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Background: The International Neuroblastoma Risk Group (INRG) classifier utilizes a staging system based on pretreatment imaging criteria in which image-defined risk factors (IDRFs) are used to evaluate the extent of locoregional disease. Children's Oncology Group (COG) study ANBL0531 prospectively examined institutional determination of IDRF status and compared that to a standardized central review., Methods: Between 9/2009-6/2011, patients with intermediate-risk neuroblastoma were enrolled on ANBL0531 and had IDRF assessment at treating institutions. Paired COG pediatric surgeons and radiologists performed blinded central review of diagnostic imaging for the presence or absence of IDRFs. Second blinded review was performed in cases of discordance. Comparison of local and central review was performed using the Kappa coefficient to determine concordance in IDRF assessment., Results: 211 patients enrolled in ANBL0531 underwent IDRF assessment; 3 patients were excluded due to poor image quality. Central reviewer pairs agreed on the presence or absence of any IDRF in 170/208 (81.7%; κ = 0.48) cases. Thirteen (6.3%) cases could not be adjudicated after second blinded review. Radiologists were more likely to identify IRDFs as present than surgeons (p < 0.001). Local and central reviewers agreed on the presence or absence of any IDRF in only108/208 (51.9%; κ = 0.06) cases., Conclusions: Among experienced pediatric surgeons and radiologists participating in central review, concordance was moderate, with agreement in 81.7% of cases. On comparison of local and central assessment of IDRFs, concordance was poor. These data indicate that greater standardization, education, technology, and training are needed to improve the assessment of IDRFs in children with neuroblastoma., Level of Evidence: Treatment Study, Level III., Competing Interests: Conflict of interset Author AN serves on a data safety monitoring board for Novartis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: National Wilms Tumor Study-5 (NWTS-5) and AREN0321 evaluated the outcomes of children with rhabdoid tumor of the kidney (RTK) and malignant rhabdoid tumor of soft tissues (MRT)., Patients and Methods: Eligible patients with RTK were enrolled prospectively on NWTS-5 (1995-2002) and treated with carboplatin and etoposide alternating with cyclophosphamide (Regimen RTK). Patients with RTK or MRT were enrolled on AREN0321 (2005-2012) and received vincristine, doxorubicin, and cyclophosphamide alternating with carboplatin, cyclophosphamide, and etoposide (Regimens UH-1 or dose-reduced Revised UH-1). We report event-free survival (EFS) and overall survival (OS) from each study., Results: Thirty patients received Regimen RTK on NWTS-5; on AREN0321, 20 received UH-1 and 19 received Revised UH-1. Patient and disease characteristics were statistically similar between studies. Patients on AREN0321 had significantly improved EFS and OS compared to those on NWTS-5 (4-year EFS = 23.1% vs. 16.7%; p = 0.020; 4-year OS = 30.6% vs. 20.0%; p = 0.014), mostly driven by patients with Stage I/II disease (p = 0.05). Median time to an event was 3.6 months on NWTS-5 compared to 7.2 months on AREN0321. There were no differences in EFS or OS by revised versus original Regimen UH-1 on AREN0321, or by renal versus extra-renal primary disease when the studies were pooled., Conclusions: The more intensive treatment regimen used on AREN0321 improved EFS and OS overall, a result driven by patients with Stage I/II disease. Despite this improvement, outcomes for patients with rhabdoid tumor remain unsatisfactory and there is a need for novel therapeutic strategies., (© 2024 Wiley Periodicals LLC.)

Background: An objective of the Children's Oncology Group AREN0534 Study was to improve the survival of patients with bilateral Wilms tumors (BWT) by using preoperative chemotherapy of limited duration and tailoring postoperative therapy based on histopathologic response. The authors report outcomes based on postoperative histopathologic responses., Methods: Patients with BWT received treatment with vincristine, dactinomycin, and doxorubicin for 6 or 12 weeks followed by surgery. Postoperative therapy was prescribed based on the highest risk tumor according to the International Society of Pediatric Oncology classification and the Children's Oncology Group staging system., Results: Analyses were performed on data from 180 evaluable children. The 4-year event-free survival (EFS) and overall survival (OS) rates were 81% (95% CI, 74%-87%) and 95% (95% CI, 91%-99%), respectively. Seven patients who had completely necrotic tumors had a 4-year EFS rate of 100%. Of 118 patients who had tumors with intermediate-risk histopathology, the 4-year EFS and OS rates were 82% (95% CI, 74%-90%) and 97% (95% CI, 94%-100%), respectively. Fourteen patients who had blastemal-type tumors had 4-year EFS and OS rates of 79% (95% CI, 56%-100%) and 93% (95% CI, 79%-100%), respectively. Eighteen patients who had diffuse anaplasia had 4-year EFS and OS rates of 61% (95% CI, 35%-88%) and 72% (95% CI, 47%-97%), respectively; and the 4-year EFS and OS rates of 7 patients who had focal anaplasia were 71% (95% CI, 38%-100%) and 100%, respectively. There was no difference in the outcomes of patients who had different histopathologic subtypes within the intermediate-risk group (P = .54)., Conclusions: A risk-adapted treatment approach for BWT results in excellent outcomes. This approach was not successful in improving the outcome of patients who had diffuse anaplasia., (© 2022 American Cancer Society.)

Introduction: Diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) represents a unique category of nephroblastomatosis. Treatment has ranged from observation to multiple regimens of chemotherapy. Wilms tumors (WTs) develop in 100% of untreated patients and between 32 and 52% of treated patients. Renal preservation rates have not been previously reported. An aim of the Children's Oncology Group (COG) study AREN0534 was to prospectively evaluate the efficacy of chemotherapy in preserving renal units and preventing WT development in children with DHPLN., Methods: Patients were enrolled through the COG protocol AREN03B2 with central radiological review. DHPLN was defined as the cortical surface of the kidney being composed of hyperplastic rests, with the entire nephrogenic zone involved, and with a thick rind capping all of one or both kidneys. Treatment was with vincristine and dactinomycin (regimen EE4A), with cross-sectional imaging at weeks 6 and 12. If the patient's disease was stable or decreasing, treatment was continued for 19 weeks. Renal preservation, WT development rates at 1 year, and overall survival (OS) are reported., Results: Nine patients were enrolled (five females and four males), with a median age at enrollment of 10.22 months (range 2.92-29.11). One patient who was enrolled was deemed unevaluable because they did not meet the radiological criteria for DHPLN, resulting in eight evaluable patients. These eight patients had DHPLN confirmed via radiological criteria (all bilateral). Initial chemotherapy was EE4A for all eight patients, with seven of eight patients starting chemotherapy without tissue diagnosis.One patient who had an upfront partial nephrectomy was found to have DHPLN in the specimen and was subsequently treated with EE4A. All patients remained alive, with a median follow-up of 6.6 years (range 4.5-9.1). No patients were anephric; 14 of 16 kidneys were functioning (87.5%). Six of eight patients (75%) did not have WT on therapy, but two of these patients relapsed within 6 months of stopping therapy; both had favorable histology WT. One patient who was diagnosed with WT on therapy relapsed at 12 months (one of eight [12.5%]) and developed anaplastic histology., Conclusions: Chemotherapy for patients with DHPLN was effective in preserving kidney function. Five-year OS is excellent, however the ideal type and duration of chemotherapy to prevent WT development remains elusive., (© 2022. Society of Surgical Oncology.)

Background: A primary objective of Children's Oncology Group study AREN0534 (Treatment for Patients With Multicentric or Bilaterally Predisposed, Unilateral Wilms Tumor) was to facilitate partial nephrectomy in 25% of children with bilaterally predisposed unilateral tumors (Wilms tumor/aniridia/genitourinary anomalies/range of developmental delays [WAGR] syndrome; and multifocal and overgrowth syndromes). The purpose of this prospective study was to achieve excellent event-free survival (EFS) and overall survival (OS) while preserving renal tissue through preoperative chemotherapy, completing definitive surgery by 12 weeks from diagnosis, and modifying postoperative chemotherapy based on histologic response., Methods: The treating institution identified whether a predisposition syndrome existed. Patients underwent a central review of imaging studies through the biology and classification study AREN03B2 and then were eligible to enroll on AREN0534. Patients were treated with induction chemotherapy determined by localized or metastatic disease on imaging (and histology if a biopsy had been undertaken). Surgery was based on radiographic response at 6 or 12 weeks. Further chemotherapy was determined by histology. Patients who had stage III or IV disease with favorable histology received radiotherapy as well as those who had stage I through IV anaplasia., Results: In total, 34 patients were evaluable, including 13 males and 21 females with a mean age at diagnosis of 2.79 years (range, 0.49-8.78 years). The median follow-up was 4.49 years (range, 1.67-8.01 years). The underlying diagnosis included Beckwith-Wiedemann syndrome in 9 patients, hemihypertrophy in 9 patients, multicentric tumors in 10 patients, WAGR syndrome in 2 patients, a solitary kidney in 2 patients, Denys-Drash syndrome in 1 patient, and Simpson-Golabi-Behmel syndrome in 1 patient. The 4-year EFS and OS rates were 94% (95% CI, 85.2%-100%) and 100%, respectively. Two patients relapsed (1 tumor bed, 1 abdomen), and none had disease progression during induction. According to Response Evaluation Criteria in Solid Tumor 1.1 criteria, radiographic responses included a complete response in 2 patients, a partial response in 21 patients, stable disease in 11 patients, and progressive disease in 0 patients. Posttherapy histologic classification was low-risk in 13 patients (including the 2 complete responders), intermediate-risk in 15 patients, and high-risk in 6 patients (1 focal anaplasia and 5 blastemal subtype). Prenephrectomy chemotherapy facilitated renal preservation in 22 of 34 patients (65%)., Conclusions: A standardized approach of preoperative chemotherapy, surgical resection within 12 weeks, and histology-based postoperative chemotherapy results in excellent EFS, OS, and preservation of renal parenchyma., (© 2020 American Cancer Society.)

Purpose: AREN0321 evaluated the activity of vincristine and irinotecan (VI) in patients with newly diagnosed diffuse anaplastic Wilms tumor (DAWT) and whether a regimen containing carboplatin (regimen UH1) in addition to regimen I agents used in the National Wilms Tumor Study 5 (NWTS-5; vincristine, doxorubicin, cyclophosphamide, and etoposide plus radiotherapy) would improve patient outcomes., Patients and Methods: Patients with stage II to IV DAWT without measurable disease received regimen UH1. Patients with stage IV measurable disease were eligible to receive VI (vincristine, 1.5 mg/m 2 per day intravenously on days 1 and 8; irinotecan, 20 mg/m 2 per day intravenously on days 1-5 and 8-12 of a 21-day cycle) in an upfront window; those with complete (CR) or partial response (PR) had VI incorporated into regimen UH1 (regimen UH2). The study was designed to detect improvement in outcomes of patients with stage II to IV DAWT compared with historical controls treated with regimen I., Results: Sixty-six eligible patients were enrolled. Of 14 patients with stage IV measurable disease who received VI, 11 (79%) achieved CR (n = 1) or PR (n = 10) after 2 cycles. Doses of doxorubicin, cyclophosphamide, and etoposide were reduced midstudy because of nonhematologic toxicity. Four patients (6%) died as a result of toxicity. Four-year event-free survival, relapse-free survival, and overall survival rates were 67.7% (95% CI, 55.9% to 79.4%), 72.9% (95% CI, 61.5% to 84.4%), and 73.7% (95% CI, 62.7% to 84.8%), respectively, compared with 57.5% (95% CI, 47.6% to 67.4%; P = .26), 57.5% (95% CI, 47.6% to 67.4%; P = .048), and 59.2% (95% CI, 49.4% to 69.0%; P = .08), respectively, in NWTS-5., Conclusion: VI produced a high response rate in patients with metastatic DAWT. AREN0321 treatment seemed to improve outcomes for patients with stage II to IV DAWT compared with NWTS-5, but with increased toxicity. The UH2 regimen warrants further investigation with modifications to reduce toxicity.

OBJECTIVE. Distinguishing nephrogenic rests from small Wilms tumors can be challenging. This retrospective study was performed to determine if imaging characteristics can be used to distinguish nephrogenic rests from Wilms tumors. MATERIALS AND METHODS. All cases of pathologically confirmed nephrogenic rests and Wilms tumors smaller than 5 cm in maximum dimension on imaging in patients younger than 5 years old were identified from the Children's Oncology Group AREN03B2 study (July 2006-August 2016). Exclusion criteria were chemotherapy before pathologic evaluation or more than 30 days between imaging and surgery; in addition, patients with nephrogenic rests occurring within or juxtaposed to a Wilms tumor and patients with diffuse hyperplastic perilobar nephroblastomatosis were excluded. Two radiologists who were blinded to pathology results assessed all lesions. The two-sample t test was used for continuous variables, and the Fisher exact test was used for categoric variables. ROC analysis was performed to determine the optimal size cutoff for distinguishing between nephrogenic rests and Wilms tumors. RESULTS. Thirty-one pathologically confirmed rests (20 perilobar, 11 intralobar) and 26 Wilms tumors smaller than 5 cm met the eligibility criteria for study inclusion. The median diameter of the nephrogenic rests was 1.3 cm (range, 0.7-3.4 cm) and the median diameter of the Wilms tumor was 3.2 cm (range, 1.8-4.9 cm) ( p < 0.001). Imaging findings supportive of Wilms tumors were spherical ( p < 0.001) and exophytic ( p < 0.001) lesions. Perilobar rests (17/20) were more likely to be homogeneous than intralobar rests (3/11) or Wilms tumor (3/26) ( p < 0.001). ROC analysis showed that the optimal size cutoff for distinguishing between nephrogenic rests and Wilms tumors was 1.75 cm. CONCLUSION. In children younger than 5 years old, the diagnosis of a Wilms tumor should be favored over a nephrogenic rest when a renal mass is spherical, exophytic, or larger than 1.75 cm. Homogeneity favors the diagnosis of perilobar nephrogenic rests, whereas intralobar rests and Wilms tumors are more likely to be inhomogeneous.

Wilms tumor is the most common pediatric renal tumor, accounting for approximately 7% of all childhood cancers. Imaging plays an important role in the detection, staging, post-therapy evaluation and surveillance of Wilms tumor. Wilms tumor can be detected during surveillance of a known cancer predisposition or after a child presents with symptoms. In this manuscript we describe an evidence-based approach to the initial evaluation of Wilms tumor using current guidelines from the Children's Oncology Group (COG). We illustrate the COG staging system for pediatric renal tumors and highlight key imaging findings that are critical for surgical management. We also discuss the controversies regarding detection and significance of <5-mm pulmonary nodules at initial staging. And finally, we present some thoughts regarding surveillance of Wilms tumor, where overall survival has now approached 90%.

Background The National Wilms Tumor Study (NWTS) approach to treating stage III favorable-histology Wilms tumor (FHWT) is Regimen DD4A (vincristine, dactinomycin, and doxorubicin) and radiation therapy. Further risk stratification is required to improve outcomes and reduce late effects. We evaluated clinical and biologic variables for patients with stage III FHWT without combined loss of heterozygosity (LOH) at chromosomes 1p and 16q treated in the Children's Oncology Group protocol AREN0532. Methods From October 2006 to August 2013, 588 prospectively treated, centrally reviewed patients with stage III FHWT were treated with Regimen DD4A and radiation therapy. Tumor LOH at 1p and 16q was determined by microsatellite analysis. Ineligible patients (n = 5) and those with combined LOH 1p/16q (n = 40) were excluded. Results A total of 535 patients with stage III disease were studied. Median follow-up was 5.2 years (range, 0.2 to 9.5). Four-year event-free survival (EFS) and overall survival estimates were 88% (95% CI, 85% to 91%) and 97% (95% CI, 95% to 99%), respectively. A total of 58 of 66 relapses occurred in the first 2 years, predominantly pulmonary (n = 36). Eighteen patients died, 14 secondary to disease. A better EFS was associated with negative lymph node status ( P < .01) and absence of LOH 1p or 16q ( P < .01), but not with gross residual disease or peritoneal implants. In contrast, the 4-year EFS was only 74% in patients with combined positive lymph node status and LOH 1p or 16q. A total of 123 patients (23%) had delayed nephrectomy. Submitted delayed nephrectomy histology showed anaplasia (n = 8; excluded from survival analysis); low risk/completely necrotic (n = 7; zero relapses), intermediate risk (n = 63; six relapses), and high-risk/blastemal type (n=7; five relapses). Conclusion Most patients with stage III FHWT had good EFS/overall survival with DD4A and radiation therapy. Combined lymph node and LOH status was highly predictive of EFS and should be considered as a potential prognostic marker for future trials.

Objective: The Children's Oncology Group study AREN0534 aimed to improve event-free survival (EFS) and overall survival (OS) while preserving renal tissue by intensifying preoperative chemotherapy, completing definitive surgery by 12 weeks from diagnosis, and modifying postoperative chemotherapy based on histologic response., Background: No prospective therapeutic clinic trials in children with bilateral Wilms tumors (BWT) exist. Historical outcomes for this group were poor and often involved prolonged chemotherapy; on NWTS-5, 4-year EFS for all children with BWT was 56%., Methods: Patients were enrolled and imaging studies were centrally reviewed to assess for bilateral renal lesions. They were treated with 3-drug induction chemotherapy (vincristine, dactinomycin, and doxorubicin) for 6 or 12 weeks based on radiographic response followed by surgery and further chemotherapy determined by histology. Radiation therapy was provided for postchemotherapy stage III and IV disease., Results: One hundred eighty-nine of 208 patients were evaluable. Four-year EFS and OS were 82.1% (95% CI: 73.5%-90.8%) and 94.9% (95% CI: 90.1%-99.7%. Twenty-three patients relapsed and 7 had disease progression. After induction chemotherapy 163 of 189 (84.0%) underwent definitive surgical treatment in at least 1 kidney by 12 weeks and 39% retained parts of both kidneys. Surgical approaches included: unilateral total nephrectomy with contralateral partial nephrectomy (48%), bilateral partial nephrectomy (35%), unilateral total nephrectomy (10.5%), unilateral partial nephrectomy (4%), and bilateral total nephrectomies (2.5%)., Conclusion: This treatment approach including standardized 3-drug preoperative chemotherapy, surgical resection within 12 weeks of diagnosis and response and histology-based postoperative therapy improved EFS and OS and preservation of renal parenchyma compared with historical outcomes for children with BWT.

Background: Desmoid fibromatosis (desmoid tumor, DT) is a soft tissue neoplasm prone to recurrence despite complete surgical resection. Numerous small retrospective reports suggest that non-cytotoxic chemotherapy using tamoxifen and sulindac may be effective for DT. We evaluated the safety and efficacy of tamoxifen and sulindac in a prospective phase II study within the Children's Oncology Group., Procedures: Eligible patients were <19 years of age who had measurable DT that was recurrent or not amenable to surgery or radiation. The primary objective was to estimate progression-free survival (PFS). Patients received tamoxifen and sulindac daily for 12 months or until disease progression or intolerable toxicity occurred. Response was assessed by magnetic resonance imaging., Results: Fifty-nine eligible patients were enrolled from 2004 to 2009; 78% were 10-18 years old. Twenty-two (38%) were previously untreated; 15 (41%) of the remaining 37 enrolling with recurrent DT had prior systemic chemotherapy and six (16%) had prior radiation. No life-threatening toxicity was reported. Twelve (40%) of 30 females developed ovarian cysts, which were asymptomatic in 11 cases. Ten patients completed therapy without disease progression or discontinuing treatment. Responses included four partial and one complete (5/59, 8%). The estimated 2-year PFS and survival rates were 36% (95% confidence interval: 0.23-0.48) and 96%, respectively. All three deaths were due to progressive DT., Conclusions: Tamoxifen and sulindac caused few serious side effects in children with DT, although ovarian cysts were common. However, the combination showed relatively little activity as measured by response and PFS rates., (Copyright © 2012 Wiley Periodicals, Inc.)

Purpose: To compare whole-body magnetic resonance (MR) imaging with conventional imaging for detection of distant metastases in pediatric patients with common malignant tumors., Materials and Methods: This institutional review board-approved, HIPAA-compliant, multicenter prospective cohort study included 188 patients (109 male, 79 female; mean age, 10.2 years; range, < 1 to 21 years) with newly diagnosed lymphoma, neuroblastoma, or soft-tissue sarcoma. Informed consent was obtained and all patients underwent noncontrast material-enhanced whole-body MR imaging and standard-practice conventional imaging. All images were reviewed centrally by 10 pairs of readers. An independent panel verified the presence or absence of distant metastases. Detection of metastasis with whole-body MR and conventional imaging was quantified by using the area under the receiver operating characteristic curve (AUC). The effects of tumor subtype, patient age, and distant skeletal and pulmonary disease on diagnostic accuracy were also analyzed., Results: Of the 134 eligible patients, 66 (33 positive and 33 negative for metastasis) were selected for image review and analysis. Whole-body MR imaging did not meet the noninferiority criterion for accuracy when compared with conventional imaging for detection of metastasis (difference between average AUCs was -0.03 [95% confidence interval: -0.10, 0.04]); however, the average AUC for solid tumors was significantly higher than that for lymphomas (P = .006). More skeletal metastases were detected by using whole-body MR imaging than by using conventional imaging (P = .03), but fewer lung metastases were detected (P < .001). Patient age did not affect accuracy., Conclusion: The noninferior accuracy for diagnosis of distant metastasis in patients with common pediatric tumors was not established for the use of whole-body MR imaging compared with conventional methods. However, improved accuracy was seen with whole-body MR imaging in patients with nonlymphomatous tumors.

Background: The objective of this study was to prospectively evaluate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as an early imaging indicator of tumor histologic response to preoperative chemotherapy and as a possible prognostic factor for event-free survival (EFS) and overall survival in pediatric patients with newly diagnosed, nonmetastatic osteosarcoma who were treated on a single, multi-institutional phase 2 trial., Methods: Three serial DCE-MRI examinations at week 0 (before treatment), week 9, and week 12 (tumor resection) were performed in 69 patients with nonmetastatic osteosarcoma to monitor the response to preoperative chemotherapy. Four DCE-MRI kinetic parameters (the influx volume transfer constant [K(trans) ], the efflux rate constant [k(ep) ], the relative extravascular extracellular space [v(e) ], and the relative vascular plasma space [v(p) ]) and the corresponding differences (ΔK(trans) , Δk(ep) , Δv(e) , and Δv(p) ) of averaged kinetic parameters between the outer and inner halves of tumors were calculated to assess their associations with tumor histologic response, EFS, and overall survival., Results: The parameters K(trans) , v(e) , v(p) , and k(ep) decreased significantly from week 0 to week 9 and week 12. The parameters K(trans) , v(p) , and Δk(ep) at week 9 were significantly different between responders and nonresponders (P = .046, P = .021, and P = .008, respectively). These 3 parameters were indicative of histologic response. The parameter Δv(e) at week 0 was a significant prognostic factor for both EFS (P = .02) and overall survival (P = .03)., Conclusions: DCE-MRI was identified as a prognostic factor for EFS and overall survival before treatment on this trial and was indicative of a histologic response to neoadjuvant therapy. Further studies are needed to verify these findings with other treatment regimens and establish the potential role of DCE-MRI in the development of risk-adapted therapy for osteosarcoma., (Copyright © 2011 American Cancer Society.)

Background: Little information exists regarding pediatric contrast-enhanced US., Objective: To assess the safety and feasibility of contrast-enhanced US of pediatric abdominal and pelvic tumors., Materials and Methods: This prospective study included eight boys and five girls (mean age, 10.8 years) with abdominal or pelvic tumors. Cohorts of three subjects underwent US with perflutren contrast agent at escalating dose levels. Neurological and funduscopic examination, electrocardiography and continuous pulse oximetry were performed before and after contrast administration. Three radiologists independently scored six imaging parameters on pre- and postcontrast sonography. Inter-reviewer agreement was measured by the Kappa statistic., Results: No neurological, retinal, electrocardiographical or pulse oximetry changes were attributable to the contrast agent. Two subjects reported minor, transient symptoms. Postcontrast US parameter scores improved slightly in 8 of 12 subjects. Postcontrast ultrasound inter-reviewer agreement improved slightly for detection of tumor margins (precontrast = 0.20, postcontrast = 0.26), local tumor invasion (precontrast = -0.01, postcontrast = 0.10) and adenopathy (precontrast = 0.35, postcontrast = 0.44)., Conclusions: Although our sample size is small, perflutren contrast agents appear to be safe and well tolerated in children. Contrast-enhanced sonography of pediatric abdominal and pelvic tumors is feasible, but larger studies are needed to define their safety and efficacy in children.

Interventional radiology techniques to treat oncological disease have already shown value in adults. The adoption and development of interventional oncology (IO) in children have been more limited and challenging. This relates to the approval process for new devices and agents, oncology group protocol limitations and the inherent hesitation of trying new treatments in children. This paper will discuss how new procedures are developed and approved, and the new therapies that will become available to better treat pediatric malignancies. Bringing the benefits of IO to children will require initiative on the part of pediatric diagnostic and interventional radiologists as well as the cooperation of our clinical colleagues.

Image-guided procedures involving the musculoskeletal (MSK) system of children can be challenging because of the variability posed by the child's age, skeletal maturity, and the stage of development. The imaging findings of the maturing MSK system and the underlying diseases affecting children, particularly those that are skeletally immature, can differ significantly from typical adults. The breadth of possible MSK procedures performed by an interventional radiology service depends on the availability of local expertise/experience as well as the referral patterns. In our practice, the majority of nonvascular MSK procedures involve children with a sequela of pain and in need of a therapeutic intervention. We describe our techniques for our more commonly performed MSK procedures, including corticosteroid injections, treating osteoid osteomas, and performance of image-guided bone biopsies and foreign body removal., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Interventional radiologists (IRs) with expertise in image guidance have an inherent skill set for the safe and reliable placement of central venous access catheters (CVACs) in children. Above and beyond the technical requirements, IRs have an integral role as consultants in evaluating children for the most appropriate catheter to meet their short- and long-term needs. This article is meant to serve as a reference for decision making along with tips and pearls on how we approach placing CVACs in pediatric patients at our Children's Hospital., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Drainage and biopsy are mainstay procedures in pediatric interventional radiology. As in the adult population, percutaneous biopsy and fluid collection drainage can be performed almost anywhere in the body, in almost all organ systems, and for myriad indications. However, there are some technique differences in children. Radiation protection is paramount, requiring alterations in imaging and guidance. Children have unique sedation and anesthetic requirements, and smaller patients provide both advantages and disadvantages that require/allow for alteration of the procedural techniques. This article will focus on these differences and describe specific techniques applicable to pediatric patients., (Copyright © 2010 Elsevier Inc. All rights reserved.)

We report an unusual case of a child with a congenital solitary functional kidney complicated by a sports-related posttraumatic Page kidney. The child developed severe hypertension and renal insufficiency requiring percutaneous intervention to preserve renal function. The literature is sparse with no definitive guidelines for the treatment of Page kidney. Following the initial unsuccessful treatment with percutaneous drainage and sclerotherapy procedures, the child ultimately required catheter-directed particle embolization of the capsular arteries to resolve a recurrent subscapsular hematoma definitively. This was successful in preserving renal function and stabilization of the clinical manifestations of the Page kidney.

Objective: Summarize current knowledge of lymphatic malformation development, biology, and clinical outcome measures., Methods: Panel presentation of lymphatic malformation biology and measurement of head and neck malformation treatment outcomes., Results: Characterization of lymphatic malformation endothelial and stromal cells may lead to biologically based treatment. Traditionally, lymphatic malformation treatment outcomes have been measured according to reduction of malformation size. Currently, methods to measure functional outcomes following lymphatic malformation treatment are lacking. This is particularly apparent when the malformation directly involves the upper aerodigestive tract., Conclusions: The etiology and pathogenesis of head and neck lymphatic malformations are poorly understood, but understanding is improving through ongoing investigation. Reduction of lymphatic malformation size is generally possible, but further work is necessary to optimize methods for measuring therapeutic outcomes in problematic areas., (Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.)

Objective: Summarize current knowledge of lymphatic malformation medical, sclerotherapy, and surgical treatment; and highlight areas of treatment controversy and treatment difficulty that need improvement., Methods: Panel presentation of various aspects of lymphatic malformation treatment., Results: The mainstay of lymphatic malformation treatment has been surgical resection, which has been refined through lesion staging and radiographic characterization. Intralesional sclerotherapy in macrocystic lymphatic malformations is effective. Suprahyoid microcystic lymphatic malformations are more difficult to treat than macrocystic lymphatic malformations in the infrahyoid and posterior cervical regions. Bilateral suprahyoid lymphatic malformations require staged treatment to prevent complications. Lymphatic malformation treatment planning is primarily determined by the presence or possibility of functional compromise. Problematic areas include chronic lymphatic malformation inflammation, dental health maintenance, macroglossia, airway obstruction, and dental malocclusion., Conclusions: Lymphatic malformation treatment improvements have been made through radiographic characterization and staging of lymphatic malformations. Direct malformation involvement of the upper aerodigestive tract can cause significant functional compromise that is difficult to treat., (Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.)

Objective: To describe a method of airway infantile hemangioma staging using standardized assessment of airway narrowing, and hemangioma location and volume, as determined with endoscopy and CT angiography., Study Design: Case series with chart review., Setting: Tertiary pediatric hospital, 2003-2008., Subjects and Methods: Subjects included airway hemangioma patients evaluated at a tertiary pediatric hospital. Data collected were age at first symptoms, diagnostic evaluation, percent airway compromise, and estimated hemangioma volume. Data were analyzed with descriptive and Fisher exact statistics., Results: Twelve patients were identified and seven had complete data sets. Mean age at first symptoms was 1.9 months (SD 1.09 months, range 0.5-4 months). Evaluation consisted of nasopharyngoscopy, microlaryngoscopy, CT angiography, and/or MRI. Mean laryngeal airway narrowing was estimated at 63.75 percent (SD 19.0%, range 40%-90%). Total hemangioma volume was less in patients with isolated (focal) endolaryngeal hemangiomas compared with airway hemangiomas associated with extralaryngeal (segmental) hemangiomas. Airway hemangioma stages were stage one (5 of 12; 41.6%), stage two (6 of 12; 50.0%), and stage three (1 of 12; 8.3%)., Conclusion: This method of airway hemangioma staging may be applicable to treatment planning and used to measure treatment outcomes.

R2* magnetic resonance imaging (R2*-MRI) can quantify hepatic iron content (HIC) by noninvasive means but is not fully investigated. Patients with iron overload completed 1.5T R2*-MRI examination and liver biopsy within 30 days. Forty-three patients (sickle cell anemia, n = 32; beta-thalassemia major, n = 6; and bone marrow failure, n = 5) were analyzed: median age, 14 years, median transfusion duration, 15 months, average (+/-SD) serum ferritin 2718 plus or minus 1994 ng/mL, and average HIC 10.9 plus or minus 6.8 mg Fe/g dry weight liver. Regions of interest were drawn and analyzed by 3 independent reviewers with excellent agreement of their measurements (intraclass correlation coefficient = 0.98). Ferritin and R2*-MRI were weakly but significantly associated (range of correlation coefficients among the 3 reviewers, 0.41-0.48; all P < .01). R2*-MRI was strongly associated with HIC for all 3 reviewers (correlation coefficients, 0.96-0.98; all P < .001). This high correlation confirms prior reports, calibrates R2*-MRI measurements, and suggests its clinical utility for predicting HIC using R2*-MRI. This study was registered at www.clinicaltrials.gov as #NCT00675038.

Background: This prospective study was designed to be the first to evaluate the toxicity of radiofrequency ablation (RFA) in patients with recurrent pediatric solid tumors., Methods: From 2003 through 2008, a phase 1/pilot study of RFA for recurrent pediatric solid tumors was conducted. A multidisciplinary cancer management team selected appropriate candidates for the study. Imaging-guided RFA was performed percutaneously. Repeat RFA was performed for recurrences when appropriate. Toxicity and imaging response was assessed at 1 month and 3 months prospectively. Accrual stopped in 2006, and data collection stopped in 2008., Results: Sixteen patients (ages 4 years-33 years; median age, 15 years) and 56 tumor sites were treated in 37 RFA sessions including 38 pulmonary, 11 musculoskeletal, and 7 hepatic lesions (82 lesion-treatments). Postprocedural pain was moderate (median 5 on a scale from 1 to 10) and lasted a median of 9 days. Prolonged hospitalization (beyond 1 day) occurred 17 times (range, 2 days-25 days; median, 3 days). Hypoxia supported by supplemental oxygen occurred in 8 of 16 patients and resolved within 1 month after each RFA. No patient had tumor lysis syndrome but myoglobinuria/hemoglobinuria occurred in 6 of 16 patients, all without renal damage. Serious complications from pulmonary RFA included 2 diaphragmatic hernias. Of 82 lesions imaged, 24 (29%) remained ablated at the end of the study., Conclusions: The toxicity from RFA of recurrent pediatric solid tumors was real but limited, and RFA may offer a local tumor control alternative in carefully selected cases., (Copyright (c) 2009 American Cancer Society.)

Background: Approximately 5% of children with Wilms tumor present with bilateral disease. The treatment challenge is to achieve a high cure rate while maintaining adequate long-term renal function. The authors of this report assessed the feasibility and outcome of nephron-sparing surgery in patients with bilateral Wilms tumor who were treated at a single institution., Methods: A retrospective review was performed of all children who were treated at St. Jude Children's Research Hospital for synchronous, bilateral Wilms tumors from 1999 through 2006. Imaging studies, surgical techniques, and pathology reports were reviewed. The outcomes evaluated included surgical complications, tumor recurrence, renal function, and patient survival., Results: Twelve patients with synchronous, bilateral Wilms tumors were identified, including 10 patients who underwent successful bilateral nephron-sparing procedures. One patient who presented with renal failure and anaplastic histology underwent bilateral nephrectomies, and 1 patient with intra-atrial tumor extension underwent an ipsilateral nephrectomy/thrombectomy and subsequent contralateral partial nephrectomy. Postoperative complications included persistent urine leak in 3 patients, macroscopic residual tumor in 2 patients, and pyelonephritis in 1 patient. Long-term complications included local tumor recurrence in 2 patients, intestinal obstruction in 2 patients, ureteropelvic junction obstruction in 1 patient, and renal failure in 1 patient. The overall survival rate was 83% (mean follow-up, 3.9 years); both patients who died had bilateral, diffuse, anaplastic histology., Conclusions: All patients who had bilateral Wilms tumors with favorable histology, except for 1 patient who had extensive tumor thrombus, underwent successful bilateral partial nephrectomies. Complications were minimal, and long-term renal function and survival were excellent. From this experience, the authors concluded that bilateral nephron-sparing surgery should be considered for all patients who have bilateral Wilms tumor with favorable histology, even if preoperative imaging studies suggest that the lesions are unresectable.

Radiation therapy is often used to achieve local control of pelvic Ewing sarcoma in children. The effects of radiation on the female reproductive tract have been well documented in adults with gynecological malignancies, but the long-term consequences of pelvic radiation in pre-pubertal or adolescent girls are not as well described. We report a case of hematometrocolpos developing in an adolescent previously treated with chemotherapy and radiation therapy for pelvic Ewing sarcoma. We describe the clinical presentation, radiographic features, gross pathology, treatment strategies, outcome, as well as putative predisposing factors and preventative interventions., ((c) 2007 Wiley-Liss, Inc.)

Interventional radiology has become increasingly involved in the diagnosis and management of the pediatric oncology patient. Percutaneous biopsy and needle aspiration can be performed for solid and liquid lesions with image guidance, both for the primary diagnosis and for management of sequelae of cancer therapy. Therapeutic options also can be performed with image guidance, including radiofrequency ablation and transarterial chemoembolization. When surgical resection is required, image guided tumor localization can be used to aid in identifying small lesions.

Objective: The outcome of desmoid tumor in children cannot be reliably predicted on the basis of histologic findings. We sought to determine whether the postoperative presence of residual or recurrent tumor can be predicted on the basis of demographic variables and baseline MRI features of the tumor. We also aimed to determine how imaging features change during adjuvant treatment and how the imaging features relate to the histologic features., Materials and Methods: Two radiologists retrospectively reviewed images from 281 MRI examinations performed at baseline and during postoperative therapy for desmoid tumor. The examinations had been performed on 17 children treated between September 1991 and March 2003. Tumor volume; distinctness of margins; involvement of bone and neurovascular bundle; and T1-weighted, T2-weighted, and STIR signal intensity and contrast enhancement pattern were recorded. Baseline imaging and demographic features were correlated with the postoperative presence of residual or recurrent tumor. Imaging changes during follow-up were compared with treatment response and outcome. The imaging features of eight tumors were compared with percentage cellularity and collagen deposition in biopsy samples obtained within 30 days of imaging., Results: Baseline involvement of the neurovascular bundle approached significance as a predictor of the presence of residual or recurrent tumor (p = 0.08). Other baseline imaging and demographic features were not predictive (p > or = 0.4). Changes in imaging features were variable during follow-up. T2-weighted and STIR signal intensity may be correlated with percentage cellularity and collagen deposition., Conclusion: MRI has limited value in prediction of the postoperative presence of residual or recurrent desmoid tumor in children. It is useful, however, for detecting disease and monitoring postoperative adjuvant therapy.

Background/purpose: Pediatric oncology patients who have undergone placement of multiple central venous catheters may have thrombosis or stenosis in the upper venous system. The purpose of this study was to identify factors that predict venous thrombosis or stenosis and to evaluate the role of Doppler ultrasonography in assessing the upper venous system of pediatric patients requiring multiple central vascular catheters., Methods: The medical records of eligible patients were reviewed with regard to demographics, primary disease, type of catheter, duration of previous central venous access, association with infection, operative notes, and Doppler ultrasonographic findings., Results: Our evaluation criteria were met in 50 cases (47 patients). In 10 cases, Doppler ultrasonography revealed abnormality in the upper venous system. Patient demographics, primary disease, type of catheter, duration of previous central venous access, or association with infection were not found to significantly predict the abnormality in the upper venous system. Placement of central venous access device was performed without difficulty when the site of placement was chosen on the basis of ultrasonographic findings., Conclusion: Doppler ultrasonography is useful in diagnosing thrombosis or stenosis in asymptomatic pediatric patients requiring placement of multiple central venous catheters.

Background: Telangiectatic osteosarcoma (TOS) is a rare subtype of osteosarcoma (OS). The authors reviewed their experience with TOS to characterize its histologic, radiologic, and clinical features., Methods: The authors reviewed records, pathology material, and imaging studies from all patients with TOS who were treated between 1978 and 2005 and compared their outcomes with the outcomes of patients with all other subtypes of high-grade osteosarcoma (OS)., Results: Among 323 patients with OS, 22 patients (6.8%) had TOS. Two additional patients who were treated in Chile on a recent OS trial were included. The median age at diagnosis of the 24 patients was 15.7 years. Four patients (17%) had metastatic disease, and 9 of 21 patients (43%) had pathologic fractures. Only 5 patients (who were treated after 1994) underwent limb-salvage surgery. Estimates of 5-year event-free survival (58.3% +/- 11.9%) and overall survival (66.8% +/- 11.6%) were similar to those for patients with other OS subtypes (P > or = .85). The absence of local disease progression and chemotherapy with > or =3 agents that were active against OS were correlated with improved outcome (P < or = .005). The presence of a pathologic fracture was not associated with surgery type or patient outcome., Conclusions: TOS was associated with a high rate of pathologic fracture. With multimodality therapy, the outcome of patients with TOS was similar to that of patients with other high-grade OS subtypes. The absence of local disease progression and chemotherapy with > or =3 active agents were associated with a favorable outcome.

Background: Pleurodesis for end-of-life care has been used in adults for decades, but little is known about the usefulness of this technique in improving the quality of care for pediatric patients., Objective: To assess whether intractable pleural effusions in pediatric oncology patients at end of life could be sufficiently relieved by pleurodesis., Material and Methods: Eleven pleurodeses were performed with doxycycline in seven pediatric cancer patients (age 3-21 years) with intractable pleural effusions at the end of life. Five patients had unilateral pleurodeses and two had a unilateral followed by bilateral pleurodeses., Results: Respiratory rates decreased in all seven patients (P = 0.016) and aeration improved significantly after chest tube placement (P = 0.033). The chest tubes were placed a median of 1 day before pleurodesis. Eight of nine chest tubes (89%) were removed before discharge at a median of 3 days after pleurodesis. Pain secondary to the pleurodesis lasted 1 day or less. Improvement in the respiratory rate remained after pleurodesis and chest tube removal (P = 0.031). Five of seven patients (70%) were able to leave the hospital to return home. The five patients discharged lived 10 to 49 days (median 19 days) after discharge., Conclusion: Pediatric oncology patients with intractable effusions at end of life can have respiratory benefit from pleurodeses and, as a result, are more likely to return home for terminal care.

Core body temperature elevation (hyperthermia) can occur during radiofrequency ablation of large centrally located tumors in small children. Hyperthermia can be predicted on the basis of long burn times, high wattage delivered by the RF system and low body weight. If hyperthermia is anticipated, cooling blankets using refrigerated air or water are recommended. The advantage of these systems is that the cooling can help maintain normal core body temperature.

Purpose: To determine the efficacy and safety of using vinblastine (Vbl) and methotrexate (Mtx) in children with desmoid-type fibromatosis that is recurrent or not amenable to treatment with radiation or surgery., Patients and Methods: A phase II study was conducted within the Pediatric Oncology Group. Patients were treated using Vbl (5 mg/m2/dose) and Mtx (30 mg/m2/dose), both administered by intravenous injection weekly for 26 weeks and every other week for an additional 26 weeks. Response was assessed by bidimensional measurements of tumor on axial imaging (magnetic resonance imaging or computed tomography)., Results: Over 35 months, 28 patients were enrolled; 27 were eligible, and 26 were assessable for response. A measurable response was documented in eight patients (31%), and 10 patients had stable disease documented as the best response to treatment. Eighteen patients had disease progression at a median time of 9.1 months. Eight patients remain free of disease progression at a median of 43.4 months from study entry. Nine patients reported no to moderate toxicity. Neutropenia was the most common toxicity (n = 22) and the most common grade 4 toxicity (n = 5). Anemia, nausea, vomiting, and elevations in hepatic transaminases were also common and were reversible with interruption of chemotherapy., Conclusion: Vbl and Mtx are well tolerated in children with desmoid-type fibromatosis. Furthermore, this combination can promote tumor regression or block tumor growth in most children.

Purpose/objective: This study aimed to develop objective models of radiation effects on musculature in children with soft tissue sarcoma using treatment dosimetry and clinical and quantitative magnetic resonance imaging (MRI) parameters that may be used to guide treatment planning or predict side effects., Methods: In the initial 13 patients undergoing external beam radiation therapy (RT) on a Phase II study of conformal or intensity-modulated RT for the treatment of soft tissue sarcoma approved by an Institutional Review Board, we evaluated quantitative MRI changes in the musculature to assess radiation-related treatment effects. Patients with soft tissue sarcoma, including Ewing's sarcoma, had quantitative T1, T2 and dynamic enhanced MRI (DEMRI) performed before, during (Week 4) and after RT (Week 12). Regions of interest were selected in consistent locations within and outside the high-dose regions (on ipsilateral and contralateral sides when available). Mean RT dose, T1, T2 and DEMRI parameters were calculated and modeled using a mixed random coefficient dose model., Results: The mean doses to the high- and low-dose regions were 56.4 Gy (41.8-75.3 Gy) and 13.0 Gy (0.1-37.5 Gy), respectively. Compared with tissues distant from the tumor bed, maximal enhancement was significantly increased in tissues adjacent to the tumor/tumor bed prior to RT (60.6 vs. 44.2, P=.045) and remained elevated after 12 weeks. T1 was significantly elevated in tissues adjacent to the tumor bed prior to RT (942.4 vs. 759.0, P=.0078). The slope of longitudinal change in T1 was greater for tissues that received low-dose irradiation than those that received high-dose irradiation (P=.0488). The effect of dose on the slope of T2 was different (P=.0333) when younger and older patients are compared., Conclusions: Acute affects of irradiation in muscle are quantifiable via MRI. These models provide evidence that quantifiable MRI parameters may be correlated with patient parameters of radiation dose and clinical factors including patient age. Long-term follow-up will be required to determine if acute changes correlate with clinically significant late effects.

We present the radiological and clinical aspects of a patient with advanced-stage Burkitt lymphoma who presented with an acute abdomen complicated by abdominal compartment syndrome.

Magnetic resonance (MR) plays a unique role in the diagnosis and management of pediatric abdominal masses. The "as low as reasonably achievable" (ALARA) radiation dose of CT is zero when substituted by MR. Whole body MR may also compete with PET imaging to stage abdominal tumors. Specific advantages of MR include determination of resectability of hepatic tumors using MRI and MRA; staging of neuroblastoma in the bone marrow, lymph nodes, liver, and spinal canal; response of bilateral Wilms tumor and nephroblastomatosis; detection of pelvic tumors with sagittal sectioning, and peritoneal tumors with contrast enhancement.

Background: MRI is an effective tool in evaluating bone marrow metastases. However, no study has defined which MRI sequences or image characteristics best correlate with bone-marrow metastases in neuroblastoma., Objective: To identify and refine MRI criteria and sequence selection for the diagnosis of bone-marrow metastases in children with neuroblastoma., Materials and Methods: Ninety-one children (mean age: 3.2 years; standard deviation: 2.8 years) enrolled in the RDOG IV study participated in our study. Forty-five children had bone metastases determined by bone-marrow aspiration or biopsy (n=4), radionuclide imaging (n=2), or both (n=39). Spine lesions were characterized using coronal T1-weighted (T1W) sagittal short tau inversion recovery (STIR) and coronal gadolinium-enhanced T1-weighted (GAD) MR sequences. Contingency table analysis was performed to determine which MRI sequences and characteristics were associated with metastases. The MRI criteria for metastatic disease were then developed for each imaging sequence. The sensitivity, specificity, predictive values, and accuracy of these criteria were determined for the whole group, children younger than 12 months old, and children 12 months and older., Results: The MR characteristics that had significant (P

Background: The objective of the current study was to determine the diagnostic accuracy of percutaneous biopsy of pediatric solid tumors, a procedure that is less invasive than open biopsy., Methods: The authors conducted a retrospective analysis of clinical data related to 202 percutaneous core-needle biopsies of solid tumors at St. Jude Children's Research Hospital over 5.5 years (from 1997 to 2003). In 103 patients, the procedure was performed to establish an initial diagnosis of a suspected malignancy; and, in 99 patients, disease recurrence was suspected. Biopsies were guided by ultrasound, computed tomography, or fluoroscopic imaging. From each tumor, 1-17 core biopsy samples (median, 6 samples) were obtained; the median needle size was 15 gauge (range, 13-20 gauge). The specimens were submitted for histopathologic analysis and other ancillary procedures (molecular pathology and/or cytogenetic analyses). The accuracy of the diagnoses from the biopsies was determined by subsequent surgery with or without pathologic assessment or by outcome., Results: When the biopsy samples were assessed for the presence of malignancy, there were 121 true-positive results (90% sensitivity), 67 true-negative results (100% specificity), and 14 false-negative results (93% accuracy). In 103 tumors, when the procedure was performed for initial diagnosis, percutaneous needle biopsy showed a sensitivity of 97%, a specificity of 100%, and an accuracy of 98%. The 99 procedures for suspected recurrence were less reliable (sensitivity, 83%; specificity, 100%; accuracy, 88%)., Conclusions: Image-guided percutaneous biopsy was highly accurate and safe in the diagnosis of pediatric malignant solid tumors. This technique may be able to supplant diagnostic open biopsy., ((c) 2005 American Cancer Society.)

Liver abscess is a rare complication of liver biopsy but has not been reported in a patient with sickle cell disease (SCD) undergoing this procedure. The authors report the case of a child with SCD, on treatment with chronic transfusions and desferrioxamine, who developed a delayed liver abscess after a liver biopsy in which Avitene, a topical hemostatic agent, was used. This is the first description of a liver abscess as a possible complication of liver biopsy in a child with SCD. The presence of a hepatic abscess should be considered in the differential diagnosis of atypical abdominal pain in patients with SCD.

Background: The optimal timing for attempting removal of the primary tumor and regional disease in patients with high-risk neuroblastoma is uncertain. The purpose of this study was to evaluate resectability of the primary tumor and regional disease, as determined radiographically, in children with high-risk neuroblastoma during neoadjuvant chemotherapy., Procedure: Patients enrolled in our institutional high-risk neuroblastoma protocol were evaluated prospectively by CT scan and/or MRI to determine the resectability of their primary tumor and regional disease at diagnosis, after two cycles of experimental therapy and after standard induction therapy. Tumors were considered to be unresectable if there was significant involvement with major vascular structures or contiguous organs, or would likely require nephrectomy to remove the entire tumor., Results: Twenty-four patients were referred prior to surgery for treatment of high-risk neuroblastoma. Seven of 24 (29%) patients were felt to be resectable at diagnosis, with an additional 9 patients becoming resectable after the initial experimental therapy. Thus, overall, 16 of 24 (67%) patients were felt to be resectable by the completion of the initial therapy. Only four additional patients of the remaining eight were considered resectable after the completion of standard induction therapy., Conclusions: Based on these data, we conclude that complete resection of the primary tumor and regional disease in children with high-risk neuroblastoma can be performed after an initial phase therapy in the majority of patients. Since earlier tumor removal may decrease the chance for the subsequent development of chemotherapy-resistant disease, we are recommending surgical resection as soon as the locoregional disease appears to be resectable.