Patients, parents and professional perspectives on molecular radiotherapy for neuroblastoma and paediatric neuroendocrine cancers.

Treatment with radioactive drugs (molecular radiotherapy, MRT) is an option for selected children with neuroblastoma and neuroendocrine cancers. As few hospitals are appropriately equipped and staffed to provide paediatric MRT, many families have to travel long distances from home for prolonged periods. To improve professional understanding of the challenges faced by children receiving these treatments and their parents, and to help them appreciate the difficulties faced by professionals in delivering complex treatments, a meeting bringing together parents, patients and professionals was held.

Endocrine dysfunction in long-term survivors of pediatric head and neck rhabdomyosarcoma.

Objective: Survivors of pediatric head and neck rhabdomyosarcoma (HNRMS) are at risk of developing endocrinopathies following local treatment, resulting from radiation damage to the pituitary gland, hypothalamus, or thyroid gland, often at a young age. Our aim was to determine the prevalence of endocrine dysfunction in long-term HNRMS survivors and compare the prevalence of anterior pituitary insufficiency (API) among different local treatment strategies: external beam radiation with photons, external beam radiation with protons, microscopically radical surgery combined with external irradiation, and macroscopic radical surgery combined with brachytherapy.

Design And Methods: Head and neck rhabdomyosarcoma survivors treated between 1993 and 2017, with ≥2 years of follow-up, without recurrent disease or secondary malignancy were eligible for this study.

Development of age-specific population-based paediatric computational phantoms for image-based data mining and other radiotherapy applications.

Computational anatomical models have many applications in paediatric radiotherapy. Age-specific computational anatomical models were historically developed to represent average and/or healthy individuals, where cancer patients may present with anatomical variations caused by the disease and/or treatment effects. We developed RT-PAL, a library of computational age-specific voxelized anatomical models tailored to represent the paediatric radiotherapy population.

Heterogeneous SSTR2 target expression and a novel :: fusion clone in a progressive metastatic lesion following Lutetium-DOTATATE molecular radiotherapy in neuroblastoma: a case report.

In this case report, we present the treatment outcomes of the first patient enrolled in the LuDO-N trial. The patient is a 21-month-old girl diagnosed with high-risk neuroblastoma (NB) and widespread skeletal metastasis. The patient initially underwent first-line therapy according to SIOPEN HRNBL-1 but was switched to second-line treatments due to disease progression, and she was finally screened for enrollment in the LuDO-N trial due to refractory disease.

The Impact of Radiation Therapy on Metastatic Rhabdomyosarcoma: Results From the EpSSG MTS 2008 Study.

Purpose: Radiation oncologists use radiation variably for children with metastatic rhabdomyosarcoma (RMS). Data from the European paediatric Soft tissue sarcoma Study Group (EpSSG) MTS 2008 study were retrospectively analyzed to validate the previous observation that the use of radiation is associated with improved outcomes and guide future recommendations on radiation use in this patient group.

Methods And Materials: The radiation delivered to 216 patients aged 0 to 21 years with metastatic RMS was retrospectively reviewed and classified as radical (all sites of disease irradiated within the protocol parameters), partial (some sites irradiated within the protocol parameters), and none (no radiation or delivered outside the protocol parameters).

Paediatric radiotherapy in the United Kingdom: an evolving subspecialty and a paradigm for integrated teamworking in oncology.

Many different malignancies occur in children, but overall, cancer in childhood is rare. Survival rates have improved appreciably and are higher compared with most adult tumour types. Treatment schedules evolve as a result of clinical trials and are typically complex and multi-modality, with radiotherapy an integral component of many.

Clinical perspectives on dosimetry in molecular radiotherapy.

Molecular radiotherapy is the use of systemically administered unsealed radioactive sources to treat cancer. Theragnostics is the term used to describe paired radiopharmaceuticals localising to a specific target, one optimised for imaging, the other for therapy. For many decades, molecular radiotherapy has developed empirically.

Facial deformation following treatment for pediatric head and neck rhabdomyosarcoma; the difference between treatment modalities. Results of a trans-Atlantic, multicenter cross-sectional cohort study.

Background: The four different local therapy strategies used for head and neck rhabdomyosarcoma (HNRMS) include proton therapy (PT), photon therapy (RT), surgery with radiotherapy (Paris-method), and surgery with brachytherapy (AMORE). Local control and survival is comparable; however, the impact of these different treatments on facial deformation is still poorly understood. This study aims to quantify facial deformation and investigates the differences in facial deformation between treatment modalities.

Image guidance and interfractional anatomical variation in paediatric abdominal radiotherapy.

Objectives: To identify variables predicting interfractional anatomical variations measured with cone-beam CT (CBCT) throughout abdominal paediatric radiotherapy, and to assess the potential of surface-guided radiotherapy (SGRT) to monitor these changes.

Methods: Metrics of variation in gastrointestinal (GI) gas volume and separation of the body contour and abdominal wall were calculated from 21 planning CTs and 77 weekly CBCTs for 21 abdominal neuroblastoma patients (median 4 years, range: 2 - 19 years). Age, sex, feeding tubes, and general anaesthesia (GA) were explored as predictive variables for anatomical variation.

Deep learning based synthetic CT from cone beam CT generation for abdominal paediatric radiotherapy.

. Adaptive radiotherapy workflows require images with the quality of computed tomography (CT) for re-calculation and re-optimisation of radiation doses. In this work we aim to improve the quality of on-board cone beam CT (CBCT) images for dose calculation using deep learning.

Radiotherapy quality assurance in paediatric clinical trials: first report from six QUARTET-affiliated trials.

Background And Purpose: SIOP Europe's QUARTET project launched in 2016; aiming to improve access to high-quality radiotherapy for children and adolescents treated within clinical trials across Europe. The aim of this report is to present the profile of institutions participating in six QUARTET-affiliated trials and a description of the initial individual case review (ICR) outcomes.

Methods: This is a two-part analysis.

Overcoming inter-observer planning variability in target volume contouring and dose planning for high-risk neuroblastoma - a European multicenter effort of the SIOPEN radiotherapy committee.

Background And Purpose: To establish an international quality standard for contouring and planning for high-risk neuroblastoma within the prospective High-Risk Neuroblastoma Study 2 of SIOP-Europe-Neuroblastoma (SIOPEN HR-NBL2), which includes a randomized question on dose escalation for residual disease.

Materials And Methods: Data on four patients with high-risk neuroblastoma were selected and distributed to the radiotherapy committee of the HR-NBL2 study for independent contouring and planning. Differences in contouring were analyzed using apparent and kappa-corrected agreement.

Paediatric differentiated thyroid carcinoma: a UK National Clinical Practice Consensus Guideline.

This guideline is written as a reference document for clinicians presented with the challenge of managing paediatric patients with differentiated thyroid carcinoma up to the age of 19 years. Care of paediatric patients with differentiated thyroid carcinoma differs in key aspects from that of adults, and there have been several recent developments in the care pathways for this condition; this guideline has sought to identify and attend to these areas. It addresses the presentation, clinical assessment, diagnosis, management (both surgical and medical), genetic counselling, follow-up and prognosis of affected patients.

Contemporary paediatric radiation oncology.

Treatment with ionising radiation is a valuable component of treatment schedules for a many children and young people with cancer. While some form of radiotherapy has been in use for over 100 years, a series of innovations has revolutionised paediatric radiation oncology. Mostly, high-energy X-ray photons are used, but proton beam radiotherapy is increasingly offered, especially in children and young people.

QUARTET: A SIOP Europe project for quality and excellence in radiotherapy and imaging for children and adolescents with cancer.

The European Society for Paediatric Oncology (SIOPE) Radiation Oncology Working Group presents the QUARTET Project: a centralised quality assurance programme designed to standardise care and improve the quality of radiotherapy and imaging for international clinical trials recruiting children and adolescents with cancer throughout Europe. QUARTET combines the paediatric radiation oncology expertise of SIOPE with the infrastructure and experience of the European Organisation for Research and Treatment of Cancer to deliver radiotherapy quality assurance programmes for large, prospective, international clinical trials. QUARTET-affiliated trials include children and adolescents with brain tumours, neuroblastoma, sarcomas including rhabdomyosarcoma, and renal tumours including Wilms' tumour.

A Phase II Trial of a Personalized, Dose-Intense Administration Schedule of Lutetium-DOTATATE in Children With Primary Refractory or Relapsed High-Risk Neuroblastoma-LuDO-N.

Background: Half the children with high-risk neuroblastoma die with widespread metastases. Molecular radiotherapy is an attractive systemic treatment for this relatively radiosensitive tumor. I-mIBG is the most widely used form in current use, but is not universally effective.

Impact of cyclic changes in pharmacokinetics and absorbed dose in pediatric neuroblastoma patients receiving [Lu]Lu-DOTATATE.

Purpose: Recent reports personalizing the administered activity (AA) of each cycle of peptide receptor radionuclide therapy based on the predicted absorbed dose (AD) to the kidneys (dose-limiting organ) have been promising. Assuming identical renal pharmacokinetics for each cycle is pragmatic, however it may lead to over- or under-estimation of the optimal AA. Here, we investigate the influence that earlier cycles of [Lu]Lu-DOTATATE had on the biokinetics and AD of subsequent cycles in a recent clinical trial that evaluated the safety and activity of [Lu]Lu-DOTATATE in pediatric neuroblastoma (NBL).

Bladder function after conservative surgery and high-dose rate brachytherapy for bladder-prostate rhabdomyosarcoma.

Background: Conservative surgery (CS) brachytherapy (BT) techniques for local therapy in bladder-prostate rhabdomyosarcoma (BP-RMS) seek to retain organ function. We report bladder function after high-dose rate (HDR) BT combined with targeted CS for any vesical component of BP-RMS.

Procedure: Prospective cohort of all BP-RMS patients between 2014 and 2019 receiving HDR-BT (iridium-192, 27.

Localised rhabdomyosarcoma in infants (<12 months) and young children (12-36 months of age) treated on the EpSSG RMS 2005 study.

Background: Infants (<12 months) with rhabdomyosarcoma have historically had poorer outcome than the older age groups. We present outcomes for infants and young children aged 12-36 months with localised rhabdomyosarcoma with a particular emphasis on infants.

Patients And Methods: All children less than 36 months of age enrolled on the EpSSG RMS 2005 study for localised disease are included.

Renal protection during 177lutetium DOTATATE molecular radiotherapy in children: a proposal for safe amino acid infusional volume during peptide receptor radionuclide therapy.

Peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues such as 177-lutetium DOTATATE is an effective treatment modality for neuroendocrine tumours, paragangliomas, and neuroblastomas. However, renal and haematopoietic toxicities are the major limitations of this therapeutic approach. The renal toxicity of PRRT is mediated by renal proximal tubular reabsorption and interstitial retention of the radiolabelled peptides resulting in excessive renal irradiation that can be dose-limiting.

Treatment outcome with a selective RET tyrosine kinase inhibitor selpercatinib in children with multiple endocrine neoplasia type 2 and advanced medullary thyroid carcinoma.

Background: Medullary thyroid carcinoma (MTC) in the context of multiple endocrine neoplasia type 2 (MEN2) is caused by mutations in the RET proto-oncogene. Therefore, in children with MEN2 and advanced MTC, the RET tyrosine kinase (TK) pathway is a target for treatment with selpercatinib, a selective RET TK inhibitor.

Patients And Methods: A retrospective review of the clinical, genetic, biochemical (calcitonin and carcinoembryonic antigen [CEA]) and imaging data of six medically untreated children with MEN2 and recurrent and or progressive MTC.