Long-term outcomes and patterns of relapse in patients with bilateral Wilms tumor or bilaterally predisposed unilateral Wilms tumor, a report from the COG AREN0534 study.

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.

Comparison of Outcomes Between Surveillance Ultrasound and Completion Lymph Node Dissection in Children and Adolescents With Sentinel Lymph Node-Positive Cutaneous Melanoma.

OBJECTIVE: To determine the impact of nodal basin ultrasound (US) surveillance versus completion lymph node dissection (CLND) in children and adolescents with sentinel lymph node (SLN) positive melanoma. BACKGROUND: Treatment for children and adolescents with melanoma are extrapolated from adult trials. However, there is increasing evidence that important clinical and biological differences exist between pediatric and adult melanoma. METHODS: Patients ≤18 years diagnosed with cutaneous melanoma between 2010 and 2020 from 14 pediatric hospitals were included. Data extracted included demographics, histopathology, nodal basin strategies, surveillance intervals, and survival information. RESULTS: Of 252 patients, 90.1% (n=227) underwent SLN biopsy (SLNB), 50.9% (n=115) had at least 1 positive node. A total of 67 patients underwent CLND with 97.0% (n=65/67) performed after a positive SLNB. In contrast, 46 total patients underwent US observation of nodal basins with 78.3% (n=36/46) of these occurring after positive SLNB. Younger patients were more likely to undergo US surveillance (median age 8.5 y) than CLND (median age 11.3 y; P =0.0103). Overall, 8.9% (n=21/235) experienced disease recurrence: 6 primary, 6 nodal, and 9 distant. There was no difference in recurrence (11.1% vs 18.8%; P =0.28) or death from disease (2.2% vs 9.7%; P =0.36) for those who underwent US versus CLND, respectively. CONCLUSIONS: Children and adolescents with cutaneous melanoma frequently have nodal metastases identified by SLN. Recurrence was more common among patients with thicker primary lesions and positive SLN. No significant differences in oncologic outcomes were observed with US surveillance and CLND following the identification of a positive SLN.

Management and Outcomes of Wilms Tumor With Suprarenal Intravascular Extension: A Pediatric Surgical Oncology Research Collaborative Study.

OBJECTIVE: The purpose of this study was to describe management and outcomes from a contemporary cohort of children with Wilms tumor complicated by inferior vena caval thrombus. BACKGROUND: The largest series of these patients was published almost 2 decades ago. Since then, neoadjuvant chemotherapy has been commonly used to manage these patients, and outcomes have not been reported. METHODS: Retrospective review of 19 North American centers between 2009 and 2019. Patient and disease characteristics, management, and outcomes were investigated and analyzed. RESULTS: Of 124 patients, 81% had favorable histology (FH), and 52% were stage IV. IVC thrombus level was infrahepatic in 53 (43%), intrahepatic in 32 (26%), suprahepatic in 14 (11%), and cardiac in 24 (19%). Neoadjuvant chemotherapy using a 3-drug regimen was administered in 82% and postresection radiation in 90%. Thrombus level regression was 45% overall, with suprahepatic level showing the best response (62%). Cardiopulmonary bypass (CPB) was potentially avoided in 67%. The perioperative complication rate was significantly lower after neoadjuvant chemotherapy [(25%) vs upfront surgery (55%); P =0.005]. CPB was not associated with higher complications [CPB (50%) vs no CPB (27%); P =0.08]. Two-year event-free survival was 93% and overall survival was 96%, higher in FH cases (FH 98% vs unfavorable histology/anaplastic 82%; P =0.73). Neither incomplete resection nor viable thrombus cells affected event-free survival or overall survival. CONCLUSIONS: Multimodal therapy resulted in excellent outcomes, even with advanced-stage disease and cardiac extension. Neoadjuvant chemotherapy decreased the need for CPB to facilitate resection. Complete thrombectomy may not always be necessary.

Neuroblastoma, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

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.

Variability in Surveillance Strategies Following Resection of Sacrococcygeal Teratoma.

INTRODUCTION: Surveillance following sacrococcygeal teratoma (SCT) resection varies. The purpose of this study was to describe the clinical characteristics and outcomes of patients undergoing SCT resection and examine current institutional practices to detect recurrence. METHODS: A single-institution retrospective review of children who underwent resection of an SCT from January 1, 2010 to December 31, 2020 was performed. Data were summarized and surveillance strategies compared between histopathologic subtypes using nonparametric methods. RESULTS: Thirty six patients (75.0% female) underwent SCT removal at a median age of 8 d. Histopathology revealed 27 mature teratomas (75.0%), eight immature teratomas (22.2%), and one malignant germ cell tumor (2.8%). Median postoperative follow-up was 3.17 y (interquartile range [IQR]: 2.31-4.38 y). Patients had a median of 2.32 clinic visits per year (IQR: 2.00-2.70), alpha-fetoprotein levels were obtained at a median of 2.01 times per year (IQR: 0-1.66), and surveillance imaging was performed at a median of 2.31 times per year (IQR: 0-2.84). Patients with immature teratomas had alpha-fetoprotein laboratories obtained more frequently than patients with mature teratomas (3.10 times/year versus 0.93 times/year, P = 0.001). There was no significant difference in the number of imaging studies obtained between groups. Two patients (5.6%) developed recurrence, which were identified on magnetic resonance imaging at 191 and 104 d postresection, respectively. CONCLUSIONS: Postoperative surveillance practices varied widely. Recurrence was noted in a single malignant case in the first year following resection. Multi-institutional studies are needed to determine the optimal surveillance strategy to detect recurrence of SCT.

Minimally invasive and robotic-assisted approaches applied to pediatric surgical oncology.

The management of pediatric tumors is complex, with surgery, chemotherapy, and radiotherapy being cornerstones in their treatment. Tumor removal is increasingly performed by a minimally invasive approach, which allows for quicker postoperative recovery and less postoperative pain. The goal of this report is to give an overview of minimally invasive surgical approaches for common pediatric tumors, with a focus on technical considerations and postoperative outcomes.

Oncofertility care for children, adolescents, and young adults at risk for treatment-related fertility loss.

As therapy for childhood malignancies becomes more sophisticated and survival has improved, long-term therapy-related sequelae have emerged. Loss of reproductive potential among childhood cancer survivors is one such concern that has become increasingly recognized among patients, families, and healthcare providers. The risk status for infertility based upon therapy received, state of current reproductive technology and outcomes, and an emphasis on adequate referral and counseling for fertility preservation options are reviewed. Contributing factors to infertility are discussed, and options for female and male preservation based upon age and pubertal status are summarized. This article highlights the current state of fertility opportunities for children and adolescents undergoing therapy for cancer. Providers caring for these young patients should be familiar with such options and should routinely initiate evaluations for eligibility of fertility preservation.

Rare tumors II: Adrenocortical tumors, neuroendocrine tumors of the appendix, pheochromocytoma and paraganglioma, pancreatoblastoma and solid pseudopapillary tumors of the pancreas.

Very rare tumors are usually divided into two groups: One includes tumors that are rare among both children and adults; the other one encompasses tumors that frequently occur in adults but are rarely observed in children. In this review, we focus on adrenocortical tumors, neuroendocrine tumors of the appendix, pheochromocytoma and paraganglioma, pancreatoblastoma and solid pseudopapillary tumors of the pancreas, with special attention to the role of surgery as main curative intervention or as part of the multimodal treatment.

Surgical management of rare tumors (Part 1).

With an annual cumulative occurrence of approximately 15,000 in North America, all childhood cancers are rare. Very rare cancers as defined by both the European Cooperative Study Group for Rare Pediatric Cancers and the Children's Oncology Group fall into two principal categories: those so uncommon (fewer than 2 cases/million) that their study is challenging even through cooperative group efforts (e.g., pleuropulmonary blastoma and desmoplastic small round cell tumor) and those that are far more common in adults and therefore rarely studied in children (e.g., thyroid, melanoma, and gastrointestinal stromal tumor). Treatment strategies for these latter tumors are typically based on adult guidelines, although the pediatric variants of these tumors may harbor different genetic signatures and demonstrate different behavior. If melanoma and differentiated thyroid cancer are excluded, other rare cancer types account for only 2% of the cancers in children aged 0 to 14. This article highlights several of the most common rare tumor types.

Bilateral Wilms tumor with anaplasia: A report from the Children's Oncology Group Study AREN0534.

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.

Survival outcomes in pediatric patients with metastatic Ewing sarcoma who achieve a rapid complete response of pulmonary metastases.

PURPOSE: Our objectives were to compare overall survival (OS) and pulmonary relapse between patients with metastatic Ewing sarcoma (EWS) at diagnosis who achieve rapid complete response (RCR) and those with residual pulmonary nodules after induction chemotherapy (non-RCR). PATIENTS AND METHODS: This retrospective cohort study included children under 20 years with metastatic EWS treated from 2007 to 2020 at 19 institutions in the Pediatric Surgical Oncology Research Collaborative. Chi-square tests were conducted for differences among groups. Kaplan-Meier curves were generated for OS and pulmonary relapse. RESULTS: Among 148 patients with metastatic EWS at diagnosis, 61 (41.2%) achieved RCR. Five-year OS was 71.2% for patients who achieved RCR, and 50.2% for those without RCR (p = .04), and in multivariable regression among patients with isolated pulmonary metastases, RCR (hazards ratio [HR] 0.42; 95% confidence interval [CI]: 0.17-0.99) and whole lung irradiation (WLI) (HR 0.35; 95% CI: 0.16-0.77) were associated with improved survival. Pulmonary relapse occurred in 57 (37%) patients, including 18 (29%) in the RCR and 36 (41%) in the non-RCR groups (p = .14). Five-year pulmonary relapse rates did not significantly differ based on RCR (33.0%) versus non-RCR (47.0%, p = .13), or WLI (38.8%) versus no WLI (46.0%, p = .32). DISCUSSION: Patients with EWS who had isolated pulmonary metastases at diagnosis had improved OS if they achieved RCR and received WLI, despite having no significant differences in rates of pulmonary relapse.

Point-of-Care Lung Ultrasound to Evaluate Lung Isolation During One-Lung Ventilation in Children: A Blinded Observational Feasibility Study.

BACKGROUND: Minimally invasive thoracic surgical techniques require effective lung isolation using one-lung ventilation (OLV). Verification of lung isolation may be confirmed by auscultation, visual confirmation using fiberoptic bronchoscopy (FOB), or more recently, point-of-care ultrasound (POCUS). The aim of this study was to prospectively compare lung ultrasound with clinical auscultation to confirm OLV before thoracic surgery in pediatric patients. METHODS: This prospectively blinded feasibility study included 40 patients ranging in age from 0 to 20 years. After confirmation of lung separation by the primary anesthesia team using FOB, the sonographer and the auscultator, both blinded to the laterality of surgery and lung separation, entered the operating room. The sonographer evaluated for pleural lung sliding and the auscultator listened for breath sounds. Successful lung separation was definitively confirmed by direct visualization of lung collapse during the operation. RESULTS: In confirming effective single-lung ventilation, lung ultrasound had a diagnostic accuracy of 95% (95% confidence interval [CI], 82.7%-98.5%). In contrast, auscultation could only reliably confirm lung isolation with 68% accuracy (95% CI, 51.5%-80.4%). The McNemar test showed a statistically significant difference between the use of lung ultrasound and auscultation (P < .001). The median time to perform ultrasonography was 67 seconds (interquartile range [IQR], 46-142) and the median time to perform auscultation was 21 seconds (IQR, 10-32). CONCLUSIONS: Based on the initial results of our feasibility trial, lung ultrasound proved to be a fast and reliable method to verify single-lung ventilation in pediatric patients presenting for thoracic surgery with a high degree of diagnostic accuracy.

The varied spectrum of nephroblastomatosis, nephrogenic rests, and Wilms tumors: Review of current definitions and challenges of the field.

The diagnosis of multiple or diffuse renal lesions in a child is challenging by imaging and/or pathology. Optimal management requires distinguishing benign lesions such as nephrogenic rests from cancerous lesions such as Wilms tumor, but this is often difficult or impossible. This difficulty is compounded by the overlapping nature of our current radiologic and pathologic definitions of lesions along the spectrum of nephrogenic rests/nephroblastomatosis. We provide a review of these issues, as a collaborative effort between the Children's Oncology Group Renal Tumor Committee and International Society of Pediatric Oncology Renal Tumor Study Group. Our aim is to discuss current challenges in diagnosis and management of these renal lesions, encouraging future work toward consensus definitions for research and patient care.

Children's Oncology Group's 2023 blueprint for research: Renal tumors.

Every year, approximately 600 infants, children, and adolescents are diagnosed with renal cancer in the United States. In addition to Wilms tumor (WT), which accounts for about 80% of all pediatric renal cancers, clear cell sarcoma of the kidney, renal cell carcinoma, malignant rhabdoid tumor, as well as more rare cancers (other sarcomas, rare carcinomas, lymphoma) and benign tumors can originate within the kidney. WT itself can be divided into favorable histology (FHWT), with a 5-year overall survival (OS) exceeding 90%, and anaplastic histology, with 4-year OS of 73.7%. Outcomes of the other pediatric renal cancers include clear cell sarcoma (5-year OS: 90%), malignant rhabdoid tumor (5-year OS: 10% for stages 3 and 4), and renal cell carcinoma (4-year OS: 84.8%). Recent clinical trials have identified novel biological prognostic markers for FHWT, and a series of Children's Oncology Group (COG) trials have demonstrated improving outcomes with therapy modification, and opportunities for further care refinement.

Multi-institutional assessment of the prevalence of neuroendocrine tumors in children undergoing laparoscopic appendectomy for acute appendicitis in the United States.

As non-operative management of acute appendicitis in children has become more common, missed incidental appendiceal pathology can be an unintended consequence. We assessed the prevalence of neuroendocrine tumors in appendectomy specimens from eight US children's hospitals from 2012 to 2021. The prevalence of neuroendocrine tumors (NET) was found to be 1:271, with a median age of 14 years and 62% female. Most tumors were small (median 6 mm; interquartile range [IQR]: 3-10), and no recurrence was noted during the follow-up period (median 22.5 months; IQR: 3-53). The possibility of delayed diagnosis of these tumors should be part of the discussion for non-operative management of pediatric acute appendicitis.

Reducing Unnecessary Oophorectomies for Benign Ovarian Neoplasms in Pediatric Patients.

Importance: Although most ovarian masses in children and adolescents are benign, many are managed with oophorectomy, which may be unnecessary and can have lifelong negative effects on health. Objective: To evaluate the ability of a consensus-based preoperative risk stratification algorithm to discriminate between benign and malignant ovarian pathology and decrease unnecessary oophorectomies. Design, Setting, and Participants: Pre/post interventional study of a risk stratification algorithm in patients aged 6 to 21 years undergoing surgery for an ovarian mass in an inpatient setting in 11 children's hospitals in the United States between August 2018 and January 2021, with 1-year follow-up. Intervention: Implementation of a consensus-based, preoperative risk stratification algorithm with 6 months of preintervention assessment, 6 months of intervention adoption, and 18 months of intervention. The intervention adoption cohort was excluded from statistical comparisons. Main Outcomes and Measures: Unnecessary oophorectomies, defined as oophorectomy for a benign ovarian neoplasm based on final pathology or mass resolution. Results: A total of 519 patients with a median age of 15.1 (IQR, 13.0-16.8) years were included in 3 phases: 96 in the preintervention phase (median age, 15.4 [IQR, 13.4-17.2] years; 11.5% non-Hispanic Black; 68.8% non-Hispanic White); 105 in the adoption phase; and 318 in the intervention phase (median age, 15.0 [IQR, 12.9-16.6)] years; 13.8% non-Hispanic Black; 53.5% non-Hispanic White). Benign disease was present in 93 (96.9%) in the preintervention cohort and 298 (93.7%) in the intervention cohort. The percentage of unnecessary oophorectomies decreased from 16.1% (15/93) preintervention to 8.4% (25/298) during the intervention (absolute reduction, 7.7% [95% CI, 0.4%-15.9%]; P = .03). Algorithm test performance for identifying benign lesions in the intervention cohort resulted in a sensitivity of 91.6% (95% CI, 88.5%-94.8%), a specificity of 90.0% (95% CI, 76.9%-100%), a positive predictive value of 99.3% (95% CI, 98.3%-100%), and a negative predictive value of 41.9% (95% CI, 27.1%-56.6%). The proportion of misclassification in the intervention phase (malignant disease treated with ovary-sparing surgery) was 0.7%. Algorithm adherence during the intervention phase was 95.0%, with fidelity of 81.8%. Conclusions and Relevance: Unnecessary oophorectomies decreased with use of a preoperative risk stratification algorithm to identify lesions with a high likelihood of benign pathology that are appropriate for ovary-sparing surgery. Adoption of this algorithm might prevent unnecessary oophorectomy during adolescence and its lifelong consequences. Further studies are needed to determine barriers to algorithm adherence.

Histologic type predicts disparate outcomes in pediatric hepatocellular neoplasms: A Pediatric Surgical Oncology Research Collaborative study.

BACKGROUND: Hepatocellular carcinoma (HCC) is a rare cancer in children, with various histologic subtypes and a paucity of data to guide clinical management and predict prognosis. METHODS: A multi-institutional review of children with hepatocellular neoplasms was performed, including demographic, staging, treatment, and outcomes data. Patients were categorized as having conventional HCC (cHCC) with or without underlying liver disease, fibrolamellar carcinoma (FLC), and hepatoblastoma with HCC features (HB-HCC). Univariate and multivariate analyses identified predictors of mortality and relapse. RESULTS: In total, 262 children were identified; and an institutional histologic review revealed 110 cHCCs (42%; 69 normal background liver, 34 inflammatory/cirrhotic, 7 unknown), 119 FLCs (45%), and 33 HB-HCCs (12%). The authors observed notable differences in presentation and behavior among tumor subtypes, including increased lymph node involvement in FLC and higher stage in cHCC. Factors associated with mortality included cHCC (hazard ratio [HR], 1.63; P = .038), elevated α-fetoprotein (HR, 3.1; P = .014), multifocality (HR, 2.4; P < .001), and PRETEXT (pretreatment extent of disease) stage IV (HR, 5.76; P < .001). Multivariate analysis identified increased mortality in cHCC versus FLC (HR, 2.2; P = .004) and in unresectable tumors (HR, 3.4; P < .001). Disease-free status at any point predicted survival. CONCLUSIONS: This multi-institutional, detailed data set allowed a comprehensive analysis of outcomes for children with these rare hepatocellular neoplasms. The current data demonstrated that pediatric HCC subtypes are not equivalent entities because FLC and cHCC have distinct anatomic patterns and outcomes in concert with their known molecular differences. This data set will be further used to elucidate the impact of histology on specific treatment responses, with the goal of designing risk-stratified algorithms for children with HCC. LAY SUMMARY: This is the largest reported granular data set on children with hepatocellular carcinoma. The study evaluates different subtypes of hepatocellular carcinoma and identifies key differences between subtypes. This information is pivotal in improving understanding of these rare cancers and may be used to improve clinical management and subsequent outcome in children with these rare malignancies.

Implications of Tumor Characteristics and Treatment Modality on Local Recurrence and Functional Outcomes in Children With Chest Wall Sarcoma: A Pediatric Surgical Oncology Research Collaborative Study.

OBJECTIVE: To determine the impact of tumor characteristics and treatment approach on (1) local recurrence, (2) scoliosis development, and (3) patient-reported quality of life in children with sarcoma of the chest wall. SUMMARY OF BACKGROUND DATA: Children with chest wall sarcoma require multimodal therapy including chemotherapy, surgery, and/or radiation. Despite aggressive therapy which places them at risk for functional impairment and scoliosis, these patients are also at significant risk for local recurrence. METHODS: A multi-institutional review of 175 children (median age 13 years) with chest wall sarcoma treated at seventeen Pediatric Surgical Oncology Research Collaborative institutions between 2008 and 2017 was performed. Patient-reported quality of life was assessed prospectively using PROMIS surveys. RESULTS: The most common diagnoses were Ewing sarcoma (67%) and osteosarcoma (9%). Surgical resection was performed in 85% and radiation in 55%. A median of 2 ribs were resected (interquartile range = 1-3), and number of ribs resected did not correlate with margin status ( P = 0.36). Local recurrence occurred in 23% and margin status was the only predictive factor(HR 2.24, P = 0.039). With a median follow-up of 5 years, 13% developed scoliosis (median Cobb angle 26) and 5% required corrective spine surgery. Scoliosis was associated with posteriorrib resection (HR 8.43; P= 0.003) and increased number of ribs resected (HR 1.78; P = 0.02). Overall, patient-reported quality of life is not impaired after chest wall tumor resection. CONCLUSIONS: Local recurrence occurs in one-quarter of children with chest wall sarcoma and is independent of tumor type. Scoliosis occurs in 13% of patients, but patient-reported quality of life is excellent.

Gastroblastoma with a novel EWSR1-CTBP1 fusion presenting in adolescence.

Gastroblastomas are rare tumors with a biphasic epithelioid/spindle cell morphology that typically present in early adulthood and have recurrent MALAT1-GLI1 fusions. We describe an adolescent patient with Wiskott-Aldrich syndrome who presented with a large submucosal gastric tumor with biphasic morphology. Despite histologic features consistent with gastroblastoma, a MALAT1-GLI1 fusion was not found in this patient's tumor; instead, comprehensive molecular profiling identified a novel EWSR1-CTBP1 fusion and no other significant genetic alterations. The tumor also overexpressed NOTCH and FGFR by RNA profiling. The novel fusion and expression profile suggest a role for epithelial-mesenchymal transition in this tumor, with potential implications for the pathogenesis of biphasic gastric tumors such as gastroblastoma.

Thoracoscopy vs thoracotomy for the management of metastatic osteosarcoma: A Pediatric Surgical Oncology Research Collaborative Study.

Complete surgical resection of pulmonary metastatic disease in patients with osteosarcoma is crucial to long-term survival. Open thoracotomy allows palpation of nodules not identified on imaging but the impact on survival is unknown. The objective of this study was to compare overall survival (OS) and pulmonary disease-free survival (DFS) in children who underwent thoracotomy vs thoracoscopic surgery for pulmonary metastasectomy. A multi-institutional collaborative group retrospectively reviewed 202 pediatric patients with osteosarcoma who underwent pulmonary metastasectomy by thoracotomy (n = 154) or thoracoscopy (n = 48). Results were analyzed by Kaplan-Meier survival estimates and multivariate Cox proportional hazard regression models. With median follow-up of 45 months, 135 (67.5%) patients had a pulmonary relapse and 95 (47%) patients were deceased. Kaplan-Meier analysis showed no significant difference in 5-year pulmonary DFS (25% vs 38%; P = .18) or OS (49% vs 42%, P = .37) between the surgical approaches of thoracotomy and thoracoscopy. In Cox regression analysis controlling for other factors impacting outcome, there was a significantly increased risk of mortality (HR 2.11; P = .027; 95% CI 1.09-4.09) but not pulmonary recurrence (HR 0.96; P = .90; 95% CI 0.52-1.79) with a thoracoscopic approach. However, in the subset analysis limited to patients with oligometastatic disease, thoracoscopy had no increased risk of mortality (HR 1.16; P = .62; 0.64-2.11). In conclusion, patients with metastatic osteosarcoma and limited pulmonary disease burden demonstrate comparable outcomes after thoracotomy and thoracoscopy for metastasectomy. While significant selection bias in these surgical cohorts limits the generalizability of the conclusions, clinical equipoise for a randomized clinical trial in patients with oligometastatic disease is supported.