BACKGROUND:Survivors of Ewing sarcoma (EWS) are at significant long-term risk of treatment- and disease-related complications. The purpose of this study was to characterize long-term outcomes in EWS survivors according to treatment regimen. METHODS:Five-year survivors of EWS diagnosed between 1970 and 1999 from the Childhood Cancer Survivor Study were included. Late mortality (>5 years from diagnosis), subsequent malignant neoplasms (SMNs), and severe to fatal chronic health conditions (CHCs) by chemotherapy regimen were compared. Patients were compared to siblings via cumulative incidence and proportional hazards models. Standardized mortality ratios (SMRs) compared late mortality between survivors and the general population. RESULTS:Survivors (N = 739) had higher all-cause (SMR, 6.16; 95% CI, 5.36-7.05), SMN-related (SMR, 9.24; 95% CI, 6.92-12.08), cardiac-related (SMR, 4.53; 95% CI, 2.81-6.93), and noncardiopulmonary health-related (SMR, 2.04; 95% CI, 1.25-3.15) mortality compared with the general population. Compared with siblings (N = 5040), survivors had an increased risk of developing CHCs (any: hazard ratio [HR], 5.49; 95% CI, 4.58-6.59; cardiovascular: HR, 4.59; 95% CI, 3.67-5.74; neurological: HR, 2.82; 95% CI, 1.72-4.63; respiratory: HR, 5.37; 95% CI, 2.76-10.5; renal: HR, 4.61; 95% CI, 2.26-9.40). Between chemotherapy groups within EWS, there were no statistically significant differences in all-cause, SMN-caused, or health-related late mortality and the risk of developing SMNs or CHCs (any, cardiovascular, neurological, or respiratory), except that the vincristine, doxorubicin, and cyclophosphamide (VDC) plus ifosfamide and etoposide (IE) group had a higher risk of renal complications (HR, 2.55; 95% CI, 1.07-11.7; 30-year incidence was 0.56% for VDC and 3.2% for VDC/IE). CONCLUSIONS:No differences in late mortality, SMNs, and most CHCs were observed between patients who received VDC versus VDC/IE. Aging EWS survivors' elevated risk of morbidity and mortality underscores the need for lifelong survivorship care and therapies that reduce the risk for late effects.

Objective Evaluate late effects in survivors of childhood pelvic sarcoma by disease origin (bony vs. soft-tissue) and local control modality (bone surgery, pelvic organ resection, radiotherapy). Methods Among 5-year pediatric pelvic sarcoma survivors, we assessed long-term outcomes including late (>5 years) mortality, graded chronic health conditions (CHCs), subsequent malignant neoplasms (SMNs), physical function/activity, cancer-related pain, and pregnancy/siring a pregnancy. Associations with disease origin and local control modality were analyzed using cumulative incidence and Cox or multivariable logistic regression. Results Among 745 eligible survivors, the 35-year cumulative incidence of late all-cause and health-related mortality was 25.7% (95%CI=22.1%-29.3%) and 12.2% (95%CI=9.4%-15.1%), vs. 2.5% (95%CI=1.3%-3.7%) and 1.4% (95%CI=0.5%-2.4%) in matched US population. Cumulative incidence of severe/life-threatening CHCs was 47.6% (95%CI=43.0%-52.1%) for survivors vs. 12.2% (95%CI=11.3%-13.2%) for siblings. Cumulative incidence of SMNs was 7.6% (95%CI=5.0%-10.2%). Bone sarcomas were associated with increased all-cause mortality (HR=1.92, 95%CI=1.16-3.17), health-related mortality (HR=2.12, 95%CI=1.03-4.38), and CHCs (HR=2.55, 95%CI=1.65-3.95) vs. soft-tissue sarcomas. Analyzing all survivors, radiotherapy was associated with increased CHCs (HR=2.42, 95%CI=1.53-3.81), multiple CHCs (HR=2.27, 95%CI=1.03-4.97), functional impairment (OR=2.21, 95%CI=1.30-3.74), and pain (OR=2.29, 95%CI=1.33-3.93). Bone surgery was associated with functional impairment (OR=2.64, 95%CI=1.30-5.37), performance limitations (OR=2.12, 95%CI=1.19-3.79), and pain (OR=2.59, 95%CI=1.37-4.89). Pelvic organ resection was associated with decreased pregnancy (OR=0.25, 95%CI=0.10-0.63). Conclusions Late effects differed by pelvic sarcoma origin (bone vs. soft-tissue) and local control modality. The associations between local control choices and late effects in this study can guide counseling of patients and families at the time of diagnosis, treatment, local control, or after completion of therapy.Clinical Trial Registration: ClinicalTrials.gov ID: NCT01120353

OBJECTIVE:To evaluate the impact of surgical guidelines on the management of children with hepatoblastoma. BACKGROUND:The Children's Oncology Group study AHEP0731 was the first pediatric cooperative group trial to propose guidelines for the surgical management of children with hepatoblastoma. METHODS:AHEP0731 enrolled children with hepatoblastoma between 2009 and 2018. Surgical guidelines were based upon radiographic extent of disease (PRETEXT, POST-TEXT). Planned non-real-time central review of imaging was completed at diagnosis and after two, four, and six cycles of chemotherapy to determine guideline adherence. Resection rate, event-free survival (EFS), overall survival (OS), and complications were compared between guideline adherent and nonadherent groups. RESULTS:Of 226 enrolled patients, 221 were evaluable of whom 205 (93%) underwent definitive surgical resection. Guideline adherence for protocol recommended timing of resection was 65% (133/205). The nonadherent group included 44/205 (21%) patients who underwent early resection and 28/205 (14%) patients who underwent late resection or late transplantation. Eighty-five patients met criteria for early referral to a liver transplant center, of whom 55 (65%) were referred within the recommended timeframe. Twelve patients received liver transplants outside of surgical guidelines. There were no significant differences in EFS, OS, or complication rates between adherent and nonadherent groups. CONCLUSIONS:Implementation of surgical guidelines, in combination with effective chemotherapy and radiologic staging, produced a higher rate of definitive tumor resection compared to historical trials. Nonadherence with surgical guidelines resulted in liver transplantation in some patients for whom partial hepatectomy might have been an option.

Lymphadenopathy (LAD) is common in children, and often nonpathologic, but requires a thorough evaluation with a detailed history and physical before being designated as "benign idiopathic." Cervical LAD is the most common location in children. History should focus on patient and lymph node characteristics and patient exposures, while physical should include characteristics of the lesion, evaluation of the region, and systemic findings. Based on these findings, a differential can be generated, which includes infectious, malignant, immunologic, or iatrogenic etiologies. Options for further testing include imaging (most often with ultrasound and/or chest radiograph), laboratory markers, and biopsy in rare instances.

Conventional diffusion-controlled drug delivery systems (DDS) can have undesirable initial burst release, leading to potential systemic toxicity, and the rate of basal release can deplete content, shortening the duration of effect. Here, it is hypothesized that conventional drug delivery systems-using liposomes as an example-can be enhanced by incorporation of an aptamer that binds specifically to the encapsulated drug. Affinity of the aptamer to the drug within liposomes (Lipo-Apt) would slow release. It is demonstrated that this approach works with a range of relatively small and hydrophilic molecules, including tetrodotoxin (TTX), serotonin (Ser), and kanamycin (Kan). The in vivo utility of this system in providing prolonged local anesthesia with TTX injected at the sciatic nerve in rats is further demonstrated. A single injection of TTX-loaded Lipo-Apt results in 6.6 d of nerve blockade, a fourfold improvement over the duration achieved by liposomes without aptamers, and 26-fold over the aptamer-drug complex. In part, the improved efficacy of Lipo-Apt is also due to slower release reducing systemic toxicity, which allows delivery of larger drug doses. These studies demonstrate that Lipo-Apt is a promising approach to enhancing control of release of drugs by DDS, reducing toxicity and enhancing duration of effect.

To evaluate the impact of surgical guidelines on the management of children with hepatoblastoma. The Children’s Oncology Group study AHEP0731 was the first pediatric cooperative group trial to propose guidelines for the surgical management of children with hepatoblastoma. AHEP0731 enrolled children with hepatoblastoma between 2009 and 2018. Surgical guidelines were based upon radiographic extent of disease (PRETEXT, POST-TEXT). Planned non-real-time central review of imaging was completed at diagnosis and after two, four, and six cycles of chemotherapy to determine guideline adherence. Resection rate, event-free survival (EFS), overall survival (OS), and complications were compared between guideline adherent and nonadherent groups. Of 226 enrolled patients, 221 were evaluable of whom 205 (93%) underwent definitive surgical resection. Guideline adherence for protocol recommended timing of resection was 65% (133/205). The nonadherent group included 44/205 (21%) patients who underwent early resection and 28/205 (14%) patients who underwent late resection or late transplantation. Eighty-five patients met criteria for early referral to a liver transplant center, of whom 55 (65%) were referred within the recommended timeframe. Twelve patients received liver transplants outside of surgical guidelines. There were no significant differences in EFS, OS, or complication rates between adherent and nonadherent groups. Implementation of surgical guidelines, in combination with effective chemotherapy and radiologic staging, produced a higher rate of definitive tumor resection compared to historical trials. Nonadherence with surgical guidelines resulted in liver transplantation in some patients for whom partial hepatectomy might have been an option.

Primary pediatric lung tumors are uncommon and have many overlapping clinical and imaging features. In contrast to adult lung tumors, these rare pediatric neoplasms have a relatively broad histologic spectrum. Informed by a single-institution 13-year retrospective record review, we present an overview of the most common primary pediatric lung neoplasms, with a focus on the role of positron emission tomography (PET), specifically 18F-fluorodeoxyglucose (FDG) PET and 18 Ga-DOTATATE PET, in the management of primary pediatric lung tumors. In addition to characteristic conventional radiographic and cross-sectional imaging findings, knowledge of patient age, underlying cancer predisposition syndromes, and PET imaging features may help narrow the differential. While metastases from other primary malignancies remain the most commonly encountered pediatric lung malignancy, the examples presented in this Pictorial Essay highlight many of the important conventional radiologic and PET imaging features of primary pediatric lung malignancies.

PURPOSE:Treatment strategies for osteosarcoma evolving between 1970 and 1999 improved 5-year survival and continue as standard of care today. This report evaluates the impact of these evolving therapies on long-term health outcomes. METHODS:Five-year survivors of childhood osteosarcoma in CCSS treated from 1970 to 1999 were evaluated for late (>5 years from diagnosis) mortality, chronic health conditions (CHCs), and health status using piecewise-exponential and logistical models. Comparisons were made between survivors and siblings without cancer, and among survivors examining historical and current standard chemotherapies (e.g., methotrexate/doxorubicin/cisplatin [MAP] vs. others), specific chemotherapy agents and surgical approaches (amputation vs. limb salvage [LS]). Models were evaluated adjusting for attained age, sex, race, ethnicity, and age at diagnosis. RESULTS:A total of 1257 survivors of osteosarcoma were followed on average for 24.4 years. Twenty-year all-cause late mortality was 13.3% (95% confidence interval [CI]: 11.7%-14.9%) overall and 11.7% (95% CI: 6.9%-16.5%) for the subset treated with MAP plus LS. Survivors were at higher risk of CHCs (rate ratio [RR] 3.7, 95% CI: 3.2-4.3) than the sibling cohort, most notably having more serious cardiac, musculoskeletal, and hearing CHCs. Within the survivor cohort, the risk of severe CHCs was twice as high with MAP versus no chemotherapy (RR 2.1, 95% CI: 1.3-3.4). Compared with primary amputation, serious musculoskeletal CHCs were higher after LS (RR 6.6, 95% CI: 3.6-13.4), without discernable differences in health status. CONCLUSION:Contemporary osteosarcoma therapy with MAP plus LS, while improving 5-year disease-free survival, continues to be associated with a high burden of late mortality, CHCs, and health status limitations.

Allison F O’Neill,1 Raul C Ribeiro,2 Emilia M Pinto,3 Michael R Clay,4 Gerard P Zambetti,3 Brent A Orr,3 Christopher B Weldon,5 Carlos Rodriguez-Galindo2,6 1Department of Pediatric Oncology, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, MA, USA; 2Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA; 3Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN, USA; 4Department of Pathology, Children’s Hospital Colorado, Denver, CO, USA; 5Department of Surgery, Boston Children’s Hospital, Boston, MA, USA; 6Department of Global Pediatric Medicine, St. Jude Children’s Research Hospital, Memphis, TN, USACorrespondence: Allison F O’Neill, Department of Pediatric Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue – DA3111, Boston, MA, 02215, USA, Email Allison_oneill@dfci.harvard.eduAbstract: Adrenocortical tumors (ACTs) are infrequent neoplasms in children and adolescents and are typically associated with clinical symptoms reflective of androgen overproduction. Pediatric ACTs typically occur in the context of a germline TP53 mutation, can be cured when diagnosed at an early stage, but are difficult to treat when advanced or associated with concurrent TP53 and ATRX alterations. Recent work has demonstrated DNA methylation patterns suggestive of prognostic significance. While current treatment standards rely heavily upon surgical resection, chemotherapy, and hormonal modulation, small cohort studies suggest promise for multi-tyrosine kinases targeting anti-angiogenic pathways or immunomodulatory therapies. Future work will focus on novel risk stratification algorithms and combination therapies intended to mitigate toxicity for patients with perceived low-risk disease while intensifying therapy or accelerating discoveries aimed at improving survival for patients with difficult-to-treat disease.Keywords: adrenocortical, pediatric, management, discovery, carcinoma, tumors

BACKGROUND:Children living in poverty and those of marginalized race or ethnicity experience inferior disease outcomes across many cancers. Whether survival disparities exist in osteosarcoma is poorly defined. We investigated the association between race, ethnicity, and proxied poverty exposures and event-free and overall survival for children with nonmetastatic osteosarcoma receiving care on a cooperative group trial. METHODS:We conducted a retrospective cohort study of US patients with nonmetastatic, osteosarcoma aged 5-21 years enrolled on the Children's Oncology Group trial AOST0331. Race and ethnicity were categorized to reflect historically marginalized populations, as Hispanic, non-Hispanic Black, non-Hispanic Other, and non-Hispanic White. Poverty was proxied at the household and neighborhood levels. Overall survival and event-free survival functions of time from trial enrollment were estimated using the Kaplan-Meier method. Hypotheses of associations between risks for event-free survival, death, and postrelapse death with race and ethnicity were assessed using log-rank tests. RESULTS:Among 758 patients, 25.6% were household-poverty and 28.5% neighborhood-poverty exposed. Of the patients, 21% of children identified as Hispanic, 15.4% non-Hispanic Black, 5.3% non-Hispanic Other, and 54.0% non-Hispanic White. Neither household or neighborhood poverty nor race and ethnicity were statistically significantly associated with risks for event-free survival or death. Postrelapse risk for death differed statistically significantly across race and ethnicity with non-Hispanic Black patients at greatest risk (4-year postrelapse survival 35.7% Hispanic vs 13.0% non-Hispanic Black vs 43.8% non-Hispanic Other vs 38.9% non-Hispanic White; P = .0046). CONCLUSIONS:Neither proxied poverty exposures or race and ethnicity were associated with event-free survival or overall survival, suggesting equitable outcomes following frontline osteosarcoma trial-delivered therapy. Non-Hispanic Black children experienced statistically significant inferior postrelapse survival. Investigation of mechanisms underlying postrelapse disparities are paramount.

10003 Background: A subset of children with INRGSS Stage MS neuroblastoma (NBL) may be observed without treatment, while others have rapidly evolving symptoms that can be life-threatening. ANBL1232 adapted a previously developed semi-quantitative objective scoring system (OSS) to assign a numeric value to symptoms and laboratory abnormalities. The goal was to standardize monitoring, therapy initiation, and treatment duration in this cohort. Methods: Patients with newly diagnosed Stage MS NBL were eligible for this prospective trial. An OSS score (OSSS) was assigned at enrollment; the total number was based on scoring in 5 systems: gastrointestinal (GI), respiratory, circulatory, renal, and hepatic. Within the 5 systems, individual clinical and laboratory parameters were scored as not present = 0, mild/moderate = 1 [Grade 2 CTCAEv4.0 adverse event (AE)] or severe = 2 (Grade ≥3 AE). The OSSS was the sum of highest score within each organ system (maximum score: 2 per system, 10 total). Asymptomatic MS patients with an OSSS < 2 who were either < 3 months (mo) of age without hepatomegaly or 3-18 mo of age with favorable biology tumors were eligible for observation without initial treatment. Observed patients underwent monthly physical examinations and laboratory assessments for the first 6 mo following diagnosis. Tumor imaging was performed every 3 mo for 1 year, then every 6-12 mo through 36 mo. An OSSS ≥2 or a protocol-defined increase in primary tumor size prompted initiation of therapy. Results: From July 2014 to February 2021, 89 eligible and evaluable patients with newly diagnosed stage MS NBL enrolled. Among these, 18 (20.2%; 5 male and 13 female) were eligible for observation. Observed patients were older at diagnosis (median age: 2.87 vs. 1.81 mo, p = 0.23) and more likely to have primary tumors without image-defined risk factors (62.5% vs. 30.0%, p = 0.0166) than those assigned to therapy up front. Nearly all observed patients (17/18) had abdominal/adrenal primaries. The initial OSSS was 0 in all observed patients. Median reported observation time was 36 mo (range: 1-36 mo); 13 patients completed all required monthly assessments for the first 6 mo. No patients in the observation cohort required initiation of therapy for an increase in OSSS. One patient with OSSS = 1 at mo 3 had complete GI symptom resolution by mo 5. Conclusions: An OSSS of 0 at diagnosis can aid in identifying a favorable group of patients with stage MS NBL who can be safely observed. No patients in the observation cohort developed evidence of organ dysfunction or OSSS > 1 despite frequent physical examination and comprehensive laboratory testing, suggesting that follow up may be safely liberalized in this population over time. Clinical and laboratory criteria implemented at diagnosis could be used to identify patients requiring prompt treatment. Clinical trial information: NCT02176967 .

Two percent of pediatric malignancies arise primarily in the liver; roughly 60% of these cancers are hepatoblastoma (HB). Despite the rarity of these cases, international collaborative efforts have led to the consistent histological classification and staging systems, which facilitate ongoing clinical trials. Other primary liver malignancies seen in children include hepatocellular carcinoma (HCC) with or without underlying liver disease, fibrolamellar carcinoma (FLC), undifferentiated embryonal sarcoma of the liver (UESL), and hepatocellular neoplasm not otherwise specified (HCN-NOS). This review describes principles of surgical management of malignant pediatric primary liver tumors, within the context of comprehensive multidisciplinary care.

Background Multimodal cancer therapy places childhood cancer survivors at increased risk for chronic health conditions, subsequent malignancies, and premature mortality as they age. We aimed to estimate the cumulative burden of late (>5 years from cancer diagnosis), major surgical interventions among childhood cancer survivors, compared with their siblings, and to examine associations between specific childhood cancer treatments and the burden of late surgical interventions.Methods We analysed data from the Childhood Cancer Survivor Study (CCSS), a retrospective cohort study with longitudinal prospective follow-up of 5-year survivors of childhood cancer (diagnosed before age 21 years) treated at 31 institutions in the USA, with a comparison group of nearest-age siblings of survivors selected by simple random sampling. The primary outcome was any self-reported late, major surgical intervention (defined as any anaesthesia-requiring operation) occurring 5 years or more after the primary cancer diagnosis. The cumulative burden was assessed with mean cumulative counts (MCC) of late, major surgical interventions. Piecewise exponential regression models with calculation of adjusted rate ratios (RRs) evaluated associations between treatment exposures and late, major surgical interventions.Findings Between Jan 1, 1970, and Dec 31, 1999, 25 656 survivors were diagnosed (13 721 male, 11 935 female; median follow-up 21 & BULL;8 years [IQR 16 & BULL;5-28 & BULL;4]; median age at diagnosis 6 & BULL;1 years [3 & BULL;0-12 & BULL;4]); 5045 nearest-age siblings were also included as a comparison group. Survivors underwent 28 202 late, major surgical interventions and siblings underwent 4110 late, major surgical interventions. The 35-year MCC of a late, major surgical intervention was 206 & BULL;7 per 100 survivors (95% CI 202 & BULL;7-210 & BULL;8) and 128 & BULL;9 per 100 siblings (123 & BULL;0-134 & BULL;7). The likelihood of a late, major surgical intervention was higher in survivors versus siblings (adjusted RR 1 & BULL;8, 95% CI 1 & BULL;7-1 & BULL;9) and in female versus male survivors (1 & BULL;4; 1 & BULL;4-1 & BULL;5). Survivors diagnosed in the 1990s (adjusted RR 1 & BULL;4, 95% CI 1 & BULL;3-1 & BULL;5) had an increased likelihood of late surgery compared with those diagnosed in the 1970s. Survivors received late interventions more frequently than siblings in mostanatomical regions or organ systems, includingCNS (adjusted RR16 & BULL;9, 95%CI9 & BULL;4-30 & BULL;4), endocrine (6 & BULL;7, 5 & BULL;2-8 & BULL;7), cardiovascular (6 & BULL;6, 5 & BULL;2-8 & BULL;3), respiratory (5 & BULL;3, 3 & BULL;4-8 & BULL;2), spine (2 & BULL;4, 1 & BULL;8-3 & BULL;2), breast (2 & BULL;1, 1 & BULL;7-2 & BULL;6), renal or urinary (2 & BULL;0, 1 & BULL;5-2 & BULL;6), musculoskeletal (1 & BULL;5, 1 & BULL;4-1 & BULL;7), gastrointestinal (1 & BULL;4, 1 & BULL;3-1 & BULL;6), and head and neck (1 & BULL;2, 1 & BULL;1-1 & BULL;4) interventions. Survivors of Hodgkin lymphoma (35-year MCC 333 & BULL;3 [95% CI 320 & BULL;1-346 & BULL;6] per 100 survivors), Ewing sarcoma (322 & BULL;9 [294 & BULL;5-351 & BULL;3] per 100 survivors), and osteosarcoma (269 & BULL;6 [250 & BULL;1-289 & BULL;2] per 100 survivors) had the highest cumulative burdens of late, major surgical interventions. Locoregional surgery or radiotherapy cancer treatment were associated with undergoing late surgical intervention in the same body region or organ system. Interpretation Childhood cancer survivors have a significant burden of late, major surgical interventions, a late effect that has previously been poorly quantified. Survivors would benefit from regular health-care evaluations aiming to anticipate impending surgical issues and to intervene early in the disease course when feasible.Funding US National Institutes of Health, US National Cancer Institute, American Lebanese Syrian Associated Charities, and St Jude Children's Research Hospital.Copyright & COPY; 2023 Elsevier Ltd. All rights reserved.

The appropriate management of pediatric liver malignancies, primarily hepatoblastoma and hepatocellular carcinoma, requires an in depth understanding of contemporary preoperative risk stratification, experience with advanced hepatobiliary surgery, and a good relationship with one's local or regional liver transplant center. While chemotherapy regimens have become more effective, operative indications more well-defined, and overall survival improved, the complexity of liver surgery in small children provides ample opportunity for protocol violation, inadequate resection, and iatrogenic morbidity. These guidelines represent the distillation of contemporary literature and expert opinion as a means to provide a framework for preoperative planning and intraoperative decision-making for the pediatric surgeon.

INTRODUCTION:Neuroblastoma is the most common extracranial pediatric tumor, accounting for 5-8% of all childhood cancers. Neuroblastomas arise from catecholamine-secreting neural crest cells and their metabolites, vanillylmandelic acid and homovanillic acid, that are readily detected in urine. Although rarely seen in clinical practice, case reports exist documenting severe intraoperative hypertension. However, data on the incidence of intraoperative hypertension are lacking.METHODS:This report is a single-center retrospective review of patients with neuroblastoma who underwent surgical resection (n = 102) at Boston Children's Hospital from July 1, 2012 to February 28, 2021. Significant intraoperative hypertension was defined as maximum systolic blood pressure greater than 95th percentile +12 mmHg based on normative blood pressure data. Statistical analysis was performed using Fisher's exact test, Wilcoxon rank-sum test, and logistic regression.RESULTS:The overall incidence of intraoperative hypertension was 13% (n = 13/102). Higher American Society of Anesthesiologists (ASA) physical status was associated with intraoperative hypertension. Antihypertensive medications were administered intraoperatively in 9% of cases (n = 9), and the use was significantly associated with intraoperative hypertension. Of patients with preoperative urine catecholamine data (n = 82), all 10 patients who had intraoperative hypertension were noted to have elevated preoperative urine catecholamines. Intraoperative hypertension was not associated with postoperative hypertension, postoperative hypotension, or increased intensive care unit length of stay.DISCUSSION/CONCLUSION:Intraoperative hypertension in patients with neuroblastoma remains a relatively uncommon occurrence; however, it does occur at a frequency higher than previously described. While intraoperative hypertension is associated with an increased use of antihypertensive medications in the operating room, it is not associated with adverse perioperative outcomes.

BackgroundSurvival for children with metastatic hepatoblastoma (HB) remains suboptimal. We report the response rate and outcome of two courses of vincristine/irinotecan/temsirolimus (VIT) in children with high-risk (HR)/metastatic HB. ProceduresPatients with newly diagnosed HB received HR window chemotherapy if they had metastatic disease or a serum alpha-fetoprotein (AFP) level less than 100 ng/mL. Patients received vincristine (days 1 and 8), irinotecan (days 1-5), and temsirolimus (days 1 and 8). Cycles were repeated every 21 days. Responders had either a 30% decrease using RECIST (Response Evaluation Criteria in Solid Tumors) criteria OR a 90% (>1 log(10) decline) AFP decline after two cycles. Responders received two additional cycles of VIT intermixed with six cycles of cisplatin/doxorubicin/5-fluorouracil/vincristine (C5VD). Nonresponders received six cycles of C5VD alone. ResultsThirty-six eligible patients enrolled on study. The median age at enrollment was 27 months (range: 7-170). Seventeen of 36 patients were responders (RECIST and AFP = 3, RECIST only = 4, AFP only = 10). The median AFP at diagnosis was 222,648 ng/mL and the median AFP following two VIT cycles was 19,262 ng/mL. Three-year event-free survival was 47% (95% confidence interval [CI]: 30%-62%), while overall survival was 67% (95% CI: 49%-80%). ConclusionVIT did not achieve the study efficacy endpoint. Temsirolimus does not improve the response rate seen in patients treated with vincristine and irinotecan (VI) alone as part of the initial treatment regimen explored in this study. Additionally, AFP response may be a more sensitive predictor of disease response than RECIST in HB.

PURPOSE To evaluate long-term morbidity and mortality among unilateral, nonsyndromic Wilms tumor (WT) survivors according to conventional treatment regimens. METHODS Cumulative incidence of late mortality (≥ 5 years from diagnosis) and chronic health conditions (CHCs) were evaluated in WT survivors from the Childhood Cancer Survivor Study. Outcomes were evaluated by treatment, including nephrectomy combined with vincristine and actinomycin D (VA), VA + doxorubicin + abdominal radiotherapy (VAD + ART), VAD + ART + whole lung radiotherapy, or receipt of ≥ 4 chemotherapy agents. RESULTS Among 2,008 unilateral WT survivors, 142 deaths occurred (standardized mortality ratio, 2.9, 95% CI, 2.5 to 3.5; 35-year cumulative incidence of death, 7.8%, 95% CI, 6.3 to 9.2). The 35-year cumulative incidence of any grade 3-5 CHC was 34.1% (95% CI, 30.7 to 37.5; rate ratio [RR] compared with siblings 3.0, 95% CI, 2.6 to 3.5). Survivors treated with VA alone had comparable risk for all-cause late mortality relative to the general population (standardized mortality ratio, 1.0; 95% CI, 0.5 to 1.7) and modestly increased risk for grade 3-5 CHCs compared with siblings (RR, 1.5; 95% CI, 1.1 to 2.0), but remained at increased risk for intestinal obstruction (RR, 9.4; 95% CI, 3.9 to 22.2) and kidney failure (RR, 11.9; 95% CI, 4.2 to 33.6). Magnitudes of risk for grade 3-5 CHCs, including intestinal obstruction, kidney failure, premature ovarian insufficiency, and heart failure, increased by treatment group intensity. CONCLUSION With approximately 40% of patients with newly diagnosed WT currently treated with VA alone, the burden of late mortality/morbidity in future decades is projected to be lower than that for survivors from earlier eras. Nevertheless, the risk of late effects such as intestinal obstruction and kidney failure was elevated across all treatment groups, and there was a dose-dependent increase in risk for all grade 3-5 CHCs by treatment group intensity.

Delivery of hydrophilic small molecule therapeutics by traditional drug delivery systems is challenging. Herein, we have used the specific interaction between DNA aptamers and drugs to create simple and effective drug depot systems. The specific binding of a phosphorothioate-modified aptamer to drugs formed non-covalent aptamer/drug complexes, which created a sustained release system. We demonstrated the effectiveness of this system with small hydrophilic molecules, the site 1 sodium channel blockers tetrodotoxin and saxitoxin. The aptamer-based delivery system greatly prolonged the duration of local anesthesia and reduced systemic toxicity. The beneficial effects of the aptamers were restricted to the compounds they were specific to. These studies establish aptamers as a class of highly specific, modifiable drug delivery systems, and demonstrate potential usefulness in the management of postoperative pain.

Background: Chyle leaks are a common post-operative complication following solid-tumor resection in pe-diatric patients. Current treatments for persistent chyle leaks are limited, leading many patients to experience prolonged hospitalization, nutritional deficits and/or delays in cancer therapies. Lymphatic embolization is an emerging treatment option for chyle leaks, however, limited reports exist of its use in pediatric populations.Methods: We conducted a retrospective review of pediatric patients (<18) who underwent lymphangiogram with intent for lymphatic embolization for the management of chyle leaks following solid-tumor resection between 2017 and 2022.Results: Seven patients underwent a total of 11 attempted lymphatic embolization procedures after current standard of care treatments failed to resolve the leak. Lymphangiograms identified a chyle leak in 6 of 7 patients and embolization had a technical success rate of 73%. The complication rate was 9% and complications were limited to one episode of inadvertent gastric wall perforation that did not result in a gastric leak. Lymphatic embolization was ultimately associated with chyle leak resolution in 100% of patients within a median of 24 days, however, repeat embolization was required in 5 of 7 patients (83%).Conclusion: Lymphatic embolization appears to be a safe and effective treatment for persistent chyle leaks in pediatric patients, leads to a direction reduction in chyle output, and has high rates of technical and clinical success. Complete resolution of the chyle leak may require multiple embolization procedures. Further work is needed to determine whether earlier intervention may offer benefit for the management of pediatric chyle leaks. Level of Evidence: IV. (c) 2023 Elsevier Inc. All rights reserved.