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Purpose: Childhood cancer is rare, and treatment is frequently associated with long-term morbidity. Disparities in survival and long-term side effects encourage the establishment of networks to increase access to complex organ-conservative strategies, such as brachytherapy. We report our experience of an international cooperation model in childhood cancers., Methods and Materials: We examined the outcome of all children referred to our center from national or international networks to be treated according to a multimodal organ-conservative approach, including brachytherapy., Results: We identified 305 patients whose median age at diagnosis was 2.2 years (range, 1.4 months to 17.2 years). Among these patients, 99 (32.4%) were treated between 2015 and 2020; 172 (56.4%) were referred from national centers; and 133 (43.6%) were international patients from 31 countries (mainly Europe). Also, 263 patients were referred for primary treatment and 42 patients were referred for salvage treatment. Genitourinary tumors were the most frequent sites, with 56.4% bladder/prostate rhabdomyosarcoma and 28.5% gynecologic tumors. In addition to brachytherapy, local treatment consisted of partial tumor resection in 207 patients (67.9%), and 39 patients (13%) had additional external radiation therapy. Median follow-up was 58 months (range, 1 month to 48 years), 93 months for national patients, and 37 months for international patients (P < .0001). Five-year local control, disease-free survival, and overall survival rates were 90.8% (95% confidence interval [CI], 87.3%-94.4%), 84.4% (95% CI, 80.1%-89.0%), and 93.3% (95% CI, 90.1%-96.5%), respectively. Patients referred for salvage treatment had poorer disease-free survival (P < .01). Implementation of image guided pulse-dose-rate brachytherapy was associated with better local control among patients with rhabdomyosarcoma referred for primary treatment (hazard ratio, 9.72; 95% CI, 1.24-71.0). At last follow-up, 16.7% patients had long-term severe treatment-related complications, and 2 patients (0.7%) had developed second malignancy., Conclusions: This retrospective series shows the feasibility of a multinational referral network for brachytherapy allowing high patient numbers in rare pediatric cancers. High local control probability and acceptable late severe complication probability could be achieved despite very challenging situations. This cooperation model could serve as a basis for generating international reference networks for high-tech radiation such as brachytherapy to increase treatment care opportunities and cure probability., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: There is limited evidence to define the role of radiation therapy in children with metastatic rhabdomyosarcoma (mRMS). In the international BERNIE study, children with mRMS or non-RMS soft tissue sarcoma were randomized to receive standard chemotherapy with or without bevacizumab, with radiation therapy to all disease sites recommended after chemotherapy cycle 6. We retrospectively evaluated the impact of radiation therapy on survival in the mRMS cohort., Methods and Materials: Patients were grouped according to the radiation therapy they received: radical, partial, or none. Radical irradiation was defined as radiation therapy delivered to all disease sites, unless a site was completely surgically resected. Partial irradiation was defined as radiation therapy to ≥1, but not all, disease sites. Landmark analysis excluded patients with an event before day 221. Overall survival (OS) and event-free survival (EFS) were modeled using Cox proportional hazards models., Results: Of 102 patients with mRMS, 97 were included in the analysis for OS and 85 for EFS. Overall, 27 patients received radical irradiation, 46 partial irradiation, and 24 no irradiation. EFS was not significantly different among patient groups after adjustment for prognostic factors (hazard ratio [HR] = 0.520; P = .054 for any vs no irradiation). Radiation therapy was associated with improved OS compared with no radiation therapy (adjusted HR = 0.249; P = .00025), with OS being greater for radical versus partial irradiation (HR = 0.245; P = .039). The 3-year OS rate was 84%, 54%, and 23% for patients receiving radical, partial, and no irradiation, respectively. Radical treatment (surgery, irradiation, or both) of the primary site improved EFS and OS compared with no treatment., Conclusions: These findings demonstrate variability in the application of radiation therapy for mRMS and support the routine use of radical treatment to the primary site. Radical irradiation to metastatic sites may further improve OS. The burden of such treatment should be balanced against prognosis; further studies are needed., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To examine dose-volume effect relationships for anorectal morbidity in children treated with image-guided brachytherapy for pelvic tumors., Methods and Materials: Medical records of all consecutive children with pelvic tumors treated in our center and receiving image-guided pulsed-dose-rate brachytherapy with or without external beam radiation therapy (EBRT) between 2005 and 2019 were reviewed. The effect of the minimal doses to the most exposed 0.5 cm 3 , 1 cm 3 , and 2 cm 3 of the anorectum (respectively: D 0.5cm 3 , D 1cm 3 , and D 2cm 3 ), total reference air kerma (TRAK), and volume of 100% isodose was examined for anorectal toxicities., Results: Seventy-eight consecutive children were included. Median age was 2.9 years (range, 0.8-14.9 years). Most of the tumors were bladder or prostate (67%) or vaginal (22%) rhabdomyosarcoma. Six patients received EBRT in addition to brachytherapy. Median follow-up was 21.3 months. At last follow-up, 30 children (38%) had experienced Common Terminology Criteria for Adverse Events version 5 grade ≥1 acute or late anorectal events: 24% had grade 1 events, 7.7% had grade 2 events, and 6.4% had grade 3 events. No toxicity greater than grade 3 was observed (eg, fistula or stricture). In univariate analysis, the D 0.5cm 3 and D 1cm 3 were significant for probability of grade 1 to 3 (P = .009 and P = .017, respectively) and grade 2 to 3 anorectal morbidity (P = .007 and P = .049, respectively). There was no significant correlation for D 2cm 3 (P = .057 for grade 1-3; P = .407 for grade 2-3). A 10% probability (95% confidence interval, 4%-20%) for anorectal toxicity of grade 2 or greater was reached for a D 0.5cm 3 = 52 Gy. The age, EBRT use, TRAK, and treated volume values were not significant., Conclusions: To our knowledge, this study is the first to show a significant dose-volume effect relationships for anorectal morbidity in children undergoing treatment with brachytherapy. Integrating these data into brachytherapy treatment planning could help to optimize the therapeutic index in these young patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To report the results of a conservative strategy based on partial surgery combined with brachytherapy in a prospective cohort of children with bladder-prostate rhabdomyosarcoma (BP RMS)., Methods and Materials: We prospectively documented the outcome of children treated in our department between 1991 and 2015 for BP RMS and undergoing a multimodal approach combining conservative surgery (partial cystectomy and/or partial prostatectomy) and perioperative interstitial low-dose-rate or pulse-dose-rate brachytherapy. Before brachytherapy, children had received chemotherapy with modalities depending on their risk group of treatment., Results: A total of 100 patients were identified, with a median age of 28 months (range, 5.6 months-14 years). According to the Intergroup Rhabdomyosarcoma Study (IRS) group, 84 were IRS-III, and 12 were IRS-IV tumors. Four patients were treated at relapse. The median number of chemotherapy cycles before local therapy was 6 (range, 4-13). After surgery, 63 patients had a macroscopic tumor residuum. Five patients underwent a brachytherapy boost before pelvic external beam radiation therapy because of nodal involvement, and 95 had exclusive brachytherapy. Median follow-up was 64 months (range, 6 months-24.5 years). Five-year disease-free and overall survival rates were 84% (95% confidence interval 80%-88%) and 91% (95% confidence interval 87%-95%), respectively. At last follow-up most survivors presented with only mild to moderate genitourinary sequelae and a normal diurnal urinary continence. Five patients required a secondary total cystectomy: 3 for a nonfunctional bladder and 2 for relapse., Conclusion: Brachytherapy is effective as part of a conservative strategy for BP RMS, with a relatively low delayed toxicity as compared with previously published studies using external beam radiation therapy. Longer follow-up is required to ensure that the functional results are maintained over time., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To report the Institut Gustave Roussy brachytherapy (BT) experience in the management of vulval and vaginal rhabdomyosarcoma with special emphasis on long-term outcome., Patients and Methods: Between 1971 and 2005, the data concerning 39 girls who had undergone BT as a part of their treatment were retrospectively analyzed. Of the 39 girls, 20 had been treated before 1990, when the BT volume encompassed the initial tumor extension. After 1990, only residual disease was included in the BT volume. Side effects were classified using the Common Terminology Criteria for Adverse Events, version 3.0., Results: The median age was 16.3 months at diagnosis. Vaginal or vulvar rhabdomyosarcoma was diagnosed in 26 and 6 patients, respectively. The median follow-up was 8.4 years. The 5-year overall survival rate was 91%. Of the 39 patients, 6 developed a relapse. Of the 20 patients treated before 1990, 6 experienced Grade 1-2 renal/genitourinary function symptoms and 75% developed sequelae, in the form of vaginal or urethral sclerosis or stenosis. Four patients received follow-up treatment for psychological disorders. Of the 19 patients treated after 1990, 2 developed acute side effects, with maximal Grade 1-2 renal/genitourinary function symptoms, and 20% developed vaginal or urethral sclerosis or stenosis. Two cases of psychological disturbances were also documented., Conclusion: Reducing the BT volume coverage, better indications for surgery, and more efficient chemotherapy, all combined within a multidisciplinary approach, tended to improve results in terms of both survival and long-term sequelae.