Brachytherapy for rhabdomyosarcoma: Survey of international clinical practice and development of guidelines.

BACKGROUND AND PURPOSE: The 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 METHODS: An 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. RESULTS: The 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. CONCLUSIONS: Consensus 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).

Surgical Management of Wilms Tumors with Intravenous Extension: A Multicenter Analysis of Clinical Management with Technical Insights.

BACKGROUND: About 5% of Wilms tumors present with vascular extension, which sometimes extends to the right atrium. Vascular extension does not affect the prognosis, but impacts the surgical strategy, which is complex and not fully standardized. Our goal is to identify elements of successful surgical management of Wilms tumors with vascular extensions. PATIENTS AND METHODS: A retrospective study of pediatric Wilms tumors treated at three sites (January 1999-June 2019) was conducted. The inclusion criterion was the presence of a renal vein and vena cava thrombus at diagnosis. Tumor stage, pre and postoperative treatment, preoperative imaging, operative report, pathology, operative complications, and follow-up data were reviewed. RESULTS: Of the 696 pediatric patients with Wilms tumors, 69 (9.9%) met the inclusion criterion. In total, 24 patients (37.5%) had a right atrial extension and two presented with Budd-Chiari syndrome at diagnosis. Two died at diagnosis owing to pulmonary embolism. All patients received neoadjuvant chemotherapy and thrombus regressed in 35.6% of cases. Overall, 14 patients had persistent intra-atrial thrombus extension (58%) and underwent cardiopulmonary bypass. Most thrombi (72%) were removed intact with nephrectomy. Massive intraoperative bleeding occurred during three procedures. Postoperative renal insufficiency was identified as a risk factor for patient survival (p = 0.01). With a median follow-up of 9 years (range: 0.5-20 years), overall survival was 89% and event-free survival was 78%. CONCLUSIONS: Neoadjuvant chemotherapy with proper surgical strategy resulted in a survival rate comparable to that of children with Wilms tumors without intravascular extension. Clinicians should be aware that postoperative renal insufficiency is associated with worse survival outcomes.

Single-cell multiomics reveals the interplay of clonal evolution and cellular plasticity in hepatoblastoma.

Hepatoblastomas (HB) display heterogeneous cellular phenotypes that influence the clinical outcome, but the underlying mechanisms are poorly understood. Here, we use a single-cell multiomic strategy to unravel the molecular determinants of this plasticity. We identify a continuum of HB cell states between hepatocytic (scH), liver progenitor (scLP) and mesenchymal (scM) differentiation poles, with an intermediate scH/LP population bordering scLP and scH areas in spatial transcriptomics. Chromatin accessibility landscapes reveal the gene regulatory networks of each differentiation pole, and the sequence of transcription factor activations underlying cell state transitions. Single-cell mapping of somatic alterations reveals the clonal architecture of each tumor, showing that each genetic subclone displays its own range of cellular plasticity across differentiation states. The most scLP subclones, overexpressing stem cell and DNA repair genes, proliferate faster after neo-adjuvant chemotherapy. These results highlight how the interplay of clonal evolution and epigenetic plasticity shapes the potential of HB subclones to respond to chemotherapy.

Long-term outcome of combined radiologic and surgical strategy for the management of biliary complications after pediatric liver transplantation.

OBJECTIVES: We aimed to analyze the risk factors for management failure of BC after pediatric liver transplantation (pLT) by retrospectively analyzing primary pLT performed between 1997 and 2018 (n = 620 patients). RESULTS: In all, 117/620 patients (19%) developed BC. The median (range) follow-up was 9 (1.4-21) years. Patient survival at 1, 5 and 10 years was 88.9%, 85.7%, 84.4% and liver graft survival was 82.4%, 77.4%, and 74.3% respectively. Graft not patient survival was impaired by BC (p = 0.01). Multivariate analysis identified the number of dilatation courses > 2 (p = 0.008), prolonged cold ischemia time (p = 0.004), anastomosed multiple biliary ducts (p = 0.019) and hepatic artery thrombosis (p = 0.01) as factors associated with impaired graft survival. The number of dilatation courses > 2 (p < 0.001) and intrahepatic vs anastomotic stricture (p = 0.014) were associated with management failure. Thus, repeated (> 2) radiologic dilatation courses are associated with impaired graft survival and management failure. Overall, graft but not patient survival was impaired by BC.

Corrigendum to "Expert management of congenital portosystemic shunts and their complications" [JHEP Reports 6 (2024)].

[This corrects the article DOI: 10.1016/j.jhepr.2023.100933.].

Reappraisal of prognostic factors used in the European Pediatric Soft Tissue Sarcoma Study Group RMS 2005 study for localized rhabdomyosarcoma to optimize risk stratification and generate a prognostic nomogram.

BACKGROUND: The objective of this study was to investigate the role of clinical factors together with FOXO1 fusion status in patients with nonmetastatic rhabdomyosarcoma (RMS) to develop a predictive model for event-free survival and provide a rationale for risk stratification in future trials. METHODS: The authors used data from patients enrolled in the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS 2005 study (EpSSG RMS 2005; EudraCT number 2005-000217-35). The following baseline variables were considered for the multivariable model: age at diagnosis, sex, histology, primary tumor site, Intergroup Rhabdomyosarcoma Studies group, tumor size, nodal status, and FOXO1 fusion status. Main effects and significant second-order interactions of candidate predictors were included in a multiple Cox proportional hazards regression model. A nomogram was generated for predicting 5-year event-free survival (EFS) probabilities. RESULTS: The EFS and overall survival rates at 5 years were 70.9% (95% confidence interval, 68.6%-73.1%) and 81.0% (95% confidence interval, 78.9%-82.8%), respectively. The multivariable model retained five prognostic factors, including age at diagnosis interacting with tumor size, tumor primary site, Intergroup Rhabdomyosarcoma Studies clinical group, and FOXO1 fusion status. Based on each patient's total score in the nomogram, patients were stratified into four groups. The 5-year EFS rates were 94.1%, 78.4%, 65.2%, and 52.1% in the low-risk, intermediate-risk, high-risk, and very-high-risk groups, respectively, and the corresponding 5-year overall survival rates were 97.2%, 91.5%, 74.3%, and 60.8%, respectively. CONCLUSIONS: The results presented here provide the rationale to modify the EpSSG stratification, with the most significant change represented by the replacement of histology with fusion status. This classification was adopted in the new international trial launched by the EpSSG.

Mutational signature, cancer driver genes mutations and transcriptomic subgroups predict hepatoblastoma survival.

BACKGROUND: Hepatoblastoma is the most frequent pediatric liver cancer. The current treatments lead to 80% of survival rate at 5 years. In this study, we evaluated the clinical relevance of molecular features to identify patients at risk of chemoresistance, relapse and death of disease. METHODS: All the clinical data of 86 children with hepatoblastoma were retrospectively collected. Pathological slides were reviewed, tumor DNA sequencing (by whole exome, whole genome or target) and transcriptomic profiling with RNAseq or 300-genes panel were performed. Associations between the clinical, pathological, mutational and transcriptomic data were investigated. RESULTS: High-risk patients represented 44% of our series and the median age at diagnosis was 21.9 months (range: 0-208). Alterations of the WNT/ß-catenin pathway and of the 11p15.5 imprinted locus were identified in 98% and 74% of the tumors, respectively. Other cancer driver genes mutations were only found in less than 11% of tumors. After neoadjuvant chemotherapy, disease-specific survival and poor response to neoadjuvant chemotherapy were associated with 'Liver Progenitor' (p = 0.00049, p < 0.0001) and 'Immune Cold' (p = 0.0011, p < 0.0001) transcriptomic tumor subtypes, SBS35 cisplatin mutational signature (p = 0.018, p = 0.001), mutations in rare cancer driver genes (p = 0.0039, p = 0.0017) and embryonal predominant histological type (p = 0.0013, p = 0.0077), respectively. Integration of the clinical and molecular features revealed a cluster of molecular markers associated with resistance to chemotherapy and survival, enlightening transcriptomic 'Immune Cold' and Liver Progenitor' as a predictor of survival independent of the clinical features. CONCLUSIONS: Response to neoadjuvant chemotherapy and survival in children treated for hepatoblastoma are associated with genomic and pathological features independently of the clinical features.

Expert management of congenital portosystemic shunts and their complications.

Congenital portosystemic shunts are often associated with systemic complications, the most challenging of which are liver nodules, pulmonary hypertension, endocrine abnormalities, and neurocognitive dysfunction. In the present paper, we offer expert clinical guidance on the management of liver nodules, pulmonary hypertension, and endocrine abnormalities, and we make recommendations regarding shunt closure and follow-up.

Thoracoscopy for Pediatric Thoracic Neurogenic Tumors-A European Multi-Center Study.

OBJECTIVES: To assess the efficacy of thoracoscopy and the outcome for children with thoracic neurogenic tumors. METHODS: We performed a retrospective review of 15 European centers between 2000 and 2020 with patients who underwent thoracoscopy for a neurogenic mediastinal tumor. We assessed preoperative data, complications, and outcomes. Results were expressed with the median and range values. RESULTS: We identified 119 patients with a median age of 4 years old (3 months-17 years). The diameter was 5.7 cm (1.1-15). INRG stage was L1 n = 46, L2 n = 56, MS n = 5, M n = 12. Of 69 patients with image-defined risk factors (IDRF), 29 had only (T9-T12) locations. Twenty-three out of 34 patients with preoperative chemotherapy had an 18 mm (7-24) decrease in diameter. Seven out of 31 patients lost their IDRF after chemotherapy. Fourteen had a conversion to thoracotomy. The length of the hospital stay was 4 days (0-46). The main complications included chylothorax (n = 7) and pneumothorax (n = 5). Long-term complications included Horner's syndrome (n = 5), back pain, and scoliosis (n = 5). Pathology was 53 neuroblastomas, 36 ganglioneuromas, and 30 ganglioneuroblastomas. Fourteen had a postoperative residue. With a median follow-up of 21 months (4-195), 9 patients had a recurrence, and 5 died of disease. Relapses were associated with tumor biology, histology, and the need for chemotherapy (p = 0.034, <0.001, and 0.015, respectively). Residues were associated with preoperative IDRF (excluding T9-T12 only) and the need for preoperative chemotherapy (p = 0.04 and 0.020). CONCLUSION: Our results show that thoracoscopy is safe, with good outcomes for thoracic neurogenic tumors in selected cases. Surgical outcomes are related to the IDRFs, whereas oncologic outcomes are related to tumor histology and biology.

Outcome and late effects of patients treated for childhood vaginal malignant germ cell tumors.

PURPOSE: Vaginal malignant germ cell tumors (MGCT) are rare, occurring in children less than 2 years old and raise the question of the optimal local treatment. METHODS: We included children treated for vaginal MGCT according to the French TGM-95/2013 regimen. Patients were classified as standard risk (SR: localized disease and alpha-fetoprotein (AFP) < 10,000 ng/mL) or high risk (HiR: metastatic and/or AFP > 10,000 ng/mL) and were treated, respectively, with three to five VBP (vinblastine-bleomycin-cisplatin) or four to six VIP (etoposide-ifosfamide-cisplatin), followed by conservative surgery and/or brachytherapy in case of post-chemotherapy residuum. RESULTS: Fourteen patients were included (median age = 12 months), of which six (43%) were classified as HiR. AFP levels were normalized after first-line chemotherapy in all cases but one. A vaginal post-chemotherapy residuum (median size = 8 mm, range: 1-24 mm) was observed in 13/14 patients, treated by complete resection in seven of 13 (viable cells in three of seven), incomplete resection in four of 13 (viable cells in two of four), with adjuvant brachytherapy in two of 13, and exclusive brachytherapy in two of 13 (viable cells in one of six). Among the six patients with viable disease, four patients received adjuvant chemotherapy. One patient (SR) experienced immediate postoperative relapse despite presenting no viable residual cells and was treated with four VIP cycles and brachytherapy. At last follow-up (median = 4.6 years, range: 0.5-16), all patients were alive in complete remission. Five patients suffered from vaginal sequelae with synechiae and/or stenosis (of whom four had undergone brachytherapy). CONCLUSION: Childhood vaginal MGCTs show a highly favorable prognosis with risk-adapted chemotherapy and local treatment of post-chemotherapy residuum (preferably by conservative surgery with partial vaginectomy). Brachytherapy could be an alternative when conservative surgery is not deemed possible or in cases of incomplete resection with residual viable cells.

Pediatric hepatic hemangiomas: spectrum and prognostic significance of initial ultrasound findings.

BACKGROUND: Hepatic hemangiomas may be associated with serious complications; however, it is unknown whether ultrasound (US) features can predict complications. OBJECTIVE: To analyze initial US features of hepatic hemangiomas predictive of complications. MATERIALS AND METHODS: This is a single-center retrospective cohort study of clinical, biological, and imaging data of infants with hepatic hemangioma between 2000 and 2018. Patients were categorized as having or not having any complication(s). Associations between initial US features and complications were analyzed through logistic regression. Receiver operating characteristic (ROC) curve analyses were performed to determine optimal cutoff values for continuous variables. Stepwise forward logistic regression was used to construct risk prediction models with training and validation sets. Model calibration and discrimination were evaluated using Hosmer-Lemeshow tests, area under the ROC curve, and overall accuracy. RESULTS: Of 112 infants with hepatic hemangioma, 67 (60%) had focal, 32 (28%) had multifocal, and 13 (12%) had diffuse lesions, with complication rates of 51%, 34%, and 92%, respectively, mostly cardiac (54/57, 95%). The US characteristics of the hemangiomas were diverse. Risk factors for complications included diffuse subtype; large tumor volume (focal forms); elevated peak systolic hepatic arterial velocity (PSV); and hepatic vein dilation. For focal forms, initial tumor volume >40 ml and PSV >100 cm/s had >70% sensitivity and specificity, respectively, to predict complications; a model including these variables had 75% overall accuracy in the validation set. For multifocal/diffuse forms, a PSV >115 cm/s had sensitivity and specificity to predict complications of >70%; a model including this variable had 78% overall accuracy in the validation set. CONCLUSION: Diffuse subtype, large tumor volume, elevated hepatic arterial PSV, and hepatic vein dilation are risk factors for complications of hepatic hemangiomas.

Prevalence, management and efficacy of treatment in portal vein obstruction after paediatric liver transplantation: protocol of the retrospective international multicentre PORTAL registry.

INTRODUCTION: Portal vein obstruction (PVO) consists of anastomotic stenosis and thrombosis, which occurs due to a progression of the former. The aim of this large-scale international study is to assess the prevalence, current management practices and efficacy of treatment in patients with PVO. METHODS AND ANALYSIS: The Portal vein Obstruction Revascularisation Therapy After Liver transplantation registry will facilitate an international, retrospective, multicentre, observational study, with 25 centres around the world already actively involved. Paediatric patients (aged <18 years) with a diagnosed PVO between 1 January 2001 and 1 January 2021 after liver transplantation will be eligible for inclusion. The primary endpoints are the prevalence of PVO, primary and secondary patency after PVO intervention and current management practices. Secondary endpoints are patient and graft survival, severe complications of PVO and technical success of revascularisation techniques. ETHICS AND DISSEMINATION: Medical Ethics Review Board of the University Medical Center Groningen has approved the study (METc 2021/072). The results of this study will be disseminated via peer-reviewed publications and scientific presentations at national and international conferences. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NL9261).

Outcome of patients with undifferentiated embryonal sarcoma of the liver treated according to European soft tissue sarcoma protocols.

BACKGROUND: To assess the outcomes of pediatric patients with undifferentiated embryonal sarcoma of the liver (UESL) and treatment including at least surgery and systemic chemotherapy. METHODS: This study included patients aged up to 21 years with a pathological diagnosis of UESL prospectively enrolled from 1995 to 2016 in three European trials focusing on the effects of surgical margins, preoperative chemotherapy, use of radiotherapy (RT), and chemotherapy. RESULTS: Out of 65 patients with a median age at diagnosis of 8.7 years (0.6-20.8), 15 had T2 tumors, and one had lymph node spread, 14 were Intergroup Rhabdomyosarcoma Study (IRS) I, nine IRS II, 38 IRS III, and four IRS IV. Twenty-eight upfront surgeries resulted in five operative spillages and 11 infiltrated surgical margins, whereas 37 delayed surgeries resulted in no spillages (p = .0119) and three infiltrated margins (p = .0238). All patients received chemotherapy, including anthracyclines in 47. RT was administered in 15 patients. With a median follow-up of 78.6 months, 5-year overall and event-free survivals (EFS) were 90.1% (95% confidence interval [CI]: 79.2-95.5) and 89.1% (95% CI: 78.4-94.6), respectively. Two out four local relapses had previous infiltrated margins and two out of three patients with metastatic relapses received reduced doses of alkylating agents. Infiltrated margins (p = .1607), T2 stage (p = .3870), use of RT (p = .8731), and anthracycline-based chemotherapy (p = .1181) were not correlated with EFS. CONCLUSIONS: Multimodal therapy improved the outcome of UESL. Neoadjuvant chemotherapy for pediatric patients increases the probability of complete surgical resection. The role of anthracyclines and RT for localized disease remains unclear.

Biliary drainage surgery before or after 3 months of life versus primary liver transplantation in children with biliary atresia: comparative cohort study.

BACKGROUND: Early biliary drainage surgery (BDS; Kasai) is associated with longer transplant-free survival in biliary atresia. However, evidence is lacking on whether an age limit can be established at which liver transplantation should be performed as first-line treatment for children with a delayed diagnosis of biliary atresia. The aim of the current study was to compare the outcome of a large cohort of children with biliary atresia who underwent BDS after 90 days of life with those who underwent early BDS (before 90 days) and those who did not receive BDS and were directly referred for primary liver transplantation. METHODS: All patients with biliary atresia treated at Bicêtre, Paris-Saclay University Hospital between 1995 and 2017 were analysed in this STROBE-compliant study. Three groups were defined: BDS before 90 days of life (early BDS); BDS after 90 days of life (late BDS); and patients without BDS who were referred for primary liver transplantation (no BDS). Patient characteristics, overall survival, and native liver survival were compared. RESULTS: Of 424 children with biliary atresia, 69 patients (16 per cent) were older than 90 days when they underwent BDS. Twenty-five patients had no BDS and were referred for primary liver transplantation (6 per cent). The main reason for not performing BDS was manifest portal hypertension (18/25). Two- and 5-year transplant-free survival were significantly higher in patients with late BDS compared with no BDS (53.5 versus 12.0 per cent respectively for 2-year data and 30.4 versus 4.0 per cent respectively for 5-year data, P < 0.001). Five- and 10-year overall survival did not differ between early BDS (92 and 91 per cent respectively), late BDS (88 and 83 per cent respectively) and no BDS (80 and 80 per cent respectively, P = 0.061). CONCLUSION: Age alone should not routinely be considered a contraindication to BDS in patients older than 90 days. Liver transplantation in infancy (less than 12 months) could be avoided in 88 per cent of cases with late diagnosis of biliary atresia and is delayed significantly even when BDS is performed after 3 months. Overall survival is at least equal to patients who are referred for primary liver transplantation.

The Use of Cavitron Ultrasonic Surgical Aspirator for High-Risk Neuroblastoma with Image-Defined Risk Factors in Children.

Aim of the study: The cavitron ultrasonic surgical aspirator (CUSA) has gained popularity in adult surgical oncology, but its application in children is limited to liver surgery and neurosurgical procedures. The complete resection of neuroblastoma with image-defined risk factors (IDRFs) is still considered one of the most difficult procedures to achieve in pediatric surgical oncology, with a high morbidity rate and potential risk of intraoperative mortality. The aim of our study is to describe the application of ultrasonic dissection in neuroblastoma with IDRFs. Methods: A retrospective study was performed, analyzing patients operated on from 2000 to 2018. Patient characteristics, resection completeness, and postoperative surgical and oncology outcomes were analyzed. Main results: Twenty-six patients with high-risk neuroblastoma and IDRFs were operated on in the study period with a CUSA. A complete macroscopic resection was performed in 50% of patients, while the other half was operated on with minimal residual (<5 mL). Six post-operative complications occurred without the need for surgery (Clavien−Dindo < 3). The overall survival was 50%, with a median follow-up of 69.6 months (5.6−140.4). Conclusions: The application of the CUSA in neuroblastoma with IDRFs can be considered an effective and safe alternative technique to achieve a radical resection.

Developments in the Surgical Approach to Staging and Resection of Rhabdomyosarcoma.

Although survival after rhabdosarcoma treatment has improved over the years, one third of patients still develop locoregional relapse. This review aims to highlight developments pertaining to staging and local treatment of specific RMS tumor sites, including head and neck, chest/trunk, bladder-prostate, female genito-urinary, perianal, and extremity sites.

International registry of congenital porto-systemic shunts: a multi-centre, retrospective and prospective registry of neonates, children and adults with congenital porto-systemic shunts.

BACKGROUND: Congenital portosystemic shunts (CPSS) are rare vascular malformations associated with the risk of life-threatening systemic conditions, which remain underdiagnosed and often are identified after considerable diagnostic delay. CPSS are characterized by multiple signs and symptoms, often masquerading as other conditions, progressing over time if the shunt remains patent. Which patients will benefit from shunt closure remains to be clarified, as does the timing and method of closure. In addition, the etiology and pathophysiology of CPSS are both unknowns. This rare disorder needs the strength of numbers to answer these questions, which is the purpose of the international registry of CPSS (IRCPSS). METHOD: A retrospective and prospective registry was designed using secuTrial® by the ISO certified Clinical Research Unit. Given that a significant number of cases entered in the registry are retrospective, participants have the opportunity to use a semi-structured minimal or complete data set to facilitate data entry. In addition, the design allows subjects to be entered into the IRCPSS according to clinically relevant events. Emphasis is on longitudinal follow-up of signs and symptoms, which is paramount to garner clinically relevant information to eventually orient patient management. The IRCPSS includes also three specific forms to capture essential radiological, surgical, and cardiopulmonary data as many times as relevant, which are completed by the specialists themselves. Finally, connecting the clinical data registry with a safe image repository, using state-of-the-art pseudonymization software, was another major focus of development. Data quality and stewardship is ensured by a steering committee. All centers participating in the IRCPSS have signed a memorandum of understanding and obtained their own ethical approval. CONCLUSION: Through state-of-the-art management of data and imaging, we have developed a practical, user-friendly, international registry to study CPSS in neonates, children, and adults. Via this multicenter and international effort, we will be ready to answer meaningful and urgent questions regarding the management of patients with CPSS, a condition often ridden with significant diagnostic delay contributing to a severe clinical course.

Implementation of Image-Guided Brachytherapy for Pediatric Vaginal Cancers: Feasibility and Early Clinical Results.

Background: Brachytherapy (BT) has a major role in pediatric cancers of the lower genital tract, as part of a multimodal organ conservative strategy. Scarce data are available on the location of image-guided BT. Methods: Medical records of all consecutive girls treated in our center between 2005 and 2020 for a vaginal tumor with exclusive image-guided PDR-BT were retrospectively examined, with a focus on treatment parameters, patient compliance, and clinical outcome, including analysis of local control, survival and late toxicity rates. Results: Twenty-six patients were identified, with a median age of 25 months. Histological types were rhabdomyosarcoma, malignant germ cell tumor (MGCT) and clear cell adenocarcinoma in 18 (69%), 7 (27%) and 1 (4%) patients, respectively. Ten (33%) patients had prior surgery and 25 (96%) received chemotherapy prior to BT. The median prescribed dose was 60 Gy through pulses of 0.42 Gy. Global compliance was satisfactory, but three (12%) patients required replanning because of applicator displacement. After a median follow-up of 47.5 months, one patient with MGCT referred for salvage treatment of a local recurrence had a local and metastatic relapse. The local control rate probability was 96% at the last follow-up. Late toxicity rates ≥ grade 2 and ≥ grade 3 were reported in 23% and 11%, respectively, with gynecological toxicities being the most frequent side effect. Two patients required dilatation for vaginal stenosis. Conclusions: PDR-BT allowed similar local control compared to the historical low-dose rate technique. An indirect comparison suggests fewer treatment-related toxicities by integrating image guidance and optimization capabilities, but longer follow-up is necessary. Due to the rarity of the disease and the technical aspects of BT in these very young patients, referral to specialized high-volume centers is recommended.

Long-term urological complications after conservative local treatment (surgery and brachytherapy) in children with bladder-prostate rhabdomyosarcoma: A single-team experience.

BACKGROUND: Outcome of children with bladder-prostate rhabdomyosarcoma (RMS) has improved with multimodal therapies, including surgery and/or radiotherapy for local treatment. Our aim was to report long-term urological complications after a conservative approach combining conservative surgery and brachytherapy. PATIENTS AND METHODS: Eighty-six patients, free of disease, were retrospectively reviewed. Symptoms related to urinary tract obstruction, incontinence, infection, and lithiasis were reported and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) classification. Only symptomatic patients underwent urodynamic studies. Risk factors for complications were analyzed. RESULTS: There were 76 males and 10 females. The median follow-up was 6.3 years (18 months to 24 years). Complications occurred after a median follow-up of 5 years (0-21). Twenty-two patients (26%) had long-term urological complications. Urinary tract obstruction was found in 15 patients (17%) and urinary incontinence in 14 patients (16%). Recurrent urinary tract infection occurred in four patients and urinary lithiasis in four (5%). The underlying physiopathology included bladder dysfunction in 15 patients (17%), urethral stenosis in six (7%), and ureterovesical junction stenosis in five (6%). On univariate analysis, posterior bladder wall dissection (p = .001), bladder neck trigone dissection (p = .010), and partial prostatectomy (p = .023) were significantly associated with an increased risk of bladder dysfunction; on multivariate analysis, only age ≤2 years (p = .028) at operation and posterior bladder wall dissection (p = .006) were found to be significant. CONCLUSION: The conservative surgical approach combined with brachytherapy for bladder-prostate RMS leads to long-term urological complications in 26% of survivors. Optimizing brachytherapy doses for young children and establishing a clear and long-term follow-up protocol could help to reduce these complications.