Several studies have established that patients with localized perinatal neuroblastoma can be safely observed; however, long-term outcomes have not been previously reported. We evaluated long-term outcomes of infants with suspected perinatal neuroblastoma enrolled on the Children's Oncology Group (COG) ANBL00P2, which included an expectant observation approach. Among 87 eligible patients, the 10-year event-free survival (EFS) was 93.7%, and overall survival (OS) was 98.0%. Most tumors regressed spontaneously; only three patients reported progression to higher stage disease. This report reinforces the long-term safety of non-interventional management in perinatal neuroblastoma, sparing infants unnecessary surgery and associated risks.

Objective: To evaluate age, tumor nephrectomy weight (TNW), or tumor diameter (TD) as continuous prognostic variables for outcomes in early-stage favorable histology Wilms tumor (FHWT) after accounting for biology and treatment. Background: Patient age (<2 vs ≥2 years) and TNW (<550 g vs ≥550 g) have been used to risk-stratify children with stage I FHWT on Children’s Oncology Group (COG) studies and select patients for omission of chemotherapy. Methods: Included patients had stage I or II FHWT per central review and were treated with nephrectomy only, EE4A, or DD4A on COG trials. Restricted cubic splines models were used to estimate the stage-specific effects of age, TNW, and TD on event-free survival (EFS) and overall survival (OS), accounting for treatment and biology. Results: In pooled analyses of 775 stage I and 936 stage II patients, age was not significantly associated with EFS or OS for stage I or II patients after accounting for adverse biology that is more prevalent with older age. Greater TNW and larger TD were associated with increased risk of relapse in stage I and increased risk of death in stage II, but not when restricted to patients <4 years old. Conclusions: Age, TNW, and TD are each prognostic for EFS or OS in some cohorts of patients with stage I or II FHWT. However, after accounting for adverse biology that becomes more prevalent at older ages, these factors are no longer independently prognostic. The next COG FHWT study will implement and validate these findings.

OBJECTIVE:To evaluate age, tumor nephrectomy weight (TNW), or tumor diameter (TD) as continuous prognostic variables for outcomes in early-stage favorable histology Wilms tumor (FHWT) after accounting for biology and treatment. BACKGROUND:Patient age (<2 vs ≥2 years) and TNW (<550 g vs ≥550 g) have been used to risk-stratify children with stage I FHWT on Children's Oncology Group (COG) studies and select patients for omission of chemotherapy. METHODS:Included patients had stage I or II FHWT per central review and were treated with nephrectomy only, EE4A, or DD4A on COG trials. Restricted cubic splines models were used to estimate the stage-specific effects of age, TNW, and TD on event-free survival (EFS) and overall survival (OS), accounting for treatment and biology. RESULTS:In pooled analyses of 775 stage I and 936 stage II patients, age was not significantly associated with EFS or OS for stage I or II patients after accounting for adverse biology that is more prevalent with older age. Greater TNW and larger TD were associated with increased risk of relapse in stage I and increased risk of death in stage II, but not when restricted to patients <4 years old. CONCLUSIONS:Age, TNW, and TD are each prognostic for EFS or OS in some cohorts of patients with stage I or II FHWT. However, after accounting for adverse biology that becomes more prevalent at older ages, these factors are no longer independently prognostic. The next COG FHWT study will implement and validate these findings.

Background: Prognosis for patients with high -risk neuroblastoma (HR-NBL) is guarded despite aggressive therapy, and few studies have characterized outcomes after radiotherapy in relation to radiation treatment fields. Methods: Multi -institutional retrospective cohort of 293 patients with HR-NBL who received autologous stem cell transplant (ASCT) and EBRT between 1997 -2021. LRR was defined as recurrence at the primary site or within one nodal echelon beyond disease present at diagnosis. Follow-up was defined from the end of EBRT. Event -free survival (EFS) and OS were analyzed by Kaplan -Meier method. Cumulative incidence of locoregional progression (CILP) was analyzed using competing risks of distant -only relapse and death with Gray 's test. Results: Median follow-up was 7.0 years (range: 0.01 -22.4). Five-year CILP, EFS, and OS were 11.9 %, 65.2 %, and 77.5 %, respectively. Of the 31 patients with LRR and imaging review, 15 (48.4 %) had in -field recurrences ( >12 Gy), 6 (19.4 %) had marginal failures ( <= 12 Gy), and 10 (32.3 %) had both in -field and marginal recurrences. No patients receiving total body irradiation (12 Gy) experienced marginal -only failures (p = 0.069). On multivariable analyses, MYCN amplification had higher risk of LRR (HR: 2.42, 95 % CI: 1.06 -5.50, p = 0.035) and post -consolidation isotretinoin and anti-GD2 antibody therapy (HR: 0.42, 95 % CI: 0.19 -0.94, p = 0.035) had lower risk of LRR. Conclusions: Despite EBRT, LRR remains a contributor to treatment failure in HR-NBL with approximately half of LRRs including a component of marginal failure. Future prospective studies are needed to explore whether radiation fields and doses should be defined based on molecular features such as MYCN amplification, and/or response to chemotherapy.

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.

INTRODUCTION:Children with WAGR (Wilms tumor, aniridia, genitourinary anomalies, and range of development delays) syndrome are predisposed to Wilms tumor (WT) and intrinsic kidney disease. Using the comprehensive International WAGR Syndrome Association (IWSA) survey of children with WAGR syndrome, we analyzed tumor characteristics, treatment and congenital risk factors, and kidney function in children with WAGR and WT. METHODS:Descriptive statistics were utilized including demographics, treatment strategies, and patient outcomes. Comparisons were made between patients with WAGR and WT to those with WAGR alone. A multivariable logistic regression was completed for risk of developing WT and to identify predictors of chronic kidney disease (CKD). RESULTS:Sixty-four of 145 children with WAGR developed WT (44.1%). Three relapsed and one died. CKD developed in five children with WAGR without WT (5/81, 6.2%), and in 34 with WAGR and WT (34/64, 28.3%). Children with WAGR and WT were younger (p = .017), and had a greater association with CKD than WAGR children without WT (p < .0001). Two children with WT required hemodialysis, and one underwent kidney transplantation. By univariate analysis, CKD at any stage was associated with complete nephrectomy for the WT surgery (p < .0001), chemotherapy duration greater than 12 months, and three-drug therapy. Upon multivariate analysis, prior nephrectomy was the only significant variable (p = .0002). CONCLUSIONS:Epidemiological analysis of children with WAGR demonstrated favorable oncologic outcomes, but high rate of early CKD in those who developed WT. Further study of the use of nephron-sparing surgery in children with WAGR and strategies to delay or treat early CKD are needed.

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.

Children with renal masses require surgical management to provide accurate surgical staging and skilled resection of the tumor. This document includes evidence-based recommendations for pediatric surgeons regarding the resection, staging, and proper nodal basin evaluation.

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.

Neuroblastoma (NB) is the most common solid extracranial malignancy of childhood with an incidence of 1 per 100,000 in the United States compromising approximately 10 % of childhood cancer. Unfortunately, patients with high-risk NG continue to have long-term survival less than 50 %. Both Children's Oncology Group and the International Society of Paediatric Oncology have demonstrated the important role of surgery in the treatment of high-risk NB. Herein, we compose the results of an extensive literature review as well as expert opinion from leaders in pediatric surgical oncology, to present the critical elements of effective surgery for high-risk neuroblastoma.

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. 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. 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. 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.

A patient developed the severe amnesic syndrome 8 years after temporal lobe surgery for epilepsy. He underwent left temporal lobectomy (6 cm, 43.5 g; hippocampal sclerosis) aged 19, and remained seizure free for 8 years until a convulsion followed a head injury. He became severely amnesic after a fourth convulsion 16 months later. He was right-handed, pre-operative IQ was average, verbal memory poor and non-verbal memory normal. Post-operatively, these were unchanged. After the first post-operative seizure he began professional training. After onset of amnesia IQ was unchanged, anterograde memory severely impaired and retrograde amnesia dense for at least 16 months. He died 2 years later. Magnetic resonance imaging before amnesia showed absence of anterior left temporal lobe, atrophy of left fornix and mamillary body, and normal right temporal lobe. Four months after onset of amnesia, right hippocampal volume had reduced by 36%. Autopsy showed: previous left temporal lobectomy with absence of left amygdala and hippocampus, atrophy of fornix and mamillary body; neuronal loss in the right hippocampus, severe in CA1 and CA4; intact right amygdala and parahippocampal gyrus; recent diffuse damage associated with cause of death. A convulsion can cause severe hippocampal damage in adult life. Hippocampal zones CA1 and/or CA4 are critical for maintaining memory and the amygdala and parahippocampal gyrus cortex alone cannot support acquisition of new memories.

You have accessJournal of UrologyCME1 May 2022MP17-16 LONG-TERM OUTCOMES FOR PATIENTS WITH ANAPLASTIC BILATERAL WILMS TUMORS ENROLLED ON COG AREN0534 Rodrigo L.P. Romao, Jennifer H. Aldrink, Brett Tornwall, Kathleen Kieran, Andrew Murphy, Andrew Davidoff, Daniel Benedetti, Jeffrey Dome, Elizabeth Perlman, Ethan Smith, Conrad Fernandez, James Geller, Jack Brzezinski, Lindsay Renfro, Marcus Malek, David Mansur, Elizabeth Mullen, Nicholas Cost, Robert C. Shamberger, and Peter F. Ehrlich Rodrigo L.P. RomaoRodrigo L.P. Romao More articles by this author , Jennifer H. AldrinkJennifer H. Aldrink More articles by this author , Brett TornwallBrett Tornwall More articles by this author , Kathleen KieranKathleen Kieran More articles by this author , Andrew MurphyAndrew Murphy More articles by this author , Andrew DavidoffAndrew Davidoff More articles by this author , Daniel BenedettiDaniel Benedetti More articles by this author , Jeffrey DomeJeffrey Dome More articles by this author , Elizabeth PerlmanElizabeth Perlman More articles by this author , Ethan SmithEthan Smith More articles by this author , Conrad FernandezConrad Fernandez More articles by this author , James GellerJames Geller More articles by this author , Jack BrzezinskiJack Brzezinski More articles by this author , Lindsay RenfroLindsay Renfro More articles by this author , Marcus MalekMarcus Malek More articles by this author , David MansurDavid Mansur More articles by this author , Elizabeth MullenElizabeth Mullen More articles by this author , Nicholas CostNicholas Cost More articles by this author , Robert C. ShambergerRobert C. Shamberger More articles by this author , and Peter F. EhrlichPeter F. Ehrlich More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002550.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Anaplastic histology in the setting of bilateral Wilms tumor (BWT) is associated with poor prognosis - NWTS-5 4-year EFS and OS were 43.8% and 55.2%, respectively. AREN0534 sought to improve outcomes for BWT. We analyzed the events and long-term outcomes for the rare subgroup of patients with BWT and anaplasia. METHODS: AREN0534 was open to enrollment from 2009 to 2015. Patients with focal(FA) or diffuse(DA) anaplasia were included in this sub-analysis. Location of relapse, progression and 7-year EFS and OS with 95% CI are reported. RESULTS: There were 25 patients with anaplastic BWT (17 DA and 8 with FA). 1/8 patients with FA had bilateral FA and 4/17 patients with DA had bilateral DA. There were 18 females and 7 males; median age of enrollment was 43.1 months (24.1- 113.7). For FA, 7-year EFS was 62.5%(95% CI, 24.99-100) and OS was 87.5%(95% CI, 62.8-100). One patient with FA died from local relapse due to FHWT in the contralateral kidney at 5 years off therapy. A second patient with stage II FA had progressive disease while on therapy. This patient did not have nodes sampled. Pathology at progression was DA. For DA, 7-year EFS was 58.8% (95% CI, 25.7-91.9) and OS was 70.1% (95% CI, 36.5-100). 7 patients had events, 3 with local tumor progression (all died) and 4 with relapse (2 died). All 4 relapses had initial positive surgical margins and occurred within a year of ending therapy. The sites of relapse were local (2), and lung only (2). Of the 10 patients who were without an event, 5 had positive margins. CONCLUSIONS: Patients with BWT and anaplasia often have discordant pathology. Late events are rare. Margin status at the time of definitive surgery does not seem to impact outcomes in the context of contemporary multimodal therapy including radiation to positive margins. Source of Funding: This project was supported by grants CA98543 (Children’s Oncology Group Chair’s grant) and CA98413 (COG SDC grant) from the National Institutes of Health. U10CA180899 © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e292 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rodrigo L.P. Romao More articles by this author Jennifer H. Aldrink More articles by this author Brett Tornwall More articles by this author Kathleen Kieran More articles by this author Andrew Murphy More articles by this author Andrew Davidoff More articles by this author Daniel Benedetti More articles by this author Jeffrey Dome More articles by this author Elizabeth Perlman More articles by this author Ethan Smith More articles by this author Conrad Fernandez More articles by this author James Geller More articles by this author Jack Brzezinski More articles by this author Lindsay Renfro More articles by this author Marcus Malek More articles by this author David Mansur More articles by this author Elizabeth Mullen More articles by this author Nicholas Cost More articles by this author Robert C. Shamberger More articles by this author Peter F. Ehrlich More articles by this author Expand All Advertisement PDF DownloadLoading ...

Background: It is uncertain whether the presence of autoimmune thyroiditis (AIT) increases the risk of thyroid cancer in children with thyroid nodules. This study evaluated the association between AIT and thyroid cancer in pediatric patients with thyroid nodules.Methods: A cross-sectional study was performed of pediatric patients (<19 years old) with a thyroid nodule (>= 1 cm) who underwent fine-needle aspiration in an academic pediatric thyroid center. AIT was defined by the presence of thyroid autoantibodies or diffusely heterogeneous sonographic echotexture. The primary outcome was diagnosis of thyroid cancer. The association of AIT with thyroid cancer was evaluated with univariable and multivariable logistic regression. Associations of AIT with subject and nodule characteristics were also assessed.Results: Four hundred fifty-eight thyroid nodules in 385 patients (81% female) were evaluated at a median age of 15.5 years (interquartile range 13.5-17.0). Thyroid cancer was present in 108 nodules (24%). AIT was present in 95 subjects (25%) and was independently associated with an increased risk of thyroid cancer (multivariable odds ratio [OR] 2.19, 95% confidence interval [CI] 1.32-3.62). Thyroid cancer was also independently associated with younger age, nodule size, and solitary nodules, but was not associated with serum thyrotropin concentration. AIT was not associated with the likelihood of subjects undergoing thyroid surgery (p = 0.17). AIT was less commonly associated with follicular thyroid carcinoma than with papillary thyroid carcinoma (OR 0.22, CI 0.05-1.06). Among papillary thyroid carcinomas, AIT was strongly associated with the diffuse sclerosing variant (OR 4.74, CI 1.33-16.9). AIT was not associated with the extent of local, regional, or distant disease at thyroid cancer diagnosis.Conclusions: AIT is independently associated with an increased risk of thyroid cancer in children with thyroid nodules. These findings suggest that the evaluation of thyroid autoantibodies and thyroid echotexture may inform thyroid cancer risk assessment and surgical decision-making in children with thyroid nodules.

Intussusception in the pediatric population is most commonly identified in children under two years of age in the ileocecal region. Our case is a rare example of distal colo-colonic intussuscep-tion in a seven-year-old male. After air contrast enema reduction of the intussusception, he was found on fluoroscopic images and CT scan to have an intraluminal lead point in the splenic flex-ure that resulted in almost immediate recurrence and was unresectable endoscopically. He under-went a laparoscopic-assisted partial left colectomy. Final pathology confirmed the diagnosis of Burkitt's lymphoma. There is a paucity of guidance with regards to colo-colonic intussusception with suspicion for a pathologic lead point. Based on our experience, after reduction by air enema, we recommend imaging, colonoscopy with either resection or biopsies, and surgical resection if necessary to remove the lead point and establish a tissue diagnosis. Based on both the high likeli-hood of lymphoma and its responsiveness to chemotherapy, we recommend grossly negative margins with lymph node sampling rather than traditional oncologic resection with complete lymphadenectomy.