SIOP PODC-adapted treatment guidelines for craniopharyngioma in low- and middle-income settings.

Pediatric craniopharyngioma is a rare tumor with excellent survival but significant long-term morbidities due to the loco-regional tumor growth or secondary to its treatment. Visual impairment, panhypopituitarism, hypothalamic damage, and behavioral changes are among the main challenges. This tumor should be managed under the care of a multidisciplinary team to determine the optimum treatment within the available resources. This is particularly important for low middle-income countries where resources are variable. This report provides risk-stratified management guidelines for children diagnosed with craniopharyngioma in a resource-limited setting.

Response assessment in pediatric craniopharyngioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) Working Group.

BACKGROUND: Craniopharyngioma is a histologically benign tumor of the suprasellar region for which survival is excellent but quality of life is often poor secondary to functional deficits from tumor and treatment. Standard therapy consists of maximal safe resection with or without radiation therapy. Few prospective trials have been performed, and response assessment has not been standardized. METHODS: The Response Assessment in Pediatric Neuro-Oncology (RAPNO) committee devised consensus guidelines to assess craniopharyngioma response prospectively. RESULTS: Magnetic resonance imaging is the recommended radiologic modality for baseline and follow-up assessments. Radiologic response is defined by 2-dimensional measurements of both solid and cystic tumor components. In certain clinical contexts, response to solid and cystic disease may be differentially considered based on their unique natural histories and responses to treatment. Importantly, the committee incorporated functional endpoints related to neuro-endocrine and visual assessments into craniopharyngioma response definitions. In most circumstances, the cystic disease should be considered progressive only if growth is associated with acute, new-onset or progressive functional impairment. CONCLUSIONS: Craniopharyngioma is a common pediatric central nervous system tumor for which standardized response parameters have not been defined. A RAPNO committee devised guidelines for craniopharyngioma assessment to uniformly define response in future prospective trials.

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

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

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

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

Survival and functional outcomes of molecularly defined childhood posterior fossa ependymoma: Cure at a cost.

BACKGROUND: Posterior fossa ependymoma (PFE) comprises 2 groups, PF group A (PFA) and PF group B (PFB), with stark differences in outcome. However, to the authors' knowledge, the long-term outcomes of PFA ependymoma have not been described fully. The objective of the current study was to identify predictors of survival and neurocognitive outcome in a large consecutive cohort of subgrouped patients with PFE over 30 years. METHODS: Demographic, survival, and neurocognitive data were collected from consecutive patients diagnosed with PFE from 1985 through 2014 at the Hospital for Sick Children in Toronto, Ontario, Canada. Subgroup was assigned using genome-wide methylation array and/or immunoreactivity to histone H3 K27 trimethylation (H3K27me3). RESULTS: A total of 72 PFE cases were identified, 89% of which were PFA. There were no disease recurrences noted among patients with PFB. The 10-year progression-free survival rate for all patients with PFA was poor at 37.1% (95% confidence interval, 25.9%-53.1%). Analysis of consecutive 10-year epochs revealed significant improvements in progression-free survival and/or overall survival over time. This pertains to the increase in the rate of gross (macroscopic) total resection from 35% to 77% and the use of upfront radiotherapy increasing from 65% to 96% over the observed period and confirmed in a multivariable model. Using a mixed linear model, analysis of longitudinal neuropsychological outcomes restricted to patients with PFA who were treated with focal irradiation demonstrated significant continuous declines in the full-scale intelligence quotient over time with upfront conformal radiotherapy, even when correcting for hydrocephalus, number of surgeries, and age at diagnosis (-1.33 ± 0.42 points/year; P = .0042). CONCLUSIONS: Data from a molecularly informed large cohort of patients with PFE clearly indicate improved survival over time, related to more aggressive surgery and upfront radiotherapy. However, to the best of the authors' knowledge, the current study is the first, in a subgrouped cohort, to demonstrate that this approach results in reduced neurocognitive outcomes over time.

Intracystic interferon-alpha in pediatric craniopharyngioma patients: an international multicenter assessment on behalf of SIOPE and ISPN.

BACKGROUND: Craniopharyngiomas are frequent hypothalamo-pituitary tumors in children, presenting predominantly as cystic lesions. Morbidity from conventional treatment has focused attention on intracystic drug delivery, hypothesized to cause fewer clinical consequences. However, the efficacy of intracystic therapy remains unclear. We report the retrospective experiences of several global centers using intracystic interferon-alpha. METHODS: European Société Internationale d'Oncologie Pédiatrique and International Society for Pediatric Neurosurgery centers were contacted to submit a datasheet capturing pediatric patients with cystic craniopharyngiomas who had received intracystic interferon-alpha. Patient demographics, administration schedules, adverse events, and outcomes were obtained. Progression was clinical or radiological (cyst reaccumulation, novel cysts, or solid growth). RESULTS: Fifty-six children (median age, 6.3 y) from 21 international centers were identified. Median follow-up from diagnosis was 5.1 years (0.3-17.7 y). Lesions were cystic (n = 22; 39%) or cystic/solid (n = 34; 61%). Previous progression was treated in 43 (77%) patients before interferon use. In such cases, further progression was delayed by intracystic interferon compared with the preceding therapy for cystic lesions (P = 0.0005). Few significant attributable side effects were reported. Progression post interferon occurred in 42 patients (median 14 mo; 0-8 y), while the estimated median time to definitive therapy post interferon was 5.8 (1.8-9.7) years. CONCLUSIONS: Intracystic interferon-alpha can delay disease progression and potentially offer a protracted time to definitive surgery or radiotherapy in pediatric cystic craniopharyngioma, yet demonstrates a favorable toxicity profile compared with other therapeutic modalities-important factors for this developing age group. A prospective, randomized international clinical trial assessment is warranted.

Review of management and morbidity of pediatric craniopharyngioma patients in a low-middle-income country: a 12-year experience.

BACKGROUND: Management of craniopharyngioma in children is challenging, and their quality of life can be significantly affected. Series describing this from low-middle income countries (LMIC) are few. PATIENTS AND METHODS: The study provides a retrospective chart review of pediatric patients <18 years old, diagnosed with craniopharyngioma between 2003 and 2014, and treated at King Hussein Cancer Center, Jordan. RESULTS: Twenty-four patients (12 males) were identified. Median age at diagnosis was 7.4 years (0.9-16.4 years). Commonest symptoms were visual impairment and headache (71%). Review of seventeen preoperative MRIs showed hypothalamic involvement in 88% and hydrocephalus in 76%. Thirteen patients (54%) had multiple surgical interventions. Five patients (21%) had initial gross total resection. Eleven patients (46%) received radiotherapy and six (25%) intra-cystic interferon. Five years' survival was 87 ± 7% with a median follow-up of 4.5 years (0.3-12.3 years). Four patients (17%) died; one after post-operative cerebral infarction and three secondary to hypothalamic damage. At their last evaluation, all but one patient required multiple hormonal supplements. Ten patients (42%) had best eye visual acuity (VA) >20/40, and four (16%) were legally blind. Eleven patients (46%) were overweight/obese; one had gastric bypass surgery. Seven patients had hyperlipidemia, and eight developed fatty liver infiltration. Eleven patients (65%) were attending schools and one at college. Nine of the living patients (53%) expressed difficulty to engage in the community. CONCLUSIONS: Management of pediatric craniopharyngioma is particularly complex and demanding in LMIC. Multidisciplinary care is integral to optimize the care and minimize the morbidities. A management outline for LMIC is proposed.

Bridging the Distance in the Caribbean: Telemedicine as a means to build capacity for care in paediatric cancer and blood disorders.

Over the past 50 years, survival for children in high-income countries has increased from 30% to over 80%, compared to 10-30% in low and middle income countries (LMIC). Given this gap in survival, established paediatric cancer treatment centres, such as The Hospital for Sick Children (SickKids) are well positioned to share clinical expertise. Through the SickKids Centre for Global Child Health, the SickKids-Caribbean Initiative (SCI) was launched in March 2013 to improve the outcomes and quality of life for children with cancer and blood disorders in the Caribbean. The six participating Caribbean countries are among those defined by the United Nations as Small Island Developing States, due to their small size, remote location and limited accessibility. Telemedicine presents an opportunity to increase their accessibility to health care services and has been used by SCI to facilitate two series of interprofessional rounds. Case Consultation Review Rounds are a forum for learning about diagnostic work-up, management challenges and treatment recommendations for these diseases. To date, 54 cases have been reviewed by SickKids staff, of which 35 have been presented in monthly rounds. Patient Care Education Rounds provide nurses and other staff with the knowledge base needed to safely care for children and adolescents receiving treatment. Five of these rounds have taken place to date, with over 200 attendees. Utilized by SCI for both clinical and non-clinical meetings, telemedicine has enhanced opportunities for collaboration within the Caribbean region. By building capacity and nurturing expert knowledge through education, SCI hopes to contribute to closing the gap in childhood survival between high and low-resource settings.

Challenges faced by pediatric oncology fellows when patients die during their training.

PURPOSE: Given the paucity of research on the experience of pediatric oncology fellows regarding patient death, the purpose of this study was to explore the specific challenges that pediatric oncology fellows face when patients die during their training. METHODS: Six pediatric oncology fellows at two academic cancer centers in Ontario, Canada, were interviewed about their experiences with patient death during their fellowship training. The grounded theory method of data collection and data analysis was used. Line-by-line coding was used to establish themes, and constant comparison was used to establish relationships among emerging codes and themes. RESULTS: Fellows reported structural challenges that included ward duty and lack of follow-up opportunities with bereaved families. Personal challenges included feelings of vulnerability as a result of being a trainee, inexperience with patient death, and feeling alone with one's reactions to patient death. Relational challenges included duration of relationships with families and with supervising staff and perceived lack of modeling on how to cope with patient deaths. CONCLUSION: Structural changes to the fellowship model can be made in order to enhance support with patient death, including informing fellows of all patient deaths and incorporating fellows into follow-up practices with bereaved families. Moreover, integrating fellows' debriefing (facilitated by grief counselors) after a patient death into fellow training, as well as greater involvement with palliative care physicians, can lessen feelings of isolation and help fellows learn effective strategies for dealing with patient deaths from experienced palliative care physicians.

Assessment of chemotherapeutic response in children with proptosis due to optic nerve glioma.

INTRODUCTION: Some children with optic pathway gliomas present with proptosis related to intraorbital tumor extension. The radiological assessment of chemotherapeutic response in these patients can be complicated by irregular tumor shape and lack of relation between tumor volume and cosmetic effect. METHOD: We propose that proptosis measurements and derivation of a proptosis index can be a useful adjunct to the measurement of tumor volume in the radiological assessment of chemotherapeutic response. The proptosis index was derived as the ratio of the difference in proptosis between eyes postchemotherapy to that prechemotherapy. A series of six patients with proptosis and the diagnosis of an optic nerve tumor from an optic pathway glioma registry demonstrate by case example the correlation between the proptosis index and the clinical and radiographic response to chemotherapy. CONCLUSIONS: We have found that a proptosis index <1 correlates with a chemotherapeutic maintained response and an index >1 correlates with progressive disease.