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.

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.

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.

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).

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.

Risk of radiation-induced second malignant neoplasms from photon and proton radiotherapy in paediatric abdominal neuroblastoma.

Background And Purpose: State-of-the-art radiotherapy modalities have the potential of reducing late effects of treatment in childhood cancer survivors. Our aim was to investigate the carcinogenic risk associated with 3D conformal (photon) radiation (3D-CRT), intensity modulated arc therapy (IMAT) and pencil beam scanning proton therapy (PBS-PT) in the treatment of paediatric abdominal neuroblastoma.

Materials And Methods: The risk of radiation-induced second malignant neoplasm (SMN) was estimated using the concept of organ equivalent dose (OED) for eleven organs (lungs, rectum, colon, stomach, small intestine, liver, bladder, skin, central nervous system (CNS), bone, and soft tissues).

Atlas construction and spatial normalisation to facilitate radiation-induced late effects research in childhood cancer.

Reducing radiation-induced side effects is one of the most important challenges in paediatric cancer treatment. Recently, there has been growing interest in using spatial normalisation to enable voxel-based analysis of radiation-induced toxicities in a variety of patient groups. The need to consider three-dimensional distribution of doses, rather than dose-volume histograms, is desirable but not yet explored in paediatric populations.

The spleen as an organ at risk in paediatric radiotherapy: A SIOP-Europe Radiation Oncology Working Group report.

Background: Radiation may cause long-term splenic dysfunction, risking potentially fatal late sepsis. We aimed to review this complication's magnitude in paediatric radiotherapy and gauge the level of awareness of the spleen as an organ at risk.

Methods: Clinical trial protocols and radiotherapy guidelines, patient/parent information sheets, and professional guidance documents were reviewed to assess the perceived risk of radiotherapy-related splenic dysfunction.

Parents' responses to prognostic disclosure at diagnosis of a child with a high-risk brain tumor: Analysis of clinician-parent interactions and implications for clinical practice.

Background: Previous studies have found that parents of children with cancer desire more prognostic information than is often given even when prognosis is poor. We explored in audio-recorded consultations the kinds of information they seek.

Methods: Ethnographic study including observation and audio recording of consultations at diagnosis.

Personalisation of Molecular Radiotherapy through Optimisation of Theragnostics.

Molecular radiotherapy, or targeted radionuclide therapy, uses systemically administered drugs bearing a suitable radioactive isotope, typically a beta emitter. These are delivered via metabolic or other physiological pathways to cancer cells in greater concentrations than to normal tissues. The absorbed radiation dose in tumour deposits causes chromosomal damage and cell death.

68Ga-DOTATATE and 123I-mIBG as imaging biomarkers of disease localisation in metastatic neuroblastoma: implications for molecular radiotherapy.

Purpose: Iodine-131-labelled meta-iodobenzylguanidine (I-mIBG) and lutetium-177-labelled DOTATATE (Lu-DOTATATE) are used for molecular radiotherapy of metastatic neuroblastoma. These are taken up by the noradrenaline transporter (NAT) and the somatostatin receptor subtype 2 (SSTR-2), respectively. Scintigraphy of iodine-123-labelled meta-iodobenzylguanidine (I-mIBG) and gallium-68 DOTATATE (Ga-DOTATATE) PET are used to select patients for therapy.

A phase IIa trial of molecular radiotherapy with 177-lutetium DOTATATE in children with primary refractory or relapsed high-risk neuroblastoma.

Purpose: The objective of this phase IIa, open-label, single-centre, single-arm, two-stage clinical trial was to evaluate the safety and activity of 177-lutetium DOTATATE (LuDO) molecular radiotherapy in neuroblastoma.

Methods: Children with relapsed or refractory metastatic high-risk neuroblastoma were treated with up to four courses of LuDO. The administered activity was 75 to 100 MBq kg per course, spaced at 8- to 12-week intervals.

Immunohistochemical evaluation of molecular radiotherapy target expression in neuroblastoma tissue.

Purpose: Neuroblastoma may be treated with molecular radiotherapy, I meta-Iodobenzylguanidine and Lu Lutetium DOTATATE, directed at distinct molecular targets: Noradrenaline Transporter Molecule (NAT) and Somatostatin Receptor (SSTR2), respectively. This study used immunohistochemistry to evaluate target expression in archival neuroblastoma tissue, to determine whether it might facilitate clinical use of molecular radiotherapy.

Methods: Tissue bank samples of formalin fixed paraffin embedded neuroblastoma tissue from patients for whom clinical outcome data were available were sectioned and stained with haematoxylin and eosin, and monoclonal antibodies directed against NAT and SSTR2.

Clinical outcomes following proton therapy for children with central nervous system tumors referred overseas.

Background: International, multidisciplinary care of children with central nervous system (CNS) tumors presents unique challenges. The aim of this study is to report patient outcomes of U.K.

Adverse events of local treatment in long-term head and neck rhabdomyosarcoma survivors after external beam radiotherapy or AMORE treatment.

Background: Radiotherapy is a well-known cause of adverse events (AEs). To reduce AEs, an innovative local treatment was developed in Amsterdam: Ablative surgery, MOuld brachytherapy and surgical REconstruction (AMORE).

Aims: (1) to determine the prevalence of AEs in HNRMS survivors and (2) to compare AEs between survivors treated with the international standard: external beam radiotherapy (EBRT-based: London) and survivors treated with AMORE if feasible, otherwise EBRT (AMORE-based: Amsterdam).

A systematic review of 131I-meta iodobenzylguanidine molecular radiotherapy for neuroblastoma.

The optimal use and effectiveness of (131)I-meta iodobenzylguanidine ((131)I-mIBG) molecular radiotherapy for neuroblastoma remain unclear despite extensive clinical experience. This systematic review aimed to improve understanding of the current data and define uncertainties for future clinical trials. Bibliographic databases were searched for neuroblastoma and (131)I-mIBG.

Intensity-modulated arc therapy to improve radiation dose delivery in the treatment of abdominal neuroblastoma.

The standard European radiotherapy technique for children with neuroblastoma is a conventional parallel opposed pair. This frequently results in compromise on planning target volume coverage to stay within normal tissue tolerances. This study investigates the use of an intensity-modulated arc therapy (IMAT) technique to improve dose distribution and allow better protocol compliance.

Ten challenges in the management of neuroblastoma.

Neuroblastoma is a complex disease with many contradictions and challenges. It is, by and large, a cancer of babies and preschool children, but it does occur, albeit increasingly rarely, in older children, adolescents and young adults. The prognosis is very variable, with outcome related to age, stage and molecular pathology.

Results of a quality assurance review of external beam radiation therapy in the International Society of Paediatric Oncology (Europe) Neuroblastoma Group's High-risk Neuroblastoma Trial: a SIOPEN study.

Purpose: Radiation therapy is important for local control in neuroblastoma. This study reviewed the compliance of plans with the radiation therapy guidelines of the International Society of Paediatric Oncology (Europe) Neuroblastoma Group (SIOPEN) High-Risk Trial protocol.

Methods And Materials: The SIOPEN trial central electronic database has sections to record diagnostic imaging and radiation therapy planning data.

177Lu-DOTATATE molecular radiotherapy for childhood neuroblastoma.

Unlabelled: This study tested the principle that (68)Ga-DOTATATE PET/CT may be used to select children with primary refractory or relapsed high-risk neuroblastoma for treatment with (177)Lu-DOTATATE and evaluated whether this is a viable therapeutic option for those children.

Methods: Between 2008 and 2010, 8 children with relapsed or refractory high-risk neuroblastoma were studied with (68)Ga-DOTATATE PET/CT. The criterion of eligibility for (177)Lu-DOTATATE therapy was uptake on the diagnostic scan equal to or higher than that of the liver.