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[...]the wide cerebral area irradiated can be damaging, particularly causing neurocognitive defects in the paediatric population. [...]more focused forms of radiotherapy have been explored, especially radiosurgery, using platforms such as CyberKnife or Gamma Knife when technically appropriate. In essence, they found similar results to those obtained with conventional therapy in terms of tumour imaging and growth, vasculopathy, neurological or visual damage, and endocrine dysfunction, but they found a significant decrease in neurocognitive dysfunction with proton-beam therapy versus conventional radiotherapy.6 These are important findings, and seem to demonstrate that proton-beam therapy is not inferior to conventional photon therapy in this group of patients, and that proton-beam therapy did not cause any increase in rates of established radiation toxicities, including radionecrosis. Proton-beam therapy is an extremely expensive and complex technology, is not widely available, and we need to consider the opportunity cost of the investment of these funds in relation to other health-care costs, especially in less well funded economies, and availability for other childhood tumours.

Background: Isocitrate Dehydrogenase 1/2 (IDH 1/2)-wildtype (WT) astrocytomas constitute a heterogeneous group of tumors and have undergone a series of diagnostic reclassifications over time. This study aimed to investigate molecular markers, clinical, imaging, and treatment factors predictive of outcomes in WHO grade 2/3 IDH-WT astrocytomas (‘early glioblastoma’). Methodology: Patients with WHO grade 2/3 IDH-WT astrocytomas were identified from the hospital archives. They were cross-referenced with the electronic medical records systems, including neuroimaging. The expert neuro-pathology team retrieved data on molecular markers—MGMT, TERT, IDH, and EGFR. Tumors with a TERT mutation and/or EGFR amplification were reclassified as glioblastoma. Results: Fifty-four patients were identified. Sixty-three percent of the patients could be conclusively reclassified as glioblastoma based on either TERT mutation, EGFR amplification, or both. On imaging, 65% showed gadolinium enhancement on MRI. Thirty-nine patients (72%) received long-course radiotherapy, of whom 64% received concurrent chemotherapy. The median follow-up of the group was 16 months (range: 2–90), and the median overall survival (OS) was 17.3 months. The 2-year OS of the whole cohort was 31%. On univariate analysis, older age, worse performance status (PS), and presence versus absence of contrast enhancement on diagnostic MRI were statistically significant for poorer OS. Conclusion: IDH-WT WHO grade 2/3 astrocytomas are a heterogeneous group of tumors with poor clinical outcomes. The majority can be reclassified as glioblastoma, based on current WHO classification criteria, but further understanding of the underlying biology of these tumors and the discovery of novel targeted agents are needed for better outcomes.

Radiation therapy is widely used for benign and malignant brain tumours as it is effective and well tolerated. However, damage to the surrounding healthy nervous system tissue leads to a variety of complications both in the short term and long term, ranging from mild and self-limiting to irreversible and fatal. Radiation neurotoxicity is due to a combination of early inflammation and oligodendroglial damage followed later by brain tissue necrosis, white matter damage, accelerated vascular disease and the development of secondary tumours. This article explains the basic principles of radiation physics, the different modalities used in clinical practice, how radiotherapy is planned and delivered and the scientific basis of radiation damage. The main body of the article focuses on the clinical features of radiation toxicity in the brain, spinal cord, cranial and peripheral nerves with an emphasis on the distinction between early and delayed complications.

Despite the increasing precision of radiotherapy delivery, it is still frequently associated with neurological complications. This is in part due to damage to eloquent white matter (WM) tracts, which is made more likely by the fact they cannot be visualised on standard structural imaging. WM is additionally more vulnerable than grey matter to radiation damage. Primary brain malignancies also are known to spread along the WM. Diffusion tensor imaging (DTI) is the only in vivo method of delineating WM tracts. DTI is an imaging technique that models the direction of diffusion and therefore can infer the orientation of WM fibres. This review article evaluates the current evidence for using DTI to guide intracranial radiotherapy and whether it constitutes a new state-of-the-art technique. We provide a basic overview of DTI and its known applications in radiotherapy, which include using tractography to reduce the radiation dose to eloquent WM tracts and using DTI to detect or predict tumoural spread. We evaluate the evidence for DTI-guided radiotherapy in gliomas, metastatic disease, and benign conditions, finding that the strongest evidence is for its use in arteriovenous malformations. However, the evidence is weak in other conditions due to a lack of case-controlled trials.

ObjectiveThis study aims to develop a comprehensive process map for patients with brain tumours to identify opportunities for quality improvement and automated data collection. Through optimising workflows, the overall goal is to improve patient recruitment to clinical trials.DesignA two-stage mixed methods design, combining qualitative development of a process map with quantitative validation using electronic health records (EHR). Following this, a cross-sectional survey was conducted to assess how patients learn about clinical trials.SettingA single neurosurgery centre in the United Kingdom.ParticipantsThe process map was developed through stakeholder interviews with neuro-oncology multidisciplinary team members and patients (n=13). Clinical encounters were validated with EHR data from 50 patients. A cross-sectional survey presented the validated process map to 25 postoperative patients to identify the resources they used to learn about ongoing clinical trials.InterventionsPostoperative questionnaires were given to patients after brain tumour surgery, either on the ward or in follow-up clinic.Primary and secondary outcome measuresThe primary outcome was the percentage of the study cohort that was present at encounters on the process map. Key timepoints were defined if >80% of patients were present. They represent high-yield opportunities to offer information on clinical trial recruitment. The secondary outcome was the resources used by patients to learn about ongoing clinical trials.ResultsQuantitative validation of patient pathways identified 345 encounters involving 19 discrete events, including clinics, telephone follow-ups and treatments. The flow of encounters reflected the process map with 90.7% accuracy, with key timepoints identified at imaging and biopsy/surgical procedures. A cross-sectional survey conducted during outpatient neuro-oncology clinics identified that patients predominantly used self-directed internet searches (n=17, 68%) and verbal information from their neurosurgeon (n=16, 64%) to learn about clinical trials.ConclusionsThis study demonstrates the effectiveness of process mapping in identifying key timepoints for automated data collection and opportunities for quality improvement for clinical trial recruitment. Integrating online and in-clinic education strategies could enhance patient awareness and participation in clinical trials.

ObjectivesBrain tumours lead to significant morbidity including a neurocognitive, physical and psychological burden of disease. The extent to which they impact the multiple domains of health is difficult to capture leading to a significant degree of unmet needs. Mobile health tools such as Vinehealth have the potential to identify and address these needs through real-world data generation and delivery of personalised educational material and therapies. We aimed to establish the feasibility of Vinehealth integration into brain tumour care, its ability to collect real-world and (electronic) patient-recorded outcome (ePRO) data, and subjective improvement in care.DesignA mixed-methodology IDEAL stage 1 study.SettingA single tertiary care centre.ParticipantsSix patients consented and four downloaded and engaged with the mHealth application throughout the 12 weeks of the study.Main outcome measuresOver a 12-week period, we collected real-world and ePRO data via Vinehealth. We assessed qualitative feedback from mixed-methodology surveys and semistructured interviews at recruitment and after 2 weeks.Results565 data points were captured including, but not limited to: symptoms, activity, well-being and medication. EORTC QLQ-BN20 and EQ-5D-5L completion rates (54% and 46%) were impacted by technical issues; 100% completion rates were seen when ePROs were received. More brain cancer tumour-specific content was requested. All participants recommended the application and felt it improved care.ConclusionsOur findings indicate value in an application to holistically support patients living with brain cancer tumours and established the feasibility and safety of further studies to more rigorously assess this.

Purpose Radiolabelled meta -iodobenzylguanidine (mIBG), used as targeted therapy for neuroblastoma, is known to have effects on blood pressure (BP). In this study we audited BP changes in patients receiving 131 I-mIBG therapy for neuroblastoma to identify BP-related adverse events (AE) and possible predictive factors. Methods Between 2003 and 2010, 50 patients with neuroblastoma received 110 131 I-mIBG administrations. BP measurements before and after administration were compared with age- and sex-matched centile values. AE were analysed, and possible predisposing factors identified. Results This population had a baseline BP distribution higher than that of their age- and sex-matched peers, with 16% of preadministration systolic BP values above the 95th centile. Changes in BP after administration showed an approximately normal distribution with similar numbers of reduced and increased values. Four AE, all related to hypertension, occurred with one patient having generalized seizures. One AE was immediate, others occurred between 20 and 25 h after administration. No significant association between AE and patient age or sex was demonstrated. However, a significant association between AE and high preadministration BP was shown, both above the 90th centile ( p  = 0.0022) and above the 95th centile ( p  = 0.0135). Conclusion Clinically relevant hypertension following 131 I-mIBG therapy affected less than 5% of administrations, but was more common in those patients with preexisting hypertension. As hypertensive episodes may occur many hours after treatment, close monitoring of BP needs to be continued for at least 48 h after administration of 131 I-mIBG.

Background Non-functioning pituitary macroadenomas (NFPMs) may present with hypopituitarism. Pituitary surgery and radiotherapy pose an additional risk to pituitary function. Objectives To assess the incidence of hypopituitarism at presentation, the impact of treatment, and the likelihood of endocrine recovery during follow-up. Methods All patients treated surgically with and without radiotherapy for NFPMs between 1987 and 2018 who had longer than six months follow-up were identified. Demographics, presentation, investigation, treatment, and outcomes were collected. Results In total, 383 patients were identified. The median age was 57 years, with a median follow-up of 8 years. Preoperatively, 227 patients (227/375; 61%) had evidence of at least one pituitary deficiency. Anterior panhypopituitarism was more common in men ( p  = 0.001) and older patients ( p  = 0.005). Multiple hormone deficiencies were associated with large tumours ( p  = 0.03). Patients treated with surgery and radiotherapy had a higher incidence of all individual pituitary hormone deficiency, anterior panhypopituitarism, and significantly lower GH, ACTH, and TSH deficiencies free survival probability than those treated with surgery alone. Recovery of central hypogonadism, hypothyroidism, and anterior panhypopituitarism was also less likely to be reported in those treated with surgery and radiotherapy. Those with preoperative hypopituitarism had a higher risk of pituitary impairment at latest review than those presented with normal pituitary function ( p  = 0.001). Conclusion NFPMs are associated with a significant degree of hypopituitarism at time of diagnosis and post-therapy. The combination of surgery and radiotherapy is associated with a higher risk of pituitary dysfunction. Recovery of pituitary hormone deficit may occur after treatment. Patients should have regular ongoing endocrine evaluation post-treatment to assess changes in pituitary function and the need for long-term replacement therapy.

Introduction: Gliomatosis cerebri describes a rare growth pattern of diffusely infiltrating glioma. The treatment options are limited and clinical outcomes remain poor. To characterise this population of patients, we examined referrals to a specialist brain tumour centre. Methods: We analysed demographic data, presenting symptoms, imaging, histology and genetics, and survival in individuals referred to a multidisciplinary team meeting over a 10-year period. Results: In total, 29 patients fulfilled the inclusion criteria with a median age of 64 years. The most common presenting symptoms were neuropsychiatric (31%), seizure (24%) or headache (21%). Of 20 patients with molecular data, 15 had IDH wild-type glioblastoma, with an IDH1 mutation most common in the remainder (5/20). The median length of survival from MDT referral to death was 48 weeks (IQR 23 to 70 weeks). Contrast enhancement patterns varied between and within tumours. In eight patients who had DSC perfusion studies, five (63%) had a measurable region of increased tumour perfusion with rCBV values ranging from 2.8 to 5.7. A minority of patients underwent MR spectroscopy with 2/3 (66.6%) false-negative results. Conclusions: Gliomatosis imaging, histological and genetic findings are heterogeneous. Advanced imaging, including MR perfusion, could identify biopsy targets. Negative MR spectroscopy does not exclude the diagnosis of glioma.

Background An association between trastuzumab-emtansine (T-DM1) and splenic enlargement is reported in preclinical data, and has been noted anecdotally in patients receiving T-DM1 at our institution. Use of whole-body MRI examinations (WB-MRI) allows for detailed bone marrow assessment and semi-automated splenic volume calculations. Objective To retrospectively evaluate changes in splenic volume versus evidence of bone marrow hyperplasia and/or changes in portal venous pressure in patients receiving T-DM1 for metastatic breast cancer. Patients and Methods Twelve metastatic breast cancer patients underwent 29 WB-MRIs before and during T-DM1 therapy. Splenic volume, portal vein diameter, bone marrow diffusion-weighted normalised signal intensity (nSI), quantitative water diffusivity (apparent diffusion coefficient, ADC) and fat fraction (rF%) were measured and correlated. Results Splenic volume increases were observed in 92% of patients. Mean splenic volume increased from 144 cm 3 (95% CI 110–177 cm 3 ) to 209 cm 3 (95% CI 161–257 cm 3 ) on T-DM1 therapy ( p  = 0.006). Splenic volume increases correlated with treatment duration (r 2  = 0.43). Bone marrow hyperplasia was evidenced by an increase in bone marrow nSI (3.5 to 4.8, p  = 0.12), and decreases in rF% (64.3% to 57.3%, p  = 0.12) and ADC (655 μm 2 /s to 543 μm 2 /s, p  = 0.11). No changes to portal vein diameter were seen. Conclusions Previously unreported increases in splenic volume and bone marrow hyperplasia are observed on WB-MRI in patients on T-DM1 therapy. Caution must be applied to avoid misinterpreting T-DM1-induced bone marrow hyperplasia as diffuse disease progression in bone.