TEDDI : radiotherapy delivery in deep inspiration for pediatric patients - a NOPHO feasibility study

Background: Radiotherapy (RT) delivered in deep inspiration breath-hold (DIBH) is a simple technique, in which changes in patient anatomy can significantly reduce the irradiation of the organs at risk (OARs) surrounding the treatment target. DIBH is routinely used in the treatment of some adult patients to diminish the risk of late effects; however, no formalized studies have addressed the potential benefit of DIBH in children. Methods/Design: TEDDI is a multicenter, non-randomized, feasibility study. The study investigates the dosimetric benefit of RT delivered in DIBH compared to free breathing (FB) in pediatric patients. Also, the study aims to establish the compliance to DIBH and to determine the accuracy and reproducibility in a pediatric setting. Pediatric patients (aged 5-17 years) with a tumor in the mediastinum or upper abdomen with the possible need of RT will be included in the study. Written informed consent is obligatory. Prior to any treatment, patients will undergo a DIBH training session followed by a diagnostic PET/CT-or CT-staging scan in both DIBH and FB. If the patient proceeds to RT, a RT planning CT scan will be performed in both DIBH and FB and two separate treatment plans will be calculated. The superior treatment plan, i.e. equal target coverage and lowest overall dose to the OARs, will be chosen for treatment. Patient comfort will be assessed daily by questionnaires and by adherence to the respiratory management procedure. Discussion: RT in DIBH is expected to diminish irradiation of the OARs surrounding the treatment target and thereby reduce the risk of late effects in childhood cancer survivors.Peer reviewe

Pediatric Non-Rhabdomyosarcoma Soft Tissue Sarcomas:Standard of Care and Treatment Recommendations from the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG)

This paper describes the standard of care for patients with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) and the therapeutic recommendations developed by the European paediatric Soft tissue sarcoma Study Group (EpSSG). NRSTS form a very mixed group of mesenchymal extraskeletal malignancies. Their rarity, heterogeneity, and aggressiveness make the management of children and adolescents with these tumors complex and challenging. The overall cure rate for patients with NRSTS is around 70%, but survival depends on several prognostic variables, such as histotype and tumor grade, extent of disease and stage, tumor size, and tumor site. While surgery remains the mainstay of treatment for most of these tumors, a multimodal therapeutic approach including radiotherapy and chemotherapy is required in many cases. The EpSSG NRSTS 2005 study was the first prospective protocol tailored specifically to NRSTS. Together with the ARST0332 study developed by the North-American Soft Tissue Sarcoma Committee of the Children’s Oncology Group (COG), the EpSSG NRSTS 2005 study currently represents the benchmark for these tumors, establishing risk-adapted standards of care. The EpSSG has developed common treatment recommendations for the large group of adult-type NRSTS (including synovial sarcoma), and specific treatment recommendations for other particular adult-type histologies (ie, alveolar soft-part sarcoma, clear cell sarcoma and dermatofibrosarcoma protuberans); other highly malignant tumors with a biology and clinical behavior differing from those of adult-type NRSTS (ie, rhabdoid tumors and desmoplastic small round cell tumor); and soft tissue tumors of intermediate malignancy (ie desmoid-type fibromatosis, inflammatory myofibroblastic tumors, and infantile fibrosarcoma). New effective drugs are needed for patients whose NRSTS carries the worst prognosis, ie, those with unresectable tumors, metastases at diagnosis, or relapsing disease. Progress in this area relies on our ability to develop international integrated prospective collaborations, both within existing pediatric oncology networks and, importantly, between the communities of specialists treating pediatric and adult sarcoma.</p

Malignant ectomesenchymoma in children: The European pediatric Soft tissue sarcoma Study Group experience

Malignant ectomesenchymoma (MEM) is an extremely rare soft tissue tumor typical of young children, currently included in the category of skeletal muscle malignancies and characterized by a neuroblastic component. This study describes a series of 10 patients prospectively registered in the European paediatric Soft tissue sarcoma Study Group (EpSSG) database Of the 10 cases, seven had an initial local diagnosis of rhabdomyosarcoma. All patients received chemotherapy according to rhabdomyosarcoma strategy, four had radiotherapy. Overall, six patients were alive in first remission, two in second remission and one after second tumor. Only the patient with initially metastatic tumor died of disease

Paediatric CBCT protocols for image-guided radiotherapy; outcome of a survey across SIOP Europe affiliated countries and literature review

BACKGROUND: Implementation of daily cone-beam CT (CBCT) into clinical practice in paediatric image-guided radiotherapy (IGRT) lags behind compared to adults. Surveys report wide variation in practice for paediatric IGRT and technical information remains unreported. In this study we report on technical settings from applied paediatric CBCT protocols and review the literature for paediatric CBCT protocols. METHODS: From September to October 2022, a survey was conducted among 246 SIOPE-affiliated centres across 35 countries. The survey consisted of 3 parts: 1) baseline information; technical CBCT exposure settings and patient set-up procedure for 2) brain/head, and 3) abdomen. Descriptive statistics was used to summarise current practice. The literature was reviewed systematically with two reviewers obtaining consensus RESULTS: The literature search revealed 22 papers concerning paediatric CBCT protocols. Seven papers focused on dose-optimisation. Responses from 50/246 centres in 25/35 countries were collected: 44/50 treated with photons and 10/50 with protons. In total, 48 brain/head and 53 abdominal protocols were reported. 42/50 centres used kV-CBCT for brain/head and 35/50 for abdomen; daily CBCT was used for brain/head = 28/48 (58%) and abdomen = 33/53 62%. Greater consistency was seen in brain/head protocols (dose range 0.32 - 67.7 mGy) compared to abdominal (dose range 0.27 - 119.7 mGy). CONCLUSION: Although daily CBCT is now widely used in paediatric IGRT, our survey demonstrates a wide range of technical settings, suggesting an unmet need to optimise paediatric IGRT protocols. This is in accordance with the literature. However, there are only few paediatric optimisation studies suggesting that dose reduction is possible while maintaining image quality

Epithelioid hemangioendothelioma in children: The European Pediatric Soft Tissue Sarcoma Study Group experience

The European pediatric Soft tissue sarcoma Study Group analyzed all children with epithelioid hemangioendothelioma prospectively registered in the NRSTS-05 (EUDRACT 2005-001139-31) and in MTS-2008 (NCT00379457) studies: 10 patients with localized and one with metastatic disease. Median age was 14.3 years (range, 9.0-18.8). Local therapy was initial primary surgery in seven cases, and five patients received systemic therapy. No patients received radiotherapy. After a median follow-up of 50 months (range, 6-176) for living patients, nine patients remain alive off therapy and two died. Five-year progression free and overall survivals are, respectively, 77.1% (95% confidence interval [CI]: 34.5-93.9) and 74.1% (95% CI: 28.1-93.0)

Metastatic adult-type non-rhabdomyosarcoma soft tissue sarcomas in children and adolescents: A cohort study from the European paediatric Soft tissue sarcoma Study Group

Background: Limited data exist on the clinical behavior of pediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) with distant metastases at onset, and a clear standard of care has not yet been defined. Methods: This cohort study reports on pediatric adult-type metastatic NRSTS enrolled in two concurrent prospective European studies, i.e., the randomized BERNIE study and the single-arm MTS 2008 study developed by the European paediatric Soft tissue sarcoma Study Group. Treatment programs were originally designed for patients with metastatic rhabdomyosarcoma, i.e., nine courses of multidrug chemotherapy (with or without bevacizumab in the BERNIE study), followed by 12 cycles of maintenance therapy, whereas radiotherapy and/or surgery (on primary tumor and/or metastases) were delayed until after seven courses of chemotherapy had been administered. Results: The study included 61 patients <21 years old treated from July 2008 to December 2016. The lung was the site of metastases in 75% of the cases. All patients received multi-agent chemotherapy, 44% had local therapy to primary tumor, and 18% had treatment of metastases. Median time to progression/relapse was 6 months. A high rate of tumor progression was observed during the initial part of the chemotherapy program. With a median follow-up of 41.5 months (range, 2–111 months), 3-year event-free survival and overall survival were 15.4% (95% confidence interval [CI], 7.6–25.7) and 34.9% (95% CI, 22.7–47.5), respectively. There were no statistically significant differences in outcome depending on the type of treatment administered. Conclusions: The study confirmed the overall poor outcome for patients with metastatic NRSTS, whose treatment remains a challenge. Plain Language Summary: Pediatric non-rhabdomyosarcoma soft tissue sarcomas form a heterogeneous group of rare tumors. Although recent international studies have defined the standard of care for patients with localized disease, limited data are available on the clinical behavior of patients with distant metastases. This study on 61 metastatic cases treated on two prospective European protocols confirms that the chances of survival of such patients are often dismal and a standard treatment is still lacking

Treatment and Outcome Analysis of 639 Relapsed Non-Hodgkin Lymphomas in Children and Adolescents and Resulting Treatment Recommendations.

Despite poor survival, controversies remain in the treatment for refractory or relapsed pediatric non-Hodgkin lymphoma (r/r NHL). The current project aimed to collect international experience on the re-induction treatment of r/r NHL, hematopoietic stem cell transplantation (HSCT), risk factors associated with outcome, and to suggest treatment recommendations. Inclusion criteria were (i) refractory disease, disease progression or relapse of any NHL subtype except anaplastic large cell lymphoma, (ii) age < 18 years at initial diagnosis, (iii) diagnosis in/after January 2000. Data from 639 eligible patients were evaluable. The eight-year probability of overall survival was 34 ± 2% with highly significant differences according to NHL subtypes: 28 ± 3% for 254 Burkitt lymphoma/leukemia, 50 ± 6% for 98 diffuse large B-cell lymphomas, 57 ± 8% for 41 primary mediastinal large B-cell lymphomas, 27 ± 3% for 177 T-lymphoblastic lymphomas, 52 ± 10% for 34 precursor-B-cell lymphoblastic lymphomas and 30 ± 9% for 35 patients with rare NHL subtypes. Subtype-specific factors associated with survival and treatment recommendations are suggested. There were no survivors without HSCT, except in few very small subgroups. Conclusions: There is an urgent need to further improve survival in r/r NHL. The current study provides the largest real-world series, which underlines the role of HSCT and suggests treatment recommendations