Glioma consensus contouring recommendations from a MR-Linac International Consortium Research Group and evaluation of a CT-MRI and MRI-only workflow.

INTRODUCTION: This study proposes contouring recommendations for radiation treatment planning target volumes and organs-at-risk (OARs) for both low grade and high grade gliomas. METHODS: Ten cases consisting of 5 glioblastomas and 5 grade II or III gliomas, including their respective gross tumor volume (GTV), clinical target volume (CTV), and OARs were each contoured by 6 experienced neuro-radiation oncologists from 5 international institutions. Each case was first contoured using only MRI sequences (MRI-only), and then re-contoured with the addition of a fused planning CT (CT-MRI). The level of agreement among all contours was assessed using simultaneous truth and performance level estimation (STAPLE) with the kappa statistic and Dice similarity coefficient. RESULTS: A high level of agreement was observed between the GTV and CTV contours in the MRI-only workflow with a mean kappa of 0.88 and 0.89, respectively, with no statistically significant differences compared to the CT-MRI workflow (p = 0.88 and p = 0.82 for GTV and CTV, respectively). Agreement in cochlea contours improved from a mean kappa of 0.39 to 0.41, to 0.69 to 0.71 with the addition of CT information (p < 0.0001 for both cochleae). Substantial to near perfect level of agreement was observed in all other contoured OARs with a mean kappa range of 0.60 to 0.90 in both MRI-only and CT-MRI workflows. CONCLUSIONS: Consensus contouring recommendations for low grade and high grade gliomas were established using the results from the consensus STAPLE contours, which will serve as a basis for further study and clinical trials by the MR-Linac Consortium.

Children's Cancer and Leukaemia Group (CCLG): review and guidelines for the management of meningioma in children, teenagers and young adults.

Primary tumours of the meninges are rare accounting for only 0.4-4.6% of all paediatric tumours of the central nervous system. Due to the rarity of these tumours in children, and the consequent absence of collaborative prospective trials, there is no clear consensus on how the unique characteristics of paediatric meningiomas impact clinical status, management approach, and survival. Much of the evidence and treatment recommendations for paediatric meningiomas are extrapolated from adult data. Translating and adapting adult treatment recommendations into paediatric practice can be challenging and might inadvertently lead to inappropriate management. In 2009, Traunecker et al. published guidelines for the management of intracranial meningioma in children and young people on behalf of UK Children's Cancer and Leukaemia Group (CCLG). Ten years later we have developed the updated guidelines following a comprehensive appraisal of the literature. Complete surgical resection is the treatment of choice for symptomatic meningiomas, while radiotherapy remains the only available adjuvant therapy and may be necessary for those tumours that cannot be completely removed. However, significant advances have been made in the identification of the genetic and molecular alterations of meningioma, which has not only a potential value in the development of therapeutic agents but also in surveillance of childhood meningioma survivors. This guideline builds upon the CCLG 2009 guideline. We summarise recommendations for the diagnosis, treatment, surveillance and long-term follow-up of children and adolescents with meningioma.

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.

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.

Multiple synchronous sites of origin of vestibular schwannomas in neurofibromatosis Type 2.

BACKGROUND: Neurofibromatosis Type 2 (NF2) is a dominantly inherited tumour syndrome with a phenotype which includes bilateral vestibular (eighth cranial nerve) schwannomas. Conventional thinking suggests that these tumours originate at a single point along the superior division of the eighth nerve. METHODS: High resolution MRI was performed in children genetically proven to have NF2. The superior vestibular nerve (SVN) and inferior vestibular nerve (IVN) were visualised along their course with points of tumour origin calculated as a percentage relative to the length of the nerve. RESULTS: Out of 41 patients assessed, 7 patients had no identifiable eighth cranial nerve disease. In 16 patients there was complete filling of the internal auditory meatus by a tumour mass such that its specific neural origin could not be determined. In the remaining 18 cases, 86 discrete separate foci of tumour origin on the SVN or IVN could be identified including 23 tumours on the right SVN, 26 tumours on the right IVN, 18 tumours on the left SVN and 19 tumours on the left IVN. DISCUSSION: This study, examining the origins of vestibular schwannomas in NF2, refutes their origin as being from a single site on the transition zone of the superior division of the vestibular nerve. We hypothesise a relationship between the number of tumour foci, tumour biology and aggressiveness of disease. The development of targeted drug therapies in addition to bevacizumab are therefore essential to improve prognosis and quality of life in patients with NF2 given the shortcomings of surgery and radiation treatments when dealing with the multifocality of the disease.

Surface guided radiotherapy practice in paediatric oncology: a survey on behalf of the SIOPE Radiation Oncology Working Group.

INTRODUCTION: Surface guided radiotherapy (SGRT) is increasingly being implemented to track patient's surface movement and position during radiation therapy. However, limited information is available on the SGRT use in paediatrics. The aim of this double survey was to map SIOPE (European Society for Paediatric Oncology)-affiliated centres using SGRT and to gain information on potential indications, observed, or expected benefits. METHODS: A double online survey was distributed to 246 SIOPE-affiliated radiotherapy (RT) centres. Multiple choices, yes/no, and open answers were included. The first survey (41 questions) was active from February to March 2021. A shortened version (13 questions) was repeated in March 2023 to detect trends in SGRT use within the same community. RESULTS: Respectively, 76/142 (54%) and 28/142 (20%) responding centres used and planned to use SGRT clinically, including 4/34 (12%) new centres since 2021. Among the SGRT users, 33/76 (43%) already applied this technology to paediatric treatments. The main benefits of improved patient comfort, better monitoring of intrafraction motion, and more accurate initial patient set-up expected by future users did not differ from current SGRT-users (P = .893). Among non-SGRT users, the main hurdles to implement SGRT were costs and time for installation. In paediatrics, SGRT is applied to all anatomical sites. CONCLUSION: This work provides information on the practice of SGRT in paediatrics across SIOPE-affiliated RT centres which can serve as a basis for departments when considering the purchase of SGRT systems. ADVANCES IN KNOWLEDGE: Since little information is available in the literature on the use of SGRT in paediatrics, the results of this double survey can serve as a basis for departments treating children when considering the purchase of an SGRT system.

Reported Hearing Outcome Measures Following Stereotactic Radiosurgery for Vestibular Schwannoma: A Scoping Review.

Background Evidence on hearing outcome measures when assessing hearing preservation following stereotactic radiosurgery (SRS) for adults with vestibular schwannoma (VS) has not previously been collated in a structured review. Objective The objective of the present study was to perform a scoping review of the evidence regarding the choice of hearing outcomes and other methodological characteristics following SRS for adults with VS. Methods The protocol was registered in the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) and reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses extension guidelines for scoping reviews. A systematic search of five online databases revealed 1,591 studies, 247 of which met the inclusion criteria. Results The majority of studies ( n = 213, 86%) were retrospective cohort or case series with the remainder ( n = 34, 14%) prospective cohort. Pure-tone audiometry and speech intelligibility were included in 222 (90%) and 158 (64%) studies, respectively, often summarized within a classification scheme and lacking procedural details. Fifty-nine (24%) studies included self-report measures. The median duration of follow-up, when reported, was 43 months (interquartile range: 29, 4-150). Conclusion Evidence on hearing disability after SRS for VS is based on low-quality studies which are inherently susceptible to bias. This review has highlighted an urgent need for a randomized controlled trial assessing hearing outcomes in patients with VS managed with radiosurgery or radiological observation. Similarly, consensus and coproduction of a core outcome set to determine relevant hearing and communication outcome domains is required. This will ensure that patient priorities, including communication abilities in the presence of background noise and reduced participation restrictions, are addressed.

Radiotherapy intensification for atypical and malignant meningiomas: A systematic review.

Background: The outcomes of nonbenign (WHO Grades 2 and 3 [G2, G3]) meningiomas are suboptimal and radiotherapy (RT) dose intensification strategies have been investigated. The purpose of this review is to report on clinical practice and outcomes with particular attention to RT doses and techniques. Methods: The PICO criteria (Population, Intervention, Comparison, and Outcomes) were used to frame the research question, directed at outlining the clinical outcomes in patients with G2-3 meningiomas treated with RT. The same search strategy was run in Embase and MEDLINE and, after deduplication, returned 1 807 records. These were manually screened for relevance and 25 were included. Results: Tumor outcomes and toxicities are not uniformly reported in the selected studies since different endpoints and time points have been used by different authors. Many risk factors for worse outcomes are described, the most common being suboptimal RT. This includes no or delayed RT, low doses, and older techniques. A positive association between RT dose and progression-free survival (PFS) has been highlighted by analyzing the studies in this review (10/25) that report the same endpoint (5y-PFS). Conclusions: This literature review has shown that standard practice RT leads to suboptimal tumor control rates in G2-3 meningiomas, with a significant proportion of disease recurring after a relatively short follow-up. Randomized controlled trials are needed in this setting to define the optimal RT approach. Given the increasing data to suggest a benefit of higher RT doses for high-risk meningiomas, novel RT technologies with highly conformal dose distributions are preferential to achieve optimal target coverage and organs at risk sparing.

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.

Clinical practice in European centres treating paediatric posterior fossa tumours with pencil beam scanning proton therapy.

BACKGROUND AND PURPOSE: As no guidelines for pencil beam scanning (PBS) proton therapy (PT) of paediatric posterior fossa (PF) tumours exist to date, this study investigated planning techniques across European PT centres, with special considerations for brainstem and spinal cord sparing. MATERIALS AND METHODS: A survey and a treatment planning comparison were initiated across nineteen European PBS-PT centres treating paediatric patients. The survey assessed all aspects of the treatment chain, including but not limited to delineations, dose constraints and treatment planning. Each centre planned two PF tumour cases for focal irradiation, according to their own clinical practice but based on common delineations. The prescription dose was 54 Gy(RBE) for Case 1 and 59.4 Gy(RBE) for Case 2. For both cases, planning strategies and relevant dose metrics were compared. RESULTS: Seventeen (89 %) centres answered the survey, and sixteen (80 %) participated in the treatment planning comparison. In the survey, thirteen (68 %) centres reported using the European Particle Therapy Network definition for brainstem delineation. In the treatment planning study, while most centres used three beam directions, their configurations varied widely across centres. Large variations were also seen in brainstem doses, with a brainstem near maximum dose (D2%) ranging from 52.7 Gy(RBE) to 55.7 Gy(RBE) (Case 1), and from 56.8 Gy(RBE) to 60.9 Gy(RBE) (Case 2). CONCLUSION: This study assessed the European PBS-PT planning of paediatric PF tumours. Agreement was achieved in e.g. delineation-practice, while wider variations were observed in planning approach and consequently dose to organs at risk. Collaboration between centres is still ongoing, striving towards common guidelines.

Surgery versus radiosurgery for vestibular schwannoma: Shared decision making in a multidisciplinary clinic.

Background: Our neurosurgical unit adopted a model of shared decision-making (SDM) based on multidisciplinary clinics for vestibular schwannoma (VS). A unique feature of this clinic is the interdisciplinary counseling process with a surgeon presenting the option of surgery, an oncologist radiosurgery or radiotherapy, and a specialist nurse advocating for the patient. Methods: This is a retrospective cohort study. All new patients seen in the combined VS clinic and referred from the skull base multidisciplinary team (MDT) from beginning of June 2013 to end of January 2019 were included. Descriptive statistics and frequency analysis were carried out for the full cohort. Results: Three hundred and fifty-four patients presenting with new or previously untreated VS were included in the analysis. In our cohort, roughly one-third of patients fall into each of the treatment strategies with slightly smaller numbers of patients undergoing surgery than watch, wait and rescan (WWR) ,and SRS (26.6% vs. 32.8% and 37.9%, respectively). Conclusion: In our experience, the combined surgery/oncology/specialist nurse clinic streamlines the patient experience for those with a VS suitable for either microsurgical or SRS/radiotherapy treatment. Decision-making in this population of patients is complex and when presented with all treatment options patients do not necessarily choose the least invasive option as a treatment. The unique feature of our clinic is the multidisciplinary counseling process with a specialist nurse advocating and guiding the patient. Treatment options are likely to become more rather than less complex in future years making combined clinics more valuable than ever in the SDM process.

Proton Beam Therapy in the Oligometastatic/Oligorecurrent Setting: Is There a Role? A Literature Review.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) and stereotactic radiosurgery (SRS) with conventional photon radiotherapy (XRT) are well-established treatment options for selected patients with oligometastatic/oligorecurrent disease. The use of PBT for SABR-SRS is attractive given the property of a lack of exit dose. The aim of this review is to evaluate the role and current utilisation of PBT in the oligometastatic/oligorecurrent setting. METHODS: Using Medline and Embase, a comprehensive literature review was conducted following the PICO (Patients, Intervention, Comparison, and Outcomes) criteria, which returned 83 records. After screening, 16 records were deemed to be relevant and included in the review. RESULTS: Six of the sixteen records analysed originated in Japan, six in the USA, and four in Europe. The focus was oligometastatic disease in 12, oligorecurrence in 3, and both in 1. Most of the studies analysed (12/16) were retrospective cohorts or case reports, two were phase II clinical trials, one was a literature review, and one study discussed the pros and cons of PBT in these settings. The studies presented in this review included a total of 925 patients. The metastatic sites analysed in these articles were the liver (4/16), lungs (3/16), thoracic lymph nodes (2/16), bone (2/16), brain (1/16), pelvis (1/16), and various sites in 2/16. CONCLUSIONS: PBT could represent an option for the treatment of oligometastatic/oligorecurrent disease in patients with a low metastatic burden. Nevertheless, due to its limited availability, PBT has traditionally been funded for selected tumour indications that are defined as curable. The availability of new systemic therapies has widened this definition. This, together with the exponential growth of PBT capacity worldwide, will potentially redefine its commissioning to include selected patients with oligometastatic/oligorecurrent disease. To date, PBT has been used with encouraging results for the treatment of liver metastases. However, PBT could be an option in those cases in which the reduced radiation exposure to normal tissues leads to a clinically significant reduction in treatment-related toxicities.

Radiation treatment of benign tumors in NF2-related-schwannomatosis: A national study of 266 irradiated patients showing a significant increase in malignancy/malignant progression.

Background: Radiation treatment of benign tumors in tumor predisposition syndromes is controversial, but short-term studies from treatment centers suggest safety despite apparent radiation-associated malignancy being reported. We determined whether radiation treatment in NF2-related schwannomatosis patients is associated with increased rates of subsequent malignancy (M)/malignant progression (MP). Methods: All UK patients with NF2 were eligible if they had a clinical/molecular diagnosis. Cases were NF2 patients treated with radiation for benign tumors. Controls were matched for treatment location with surgical/medical treatments based on age and year of treatment. Prospective data collection began in 1990 with addition of retrospective cases in 1969. Kaplan-Meier analysis was performed for malignancy incidence and survival. Outcomes were central nervous system (CNS) M/MP (2cm annualized diameter growth) and survival from index tumor treatment. Results: In total, 1345 NF2 patients, 266 (133-Male) underwent radiation treatments between 1969 and 2021 with median first radiotherapy age of 32.9 (IQR = 22.4-46.0). Nine subsequent CNS malignancies/MPs were identified in cases with only 4 in 1079 untreated (P < .001). Lifetime and 20-year CNS M/MP was ~6% in all irradiated patients-(4.9% for vestibular schwannomas [VS] radiotherapy) versus <1% in the non-irradiated population (P < .001/.01). Controls were well matched for age at NF2 diagnosis and treatment (Males = 133%-50%) and had no M/MP in the CNS post-index tumor treatment (P = .0016). Thirty-year survival from index tumor treatment was 45.62% (95% CI = 34.0-56.5) for cases and 66.4% (57.3-74.0) for controls (P = .02), but was nonsignificantly worse for VS radiotherapy. Conclusion: NF2 patients should not be offered radiotherapy as first-line treatment of benign tumors and should be given a frank discussion of the potential 5% excess absolute risk of M/MP.

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. This is to reduce the radiation exposure of healthy normal tissues and so the likelihood of adverse effects. Other methods of radiotherapy delivery include brachytherapy and molecular radiotherapy. The most appropriate treatment technique should be selected for every child. Advances in computers and imaging, developments in the technology of radiation delivery and a better understanding of pathology and molecular biology of cancer, coupled with parallel improvements in surgery and systemic therapy, have led to a transformation of practice in recent decades. Initially an empirical art form, radiotherapy for children has become a technically advanced, evidence-based cornerstone of increasingly personalised cancer medicine with solid scientific foundations. Late sequelae of treatment-the adverse effects once accepted as the cost of cure-have been significantly reduced in parallel with increased survival rates. The delivery of radiotherapy to children and young people requires a specialised multiprofessional team including radiation oncologists, therapeutic radiographers, play specialists and physicists among others. This article reviews the types of radiotherapy now available and outlines the pathway of the child through treatment. It aims to demonstrate to paediatricians how contemporary paediatric radiation oncology differs from past practice.

The European Particle Therapy Network (EPTN) consensus on the follow-up of adult patients with brain and skull base tumours treated with photon or proton irradiation.

PURPOSE: Treatment-related toxicity after irradiation of brain tumours has been underreported in the literature. Furthermore, there is considerable heterogeneity on how and when toxicity is evaluated. The aim of this European Particle Network (EPTN) collaborative project is to develop recommendations for uniform follow-up and toxicity scoring of adult brain tumour patients treated with radiotherapy. METHODS: A Delphi method-based consensus was reached among 24 international radiation-oncology experts in the field of neuro-oncology concerning the toxicity endpoints, evaluation methods and time points. RESULTS: In this paper, we present a basic framework for consistent toxicity scoring and follow-up, using multiple levels of recommendation. Level I includes all recommendations that are considered minimum of care, whereas level II and III are optional evaluations in the advanced clinical or research setting, respectively. Per outcome domain, the clinical endpoints and evaluation methods per level are listed. Where relevant, the organ at risk threshold doses for recommended referral to specific organ specialists are defined. CONCLUSION: These consensus-based recommendations for follow-up will enable the collection of uniform toxicity data of brain tumour patients treated with radiotherapy. With adoptation of this standard, collaboration will be facilitated and we can further propel the research field of radiation-induced toxicities relevant for these patients. An online tool to implement this guideline in clinical practice is provided at www.cancerdata.org.

Estimating the percentage of patients who might benefit from proton beam therapy instead of X-ray radiotherapy.

OBJECTIVES: High-energy Proton Beam Therapy (PBT) commenced in England in 2018 and NHS England commissions PBT for 1.5% of patients receiving radical radiotherapy. We sought expert opinion on the level of provision. METHODS: Invitations were sent to 41 colleagues working in PBT, most at one UK centre, to contribute by completing a spreadsheet. 39 responded: 23 (59%) completed the spreadsheet; 16 (41%) declined, arguing that clinical outcome data are lacking, but joined six additional site-specialist oncologists for two consensus meetings. The spreadsheet was pre-populated with incidence data from Cancer Research UK and radiotherapy use data from the National Cancer Registration and Analysis Service. 'Mechanisms of Benefit' of reduced growth impairment, reduced toxicity, dose escalation and reduced second cancer risk were examined. RESULTS: The most reliable figure for percentage of radical radiotherapy patients likely to benefit from PBT was that agreed by 95% of the 23 respondents at 4.3%, slightly larger than current provision. The median was 15% (range 4-92%) and consensus median 13%. The biggest estimated potential benefit was from reducing toxicity, median benefit to 15% (range 4-92%), followed by dose escalation median 3% (range 0 to 47%); consensus values were 12 and 3%. Reduced growth impairment and reduced second cancer risk were calculated to benefit 0.5% and 0.1%. CONCLUSIONS: The most secure estimate of percentage benefit was 4.3% but insufficient clinical outcome data exist for confident estimates. The study supports the NHS approach of using the evidence base and developing it through randomised trials, non-randomised studies and outcomes tracking. ADVANCES IN KNOWLEDGE: Less is known about the percentage of patients who may benefit from PBT than is generally acknowledged. Expert opinion varies widely. Insufficient clinical outcome data exist to provide robust estimates. Considerable further work is needed to address this, including international collaboration; much is already underway but will take time to provide mature data.

Low dose cone beam CT for paediatric image-guided radiotherapy: Image quality and practical recommendations.

PURPOSE: Cone beam CT (CBCT) is used in paediatric image-guided radiotherapy (IGRT) for patient setup and internal anatomy assessment. Adult CBCT protocols lead to excessive doses in children, increasing the risk of radiation-induced malignancies. Reducing imaging dose increases quantum noise, degrading image quality. Patient CBCTs also include 'anatomical noise' (e.g. motion artefacts), further degrading quality. We determine noise contributions in paediatric CBCT, recommending practical imaging protocols and thresholds above which increasing dose yields no improvement in image quality. METHODS AND MATERIALS: Sixty CBCTs including the thorax or abdomen/pelvis from 7 paediatric patients (aged 6-13 years) were acquired at a range of doses and used to simulate lower dose scans, totalling 192 scans (0.5-12.8 mGy). Noise measured in corresponding regions of each patient and a 10-year-old phantom were compared, modelling total (including anatomical) noise, and quantum noise contributions as a function of dose. Contrast-to-noise ratio (CNR) was measured between fat/muscle. Soft tissue registration was performed on the kidneys, comparing accuracy to the highest dose scans. RESULTS: Quantum noise contributed <20% to total noise in all cases, suggesting anatomical noise is the largest determinant of image quality in the abdominal/pelvic region. CNR exceeded 3 in over 90% of cases ≥ 1 mGy, and 57% of cases at 0.5 mGy. Soft tissue registration was accurate for doses > 1 mGy. CONCLUSION: Anatomical noise dominates quantum noise in paediatric CBCT. Appropriate soft tissue contrast and registration accuracy can be achieved for doses as low as 1 mGy. Increasing dose above 1 mGy holds no benefit in improving image quality or registration accuracy due to the presence of anatomical noise.

Does the uncertainty in relative biological effectiveness affect patient treatment in proton therapy?

Clinical treatment with protons uses the concept of relative biological effectiveness (RBE) to convert the absorbed dose into an RBE-weighted dose that equals the dose for radiotherapy with photons causing the same biological effect. Currently, in proton therapy a constant RBE of 1.1 is generically used. However, empirical data indicate that the RBE is not constant, but increases at the distal edge of the proton beam. This increase in RBE is of concern, as the clinical impact is still unresolved, and clinical studies demonstrating a clinical effect of an increased RBE are emerging. Within the European Particle Therapy Network (EPTN) work package 6 on radiobiology and RBE, a workshop was held in February 2020 in Manchester with one day of discussion dedicated to the impact of proton RBE in a clinical context. Current data on RBE effects, patient outcome and modelling from experimental as well as clinical studies were presented and discussed. Furthermore, representatives from European clinical proton therapy centres, who were involved in patient treatment, laid out their current clinical practice on how to consider the risk of a variable RBE in their centres. In line with the workshop, this work considers the actual impact of RBE issues on patient care in proton therapy by reviewing preclinical data on the relation between linear energy transfer (LET) and RBE, current clinical data sets on RBE effects in patients, and applied clinical strategies to manage RBE uncertainties. A better understanding of the variability in RBE would allow development of proton treatments which are safer and more effective.

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.

Proton beam therapy: perspectives on the National Health Service England clinical service and research programme.

The UK has an important role in the evaluation of proton beam therapy (PBT) and takes its place on the world stage with the opening of the first National Health Service (NHS) PBT centre in Manchester in 2018, and the second in London coming in 2020. Systematic evaluation of the role of PBT is a key objective. By September 2019, 108 patients had started treatment, 60 paediatric, 19 teenagers and young adults and 29 adults. Obtaining robust outcome data is vital, if we are to understand the strengths and weaknesses of current treatment approaches. This is important in demonstrating when PBT will provide an advantage and when it will not, and in quantifying the magnitude of benefit.The UK also has an important part to play in translational PBT research, and building a research capability has always been the vision. We are perfectly placed to perform translational pre-clinical biological and physical experiments in the dedicated research room in Manchester. The nature of DNA damage from proton irradiation is considerably different from X-rays and this needs to be more fully explored. A better understanding is needed of the relative biological effectiveness (RBE) of protons, especially at the end of the Bragg peak, and of the effects on tumour and normal tissue of PBT combined with conventional chemotherapy, targeted drugs and immunomodulatory agents. These experiments can be enhanced by deterministic mathematical models of the molecular and cellular processes of DNA damage response. The fashion of ultra-high dose rate FLASH irradiation also needs to be explored.