The growth rate and clinical outcomes of radiation induced meningioma undergoing treatment or active monitoring.

INTRODUCTION: Radiation induced meningioma (RIM) incidence is increasing in line with improved childhood cancer survival. No optimal management strategy consensus exists. This study aimed to delineate meningioma growth rates from tumor discovery and correlate with clinical outcomes. METHODS: Retrospective study of patients with a RIM, managed at a specialist tertiary neuroscience center (2007-2019). Tumor volume was measured from diagnosis and at subsequent interval scans. Meningioma growth rate was determined using a linear mixed-effects model. Clinical outcomes were correlated with growth rates accounting for imaging and clinical prognostic factors. RESULTS: Fifty-four patients (110 meningiomas) were included. Median duration of follow-up was 74 months (interquartile range [IQR], 41-102 months). Mean radiation dose was 41 Gy (standard deviation [SD] = 14.9) with a latency period of 34.4 years (SD = 13.7). Median absolute growth rate was 0.62 cm3/year and the median relative growth rate was 72%/year. Forty meningiomas (between 27 patients) underwent surgical intervention after a median follow-up duration of 4 months (IQR 2-35). Operated RIMs were clinically aggressive, likely to be WHO grade 2 at first resection (43.6%) and to progress after surgery (41%). Median time to progression was 28 months (IQR 13-60.5). A larger meningioma at discovery was associated with growth (HR 1.2 [95% CI 1.0-1.5], P = 0.039) but not progression after surgery (HR 2.2 [95% CI 0.7-6.6], P = 0.181). Twenty-seven (50%) patients had multiple meningiomas by the end of the study. CONCLUSION: RIMs exhibit high absolute and relative growth rates after discovery. Surgery is recommended for symptomatic or rapidly growing meningiomas only. Recurrence risk after surgery is high.

Permanent hair loss associated with taxane chemotherapy use in breast cancer: A retrospective survey at two tertiary UK cancer centres.

PURPOSE: Taxane chemotherapy is commonly used in the management of breast cancer. Hair loss (alopecia) is an expected side effect which may have a significant effect on quality of life. Alopecia is normally temporary but permanent chemotherapy-induced alopecia (pCIA) is increasingly recognised especially following docetaxel chemotherapy. However, the prevalence following docetaxel is not well understood and there is no published literature for paclitaxel chemotherapy. The aim of this study is to investigate the prevalence and patterns of pCIA resulting from both docetaxel and paclitaxel chemotherapy at two tertiary UK cancer centres. METHODS: In collaboration between Clatterbridge Cancer Centre and The Christie NHS Foundation Trusts, a retrospective survey was conducted for breast cancer patients who had received taxane chemotherapy in the neoadjuvant and adjuvant settings. Patients who had concluded chemotherapy at least a year previously were contacted by post and invited to participate by completing a questionnaire and returning it to their treatment centre. Data collected included the incidence and pattern of pCIA using the Savin pictorial hair loss scale, and the methods used by patients to manage it. Fisher's exact test was used to compare pCIA between the docetaxel and paclitaxel cohorts. RESULTS: 383 patients responded to the survey (a 63.3% overall response rate). These comprised 245 patients receiving docetaxel and 138 patients treated with paclitaxel. pCIA was reported by 23.3% of patients receiving docetaxel and 10.1% paclitaxel (p < 0.01). Overall 16.7% of patients in both groups reported the ongoing use of products or appliances such as wigs to camouflage their pCIA. In the docetaxel group, pCIA appeared to be more frequent in post-menopausal women than peri- or pre-menopausal women (37.8%, 12.3% and 19.6% respectively [Chi-square test p < 0.01]). Also in the docetaxel group, there appeared to be a trend for more severe scalp alopecia when the patient also received an aromatase inhibitor (AI) or tamoxifen and this difference was most marked in those who had received both an AI and tamoxifen as components of their treatment regime (p = 0.04). The use of scalp cooling was only recorded in the Christie paclitaxel group (n = 12). Of these 12 patients, 83.3% reported no hair loss. While overall rates of permanent eyebrow, eyelash and nostril hair loss were low, this pattern of hair loss appeared more frequent in the paclitaxel than the docetaxel group 4.3% vs. 1.8% (p = 0.29). CONCLUSIONS: Both docetaxel and paclitaxel may cause permanent scalp hair loss, but it is significantly more prevalent with docetaxel compared with paclitaxel. IMPLICATIONS FOR CANCER SURVIVORS: Clinicians should counsel patients regarding the risk of permanent alopecia prior to embarking upon taxane chemotherapy and routinely offer scalp cooling if available. More research is required to understand the pathobiology of this important and previously under recognised long-term side effect to enable more active preventive and management approaches.

Obesity is common at diagnosis of childhood pituitary adenoma and may persist following successful treatment.

OBJECTIVE: There is a paucity of data describing long-term outcomes of paediatric patients with pituitary adenoma. In this report, we describe clinical features, treatment and outcomes of a paediatric cohort. DESIGN: Retrospective cohort study. PATIENTS: Twenty-four white Caucasian patients aged <16 years from a single tertiary care centre in the United Kingdom at diagnosis followed for (median, range) 3.3, 0.7-8.4 years. MEASUREMENTS: Clinical and radiological data at diagnosis and follow-up. RESULTS: Thirteen patients had prolactinomas (54.1%, age: 15.2 years, 13.2-15.8 years; all females), including ten macroadenomas (11.0-35.0 mm). Patients presented with menstrual disorders (91%), headache (46%), galactorrhoea (46%) and obesity (body mass index [BMI] SDS > 2): (38%). Ten patients with prolactinoma were treated with dopamine agonist alone, 3 also required surgery and 2 patients, cabergoline, surgery plus radiotherapy. Five patients had Cushing's disease (20.8%, age: 14.0, 4.0-15.7 years; 2 female), including one macroadenoma (24 mm). Patients presented with obesity (100%), short stature (60%) and headache (40%). Transsphenoidal resection resulted in biochemical cure (09.00 cortisol < 50 nmol/L). Two patients relapsed 3- and 6 years following surgery, requiring radiotherapy. One patient also required bilateral adrenalectomy. Six patients had nonfunctioning pituitary adenoma (25.0%, age: 15.8, 12.5-16.0 years; 2 female), including two macroadenomas (20.0-53.0 mm). Patients presented with obesity (67%), visual field defects (50%) and headache (50%). Four required surgical resections; two recurred following surgery and required radiotherapy. On latest follow-up; 13 (54.1%) patients were obese (BMI 3.09 SDS; range: 2.05-3.73 SDS). CONCLUSION: Obesity is common at diagnosis of pituitary adenoma in childhood and may persist despite successful treatment. Adenomas were larger, more resistant to treatment, and more likely to recur than in adult populations.

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.

National UK guidelines for the management of paediatric craniopharyngioma.

Although rare, craniopharyngiomas constitute up to 80% of tumours in the hypothalamic-pituitary region in childhood. Despite being benign, the close proximity of these tumours to the visual pathways, hypothalamus, and pituitary gland means that both treatment of the tumour and the tumour itself can cause pronounced long-term neuroendocrine morbidity against a background of high overall survival. To date, the optimal management strategy for these tumours remains undefined, with practice varying between centres. In light of these discrepancies, as part of a national endeavour to create evidence-based and consensus-based guidance for the management of rare paediatric endocrine tumours in the UK, we aimed to develop guidelines, which are presented in this Review. These guidelines were developed under the auspices of the UK Children's Cancer and Leukaemia Group and the British Society for Paediatric Endocrinology and Diabetes, with the oversight and endorsement of the Royal College of Paediatrics and Child Health using Appraisal of Guidelines for Research & Evaluation II methodology to standardise care for children and young people with craniopharyngiomas.

SIOP Ependymoma I: Final results, long-term follow-up, and molecular analysis of the trial cohort-A BIOMECA Consortium Study.

BACKGROUND: SIOP Ependymoma I was a non-randomised trial assessing event free and overall survival (EFS/OS) of non-metastatic intracranial ependymoma in children aged 3-21 years treated with a staged management strategy. A further aim was to assess the response rate (RR) of subtotally resected (STR) ependymoma to vincristine, etoposide, and cyclophosphamide (VEC). We report final results with 12-year follow-up and post hoc analyses of recently described biomarkers. METHODS: Seventy-four participants were eligible. Children with gross total resection (GTR) received radiotherapy, whilst those with STR received VEC before radiotherapy. DNA methylation, 1q, hTERT, ReLA, Tenascin-C, H3K27me3, and pAKT status were evaluated. RESULTS: Five- and ten-year EFS was 49.5% and 46.7%, OS was 69.3% and 60.5%. GTR was achieved in 33/74 (44.6%) and associated with improved EFS (P = .003, HR = 2.6, 95% confidence interval (CI) 1.4-5.1). Grade 3 tumours were associated with worse OS (P = .005, HR = 2.8, 95%CI 1.3-5.8). 1q gain and hTERT expression were associated with poorer EFS (P = .003, HR = 2.70, 95%CI 1.49-6.10 and P = .014, HR = 5.8, 95%CI 1.2-28) and H3K27me3 loss with worse OS (P = .003, HR = 4.6, 95%CI 1.5-13.2). Methylation profiles showed expected patterns. 12 participants with STR did not receive chemotherapy; a protocol violation. However, best chemotherapy RR was 65.5% (19/29, 95%CI 45.7-82.1), exceeding the prespecified 45%. CONCLUSIONS: Participants with totally resected ependymoma had the best outcomes. RR of STR to VEC exceeded the pre-specified efficacy criterion. However, cases of inaccurate stratification highlighted the need for rapid central review. 1q gain, H3K27me3 loss, and hTERT expression were all associated with poorer survival outcomes.

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.

Anaplastic ependymoma with sclerotic bone metastases.

Ependymomas are glial central nervous system (CNS) tumors that arise from the ependymal layer of brain and spinal cord. These are heterogeneous group of tumors with varied histopathological features and prognosis. They frequently relapse at the primary site and may disseminate to other CNS sites. Extraneural metastases are, however, extremely rare. We present a case of ependymoma in a child with widespread metastasis to her bones, a previously unreported event.

A study of childhood cancer survivors' engagement with long-term follow-up care: 'To attend or not to attend, that is the question'.

PURPOSE: In the UK, there are over 40,000 childhood cancer survivors (CCS); this figure grows approximately 1300 annually. Two-thirds are at risk of developing serious disabling or life-threatening conditions due to adverse late effects of the cancer or treatment received in childhood. Life-long, follow-up care for the surveillance and management of late effects is recommended. This study explored CCS' views and experiences of long-term follow-up (LTFU) care within a cancer centre. METHODS: Paper questionnaires (n = 113) and qualitative interviews (n = 13). RESULTS: The majority (n = 83, 80%) of CCS reported being satisfied with their LTFU care and felt that it was important to attend long-term survivorship follow-up (n = 97, 86%). However, some were not well informed about their cancer treatment history, purpose for attending the clinic or the potential for late effects. Barriers associated with LTFU included; provision of information, lack of interpersonal relationships, practical and logistic challenges. CONCLUSIONS: Barriers identified can be addressed through strategies including provision of verbal and written information and care plans to increase CCS' knowledge of their cancer history, risk of late effects and the purpose of LTFU care, both at transition and throughout their survivorship journey; patient-centred services that enhance patient choice and flexibility of access to multiple specialities; and use of risk stratified pathways to encourage supported self-management based on cancer type, co-morbidity, and level of professional involvement required. Improving regular provision of information at critical time-points, and exploring a flexible, patient-centred delivery of LFTU care based on risk, could increase attendance and self-management in CCS.

Dosimetric Comparison and Potential for Improved Clinical Outcomes of Paediatric CNS Patients Treated with Protons or IMRT.

BACKGROUND: We compare clinical outcomes of paediatric patients with CNS tumours treated with protons or IMRT. CNS tumours form the second most common group of cancers in children. Radiotherapy plays a major role in the treatment of many of these patients but also contributes to late side effects in long term survivors. Radiation dose inevitably deposited in healthy tissues outside the clinical target has been linked to detrimental late effects such as neurocognitive, behavioural and vascular effects in addition to endocrine abnormalities and second tumours. METHODS: A literature search was performed using keywords: protons, IMRT, CNS and paediatric. Of 189 papers retrieved, 10 were deemed relevant based on title and abstract screening. All papers directly compared outcomes from protons with photons, five papers included medulloblastoma, four papers each included craniopharyngioma and low grade gliomas and three papers included ependymoma. RESULTS: This review found that while proton beam therapy offered similar clinical target coverage, there was a demonstrable reduction in integral dose to normal structures. CONCLUSIONS: This in turn suggests the potential for superior long term outcomes for paediatric patients with CNS tumours both in terms of radiogenic second cancers and out-of-field adverse effects.