RATIONALE/ OBJECTIVES:Data on longitudinal changes in pulmonary function in long-term childhood cancer survivors remain limited. Using a well-characterized cohort of childhood cancer survivors, we analyzed these changes through serial PFT assessments among those exposed to pulmonary-toxic therapy, with available radiation dosimetry data. METHODS:In this single-institutional, hospital-based, retrospective cohort study, Z-scores for FEV1, TLC, and DLCOcorr were calculated, with Z-score ≤-1.65 being considered abnormal. Patient and treatment-related risk-factors for worsening or persistently abnormal Z-scores were assessed. Associations between Z-scores and changes in six-minute walk distance (6MWT), QOL, and persistence or new development of cardiopulmonary and fatigue-related symptoms were studied. RESULTS:Among 606 survivors at a median of 27.2 (range 11.3-54.0) years from diagnosis, abnormal FEV1, TLC, and DLCOcorr Z-scores were noted in 49.5%, 51.4%, and 38.0%, respectively. Among those with ≥2 PFT assessments (n = 480), all Z-scores declined, most pronounced at ≥ 30-years from diagnosis. Each 10% increase in lung tissue receiving ≥10 Gy radiation was associated with declining or persistently abnormal FEV1 at 5-years after first PFT (OR 1.18, 95%CI 1.03-1.35). Obesity was associated with declining FEV1 and TLC; Smoking status was associated with declining DLCOcorr Z-scores. Worsening or persistently abnormal Z-scores for FEV1, TLC, and DLCOcorr were associated with decline in 6MWT distance and self-reported physical function. Decline in Z-scores were associated with greater odds of persistent or newly developed shortness of breath with exercise. Decline in DLCOcorr was associated with chronic cough, faintness, and dizziness. CONCLUSIONS:Pulmonary function declined over time in adult survivors of childhood cancer exposed to pulmonary-toxic therapy, with radiation exposure portending higher risk. Declines were associated with reduced exercise capacity and QOL and increased cardiopulmonary and fatigue-related symptoms. Our findings help identify survivors who may benefit from interventions to preserve pulmonary function.

Purpose Significant advancements in external beam radiotherapy (RT) over the past 20+ years have occurred with evolution from 2D techniques based on plain film x-rays to three-dimensional (3D) conformal and intensity modulated photon techniques. Likewise, proton radiotherapy (PRT) was also introduced and has become more widely available. Each advance in radiation technique improves targeting and has the potential to mitigate late effects associated with RT. In this study, we use metadata from past and present Children’s Oncology Group (COG) trials that included RT to describe the evolution of different RT modalities across time and disease sites. Methods Imaging and Radiation Oncology Core (IROC) database was queried for protocols with at least one patient receiving RT during 1998-2025. Protocol metadata including primary disease site, study timeline and quality assurance (QA) was extracted, as was non-identifiable patient-level variables including age, institution, year of enrollment, and RT modality utilized. Descriptive statistics were used for downstream analysis. Results The study population comprised 8,898 patients, including 7,881 from the USA and 1,017 from other countries. The median age at enrollment was 9 years; California, Texas, Florida and New York were among the top contributing states. Of the 83 included COG trials, 48 included at least one patient receiving PRT. The number of trials allowing PRT peaked in 2010 with 17 protocols. Trials involving central nervous system (CNS) tumors and rhabdomyosarcoma soft tissue sarcomas (RST) dominated both in the number of trials and enrollment. They were also among the earliest to incorporate PRT into treatment protocols. From 1998 to 2025, 3D photon-based treatments declined from 73% to 15%, while IMRT/VMAT usage rose from 26% to 89% over the same interval. The use of PRT increased from 2% pre-2000 to nearly 40% in 2021, which has since stabilized. QA review demonstrated >90% protocol compliance across all RT modalities both nationally and internationally. Conclusions Over 25 years of COG experience, photon therapy has transitioned from 3D conformal to IMRT/VMAT, while PRT use has continued to expand, particularly in CNS and RST trials. These trends highlight how pediatric cooperative-group studies continue to shape national standards and underscore the need for future work linking modality adoption with toxicity, survivorship, and access across diverse treatment settings.

10047 Background: Risk for impaired kidney function varies with radiation therapy (RT). We compared different methods for quantifying RT. Methods: Kidney function was graded in 2753 survivors (>10 years post-diagnosis, age ≥18 years) and 806 community controls (CC) per the Kidney Disease International Global Outcomes 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD). Multivariable logistic regression was used to evaluate the associations between grades 3-5 CKD and demographics and treatment exposures. RT was expressed as percentage of total kidney volume treated with 5 Gray (Gy) or more (V5), 10 Gy or more (V10) Gray, Children’s Oncology Group (COG) abdominal RT, or total body irradiation (TBI)/whole abdomen RT (WA). Model discrimination was assessed using area under the receiver operating characteristic curve (AUC). Results: 2.1% of survivors had stages 3 to 5 CKD, compared to 0.12% of CC (Odds Ratio (OR): 17.0 (95% confidence interval (CI) 2.9, 682.8), p < 0.001). Significant associations between higher risks of grades 3-5 CKD and demographic and treatment exposures were identified in separate regression models (Table). AUCs were 0.891, 0.888 and 0.896 for V5, V10, and TBI/WA, models respectively. Conclusions: TBI/WA is a more readily available exposure designation than V5 or V10. These results inform identification of survivors at highest risk for CKD. V5 V10 COG TBI/WA Predictors OR (95%CI) p OR (95%CI) p OR (95%CI) p OR (95%CI) p Race (White vs non-White) 1.68(0.81 – 3.30) 0.144 1.71(0.82 – 3.35) 0.133 1.80(0.89 – 3.44) 0.086 1.71(0.85 – 3.28) 0.116 Age at evaluation 1.09(1.04 – 1.13) <0.001 1.09(1.05 – 1.13) <0.001 1.09(1.05 – 1.13) <0.001 1.10(1.05 – 1.14) <0.001 Hypertension 8.21(4.12 – 17.61) <0.001 8.27(4.15 – 17.71) <0.001 8.61(4.41 – 18.02) <0.001 8.61(4.42 – 17.97) <0.001 Nephrectomy (yes/no) 2.44(0.88 – 6.12) 0.069 2.68(0.97 – 6.72) 0.044 4.23(1.81 – 9.48) 0.001 3.42(1.36 – 8.01) 0.006 Ifosfamide (per 1000 mg/m 2 ) 1.04(1.02 – 1.06) <0.001 1.04(1.02 – 1.05) <0.001 1.04(1.03 – 1.06) <0.001 1.04(1.03 – 1.06) <0.001 Cisplatin (per 100 mg/m 2 ) 1.46(1.26 – 1.68) <0.001 1.46(1.26 – 1.67) <0.001 1.47(1.27 – 1.68) <0.001 1.49(1.29 – 1.70) <0.001 Carboplatin (per 100 mg/m 2 ) 1.03(1.00 – 1.06) 0.024 1.03(1.00 – 1.06) 0.027 1.03(1.00 – 1.06) 0.012 1.03(1.00 – 1.06) 0.012 Calcineurin inhibitor (yes/no) 7.29(1.86 – 26.92) 0.003 7.9(11.94 – 30.52) 0.003 14.79(4.32 – 48.28) <0.001 9.31(2.43 – 33.77) 0.001 Doses Abelcet and/or Ambisome 1.02(0.94 – 1.06) 0.516 1.02(0.94 – 1.06) 0.513 1.02(0.95 – 1.06) 0.469 1.02(0.94 – 1.06) 0.555 Doses amphotericin B 1.00(0.95 – 1.03) 0.990 1.00(0.95 – 1.03) 0.998 1.00(0.96 – 1.03) 0.981 1.00(0.95 – 1.03) 0.936 V5 (per 10%) 1.14(1.04 – 1.24) 0.004 V10 (per 10%) 1.12(1.01 – 1.23) 0.021 COG abdominal radiation therapy (yes/no) 1.49(0.76 – 2.85) 0.235 TBI or WA (yes/no) 2.73(1.08 – 6.61) 0.029

10002 Background: Outcomes for pediatric patients with metastatic rhabdomyosarcoma (RMS) remain poor despite therapy intensification and novel agents. RMS13 (NCT01871766) was a phase II prospective multicenter trial evaluating a response-based approach to metastatic site radiotherapy (RT). We report outcomes related to metastatic disease management in this high-risk (HR) population. Methods: Event-free survival (EFS) and metastatic site control were analyzed for HR patients treated with interval compressed chemotherapy, risk-adapted RT to primary and metastatic site, and maintenance therapy. EFS was defined from therapy start to relapse, progression, death or last follow-up. Metastatic RT was delivered between interval-compressed and maintenance therapy for non–bone marrow metastatic sites without complete response (CR). RT omission criteria included PET negativity, lesion size <1 cm, or complete surgical resection with negative margins. Metastatic RT used protons: 25 Gy in 5 or 50.4 Gy in 28 fractions, by lesion size. Primary tumor control consisted primarily of proton RT, with limited use of surgery plus adjuvant RT. Results: From 2015 to 2020, 39 HR patients were enrolled (median age 9.5 years). Most patients were FOXO1 fusion–positive (64%), had nodal involvement (74%), and an Oberlin score >1 (67%). Median follow-up was 23.1 months overall (78.5 months for non-progressors). Five-year EFS was 31.6% (95% CI, 19.7-50.6%), differing by Oberlin score >1 – 16.2% (95% CI, 6.6–39.8%), ≤1 - 61.5% (95% CI, 40-94.6%). Twenty-six patients relapsed: 22 had distant failure (DF), 6 had local failure (LF), and 2 had both DF and LF. The 5-year cumulative incidence of LF was 14.4% (95% CI, 5–28), and 54% for DF (95% CI, 36–69), establishing DF as the predominant pattern of failure. Twenty-six patients reached the protocol window for metastatic-site RT (weeks 47–54): 11 soft-tissue metastases, 6 bone, 8 both, and 1 bone marrow only, with a 5-year EFS of 42.3% (95% CI 23.3-61.3%). Among 21 patients achieving CR at metastatic sites without RT, 5-year EFS was 38.1% (95% CI 17.3–58.9%), and cumulative incidence of any DF was 57.1% (95% CI 35.9–78.3%). Seven patients (33%) recurred at initially involved metastatic sites, primarily soft tissue. In-site recurrence occurred in 7/17 (41%) non-irradiated soft-tissue sites versus 1/12 (8%) bony sites. Only one recurrence occurred among irradiated soft-tissue sites. Conclusions: Soft-tissue metastatic sites in CR that were not irradiated had high recurrence rates, while bony sites achieved durable control without RT. Future trials should consider consolidative RT for soft-tissue metastases regardless of response in HR RMS. Clinical trial information: NCT01871766 . Recurrence by metastatic site. CR, no RT (N) Recurrence, non-RT, N(%) PR, RT (N) Recurrence, No RT, N (%) Bone metastases (n=14) 12 1 (8) 2 0 Soft-tissue metastases (n=19) 17 7 (41) 2 1 (5.9) CR, complete response; PR, partial response; RT, radiotherapy.

The Pediatric Hodgkin Consortium (PHC) hypothesized that increasing chemotherapeutic dose-density for Hodgkin lymphoma (HL) they could increase the complete response rate among favorable risk patients with HL after 8 weeks of Stanford V compared to 8 weeks of VAMP. This would translate to a decrease in patients who required radiation therapy (RT) to achieve a cure. HOD08 (NCT00846742) was a phase II multicenter investigator-initiated single- arm trial for patients ≤ 21 years of age with previously untreated stage IA or IIA HL without mediastinal bulk or extranodal disease extension and fewer than three sites of disease. Treatment consisted of a modified 8-week Stanford V regimen (vinblastine, doxorubicin, vincristine, bleomycin, mechlorethamine, etoposide and prednisone). Modified tailored field RT was administered only to disease sites achieving less than a CR. The primary objective was to increase CR rate after 8 weeks of chemotherapy by at least 20% (from an estimated 44% to 64%) compared to patients treated on a previous trial (HOD99). HOD08 enrolled 85 patients with HL and 72 were evaluable for the primary objective of whom 55 (76.4%) achieved a CR at all sites and did not receive RT. The 5-year event-free survival (EFS) and overall survival (OS) rates for the entire cohort were 87.4% (95% confidence interval (CI) 80.4%-95.0%) and 98.7% (95% CI 96.2%-100%), respectively. A dose-dense modified Stanford V regimen reduced the proportion of low-risk pediatric patients with HL who received RT while maintaining excellent outcomes. NCT00846742

Background and purpose:A novel method was developed to detect body surface changes on daily cone-beam computed tomography (CBCT) and estimate the impact on proton plan quality for pediatric patients. Materials and methods:Simulation CT, daily CBCT, and repeat CT images were collected for 21 pediatric non-central nervous system (CNS) patients. Changes in the body surface in the proton beam path (ΔSurfaceCBCT) were calculated for each spot by comparing simulation CT with daily CBCT. Subsequently, changes in water equivalent path length (WEPL) (ΔWEPLSynthetic CT) were calculated for each spot by comparing the simulation CT with the synthetic CT converted from daily CBCT. The ground truth surface (ΔSurfaceRepeat CT) and WEPL changes (ΔWEPLRepeat CT) were calculated by comparing the simulation CT with the repeat CT taken on the same day as the CBCT. Results:The root-mean-square (RMS) error between the ΔSurfaceCBCT and ΔSurfaceRepeat CT was 1.3 mm, while the RMS error between ΔWEPLSynthetic CT and ΔWEPLRepeat CT was 1.6 mm. A strong linear correlation was determined between ΔSurfaceCBCT and ΔWEPLSynthetic CT (R2 = 0.97). The non-linear regression analysis of the dose volume parameters indicated that a 5 % decrease in clinical target volume (CTV) Dmin and D99% was caused by 3.9 mm and 6.3 mm of ΔSurfaceCBCT, and 4.0 mm and 6.6 mm of ΔWEPLSynthetic CT, respectively. Conclusions:The findings revealed that a 5 mm change in body surface can lead to a significant degradation of plan quality, reducing CTV Dmin by 11.7 % and underscoring the need for adapting treatment plan.

Study Aim: Patients with high-risk Ewing sarcoma (ES) have dismal outcomes despite aggressive multimodal therapy. This phase II, single-institution study evaluated the response rate to two up-front cycles of irinotecan, temozolomide, and temsirolimus (ITT) and assessed the tolerability of maintenance therapy following standard treatment in high-risk ES. Methods: Eligible patients had newly diagnosed high-risk ES (age ≥14 years old, metastatic disease, or primary pelvic tumor). The therapy included two cycles of window therapy (ITT) followed by interval-compressed chemotherapy (vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide) and maintenance therapy (cyclophosphamide, sorafenib, and bevacizumab). A two-stage sequential design was employed to assess a >50% WHO response (CR or PR) with 80% power. Patients who required emergent radiation were excluded from receiving window therapy. Results: Sixteen patients (median age 12.2 years; range 4.8–23.6 years) were enrolled (12 evaluable for overall response, 10 for primary tumor response). Only three achieved a PR to window therapy, leading to study closure. All evaluable patients demonstrated a decline in their primary tumor volume (mean decline: 32.5%, standard deviation: 17.6%, p-value: 0.0005) and SUV peak (mean decline: 49.9%, standard deviation: 21.1%, p-value: 0.002). Maintenance therapy was well tolerated, with only 2/13 patients discontinuing due to toxicity. Conclusions: ITT did not achieve the prespecified response rate of 50%, according to WHO criteria; however, all patients exhibited decreased volume and metabolic activity, highlighting the limitations of conventional response assessments. Maintenance therapy was feasible and well tolerated. Although limited by small sample size, heterogeneous disease presentations, and the absence of a control arm, this study supports further evaluation of ITT and a maintenance approach in larger, randomized trials for high-risk ES.

Nasopharyngeal carcinoma (NPC) is rare in children and adolescents. Although radiation has been an essential component of treatment for this often-curable tumor, it can lead to severe side-effects in survivors. Therefore, the reduction of radiation-related long-term effects by limiting radiation dose is a key clinical priority. Previous pediatric clinical trials by the Children's Oncology Group (COG) and the German Society of Pediatric Oncology and Hematology (GPOH) have treated patients with induction chemotherapy followed by radiation with concomitant chemotherapy and adjuvant immunotherapy with interferon (GPOH), leading to excellent survival. These groups now take us forward into a new age of clinical trials using chemoimmunotherapy induction with anti-PD-1 therapies followed by response-adapted, dose-reduced radiation with the goal of preserving outcomes while limiting late effects and morbidities.

BACKGROUND:The relationships among treatment exposures, body composition, and estimated glomerular filtration rate (eGFR) in adult survivors of Wilms tumor have not been well studied. METHODS:We evaluated body composition with dual-energy x-ray absorptiometry (DXA) and eGFR with the updated Chronic Kidney Disease Epidemiology Collaboration equations (creatinine only-eGFRCr, cystatin C only-eGFRCysC, creatinine and cystatin C-eGFRCr+CysC) without race in 134 adults previously treated for unilateral, non-syndromic Wilms tumor at St. Jude Children's Research Hospital between 1964 and 2004 with chemotherapy and with (hemiabdomen [HA] or whole abdomen [WA]) or without radiation therapy (RT). Z-scores for DXA variables were calculated using data from the National Health and Nutrition Examination Survey. RESULTS:WART was associated with a lower relative total (p = 0.004) and trunk (p < 0.001) lean mass, eGFRCr (p = 0.008), eGFRCysC, (p < 0.001), and eGFRCr+CysC (p < 0.001), and higher values of cystatin C (p < 0.001). Linear regression demonstrated that relative total lean mass (p = 0.009) and relative trunk lean mass (p < 0.001) Z-scores, and eGFRCr (p = 0.013) were lower among those who received WART compared to No RT patients. CONCLUSIONS:WART is associated with lower relative total and trunk lean mass Z-scores and eGFR, regardless of the equation used, and is lower in survivors treated with WART compared to unirradiated survivors of unilateral, non-syndromic WT. Assessments using other GFR measures may provide greater insight into the mechanism and magnitude of kidney function loss among WART-treated WT survivors.

BACKGROUND:Adult survivors of unilateral, nonmetastatic, non-syndromic Wilms tumor (WT) treated with whole abdomen radiation therapy (WART) are at risk for impaired kidney function. The impact of bias and accuracy on estimated glomerular filtration rate (eGFR) among adult survivors of WT has not been well documented. PROCEDURE:We clinically evaluated male and female WT survivors with creatinine and cystatin C, calculated eGFR using the Chronic Kidney Disease-Epidemiology equations with and without cystatin C, and measured 99mTc diethylenetriamine pentaacetic acid (DTPA) plasma clearance. WT survivors treated with unilateral nephrectomy (UN), non-nephrotoxic chemotherapy (NNC) and WART or treated with UN, no radiation therapy, and NNC were enrolled. Correlations between 99mTc DTPA clearance and eGFR were calculated. Bias and the percentage of eGFR calculations that differed from the 99mTc DTPA clearance by 10% or less (P10) or 30% or less (P30) (accuracy) were calculated. RESULTS:Among female WT survivors, none of the eGFR calculations was statistically significantly correlated with 99mTc DTPA clearance. Among both unirradiated and WART-treated male WT survivors, 99mTc DTPA clearance correlated well with eGFR calculations that included creatinine. eGFR calculations that included creatinine were positively biased among female participants compared to 99mTc DTPA clearance, and no P30 was greater than 90% among either irradiated males or females. CONCLUSIONS:Among female survivors of unilateral, nonmetastatic, non-syndromic WT who have undergone UN, eGFR is poorly correlated with, is positively biased, and lacks sufficient accuracy, compared to 99mTc DTPA clearance.

Background Suffering at the end-of-life (EOL) can impact the perception of a “good death” and ultimately affect bereavement for families of children with cancer. Palliative radiation (pXRT) is a tool that can address pain, mitigate suffering and improve quality of life. Methods A retrospective medical record review of pediatric oncology patients who died over an 11-year period was completed. Descriptive analysis and non-parametric tests to compare groups were used. Results 2202 total deaths occurred during the study period; 167 patients met study criteria, reflecting a 7.6% incidence of pXRT use at the EOL. Most patients were white (68%) and male (59%), with a median age of 9 years. Solid tumors were most common (52%), followed by CNS tumors (38%), and leukemia (10%). pXRT was primarily used to treat pain (37%) and focused on sites including brain/spine (37%), head/neck (24%), and pelvis (12%). Mean radiation dose delivered was 23.8Gy (range: 1.8-55.8Gy) in a median of 7 fractions (range: 1-31). Side effects were rare and 58% of patients had a decrease in reported pain scores. Additionally, 87% received a pediatric palliative care (PPC) consultation which increased the likelihood for hospice referral, documented DNR preferences and decrease episodes of CPR on the day of death. Conclusions There is underutilization and significant variability in the use of pXRT during EOL in pediatric oncology. Barriers to this tool may include physician perceptions, family/patient preferences, and logistical hardships. Guidelines to standardize pXRT, alongside earlier PPC integration, may guide clinician decision making and increase pXRT utilization.

(1) Background: Proton therapy, a precise form of radiation treatment, can be significantly affected by variations in bowel content. The purpose was to identify the most beneficial gantry angles that minimize deviations from the treatment plan quality, thus enhancing the safety and efficacy of proton therapy for Wilms’ tumor patients. (2) Methods: Thirteen patients with Wilms’ tumor, enrolled in the SJWT21 clinical trial, underwent proton therapy. The variations in bowel gas were systematically monitored using daily Cone Beam Computed Tomography (CBCT) imaging. Air cavities identified in daily CBCT images were analyzed to construct daily verification plans and measure water equivalent path length (WEPL) changes. A worst-case scenario simulation was conducted to identify the safest beam angles. (3) Results: The study revealed a maximum decrease in target dose (ΔD100%) of 8.0%, which corresponded to a WEPL variation (ΔWEPL) of 11.3 mm. The average reduction in target dose, denoted as mean ΔD100%, was found to be 2.8%, with a standard deviation (SD) of 3.2%. The mean ΔWEPL was observed as 3.3 mm, with an SD of 2.7 mm. The worst-case scenario analysis suggested that gantry beam angles oriented toward the patient’s right and posterior aspects from 110° to 310° were associated with minimized WEPL discrepancies. (4) Conclusions: This study comprehensively evaluated the influence of bowel gas variability on treatment plan accuracy and proton range uncertainties in pediatric proton therapy for Wilms’ tumor.

BACKGROUND:Patients with bilateral Wilms tumor initially receive neoadjuvant chemotherapy to shrink the tumors and increase the likelihood of successful nephron-sparing surgery. Biopsy of poorly responding tumors is often done to better understand therapy resistance. The purpose of this retrospective, single-institution study was to determine whether initial chemotherapy response is associated with tumor histology, potentially obviating the need for biopsy or change in chemotherapy. METHODS:Patients with synchronous bilateral Wilms tumors who underwent surgery at St Jude Children's Research Hospital from January 2000 to March 2022 were considered for this study. A mixed-effects logistic regression model was used to evaluate the likelihood of the tumor being stromal predominant, as predicted by tumor response to neoadjuvant chemotherapy. RESULTS:A total of 68 patients were eligible for this study. Tumors that increased in size had an odds ratio of 19.5 (95% confidence interval [CI] = 2.46 to 155.03) for being stromal predominant vs any other histologic subtype. Age at diagnosis was youngest in patients with stromal-predominant tumors, with a mean age of 18.8 (14.1) months compared with all other histologic subtypes (χ2 = 7.05, P = .07). The predictive value of a tumor growing combined with patient aged younger than 18 months for confirming stromal-predominant histology was 85.7% (95% CI = 57.18% to 93.5%). CONCLUSIONS:Tumors that increased in size during neoadjuvant chemotherapy were most frequently stromal-predominant bilateral Wilms tumor, especially in younger patients. Therefore, nephron-sparing surgery, rather than biopsy, or extension or intensification of neoadjuvant chemotherapy, should be considered for bilateral Wilms tumors that increase in volume during neoadjuvant chemotherapy, particularly in patients aged younger than 18 months.

BackgroundLocal control for patients with Ewing sarcoma (EWS) who present with large tumors are suboptimal when treated with standard radiation therapy (RT) doses of 54-55.8 Gy. The purpose of this study is to determine local control and toxicity of dose-escalated RT for tumors >= 8 cm (greatest diameter at diagnosis) in pediatric and young adult patients with EWS.MethodsEligible patients <= 30 years old with newly diagnosed EWS >= 8 cm treated with definitive conformal or intensity modulated photon, or proton radiation therapy techniques were included. All patients in the study received dose-escalated RT doses. Outcomes included overall survival (OS), event-free survival (EFS), local failure rates, and toxicity.ResultsThirty-two patients were included, 20 patients presented with metastatic disease and 12 patients with localized disease. The median RT dose was 64.8 Gy (range, 59.4-69.4 Gy) with variability of doses to protect normal surrounding tissues. All patients received systemic chemotherapy. The 5-year OS and EFS for the cohort was 64.2% and 42%, respectively. The 5-year cumulative incidence of local failure was 6.6%. There were two combined local and distant failures with no isolated local failures. Twenty-nine patients experienced short term toxicity, 90% of those being radiation dermatitis. Twenty-seven patients experienced long-term toxicity, with only one experiencing grade 4 toxicity, a secondary malignancy after therapy.ConclusionThis study demonstrates that definitive RT for pediatric and young adult patients with EWS >= 8 cm provides high rates of local control, while maintaining a tolerable toxicity profile. Dose-escalated radiation therapy in children and young adult patients with Ewing sarcoma improves local control rates. The short- and long-term toxicity profile of this approach is tolerable and comparable to historical standard dose radiation therapy.

Background and purposeThe purpose of this study was to address the lack of published data on the use of brachytherapy in pediatric rhabdomyosarcoma by describing current practice as starting point to develop consensus guidelines.Materials and methodsAn international expert panel on the treatment of pediatric rhabdomyosarcoma comprising 24 (pediatric) radiation oncologists, brachytherapists and pediatric surgeons met for a Brachytherapy Workshop hosted by the European paediatric Soft tissue Sarcoma Study Group (EpSSG). The panel’s clinical experience, the results of a previously distributed questionnaire, and a review of the literature were presented.ResultsThe survey indicated the most common use of brachytherapy to be in combination with tumor resection, followed by brachytherapy as sole local therapy modality. HDR was increasingly deployed in pediatric practice, especially for genitourinary sites. Brachytherapy planning was mostly by 3D imaging based on CT. Recommendations for patient selection, treatment requirements, implant technique, delineation, dose prescription, dose reporting and clinical management were defined.ConclusionsConsensus guidelines for the use of brachytherapy in pediatric rhabdomyosarcoma have been developed through multicenter collaboration establishing the basis for future work. These have been adopted for the open EpSSG overarching study for children and adults with Frontline and Relapsed RhabdoMyoSarcoma (FaR-RMS).

Purpose: The Audiovisual-Assisted Therapeutic Ambience in Radiotherapy (AVATAR) trial was a prospective multicenter study (NCT03991156) examining the combination of video immersion with radiation therapy and was successfully conducted through the collaboration of pediatric radiation oncology teams at 10 institutions independent of any pre-existing consortium. We sought to analyze and report the methodology of trial conception and development, process map, and cost. Methods and Materials: The study enrolled patients aged 3 to 10 years preparing to undergo radiation therapy, integrated the combination of AVATAR-based video immersion with radiation therapy at each institution, and offered AVATAR use as an alternative to anesthesia, with rates of anesthesia use and outcomes of serial standardized anxiety and quality-of-life assessments assessed among the 81 children enrolled. A process map was created based on the trial timeline with the following components: study development time (time from conception of the trial to the accrual of the first patient, including design phase, agreement and approval phase, and site preparation phase), and accrual duration time (time from the first to last accrual). Costs and institutional success rates were calculated. Results: Time from inception of study to last accrual was 3.6 years (1313 days). The study development time was 417 days (31.7%), and accrual duration time was 896 days (68.3%), with the final 50% of accrual occurring in <6 months. Equipment cost was approximately $550 per institution and was covered by funding from the lead study institution. All 10 centers were successful with AVATAR implementation, defined as ≥50% of patients able to avoid anesthesia with the use of AVATAR, including centers with both photon and proton therapy. Conclusions: This report elaborates on the methodology and timeline of trial conception and development using data from a previously published supportive care study combining video immersion with radiation therapy among 10 cooperating pediatric oncology institutions. It highlights the potential for multicenter collaborations on prospective trials integrating supportive care therapies with radiation therapy.

Wilms tumor (WT) is the most common kidney tumor in pediatric patients. Intravascular extension of WT above the level of the renal veins is a rare manifestation that complicates surgical management. Patients with intravascular extension are frequently asymptomatic at diagnosis, and tumor thrombus extension is usually diagnosed by imaging. Neoadjuvant chemotherapy is indicated for thrombus extension above the level of the hepatic veins and often leads to thrombus regression, obviating the need for cardiopulmonary bypass in cases of cardiac thrombus at diagnosis. In cases of tumor extension to the retrohepatic cava, neoadjuvant therapy is not strictly indicated, but it may facilitate the regression of tumor thrombi, making resection safer. Hepatic vascular isolation and cardiopulmonary bypass increase the risk of bleeding and other complications when utilized for tumor thrombectomy. Fortunately, WT patients with vena caval with or with intracardiac extension have similar overall and event-free survival when compared to patients with WT without intravascular extension when thrombectomy is successfully performed. Still, patients with metastatic disease at presentation or unfavorable histology suffer relatively poor outcomes. Dedicated pediatric surgical oncology and pediatric cardiothoracic surgery teams, in conjunction with multimodal therapy directed by a multidisciplinary team, are preferred for optimized outcomes in this patient population.