, or documented hearing loss. Conclusion: These findings indicate a higher-than-expected rate of renal pathology in patients with congenital preauricular lesions and support a low threshold for imaging regardless of syndromic status or other risk factors. Prospective research is needed to further refine screening recommendations.

Background/Objectives: Pediatric rhabdomyosarcoma is a rare and poorly understood disease. Patients and parents can have varying experiences including barriers to care, time to treatment, and treatments offered. Here, we report on patient experiences regarding their care of pediatric rhabdomyosarcoma. Methods: Two separate online parent support groups were invited to participate in a survey. The survey included questions that sought to collect patient demographics, history of rhabdomyosarcoma, treatment timelines, and barriers to care. Results: A total of 215 surveys were completed. The average time from diagnosis to treatment was 12 days (SD = 14). Only 26% were offered fertility preservation prior to treatment. For patients with recurrence, an average of 75 days passed between detection of recurrence and treatment re-initiation. Patients traveled to centers with a dedicated sarcoma program in 52% of the cases. A total of 42% of parents sought a second opinion. Of those, the majority had to wait between one week and one month to be seen by another expert. Conclusions: The data collected from the survey suggests there are several opportunities to improve care among patients with pediatric rhabdomyosarcoma. Many patients may benefit from more efficient rhabdomyosarcoma referral networks, delivering patients to experts who can quickly begin multidisciplinary treatment.

Objectives To characterise the prevalence of impostor phenomenon (IP; tendency for high‐achieving individuals to perceive themselves as fraudulent in their successes) amongst attending staff in urology, to identify variables that predict more severe impostorism, and to study the association of IP with burnout. Subjects and Methods A survey composed of the Clance Impostor Phenomenon Scale (CIPS), demographic information, practice details, and burnout levels was e‐mailed to urologists via urological subspecialty societies. Survey results were analysed to identify associations between IP severity, survey respondent characteristics, and symptoms of professional burnout. This study was conducted in the United States of America. Results A total of 614 survey responses were received (response rate 11.0%). In all, 40% ( n = 213) of responders reported CIPS scores qualifying as either ‘frequent’ or ‘intense’ impostorism (i.e., scores of 61–100). On multivariable analysis, female gender, fewer years in practice (i.e., 0–2 years), and lower academic rank were all independently associated with higher CIPS scores (adjusted P < 0.05). Regarding burnout, 46% of responders reported burnout symptoms. On multivariable analysis, increase in CIPS score was independently associated with higher odds of burnout (odds ratio 1.06, 95% confidence interval 1.04–1.07; P < 0.001). Conclusion Impostor phenomenon is prevalent in the urological community and is experienced more severely in younger and female urologists. IP is also independently associated with burnout. Increased female representation may improve IP amongst our female colleagues. More work is needed to determine strategies that are effective in mitigating feelings of IP and professional burnout amongst urologists, particularly those earlier in their careers.

Abstract Background: Mutations in RAS is reported in embryonal rhabdomyosarcoma (ERMS). Upregulation of IGF2/IGF1R axis and IGF2 overexpression is a common finding. Targeting RAS downstream is associated with high toxicity. Combination therapies targeting parallel pathways is necessary to overcome treatment resistance. Dual inhibition of RAS downstream and IGF2/IGF1R axis can be a potential mechanism of targeted treatment. The efficacy of this mechanism was studied using a microcancer 3D exvivo tumor cell viability assay in a KRAS mutant ERMS. Design: Tumor was collected for a high-risk pediatric ERMS patient. Comprehensive genomic analysis, for identification of targetable genomic alterations, was performed by integrating WES, MPseq and RNAseq. Tumor spheroids grown in 3D environment were tested against multiple single drugs and combinations. The tumor viability was assed employing the Cell Titer Glow Luminescent Cell Viability Assay. Results were expressed as nMATP and were shown as drug-response curve exhibiting the ATP concentration changes at Cmax. Results: Genomic findings included an oncogenic KRAS (G12D) mutation. BAY-293 has a partial cell killing response as a single agent. Given to the presence of IGF2 over-expression, IGF2/IGF1R pathway was targeted by linsitinib. Addition of BAY-293 to linsitinib led to enhanced effectiveness of this agent (Table 1). Conclusion: Combination of comprehensive genomic profiling and a laboratory-based 3D micro-cancer model using the patient’s own tumor is an effective way to determine drug efficacy. Targeting RAS pathway by single agents, increases the possibility of resistance. Dual targeting of downstream pathways by MEK and PI3K pathway inhibition is highly toxic, and the clinical usage of this combination is limited. Our results have indicated inhibition of IGF-1R/IGF2 axis in combination with other agents targeting RAS pathway, can be a potential method to address these limitations. ABEL 1. Summary of molecular alterations and targeting methods Molecular alteration Drug Target Kill% at Cmax KRAS (G12D) Mutation BAY-293 RAS-SOS1 interaction 55.3 Trametinib MEK1/2 88.3 Selumetinib MEK1/2 76 Paxalisib PI3K/mTOR 89.7 Samotolisib PI3K/mTOR 92.9 Copanlisib PI3K 95.2 Perifosine AKT 89.2 IGF2 Over-expression Linsitinib IGF-1R/InsR 84.1 BMS-754807 IGF-1R/InsR 67.4 NTRK2 mutation Larotrectinib NTRK 41.9 KMT2D mutation Panobinostat HDAC 85.3 Combinations Kill% at Cmax BAY-293+Selumetinib 100 BAY-293+Samotolisib 100 BAY-293+Paxalisib 99.7 BAY-293+Linsitinib 97.5 Selumetinib+Samotolisib 93.1 Citation Format: Dorsay Sadeghian, Wan-Hsin Lin, James Smadbeck, Alan Panheiter, Michael Barrett, Alexa F. Mccune, Giannoula Karagouga, Sarah Johnson, Ryan W. Feathers, Faye R. Harris, Lindsey Kinsella, Taylor Berry, John Cheville, Panos Anastasiadis, Candace Granberg, Patricio Gargollo, Vasmatzis George. Dual inhibition of RAS and the IGF2/IGF1R pathways: a potential targeting strategy for RAS-mutated embryonal rhabdomyosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3391.