Brain and Brain Stem Necrosis After Reirradiation for Recurrent Childhood Primary Central Nervous System Tumors: A PENTEC Comprehensive Review.

PURPOSE: Reirradiation is increasingly used in children and adolescents/young adults (AYA) with recurrent primary central nervous system tumors. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) reirradiation task force aimed to quantify risks of brain and brain stem necrosis after reirradiation. METHODS AND MATERIALS: A systematic literature search using the PubMed and Cochrane databases for peer-reviewed articles from 1975 to 2021 identified 92 studies on reirradiation for recurrent tumors in children/AYA. Seventeen studies representing 449 patients who reported brain and brain stem necrosis after reirradiation contained sufficient data for analysis. While all 17 studies described techniques and doses used for reirradiation, they lacked essential details on clinically significant dose-volume metrics necessary for dose-response modeling on late effects. We, therefore, estimated incidences of necrosis with an exact 95% CI and qualitatively described data. Results from multiple studies were pooled by taking the weighted average of the reported crude rates from individual studies. RESULTS: Treated cancers included ependymoma (n = 279 patients; 7 studies), medulloblastoma (n = 98 patients; 6 studies), any CNS tumors (n = 62 patients; 3 studies), and supratentorial high-grade gliomas (n = 10 patients; 1 study). The median interval between initial and reirradiation was 2.3 years (range, 1.2-4.75 years). The median cumulative prescription dose in equivalent dose in 2-Gy fractions (EQD22; assuming α/ß value = 2 Gy) was 103.8 Gy (range, 55.8-141.3 Gy). Among 449 reirradiated children/AYA, 22 (4.9%; 95% CI, 3.1%-7.3%) developed brain necrosis and 14 (3.1%; 95% CI, 1.7%-5.2%) developed brain stem necrosis with a weighted median follow-up of 1.6 years (range, 0.5-7.4 years). The median cumulative prescription EQD22 was 111.4 Gy (range, 55.8-141.3 Gy) for development of any necrosis, 107.7 Gy (range, 55.8-141.3 Gy) for brain necrosis, and 112.1 Gy (range, 100.2-117 Gy) for brain stem necrosis. The median latent period between reirradiation and the development of necrosis was 5.7 months (range, 4.3-24 months). Though there were more events among children/AYA undergoing hypofractionated versus conventionally fractionated reirradiation, the differences were not statistically significant (P = .46). CONCLUSIONS: Existing reports suggest that in children/AYA with recurrent brain tumors, reirradiation with a total EQD22 of about 112 Gy is associated with an approximate 5% to 7% incidence of brain/brain stem necrosis after a median follow-up of 1.6 years (with the initial course of radiation therapy being given with conventional prescription doses of ≤2 Gy per fraction and the second course with variable fractionations). We recommend a uniform approach for reporting dosimetric endpoints to derive robust predictive models of late toxicities following reirradiation.

Neurocognitive Dysfunction After Treatment for Pediatric Brain Tumors: Subtype-Specific Findings and Proposal for Brain Network-Informed Evaluations.

The increasing number of long-term survivors of pediatric brain tumors requires us to incorporate the most recent knowledge derived from cognitive neuroscience into their oncological treatment. As the lesion itself, as well as each treatment, can cause specific neural damage, the long-term neurocognitive outcomes are highly complex and challenging to assess. The number of neurocognitive studies in this population grows exponentially worldwide, motivating modern neuroscience to provide guidance in follow-up before, during and after treatment. In this review, we provide an overview of structural and functional brain connectomes and their role in the neuropsychological outcomes of specific brain tumor types. Based on this information, we propose a theoretical neuroscientific framework to apply appropriate neuropsychological and imaging follow-up for future clinical care and rehabilitation trials.

Central nervous system germ cell tumor, an archetypal AYA tumor and a model for pediatric and neuro-oncology collaboration, review from the EURACAN domain 10 group.

Simple Summary: Adolescents and young adults (AYA) with cancer often fall through gaps between children's and adults' cancer services. They are consequently under-represented in clinical trials, and their survival is often inferior to that of children or adults with the same tumor type; in this paper, we use the example of central nervous system germ cell tumors (CNS-GCT), as a model of AYA tumor to illustrate this challenge. We describe how we have built bridges between pediatric and adult oncology, how this can apply to other types of brain tumors, and discuss ways to promote cancer care in the AYA population. Adolescents and young adults (AYA) with cancer are under-represented in clinical trials and have thus not benefited from the same improvement in outcomes as either younger or older patients. Central nervous system germ cell tumors (CNS-GCT) represent an ideal model of AYA tumor as their incidence peaks during adolescence and young adulthood. Since the early 90's, SIOP (International Society of Pediatric Oncology) has launched two successive European trials: SIOP CNS-GCT96 (January 1996 to December 2005) and SIOP CNS-GCTII protocols (October 2011 to July 2018), for CNS-GCTs. With the removal of the upper age limit in the SIOP CNS-GCTII trial, and closer collaboration between pediatric and adult oncologists within AYA multidisciplinary tumor boards, the proportion of adults enrolled in France has dramatically increased over time. The current article will use the example of CNS-GCT to illustrate how to build a bridge between pediatric and adult oncology, how this can apply to other types of brain tumors, and how to promote cancer care in the AYA population.

Imaging response assessment for CNS germ cell tumours: consensus recommendations from the European Society for Paediatric Oncology Brain Tumour Group and North American Children's Oncology Group.

Homogeneous and common objective disease assessments and standardised response criteria are important for better international clinical trials for CNS germ cell tumours. Currently, European protocols differ from those of North America (the USA and Canada) in terms of criteria to assess radiological disease response. An international working group of the European Society for Paediatric Oncology Brain Tumour Group and North American Children's Oncology Group was therefore established to review existing literature and current practices, identify major challenges regarding imaging assessment, and develop consensus recommendations for imaging response assessment for patients with CNS germ cell tumours. New clinical imaging standards were defined for the most common sites of CNS germ cell tumour and for the definition of locoregional extension. These new standards will allow the evaluation of response to therapy in patients with CNS germ cell tumours to be more consistent, and facilitate direct comparison of treatment outcomes across international studies.

Vinblastine monotherapy induction prior to radiotherapy for patients with intracranial germinoma during the COVID-19 pandemic.

BACKGROUND: Patients with localized intracranial germinoma have excellent survival. Reducing treatment burden and long-term sequelae is a priority. Intensive inpatient chemotherapy (e.g., carboPEI = carboplatin/etoposide/ifosfamide) has been effectively employed to reduce radiotherapy treatment volume/dose. Outpatient-based carboplatin monotherapy is associated with excellent outcomes in metastatic testicular seminoma (an identical pathology), and successful vinblastine monotherapy induction (with 77% tumor volume reduction after just two weekly vinblastine doses) has recently been reported in an intracranial germinoma patient. METHODS: Adapted UK guidelines for germ cell tumor management were distributed during the COVID-19 pandemic, including nonstandard treatment options to reduce hospital visits and/or admissions. This included vinblastine monotherapy for intracranial germinoma (6 mg/m2 intravenously, or 4 mg/m2 for moderate count suppression, delivered weekly). We describe two such patients treated using this approach. RESULTS: A 30-year-old male with a localized pineal tumor received 12-week vinblastine induction, with >60% volume reduction, prior to definitive radiotherapy. A 12-year-old female with a metastatic suprasellar tumor and progression at all sites of disease whilst awaiting proton radiotherapy received two vinblastine doses with good early response, including 36% primary tumor volume reduction. The patients tolerated vinblastine well. CONCLUSION: Patients with intracranial germinoma have excellent outcomes, and reduction of late effects remains a priority. The description of vinblastine monotherapy in these intracranial germinoma patients warrants further exploration.

Endoscopic ultrasound-guided neurolysis in advanced pancreatic cancer: current status.

Pancreatic cancer has a very poor prognosis with patients often presenting with locally advanced, inoperable or metastatic disease. A significant proportion of patients have visceral pain due to perineural infiltration or coeliac plexus involvement by the tumour. This pain is difficult to control and may become refractory to conventional pain management. Therefore, coeliac plexus neurolysis (CPN) has been proposed to ablate the neuronal transmission pathway of pain permanently. CPN is recommended for those who have uncontrolled pain, are experiencing unacceptable opioid adverse effects or are receiving escalating doses of analgesics. It is not known whether CPN performed at diagnosis as the first-line treatment ('early') would impact short-term and long-term pain control and quality of life. NICE has recommended (2018) a randomised trial comparing early endoscopic ultrasound-guided coeliac plexus neurolysis (EUS-CPN) with on-demand EUS-CPN in pancreatic cancer. In this context, we will review the current evidence on its clinical benefits.

Update of the EPTN atlas for CT- and MR-based contouring in Neuro-Oncology.

BACKGROUND AND PURPOSE: To update the digital online atlas for organs at risk (OARs) delineation in neuro-oncology based on high-quality computed tomography (CT) and magnetic resonance (MR) imaging with new OARs. MATERIALS AND METHODS: In this planned update of the neurological contouring atlas published in 2018, ten new clinically relevant OARs were included, after thorough discussion between experienced neuro-radiation oncologists (RTOs) representing 30 European radiotherapy-oncology institutes. Inclusion was based on daily practice and research requirements. Consensus was reached for the delineation after critical review. Contouring was performed on registered CT with intravenous (IV) contrast (soft tissue & bone window setting) and 3 Tesla (T) MRI (T1 with gadolinium & T2 FLAIR) images of one patient (1 mm slices). For illustration purposes, delineation on a 7 T MRI without IV contrast from a healthy volunteer was added. OARs were delineated by three experienced RTOs and a neuroradiologist based on the relevant literature. RESULTS: The presented update of the neurological contouring atlas was reviewed and approved by 28 experts in the field. The atlas is available online and includes in total 25 OARs relevant to neuro-oncology, contoured on CT and MRI T1 and FLAIR (3 T & 7 T). Three-dimensional (3D) rendered films are also available online. CONCLUSION: In order to further decrease inter- and intra-observer OAR delineation variability in the field of neuro-oncology, we propose the use of this contouring atlas in photon and particle therapy, in clinical practice and in the research setting. The updated atlas is freely available on www.cancerdata.org.

Clinical presentation and outcomes of solitary plasmacytoma in a tertiary hospital in the UK.

Solitary plasmacytoma is a rare localised neoplasm of monoclonal plasma cells. The standard treatment involves radical radiotherapy; however, a significant proportion of patients subsequently develop multiple myeloma. In this study, we evaluate the outcomes of solitary plasmacytoma in a retrospective cohort of patients treated in a single tertiary centre.The case records of plasmacytoma patients treated in a 15-year period were analysed and retrospectively followed up from the date of diagnosis. Thirty-four cases met the inclusion criteria; 27 (79%) solitary plasmacytoma of bone (SBP) and 7 (21%) extramedullary plasmacytoma (EMP). The thoracic vertebrae were the commonest sites for SBP while EMP occurred most frequently in the upper airway. Pain and spinal cord compression were the most frequent symptoms. A paraprotein was detectable in 18 (53%) patients. Over a median follow-up of 48 months, 13 (38%) developed multiple myeloma. The 5- and 10-year survival rates were 80% and 56%, respectively; median progression-free survival was 77 months. Four patients (12%) developed a second malignancy.Progression to multiple myeloma remains a formidable challenge in the management of solitary plasmacytoma, hence adjunct therapies are needed.

Clinical utility of circulating miR-371a-3p for the management of patients with intracranial malignant germ cell tumors.

BACKGROUND: The current biomarkers alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) have limited sensitivity/specificity for diagnosing malignant germ cell tumors (GCTs) and "marker-negative" patients require histological confirmation for diagnosis. However, GCTs at intracranial sites are surgically relatively inaccessible and biopsy carries risks. MicroRNAs from the miR-371~373 and miR-302/367 clusters are over-expressed in all malignant GCTs and, in particular, miR-371a-3p shows elevated serum levels at diagnosis for testicular disease. METHODS: Using our robust preamplified qRT-PCR methodology, we quantified miR-371a-3p levels in serum and cerebrospinal fluid (CSF) in a series of 4 representative clinical cases, 3 with intracranial malignant GCT and 1 with Langerhans cell histiocytosis (LCH), compared with appropriate control cases. RESULTS: Serum and/or CSF miR-371a-3p levels distinguished those with intracranial malignant GCTs from LCH and, if known in real time, could have helped clinical management. The benefits would have included (1) the only confirmatory evidence of an intracranial malignant GCT in 1 case, supporting clinical decision making; (2) early detection of intracranial malignant GCT in another, where an elevated CSF miR-371a-3p level preceded the histologically confirmed diagnosis by 2 years; and (3) confirmation of an intracranial malignant GCT relapse with an elevated serum miR-371a-3p level, where serum and CSF AFP and HCG levels were below thresholds for such a diagnosis. CONCLUSIONS: This series highlights the potential for microRNA quantification to assist the noninvasive diagnosis, prognostication, and management for patients with intracranial malignant GCTs. Serum and CSF should be collected routinely as part of future studies to facilitate the extension of these findings to larger patient cohorts.

A rapid review of evidence and recommendations from the SIOPE radiation oncology working group to help mitigate for reduced paediatric radiotherapy capacity during the COVID-19 pandemic or other crises.

OBJECTIVE: To derive evidence-based recommendations for the optimal utilisation of resources during unexpected shortage of radiotherapy capacity. METHODS AND MATERIALS: We have undertaken a rapid review of published literature on the role of radiotherapy in the multimodality treatment of paediatric cancers governing the European practise of paediatric radiotherapy. The derived data has been discussed with expert paediatric radiation oncologists to derive a hierarchy of recommendations. RESULTS: The general recommendations to mitigate the potential detriment of an unexpected shortage of radiotherapy facilities include: (1) maintain current standards of care as long as possible (2) refer to another specialist paediatric radiotherapy department with similar level of expertise (3) prioritise use of existing radiotherapy resources to treat patients with tumours where radiotherapy has the most effect on clinical outcome (4) use chemotherapy to defer the start of radiotherapy where timing of radiotherapy is not expected to be detrimental (5) active surveillance for low-grade tumours if appropriate and (6) consider iso-effective hypofractionated radiotherapy regimens only for selected patients with predicted poor prognosis. The effectiveness of radiotherapy and recommendations for prioritisation of its use for common and challenging paediatric tumours are discussed. CONCLUSION: This review provides evidence-based treatment recommendations during unexpected shortage of paediatric radiotherapy facilities. It has wider applications for the optimal utilisation of facilities, to improve clinical outcome in low- and middle-income countries, where limited resources continue to be a challenge.

Symptom interval and treatment burden for patients with malignant central nervous system germ cell tumours.

OBJECTIVE: Patients with central nervous system germ cell tumours (CNS-GCTs) commonly initially present to primary care or general paediatricians. Prolonged symptom intervals (SI) are frequently seen in CNS-GCTs and have been associated with inferior outcomes in other brain tumours. This study reviewed the clinical presentation of CNS-GCTs and examined the effect of prolonged SI. DESIGN/SETTING/PATIENTS/OUTCOMES: International multicentre 10-year retrospective study (2002-2011 inclusive), across six international paediatric oncology treatment centres. All newly diagnosed patients with CNS-GCT were included. Main outcome measure was time interval from first symptom to diagnosis. RESULTS: The study cohort included 86 (58 males:28 female) patients (59 'germinoma' and 27 'non-germinomatous' GCTs), with tumours being pineal (n=33), suprasellar (n=25), bifocal (pineal+suprasellar; n=24) and 'other' site (n=4), of which 16 (19%) were metastatic. Median age at diagnosis was 14 years (0-23 years). The time to diagnosis from first symptom (SI) was 0-69 months (median 3 months, mean 9 months). A prolonged SI (>6 months) was observed in 28/86 patients (33%) and significantly associated with metastatic disease (11/28 (39%) vs 5/58 (9%); p=0.002)) at diagnosis, but not overall survival. With prolonged SI, endocrine symptoms, particularly diabetes insipidus, were more common (21/28 (75%) vs 14/58 (24%) patients; p<0.002), but raised intracranial pressure (RICP) was less frequent (4/28 (14%) vs 43/58 (74%) patients; p<0.001)) at first symptom. CONCLUSIONS: One-third of patients with CNS-GCT have >6 months of symptoms prior to diagnosis. Delayed diagnosis is associated with metastatic disease. Early symptom recognition, particularly related to visual and hormonal disturbances in the absence of RICP, may improve timely diagnosis, reduce metastatic disease frequency and consequently reduce treatment burden and late effects.

Management of vertebral radiotherapy dose in paediatric patients with cancer: consensus recommendations from the SIOPE radiotherapy working group.

Inhomogeneities in radiotherapy dose distributions covering the vertebrae in children can produce long-term spinal problems, including kyphosis, lordosis, scoliosis, and hypoplasia. In the published literature, many often interrelated variables have been reported to affect the extent of potential radiotherapy damage to the spine. Articles published in the 2D and 3D radiotherapy era instructed radiation oncologists to avoid dose inhomogeneity over growing vertebrae. However, in the present era of highly conformal radiotherapy, steep dose gradients over at-risk structures can be generated and thus less harm is caused to patients. In this report, paediatric radiation oncologists from leading centres in 11 European countries have produced recommendations on how to approach dose coverage for target volumes that are adjacent to vertebrae to minimise the risk of long-term spinal problems. Based on available information, it is advised that homogeneous vertebral radiotherapy doses should be delivered in children who have not yet finished the pubertal growth spurt. If dose fall-off within vertebrae cannot be avoided, acceptable dose gradients for different age groups are detailed here. Vertebral delineation should include all primary ossification centres and growth plates, and therefore include at least the vertebral body and arch. For partial spinal radiotherapy, the number of irradiated vertebrae should be restricted as much as achievable, particularly at the thoracic level in young children (<6 years old). There is a need for multicentre research on vertebral radiotherapy dose distributions for children, but until more valid data become available, these recommendations can provide a basis for daily practice for radiation oncologists who have patients that require vertebral radiotherapy.

Uncommon low-grade brain tumors.

The 2016 World Health Organization (WHO) classification of primary central nervous system (CNS) tumors includes numerous uncommon (representing ≤1% of tumors) low-grade (grades I-II) brain neoplasms with varying clinical behaviors and outcomes. Generally, gross tumor or maximal safe resection is the primary treatment. Adjuvant treatments, though their exact role is unknown, may be considered individually based on pathological subtypes and a proper assessment of risks and benefits. Targetable mutations such as BRAF (proto-oncogene B-Raf), TRAIL (tumor necrosis factor apoptosis inducing ligand), and PDGFR (platelet derived growth factor receptor) have promising roles in future management.

SIOPE - Brain tumor group consensus guideline on craniospinal target volume delineation for high-precision radiotherapy.

OBJECTIVE: To develop a consensus guideline for craniospinal target volume (TV) delineation in children and young adults participating in SIOPE studies in the era of high-precision radiotherapy. METHODS AND MATERIALS: During four consensus meetings (Cambridge, Essen, Liverpool, and Marseille), conventional field-based TV has been translated into image-guided high-precision craniospinal TV by a group of expert paediatric radiation oncologists and enhanced by MRI images of liquor distribution. RESULTS: The CTVcranial should include the whole brain, cribriform plate, most inferior part of the temporal lobes, and the pituitary fossa. If the full length of both optic nerves is not included, the dose received by different volumes of optic nerve should be recorded to correlate with future patterns of relapse (no consensus). The CTVcranial should be modified to include the dural cuffs of cranial nerves as they pass through the skull base foramina. Attempts to spare the cochlea by excluding CSF within the internal auditory canal should be avoided. The CTVspinal should include the entire subarachnoid space, including nerve roots laterally. The lower limit of the spinal CTV is at the lower limit of the thecal sac, best visible on MRI scan. There is no need to include sacral root canals in the spinal CTV. CONCLUSION: This consensus guideline has the potential to improve consistency of craniospinal TV delineation in an era of high-precision radiotherapy. This proposal will be incorporated in the RTQA guidelines of future SIOPE-BTG trials using CSI.

Dosimetric comparison of five different techniques for craniospinal irradiation across 15 European centers: analysis on behalf of the SIOP-E-BTG (radiotherapy working group).

PURPOSE: Conventional techniques (3D-CRT) for craniospinal irradiation (CSI) are still widely used. Modern techniques (IMRT, VMAT, TomoTherapy®, proton pencil beam scanning [PBS]) are applied in a limited number of centers. For a 14-year-old patient, we aimed to compare dose distributions of five CSI techniques applied across Europe and generated according to the participating institute protocols, therefore representing daily practice. MATERIAL AND METHODS: A multicenter (n = 15) dosimetric analysis of five different techniques for CSI (3D-CRT, IMRT, VMAT, TomoTherapy®, PBS; 3 centers per technique) was performed using the same patient data, set of delineations and dose prescription (36.0/1.8 Gy). Different treatment plans were optimized based on the same planning target volume margin. All participating institutes returned their best treatment plan applicable in clinic. RESULTS: The modern radiotherapy techniques investigated resulted in superior conformity/homogeneity-indices (CI/HI), particularly in the spinal part of the target (CI: 3D-CRT:0.3 vs. modern:0.6; HI: 3D-CRT:0.2 vs. modern:0.1), and demonstrated a decreased dose to the thyroid, heart, esophagus and pancreas. Dose reductions of >10.0 Gy were observed with PBS compared to modern photon techniques for parotid glands, thyroid and pancreas. Following this technique, a wide range in dosimetry among centers using the same technique was observed (e.g., thyroid mean dose: VMAT: 5.6-24.6 Gy; PBS: 0.3-10.1 Gy). CONCLUSIONS: The investigated modern radiotherapy techniques demonstrate superior dosimetric results compared to 3D-CRT. The lowest mean dose for organs at risk is obtained with proton therapy. However, for a large number of organs ranges in mean doses were wide and overlapping between techniques making it difficult to recommend one radiotherapy technique over another.

High-Dose-Rate Brachytherapy in the Management of Operable Rectal Cancer: A Systematic Review.

PURPOSE: To evaluate the role of high-dose-rate endorectal brachytherapy (HDREBT) in the preoperative and definitive management of operable rectal cancer in terms of clinical outcomes and toxicities using a systematic review. METHODS AND MATERIALS: A review of published articles from January 1990 to December 2016 was conducted using the PubMed, Embase, and Scopus databases using the search terms "rectal" or "rectum" in combination with "brachytherapy," "high dose rate," "HDR," and "endorectal." Additional publications were identified by scanning references. Only studies published in English reporting clinical outcomes with ≥30 patients treated with HDREBT were included. RESULTS: The search identified 1688 articles, of which 22 met our inclusion criteria. Twelve studies were included in this systematic review. Following preoperative HDREBT with chemoradiation therapy (CRT), the pathologic complete response (pCR) rate ranged between 18% and 31% (weighted mean rate, 22.2%); R0 resection rate, between 80% and 99% (weighted mean rate, 95.5%); and sphincter-preservation rate, between 29% and 54% (weighted mean rate, 46.4%). The weighted mean 2-year progression-free survival and overall survival (OS) rates were 68.1% and 81.5%, respectively. After preoperative HDREBT alone, the pCR rate ranged between 10.4% and 27% (weighted mean rate, 23.8%), the R0 rate was 96.5% (1 study), and the sphincter-preservation rate ranged between 53.8% and 75.8% (weighted mean rate, 59.4%). The weighted mean 5-year progression-free survival and OS rates were 66.6% and 70.8%, respectively. There was only 1 study of HDREBT for nonsurgical management of rectal cancer, which reported a 2-year OS rate of 100%. CONCLUSIONS: Preoperative HDREBT either alone or in combination with CRT may result in a better pCR but may not necessarily translate into better survival, which is similar to outcomes seen following preoperative CRT alone. There were significant variations across studies in terms of patient selection, treatment approaches, and evaluation of clinical outcomes, suggesting the need for an international consensus on the dosimetric parameters and techniques of HDREBT, timing and methods of response assessment, definitions and assessment of toxicities, and optimal timing of surgery before further prospective studies. Future studies should include evaluation of the role of HDREBT in the nonsurgical curative treatment of screen-detected early cancers and organ preservation in lower rectal cancers.

Prevention of radiotherapy-induced neurocognitive dysfunction in survivors of paediatric brain tumours: the potential role of modern imaging and radiotherapy techniques.

Neurocognitive dysfunction is the leading cause of reduced quality of life in long-term survivors of paediatric brain tumours. Radiotherapy is one of the main contributors to neurocognitive sequelae. Current approaches for prevention and reduction of neurocognitive dysfunction include avoidance of radiotherapy in young children and reduction of the radiotherapy dose and volume of brain irradiated. Substantial advances have been made in brain imaging, especially with functional imaging and fibre tracking with the use of diffusion tensor imaging. Radiotherapy techniques for photon therapy have also evolved, with widespread use of techniques such as image-guided radiotherapy, volumetric modulated arc therapy, helical tomotherapy, and adaptive radiotherapy. The number of proton beam and heavy ion therapy facilities is increasing worldwide and there is great enthusiasm for clinical use of advanced MRI-guided radiotherapy systems. Here, we review the potential role of modern imaging and innovative radiotherapy techniques in minimisation of neurocognitive sequelae in children with brain tumours, and discuss various strategies to integrate these advances to drive further research.