Polites, Stephanie F.

Background: Real-time intraoperative discrimination of malignant tissue during pediatric solid tumor resection is limited, constraining margin optimization; the utility of indocyanine green (ICG) fluorescence in this population remains incompletely defined. Study Design: Prospective, observational, multi-institutional study (2019–2023) of pediatric, adolescent, and young adult patients undergoing resection of intra-abdominal solid malignancies following preoperative ICG administration. The primary endpoint was diagnostic accuracy of ICG fluorescence for tumor-containing specimens; secondary endpoints included association with margin status and surgeon-perceived intraoperative benefit. Results: Forty-three operations in 42 patients yielded 55 specimens, of which 47 (85%) were malignant. Diagnostic performance was highest in hepatic tumors (sensitivity 83%, positive predictive value 83%) and lower in adrenal and heterogeneous tumor types. ICG avidity was not associated with improved negative margin rates (86% vs 75%, p=0.47). Surgeons reported intraoperative benefit in 67% of cases, most commonly improved visualization. No ICG-related adverse events occurred. Conclusions: ICG fluorescence provides reliable tumor identification in hepatic malignancies but does not correlate with margin-negative resection, indicating limited utility for margin guidance. These data support tumor-specific application and further investigation of optimized fluorescence strategies, including dosing, timing, and alternative fluorophores, in pediatric oncologic surgery.

e22006 Background: Metastasectomy is recommended for select pediatric patients with osteosarcoma with resectable pulmonary parenchymal metastases. It is unclear whether pulmonary metastasectomy confers the same benefit to patients with hilar or mediastinal lymph node metastases (LNM). This study aims to characterize pediatric patients with osteosarcoma with thoracic LNM and their outcomes compared to those with only pulmonary parenchymal metastasis. Methods: This is a retrospective cohort study of patients aged 0-21 with osteosarcoma metastatic to the lung who underwent pulmonary metastasectomy between 2000-2024. Patients were categorized into groups based on the presence or absence of LNM on imaging reviewed by pediatric surgeons and radiologists. Descriptive statistics and Wilcoxon rank sum, chi-square or Fisher’s exact tests evaluated differences between patients with and without LNM. Kaplan-Meier survival curves with log-rank tests evaluated the relationship between the presence of LNM and outcomes. The primary outcome was overall survival (OS) with secondary outcomes of recurrence-free survival (RFS) and disease-free survival (DFS). Results: 39 patients met inclusion criteria for this study, of which 13 (33%) had LNM (Table). Of the 13 patients with LNM, 8 (62%) had a pulmonary metastasectomy after their LNM diagnosis. Patients with LNM had poorer OS after first metastasectomy (log-rank p = .027), DFS after first metastasectomy (p = .018), and RFS after diagnosis (p = .039) than patients with pulmonary parenchymal metastasis without LNM. Patients who underwent metastasectomy after their LNM diagnosis had improved OS after LNM diagnosis than patients who did not undergo metastasectomy (pairwise log-rank test with Bonferroni correction p = .015). Conclusions: Pediatric patients with osteosarcoma metastatic to the lung with LNM had poorer OS, DFS, and RFS compared to patients without LNM. These results confirm the importance of attention to the presence of nodal involvement in patients with pulmonary metastatic osteosarcoma. Despite their poor prognosis, these results suggest a persistent survival benefit to surgical intervention. Total N = 39 No LMN N = 26 LMNN = 13 p Age 13.7 (9.5, 16.1) 13.9 (9.0, 15.9) 13.7 (10.7, 16.5) .777 Female 15 (38%) 10 (38%) 5 (38%) > .999 Histology Chondroblastic Osteoblastic Telangiectatic 11 (39%)16 (57%)1 (3.6%) 9 (50%)8 (44%)1 (5.6%) 2 (20%)8 (80%)0 (0%) .162 Primary tumor site Chest wall Femur Humerus Pelvis Radius Tibia 2 (5.1%)24 (62%)5 (13%)2 (5.1%)1 (2.6%)5 (13%) 2 (7.7%)14 (54%)3 (12%)2 (7.7%)1 (3.8%)4 (15%) 0 (0%)10 (77%)2 (15%)0 (0%)0 (0%)1 (7.7%) .821 Lung metastases present at time of diagnosis 20 (51%) 13 (50%) 7 (54%) .821 Treatment protocol AOST0331 AOST06P1 CCG 7921 P9754 30 (81%)2 (5.4%)4 (11%)1 (2.7%) 19 (79%)1 (4.2%)3 (13%)1 (4.2%) 11 (85%)1 (7.7%)1 (7.7%)0 (0%) > .999 Lung nodules removed during first metastasectomy 3 (2, 6) 3 (2, 5) 6 (1, 20) .567

10043 Background: Tumor resection is a cornerstone of therapy for neuroblastoma (NB) and Wilms tumor (WT). Minimally invasive surgical approaches such as laparoscopic or robotic tumor resection hold promise to reduce surgical morbidity while maintaining excellent oncologic outcomes. This study aims to determine the utilization and outcomes of laparoscopic and robotic resection of NB and WT among children in a national cohort, hypothesizing that utilization is increasing over time and outcomes are not inferior to open resection. Methods: A retrospective cohort analysis of patients <18 years old in the 2020-2023 National Cancer Database who underwent resection of NB or WT was performed. Surgical approach trends were assessed via Cochran-Armitage tests. Conversions to open surgery, length of stay (LOS), and readmissions were compared between approaches using Kruskal-Wallis, Chi-square, and Fisher’s exact tests. Results: Among 1,262 children who underwent resection of NB (n=581) or WT (n=681), open procedures were most common (83.4%), followed by laparoscopic (13.9%), and robotic (2.7%). Utilization of each approach was stable over time aside from increased robotic resection of NB from 0% to 4% (p=.024). Approach did not vary by patient age (Table 1). Median WT size and lymph node yield were similar between approaches (both p>.05). In NB, laparoscopic procedures were performed on smaller tumors than open or robotic (p<.001). There were no robotic conversions to open; 11.4% of laparoscopic procedures were converted without change over time or difference between NB and WT (both p>.05). Median LOS was greater for open procedures than laparoscopic or robotic (p<.001). Readmission rates (p=.64) and margin status (p=.63) were similar between approaches. Outcomes did not vary by diagnosis. Conclusions: Utilization of minimally invasive approaches for NB or WT resection remains low despite noninferior or improved outcomes. Efforts to safely increase utilization are needed, especially for robotics, so that survivorship can be improved through reduced surgical morbidity. Differences in patient characteristics and outcomes by surgical approach. Characteristic or Outcome Open Laparoscopic Robotic p value Age in years (median, IQR) 3 (1, 4) 3 (1, 5) 3 (1, 7) 0.08 % female 53% 53% 44% 0.59 NB tumor size in mm (median, IQR) 72 (50, 101) 47 (35, 71) 70 (51, 86) <0.001 WT tumor size in mm (median, IQR) 110 (75, 140) 115 (93, 150) 93 (54, 125) 0.10 % metastatic disease 33% 30% 15% 0.07 % neoadjuvant therapy 35% 27% 22% 0.014 % conversion to open n/a 11% 0% 0.05 Negative margins 86% 83% 96% 0.63 # Lymph nodes assessed in WT (median, IQR) 5 (3, 8) 6 (3, 10) 4 (3, 9) 0.62 LOS in days (median, IQR) 5 (4, 7) 4 (2, 6) 4 (1, 5) <0.001 % readmission 15% 14% 9% 0.64

Abstract Neuroblastoma (NB) accounts for 10% of pediatric cancer-related deaths. High-risk NB is frequently metastatic at diagnosis and has a poor 5-year survival rate (&lt;50%) despite aggressive treatment. GD2, a disialoganglioside glycolipid that is expressed in nearly all NBs, has been validated as a promising immunotherapy target. Although GD2-CAR-T cells have been clinically evaluated, their efficacy has been limited by poor tumor infiltration and the immunosuppressive tumor microenvironment (TME), highlighting the need for alternative immune-based strategies. With inherent capacity of macrophages to infiltrate tumors, phagocytose cancer cells, and modulate TME, they represent a promising alternative strategy for immunotherapy in NB. In this study, we developed and evaluated GD2-CAR-macrophages (GD2-CAR-Ms) as a novel therapeutic approach for NB. GD2-specific CAR constructs were designed, validated, and introduced into multiple human and murine monocyte/macrophage cell lines via lentiviral transduction. Fluorescent microscopy and flow cytometry confirmed a significant enhancement in the phagocytosis of GD2-high NB cells by GD2-CAR-Ms containing Hu3F8 single-chain variable fragment (scFv). A strong positive correlation was observed between GD2 expression levels on the target cells and phagocytosis efficiency of GD2-CAR-Ms, indicating that the phagocytic activity of GD2-CAR-Ms is antigen-specific. Anti-tumor efficacy was further evaluated in vivo using an immunocompetent Mycn-expressing NB non-genetically engineered mouse model (MYCN-NGEMM). Mice treated with GD2-CAR-Ms exhibited significantly reduced tumor burden and prolonged survival compared to control groups. Notably, treatment of mice bearing GD2-high tumors resulted in markedly improved survival, including one complete remission among ten treated animals, underscoring the therapeutic potential of GD2-targeted macrophage therapy. Histological analysis showed increased deposition of connective tissues and decreased tumor cells density, suggesting TME remodeling. Furthermore, immunohistochemistry reveals increased immune cell infiltration, particularly of macrophages, neutrophils and T cells, indicating a favorable shift in the immune TME from “cold” to “hot” following GD2-CAR-M treatment. Additionally, inhibition of tumor growth was also observed in our zebrafish NB model after GD2-CAR-Ms treatment, further supporting their therapeutic potential. Together, our findings demonstrate that GD2-CAR-Ms exhibit potent antitumor activity and reshape the tumor immune microenvironment, supporting their translational potential as a therapeutic strategy for high-risk NB. Citation Format: Ke-En Tan, Kok Siong Yeo, Cheng Zhang, Caleb Baker, Shyang Hong Tan, Alexis M. Sosic, Yat-Yuen Lim, Choong-Yong Ung, Cristina Correia, Stephanie F. Polites, Yi Lin, William A. Weiss, Hu Li, Shizhen Zhu. Engineering macrophages as a novel therapeutic approach for high-risk neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7810.

Abstract Background: Pediatric and AYA sarcomas are rare, biologically heterogeneous tumors with limited noninvasive biomarkers to guide diagnosis, personalized treatment, and disease monitoring. Standard-of-care evaluation relies on invasive biopsies that carry procedural risks and imaging modalities with limited sensitivity for detecting minimal residual disease and distinguishing tumor types. Cell-free DNA (cfDNA) methylation profiling offers a minimally invasive alternative capable of capturing tumor-derived epigenomic alterations and has consistently shown strong clinical utility in adult malignancies. However, genome-wide cfDNA methylation patterns across diverse pediatric and AYA sarcoma subtypes remain poorly defined. Methods: Plasma was collected from 93 pediatric and AYA patients (pediatric &lt;18 years; AYA 15-39 years) representing 27 Ewing sarcoma, 17 rhabdomyosarcoma, 11 liposarcoma, 10 chordoma, 8 synovial sarcoma, 7 chondrosarcoma, 6 osteosarcoma, and 6 fibrosarcoma cases, plus 19 matched healthy donors. cfDNA was isolated from 1 mL plasma, quantified by Qubit, and assessed by Bioanalyzer. Libraries were prepared using the NEBNext EM-seq v2 workflow with PCR cycles scaled to cfDNA input amount. Genome-wide sequencing (15× target depth) was followed by alignment, deduplication, and methylation calling. MultiQC was used to assess depth, duplication rate, conversion efficiency, and CpG coverage. Global methylation summaries were computed, and methylKit was used to generate per-CpG and 1-kb tiling matrices and initiate differential methylation analyses. Results: Ewing sarcoma patients had significantly higher plasma cfDNA concentrations than age- and sex-matched healthy donors (24.4 vs 4.6 ng/mL, p &lt; 0.0001), whereas cfDNA levels for other sarcoma subtypes overlapped with the healthy cohort. Low or undetectable cfDNA concentrations by Qubit were far more common among non-Ewing sarcoma samples (23 of 66) than Ewing sarcoma (1 of 27). All samples achieved sufficient CpG coverage for genome-wide methylation modeling. Global methylation summaries revealed no significant differences in mean β-values across sarcoma subtypes or versus healthy donors. An independent analysis of the Ewing subset identified 299 significant differentially methylated regions (DMRs), supporting the detectability of disease-specific methylation changes. Conclusions: These results demonstrate the feasibility of high-quality cfDNA methylome profiling across a large and diverse pediatric and AYA sarcoma cohort, including in plasma samples with cfDNA concentrations below the limit of detection. While global methylation levels appear broadly similar across subtypes, proof-of-concept DMR analysis in Ewing sarcoma suggests that subtype-specific epigenomic signatures could enable future noninvasive diagnostic tools for pediatric and AYA sarcomas. Citation Format: Lilli J. Greiner, Roman O. Kowalchuk, Jeff Szymanski, Pradeep S. Chauhan, Adam Amundson, Peter J. Schoettler, Wendy Allen-Rhoades, Stephanie F. Polites, Peter S. Rose, Kelly Bailey, Linda McAllister-Lucas, Anita Mahajan, Nadia Laack, Aadel Chaudhuri. Defining genome-wide cfDNA methylation landscapes in pediatric and adolescent and young adult (AYA) bone and soft-tissue sarcomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7885.

Abstract Introduction: Detectable circulating tumor DNA (ctDNA) is associated with inferior outcomes in Ewing sarcoma (ES); however, ctDNA clears in nearly all patients within 2 of the 6 chemotherapy cycles before radiotherapy (RT) or surgery. Given a 3-year EFS of 37% on AEWS 1221 (metastatic) and 5-year EFS of 78% on AEWS 1031 (localized), current ctDNA testing fails to predict most relapses. Extracellular vesicles (EVs) are microscopic particles studied as a biomarker in multiple cancer types. We hope to improve the sensitivity of ctDNA in ES and provide the first application of EVs in ES. Methods: cfDNA was isolated from 1mL plasma, quantified by Qubit, and sequenced as NEBNext Enzymatic Methyl-seq v2 libraries. We performed a systematic unsupervised clustering analysis of 27 ES plasma cfDNA profiles using 4 differentially methylated regions (DMR) subsets (63 strong DMRs, top 30, top 15, and 10 promoter-proximal loci), 3 clustering algorithms (k-means, Ward hierarchical, PAM), and k=2-5 clusters, testing associations with tumor burden and progression. EV analysis involved antibody detection against ES surface markers, including LINGO1, ENPP1, CDH11, and CD99. Concentrations of EVs were determined by standardized and calibrated high-resolution flow cytometry then analyzed with custom-built software to automatically determine and apply gates. Samples were de-identified, randomly coded, and run in triplicates. The senior research technologist responsible for EV analysis was blinded to patient information and clinical data. Results: EV analysis included 36 pre-RT samples from 16 metastatic and 20 localized ES patients from a prospectively maintained biobank, with 27 pre-RT samples in the cfDNA analysis and 19 healthy donor (HD) samples. 35 of 36 patients had chemotherapy before sample collection. cfDNA concentrations were markedly elevated in ES patients compared with HD (24.4 vs 4.6 ng/mL, p&lt;0.0001), and 74% of ES samples exceeded the HD 95th-percentile detectability threshold (7.0 ng/mL). Across clustering configurations, ES cfDNA profiles consistently exhibited reproducible methylation substructure. One configuration (PAM clustering, k = 5, 63 strong DMRs) showed a modest but permutation-supported association with primary tumor size (nominal p ≈ 0.04; empirical p ≈ 0.03-0.04). ES samples had increased EV concentration compared to HD (p&lt;0.001), with AUC 0.988 for distinguishing between ES and HD ENPP1 (p&lt;0.0001). The highest ENPP1 EV values were in patients with large primary tumors (&gt;8 cm vs. ≤ 8cm) and metastatic disease (p=0.066). Conclusions: cfDNA- and EV-based liquid biopsy provide encouraging signals for high ES detectability pre-RT. We also show the first study of EVs as a novel biomarker in ES, which may provide complementary information to ctDNA. Multimodal liquid biopsy in ES may identify candidate patients for systemic or local therapy escalation and facilitate personalized care. Citation Format: Roman O. Kowalchuk, Lilli J. Greiner, Yohan Kim, Rubia Noori, Jeffrey Szymanski, William S. Harmsen, Pradeep S. Chauhan, Adam C. Amundson, Andrea M. McMahon, Peter J. Schoettler, Wendy A. Allen-Rhoades, Stephanie F. Polites, Peter S. Rose, Kelly M. Bailey, Linda M. McAllister-Lucas, Anita Mahajan, Fabrice Lucien-Matteoni, Nadia N. Laack, Aadel A. Chaudhuri. Multimodal liquid biopsy of Ewing sarcoma reveals high sensitivity prior to radiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1149.

ABSTRACT Purpose Malignant rhabdoid tumor of the kidney (MRTK) is a rare, aggressive tumor seen in young children. The optimal timing of resection for locally advanced tumors is not well‐defined. The purpose of this study is to evaluate modern oncologic outcomes and the impact of surgical timing. Methods A multicenter retrospective review was performed by institutions participating in the Pediatric Surgical Oncology Research Collaborative. Children younger than 21 years old with MRTK diagnosed between 2000 and 2022 were included. Results Sixty‐nine patients were identified with MRTK and met the inclusion criteria. Median age of diagnosis was 10.1 months. Overall survival (OS) at 1, 5, and 10 years was 49%, 32%, and 19%, respectively. Patients with local Stage III disease who underwent upfront resection ( n = 18) compared to those who had delayed resection after NAT ( n = 15) had a similar OS, median OS greater than 60 months versus 14.6 months, respectively; p = 0.396. The surgical timing groups were balanced in terms of the presence of metastasis, length of follow‐up, and tumor characteristics. There was one occurrence of primary intraoperative tumor spill and two occurrences of organ injury in the upfront resection group compared to none in the delayed resection group. Conclusion MRTK carries a poor prognosis despite multimodal treatment. Histologic diagnosis may not be confirmed at presentation, and MRTK cannot be reliably distinguished from Wilms tumor on imaging alone. As overall survival is similar, the decision regarding surgical timing in locally advanced tumors should be individualized based on perceived resectability, balancing the risk of intraoperative complications against the possibility of tumor progression during neoadjuvant therapy.

Objective We sought to characterize factors associated with postoperative complications in patients undergoing primary cleft lip repair (CLR). Design The National Surgical Quality Improvement Program-Pediatric database was queried to identify patients under 12 months old undergoing CLR using CPT codes. Multivariable analysis was conducted to characterize complications and associated comorbidities. Setting A multicenter sample. Patients/Participants A total of 11 957 cases (81.9% unilateral CLR and 18.1% bilateral CLR) were identified. Interventions None. Main Outcomes/Measures The postoperative outcomes of significance were surgical site infection (SSI), wound dehiscence, and unplanned reintubation within 30 days of CLR. Results The cohort had a mean age of 4.7 ± 2.0 months and a median American Society of Anesthesiologists classification of 2. SSIs occurred in 0.6% of cases and were independently associated with bilateral cleft anatomy (OR 2.16, P = .003) and longer anesthesia time (OR per minute: 1.004, P = .009). Wound dehiscence occurred in 0.4% of patients and was independently associated with bilateral cleft anatomy (OR 4.03, P < .001) but was associated with shorter anesthesia duration (OR per minute: 0.991, P < .001). Unplanned reintubation occurred in 0.2% of cases, with these patients having significantly higher rates of multiple comorbidities. Conclusion Wound dehiscence, SSI, and unplanned reintubation were rare complications following CLR. Patients with a bilateral cleft lip had increased odds of both SSI and wound dehiscence.

Abstract Neuroblastoma (NB) accounts for approximately 10% of pediatric cancer-related deaths. High-risk NB is often metastatic at diagnosis with a poor 5-year survival rate (&lt;50%) despite intensive multimodal therapy. GD2, a disialoganglioside glycolipid expressed in nearly all NBs, is a well-validated immunotherapy target. Although GD2-CAR-T cells have been clinically evaluated, their efficacy remains limited due to poor tumor infiltration and the immunosuppressive tumor microenvironment (TME), underscoring the need for alternative immune-based approaches. Given the inherent capacity of macrophages to infiltrate solid tumors, phagocytose cancer cells, and modulate the TME, we engineered the GD2-CAR macrophage (GD2-CAR-M) as a novel therapeutic platform for NB. GD2-specific CAR constructs containing the Hu3F8 single-chain variable fragment (scFv) were designed, validated, and introduced into multiple human and murine monocyte/macrophage cell lines via lentiviral transduction. Fluorescence microscopy and flow cytometry demonstrated a significant enhancement in the phagocytosis of GD2-high NB cells and the phagocytic efficiency correlating positively with GD2 expression levels, suggesting antigen-specific phagocytosis by GD2-CAR-M. Our further in vivo studies using an immunocompetent MYCN-driven NB non-genetically engineered mouse model (MYCN-NGEMM) showed that treatment with GD2-CAR-M markedly reduced tumor burden and prolonged survival compared with controls. Notably, mice bearing GD2-high-tumors exhibited significantly improved survival, including one complete remission among ten treated animals. Histological analyses revealed increased connective tissue deposition and decreased tumor cell density, suggesting TME remodeling. Single-cell RNA sequencing and immunohistochemistry further demonstrated enhanced infiltration of macrophages, neutrophils, and T cells, indicating a shift from a “cold” to a “hot” immune TME following GD2-CAR-M treatment. Consistent antitumor effects were also observed in our dbh-MYCN transgenic zebrafish with spontaneous development of NB following GD2-CAR-M administration. Taken together, GD2-CAR-M exhibits potent antigen-specific antitumor activity and promotes favorable TME remodeling in NB models. These findings highlight GD2-CAR-M as a promising translational immunotherapy strategy for high-risk NB. Citation Format: Shizhen (Jane) Zhu, Ke-En Tan, Kok Siong Yeo, Cheng Zhang, Caleb T. Baker, Alexis M. Sosic, Eddie Lim . Yat Yuen, Choong Yong Ung, Stephanie F. Polites, Yi Lin, William A. Weiss, Hu Li. Harnessing GD2-CAR macrophages to target high-risk neuroblastoma [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr B005.

ABSTRACT Background Sentinel lymph node (SLN) biopsy is a critical staging tool in skin and soft tissue cancers. Although technetium lymphoscintigraphy is the most common adjunct, indocyanine green (ICG) demonstrates a promising alternative in pediatric, adolescent, and young adult (AYA) skin and soft tissue cancers. Methods and Objectives Evaluate the safety and efficacy of ICG in SLN biopsy (SLNB) in diverse pediatric and AYA solid cancers in a multi‐institutional environment. This is a prospective, observational study conducted at 13 member institutions in the Pediatric Surgical Oncology Research Collaborative between 2019 and 2023. Eligible patients underwent SLNB for primary or recurrent solid skin and soft tissue tumors. Peritumoral ICG was administered intraoperatively. Outcomes included SLN detection rates, histopathology of excised specimens, and surgeon‐reported assessment of utility. Safety was assessed through adverse event reporting. Results Forty SLNB procedures yielded 84 specimens: 13 melanoma (32.5%), 12 squamous cell carcinoma (30%), 11 non‐rhabdomyosarcoma soft tissue sarcoma (27.5%), two rhabdomyosarcoma (5%), one Ewing sarcoma (2.5%), and one malignant peripheral nerve sheath tumor (2.5%). Histologic evaluation identified 81 lymph nodes, 75 benign (89.3%) and six malignant (7.1%); three specimens were adipose tissue (3.6%). Of 81 lymph nodes, 76% were ICG‐positive. ICG had a sensitivity of 79.5%, a specificity of 33%, and a positive predictive value of 96%. All malignant nodes were ICG‐avid. There were no adverse reactions to ICG at 30 days. Conclusions ICG is a safe and effective adjunct for SLNB in pediatric and AYA soft tissue and skin malignancies.