Rhee, Daniel S.

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.

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.

The NCCN Clinical Practice Guidelines (NCCN Guidelines) for Wilms Tumor (WT; nephroblastoma) cover strategies for the screening, diagnosis, and treatment of WT, which is the most frequent primary kidney tumor in children. WT can generally be separated into 2 histology types: favorable histology WT and anaplastic WT. Five-year survival is high for children with favorable histology WT who receive appropriate treatment; however, survival rates are much lower for patients who present with higher stage diffuse anaplastic WT. Treatment of WT can range from surgery alone to surgery plus intensive chemotherapy and radiation depending on whether the tumor is unilateral or bilateral, histology, and local stage. The goal of therapy is to maximize cure while minimizing long-term toxicities. The content featured in this issue covers the NCCN panel’s recommendations for overall management of both favorable histology WT and anaplastic WT.

AbstractNon‐rhabdomyosarcoma soft tissue sarcoma (STS) comprises most STS in pediatric patients. It is a diverse set of over 30 histologic subtypes. Treatment is based on risk group determined by tumor size, grade, and the presence of metastases. Surgical resection is a cornerstone of therapy, as tumors are often resistant to chemotherapy or radiation. While patients with isolated tumors less than 5 cm may undergo upfront resection, strong consideration should be given to neoadjuvant chemoradiotherapy to ensure negative margins at surgical resection and optimal outcomes. Sentinel lymph node biopsy is strongly recommended for clear cell and epithelioid sarcomas. The most common metastatic site is the lung, and metastases should be resected at the end of therapy, when feasible. Unfortunately, many high‐risk patients progress on therapy, and alternative strategies including earlier metastatic control require investigation.

Abstract Background To determine outcomes of children with rhabdomyosarcoma (RMS) with isolated lung metastases. Methods Data were analyzed for 428 patients with metastatic RMS treated on COG protocols. Categorical variables were compared using Chi‐square or Fisher's exact tests. Event‐free survival (EFS) and overall survival (OS) were estimated using Kaplan–Meier method and compared using the log‐rank test. Results Compared with patients with other metastatic sites ( n = 373), patients with lung‐only metastases ( n = 55) were more likely to be <10 years of age, have embryonal histology (embryonal rhabdomyosarcoma), have N0 disease, and less likely to have primary extremity tumors. Lung‐only patients had significantly better survival outcomes than patients with all other sites of metastatic disease ( p < .0001) with 5‐year EFS of 48.1 versus 18.8% and 5‐year OS of 64.1 versus 26.9%. Patients with lung‐only metastases, and those with a single extrapulmonary site of metastasis, had better survival compared with patients with two or more sites of metastatic disease ( p < .0001). In patients with ERMS and lung‐only metastases, there was no significant difference in survival between patients ≥10 years and 1–9 years (5‐year EFS: 58.3 vs. 68.2%, 5‐year OS: 66.7 vs. 67.7%). Conclusions With aggressive treatment, patients with ERMS and lung‐only metastatic disease have superior EFS and OS compared with patients with other sites of metastatic disease, even when older than 10 years of age. Consideration should be given to including patients ≥10 years with ERMS and lung‐only metastases in the same group as those <10 years in future risk stratification algorithms.

Abstract Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm of intermediate malignancy. We describe the largest cohort of IMT patients to date, aiming to further characterize this rare, poorly understood tumor. This is a multi‐institutional review of IMT patients ≤39 years, from 2000 to 2018, at 18 hospitals in the Pediatric Surgical Oncology Research Collaborative. One hundred and eighty‐two patients were identified with median age of 11 years. Thirty‐three percent of tumors were thoracic in origin. Presenting signs/symptoms included pain (29%), respiratory symptoms (25%) and constitutional symptoms (20%). Median tumor size was 3.9 cm. Anaplastic lymphoma kinase (ALK) overexpression was identified in 53% of patients. Seven percent of patients had distant disease at diagnosis. Ninety‐one percent of patients underwent resection: 14% received neoadjuvant treatment and 22% adjuvant treatment. Twelve percent of patients received an ALK inhibitor. Sixty‐six percent of surgical patients had complete resection, with 20% positive microscopic margins and 14% gross residual disease. Approximately 40% had en bloc resection of involved organs. Median follow‐up time was 36 months. Overall 5‐year survival was 95% and 5‐year event‐free survival was 80%. Predictors of recurrence included respiratory symptoms, tumor size and distant disease. Gross or microscopic margins were not associated with recurrence, suggesting that aggressive attempts at resection may not be warranted.

The NCCN Guidelines for Wilms Tumor focus on the screening, diagnosis, staging, treatment, and management of Wilms tumor (WT, also known as nephroblastoma). WT is the most common primary renal tumor in children. Five-year survival is more than 90% for children with all stages of favorable histology WT who receive appropriate treatment. All patients with WT should be managed by a multidisciplinary team with experience in managing renal tumors; consulting a pediatric oncologist is strongly encouraged. Treatment of WT includes surgery, neoadjuvant or adjuvant chemotherapy, and radiation therapy (RT) if needed. Careful use of available therapies is necessary to maximize cure and minimize long-term toxicities. This article discusses the NCCN Guidelines recommendations for favorable histology WT.

10024 Background: Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm of intermediate malignancy, predominantly seen in children and young adults. Given its rarity, data are limited. We describe the largest cohort of patients with IMT to date, with an aim to further characterize this poorly understood tumor. Methods: A multi-institutional review was performed at 18 North American hospitals participating in the Pediatric Surgical Oncology Research Collaborative to identify IMT patients ≤39 years, diagnosed from 2000-2018. Descriptive statistics are described as median and interquartile range. Multivariable analysis was used to identify predictors of event free survival (EFS). Results: 182 patients were identified with a median age of 11 years (5-17); 52% were female. 33% of tumors were thoracic, 26% abdominal/pelvic, 20% head/neck, and 14% genitourinary. Common presenting symptoms included pain (29%), respiratory symptoms (24%), weight loss (12%), and a palpable mass (10%). Median tumor size was 3.9 cm (1.9-6.5). Anaplastic lymphoma kinase (ALK) overexpression was identified via immunohistochemistry in 53% of patients tested. One third of patients had abnormal cytogenetics, with 12% of the entire cohort having an ALK mutation. 7% of patients had distant disease at diagnosis. 13% of patients received neoadjuvant therapy including chemotherapy (3%), ALK inhibitor (4%), radiation (0.5%), non-steroidal anti-inflammatories (NSAIDs) (7%), or steroids (2%). Of those who underwent resection with known margin status (n = 158), 66% had complete resection, 20% had microscopic positive margins, and 14% had gross residual disease. Just over 40% of patients had an en bloc resection of involved organs, most commonly lung (26%). 21% of patients received adjuvant therapy, including chemotherapy (3%), ALK inhibitor (9%), radiation (0.5%), NSAIDs (8%), or steroids (5%). 12% of all patients received an ALK inhibitor: 24% neoadjuvant, 62% adjuvant, and 14% without surgery. Median follow-up time was 36 months (14-69). Overall 5-year survival (OS) was 95% and 5-year EFS was 80%. Predictors of recurrence included respiratory symptoms, larger tumor size, or distant disease at diagnosis. Gender, race, age and primary site were not predictive of EFS. Likewise, there was no association of ALK overexpression or ALK mutation with EFS. The presence of gross or microscopic margins following resection was not associated with recurrence. Conclusions: IMT is a rare tumor with favorable OS. Five year recurrence rate was 20%. Presenting with respiratory symptoms, larger tumor size, or metastatic disease was associated with recurrence, while ALK positivity was not. Notably, a positive margin after resection was not associated with increased recurrence, indicating that aggressive attempts at surgical resection that would compromise form or function may not be warranted.