Search

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.

BACKGROUND Paediatric brain tumour survivors may have treatment toxicity associated with signal change on follow-up MRI. Quantitative MRI texture features can potentially be used as surrogates of the underlying tissue changes following radiation therapy. MATERIAL AND METHODS Longitudinal retrospective study in 51 paediatric primary brain tumours treated with photon (N=30) and proton (N=21) radiotherapy (RT). T2 MRI scans at baseline and multiple time point from the date of surgery to 2 years following radiotherapy were selected for the textural analysis. Scans were bias corrected, registered with the CT dose maps and with baseline scan for each patient using 3Dslicer. Regions of interest (ROI) of fixed diameter were drawn in 11 predetermined non-tumoral regions of brain including in peri-tumoural region (PTV). ROIs were placed in homogenous white/grey matter. Radiation dose was calculated in each of these 11 ROIs and texture features were extracted using pyradiomics. Data were analysed using machine learning and statistical analysis. General linear multivariate model was used to corelate primary texture features over period of 24 months and radiation dose, time, effect of dose*time together at each ROI separately. RESULTS There were Brainstem 4, Cerebellar19, Hemispheric cerebral 7 and Supratentorial midline 10 tumours. Median age at diagnosis was 8.26 years (range: 0–20). Median RT treatment dose was 28.52Gy (0-60Gy). Multivariate analysis shows significant corelation (p < 0.001) between radiation dose and longitudinal primary texture features in all 11ROIs. Time showed corelation with feature values only in 3 ROIs and dose* time showed corelation in 5ROIs. Primary (statistical) feature values showing consistent correlation with dose in all 11 ROIs over 24 months are total energy, 10%, 90%, energy, entropy, mean, median, and minimum. CONCLUSION Radiomic texture analysis is a promising modality to understand dose related textural changes in the normal part of brain in paediatric brain tumour patients treated with radiation therapy. Radiomic changes need to be related to neurological outcomes in future research.

BackgroundSIOP Ependymoma I was a non-randomised trial assessing event free and overall survival (EFS/OS) from non-metastatic intracranial ependymoma in children aged 3 to 21 years, treated with a staged management strategy. Chemotherapy efficacy in ependymoma is debated and therefore the response rate (RR) of subtotally resected (STR) ependymoma to vincristine, etoposide and cyclophosphamide (VEC) was an additional primary outcome. We report final results with 12-year follow-up and post hoc analyses of recently described biomarkers.Methods74 participants were eligible. Children with gross total resection (GTR) received radiotherapy, whilst those with STR received VEC before radiotherapy. DNA methylation and 1q status were evaluated, alongside hTERT, ReLA, Tenascin-C, H3K27me3 and pAKT expression.ResultsFive- 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=0.003, HR=2.6, 95% confidence interval (CI) 1.4-5.1). Grade 3 tumours were associated with worse OS (p=0.005, HR=2.8, 95%CI 1.3-5.8). 1q gain and hTERT expression were associated with poorer EFS (p=0.003, HR=2.70, 95%CI 1.49-6.10 and p=0.014, HR=5.8, 95%CI 1.2-28 respectively) and H3K27me3 loss with worse OS (p=0.003, HR=4.6, 95%CI 1.5-13.2). DNA methylation profiles showed expected patterns. 12 participants with STR did not receive chemotherapy; a protocol violation. However, chemotherapy RR was 65.5% (19/29, 95%CI 45.7-82.1), exceeding a prespecified 45% RR.ConclusionsRR of STR to VEC exceeded the pre-specified criterion for efficacy. However, cases of inaccurate treatment stratification highlighted the need for rapid central review. Prognostic associations for 1q gain, H3K27me3 and hTERT were confirmed.

Item does not contain fulltext 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 (

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

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.Retrospective cohort study.Twenty-four white Caucasian patients aged16 years from a single tertiary care centre in the United Kingdom at diagnosis followed for (median, range) 3.3, 0.7-8.4 years.Clinical and radiological data at diagnosis and follow-up.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).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.

Introduction Surgery and radiotherapy are established childhood ependymoma treatments. The efficacy of chemotherapy has been debated. We report final results of the SIOP Ependymoma I trial, with 12-year follow-up, in the context of a post-hoc analysis of more recently described biomarkers. Aims and Methods The trial assessed event free (EFS) and overall survival (OS) of patients aged three to 21 years with non-metastatic intracranial ependymoma, treated with a staged management strategy targeting maximum local control. The study also assessed: the response rate (RR) of subtotally resected (STR) disease to vincristine, etoposide and cyclophosphamide (VEC); and surgical operability. Children with gross total resection (GTR) received radiotherapy of 54 Gy in 30 daily fractions over six weeks, whilst those with STR received VEC before radiotherapy. We retrospectively assessed methylation and 1q status alongside hTERT, RELA, Tenascin C, H3K27me3 and pAKT expression. Results Between 1999 and 2007, 89 participants were enrolled, 15 were excluded with metastatic (n=4) or non-ependymoma tumours (n=11) leaving a final cohort of 74. Five- and ten-year EFS was 49.5% and 46.7%, OS was 69.3% and 60.5%. 1q gain was associated with poorer EFS (p=0.002, HR=3.00, 95%CI 1.49–6.10). hTERT expression was associated with worse five-year EFS (20.0% Vs 83.3%, p=0.014, HR=5.8). GTR was achieved in 33/74 (44.6%) and associated with improved EFS (p=0.006, HR=2.81, 95% confidence interval 1.35–5.84). There was an improvement in GTR rates in the latter half of the trial (1999-2002 32.4% versus 2003-2007 56.8%). Despite the protocol, 12 participants with STR did not receive chemotherapy. However, chemotherapy RR was 65.5% (19/29, 95%CI 45.7–82.1). Conclusions VEC exceeded the pre-specified RR of 45% in children over three years with STR intracranial ependymoma. However, cases of inaccurate stratification at treating centres highlights the need for rapid central review. We also confirmed associations between 1q gain, hTERT expression and outcome.

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.

Background There is increasing recognition that a small number of patients receiving docetaxel-containing regimes for early breast cancer (EBC), experience permanent alopecia. However, there is little data to inform discussions with patients regarding this serious late side effect. The aim of this study was determine the incidence, the site, the extent, and duration of the hair loss. Methods A postal questionnaire was sent (in October 2013) to patients who had received docetaxel during 2010, in the neo/adjuvant settings for EBC at our regional cancer centre. This comprised questions relating to scalp hair loss (using the Ludwig scale to provide a pictorial description of the pattern of hair loss), hair loss to other parts of the body, hair products used, and any comments that the respondents wished to add about their experience of hair loss. Univariate and multivariate analyses were undertaken to determine any other risk factors for persistent alopecia. Results 134 of 189 (71%) questionnaires were returned. Of those responding, 72 patients were pre-, 10 were peri- and 52 post-menopausal. 26 patients were taking anastrazole, 14 letrozole, 74 tamoxifen and 20 no adjuvant hormones. Of the respondents, 99 (74.4%) patients had no significant scalp hair loss, and 21 (15.8%) had significant scalp hair loss. 13 (9.8%) of patients gave equivocal responses and 1 patient did not answer the scalp hair loss question. 16 patients in the study were using products such as wigs and hair extensions. 5 patients reported no regrowth of eyebrows, 2 patients reported no eyelash regrowth, 6 no regrowth of nostril hair and 14 no regrowth to other parts such as legs. Univariate and multivariate analyses showed no significant associations with other patient and treatment characteristics (eg adjuvant endocrine therapy). Patients’ observations regarding the social and emotional consequences of permanent hair loss confirmed a significant impact on quality of life. Conclusions This retrospective questionnaire study confirms that long term significant scalp alopecia (here lasting for up to 3.5 years following completion of chemotherapy) may affect 10-15% of patients following docetaxel for EBC (taking into consideration a potential bias for no hair loss in the non- responders). This rate is higher than previous estimates. Long term hair loss to other parts of the body was also widely reported. This appears to be unrelated to other patient and treatment characteristics. Long term hair loss had a significant impact on quality of survival. This is an important quality of life issue for patients which merits prospective study to confirm incidence, to identify effective preventive and management strategies. This risk should be discussed routinely (as part of the process of informed consent) with all patients embarking upon docetaxel as a component of management of EBC. Citation Format: Nicola J Thorp, Felicity Swift, Donna Arundell, Helen Wong. Long term hair loss in patients with early breast cancer receiving docetaxel chemotherapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-17-04.

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.

This book forms part of a collection of four books which are intended to act as resources for enhancing childhood well-being. An overarching aim is to empower children to make use of play activitie...

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.

Background Breast cancer is the uncontrolled, abnormal growth of malignant breast tissue affecting predominantly women. Metastatic breast cancer (mBC) is an advanced stage of the disease when the disease has spread beyond the original organ. Hormone receptor status and human epidermal growth factor 2 (HER2) status are two predictive factors that are taken into consideration when estimating the prognosis of patients with breast cancer. Objectives To review the clinical effectiveness and cost-effectiveness evidence base for lapatinib (LAP) in combination with an aromatase inhibitor (AI) and trastuzumab (TRA) in combination with an AI for the first-line treatment of patients who have hormone receptor-positive (HR+)/human epidermal growth factor 2-positive (HER2+) mBC. Data sources Relevant electronic databases and websites, including MEDLINE, EMBASE and the Cochrane Library, were searched until May 2010. Further data were derived from the manufacturers' submissions for LAP + AI and TRA + AI. Review methods A systematic review of the clinical effectiveness and cost-effectiveness of LAP + AI and TRA + AI was undertaken. As it was deemed inappropriate to compare LAP + AI with TRA + AI, two separate assessments of cost-effectiveness versus AIs alone were undertaken. Results Three trials were included in the systematic review [the patient populations of the efficacy and safety of lapatinib combined with letrozole (EGF30008) trial, the efficacy and safety of trastuzumab combined with anastrozole (TAnDEM) trial and the efficacy and safety of letrozole combined with trastuzumab (eLEcTRA) trial]. As a result of differences in the exclusion criteria and because one trial was halted prematurely, comparisons across trials were believed to be inappropriate and meta-analysis was not possible. Individually, however, the findings from the trials all suggest that LAP + AI or TRA + AI results in improved progression-free survival and/or time to progression when compared with AIs alone. The trials do not show a statistically significant benefit in terms of overall survival. Two separate economic analyses were conducted based on the completed trials; neither LAP + AI nor TRA + AI was found to be cost-effective when compared with AI monotherapy. Limitations Because of differences in the EGF30008 and the TAnDEM trials, the Assessment Group believes the indirect comparisons analyses conducted by the manufacturers are inappropriate and, for the same reason, chooses not to compare LAP + AI with TRA + AI in an economic evaluation. Conclusions LAP + AI and TRA + AI appear to be clinically more effective than AI monotherapy, but neither is cost-effective compared with AIs alone. It was not possible to compare LAP + AI with TRA + AI. Future research should include research into treating mBC in the HR+/HER2+ population who are not TRA (or LAP) naive and into comparing the clinical effectiveness of AIs as monotherapy in patients with HER2+ and human epidermal growth factor 2-negative breast cancer. Funding The National Institute for Health Research Technology Assessment programme.