Validated quantitative needs assessment differences in the management of children with central nervous system cancer between Brazil, an upper middle-income country, and the United States of America, a high income country.

BACKGROUND: Pediatric cancer cure rates differ among high-income countries (HIC) and upper middle-income countries (UMIC). We have compared individual capacities of two major referral pediatric centers from a HIC and an UMIC caring for children with central nervous system (CNS) cancer. METHODS: A quantitative needs assessment questionnaire and key informant interviews, distributed in March of 2017, were used to evaluate the treatment of children with CNS cancer at Grupo de Apoio ao Adolescente e à Criança com Câncer (GRAACC) children's cancer center in São Paulo, Brazil and Nationwide Children's Hospital (NCH) in Columbus, Ohio, United States of America (USA). RESULTS: Both hospitals had 24-hour pediatric oncology, nursing and intensivist coverage. Supportive care available at both institutions included social workers, psychologists, child life specialists, and physical/occupational/speech therapists. Differences included two part-time neuroradiologists and one pathologist specializing in neuropathology at IOP/GRAACC/UNIFESP, whereas eight full-time neuroradiologists and two neuropathologists at NCH/OSU. There were four pediatric neurosurgeons on staff at each hospital; however, there were only 2 operative days per week at IOP/GRAACC/UNIFESP, compared with 7 days at NCH/OSU. Additionally, time to initiation of radiation therapy at IOP/GRAACC/UNIFESP extended 2-4 weeks compared with less than 1 week at NCH/OSU. CONCLUSIONS: Center-specific differences in resources exist in highly specialized hospitals caring for children with CNS cancer in HIC and UMIC. This quantitative needs assessment may facilitate the development of targeted strategies for effective interventions to improve on the management of children with CNS cancers.

Cost-effectiveness analysis of cochlear dose reduction by proton beam therapy for medulloblastoma in childhood.

BACKGROUND: The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood. METHODS: We developed a Markov model to describe health states of 6-year-old children with medulloblastoma after treatment with proton or X-ray radiotherapy. The risks of hearing loss were calculated on cochlear dose for each treatment. Three types of health-related quality of life (HRQOL) of EQ-5D, HUI3 and SF-6D were used for estimation of quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio (ICER) for proton beam therapy compared with X-ray radiotherapy was calculated for each HRQOL. Sensitivity analyses were performed to model uncertainty in these parameters. RESULTS: The ICER for EQ-5D, HUI3 and SF-6D were $21 716/QALY, $11 773/QALY, and $20 150/QALY, respectively. One-way sensitivity analyses found that the results were sensitive to discount rate, the risk of hearing loss after proton therapy, and costs of proton irradiation. Cost-effectiveness acceptability curve analysis revealed a 99% probability of proton therapy being cost effective at a societal willingness-to-pay value. CONCLUSIONS: Proton beam therapy with cochlear dose reduction improves health outcomes at a cost that is within the acceptable cost-effectiveness range from the payer's standpoint.

Survival among children with medulloblastoma in Greece: gains from transition to chemotherapy and socio-economic differentials.

The objective of this study was to quantify improvements in survival due to chemotherapy among children with medulloblastoma treated during the last three decades at a university unit in Greece, compare these gains with figures derived from a specialized unit in the United States and explore the role of extrinsic factors affecting survival. The records of all children with medulloblastoma (n=50) treated at the University Childhood Oncology Unit in Athens, Greece during the period 1973-2003 were reviewed. The role on survival of socio-demographic factors was studied by modeling the data through Cox's proportional-hazards regression, controlling for the mode of treatment (chemotherapy, yes vs. no), whereas survival of children with medulloblastoma treated in Greece was compared with that of 76 children treated in a specialized center in the United States during a respective period. After adjustment for demographic factors, children with medulloblastoma who received adjuvant therapy in Greece had an approximately four times higher instantaneous rate of remaining alive than those who did not (P=0.05). The 5-year survival of children with medulloblastoma treated at specialized medical centers in Greece and the United States was 66 and 63%, respectively. Despite the comparable figure with that of an acceptable standard, however, there was a suggestion (P=0.07) that a rural place of residence in Greece is a poor prognostic indicator. Assuming inherently similar age of occurrence in urban and rural areas, children from rural areas in this study had a more advanced age at diagnosis than those residing in urban Greece (mean age: 7.9 vs. 6.6 years) with a 5-year survival of 57 and 73%, respectively. As expected, incorporation of adjuvant chemotherapy in the treatment of Greek children with medulloblastoma has yielded remarkable improvement in 5-year survival, comparable to that of technologically advanced countries. On the contrary, children residing in rural areas of the country seem to enjoy less favorable prognosis, possibly owing to delays in diagnosis or limited access to optimal treatment facilities.

Radiotherapy in pediatric medulloblastoma: quality assessment of Pediatric Oncology Group Trial 9031.

PURPOSE: To evaluate the potential influence of radiotherapy quality on survival in high-risk pediatric medulloblastoma patients. METHODS AND MATERIALS: Trial 9031 of the Pediatric Oncology Group (POG) aimed to study the relative benefit of cisplatin and etoposide randomization of high-risk patients with medulloblastoma to preradiotherapy vs. postradiotherapy treatment. Two-hundred and ten patients were treated according to protocol guidelines and were eligible for the present analysis. Treatment volume (whole brain, spine, posterior fossa, and primary tumor bed) and dose prescription deviations were assessed for each patient. An analysis of first site of failure was undertaken. Event-free and overall survival rates were calculated. A log-rank test was used to determine the significance of potential survival differences between patients with and without major deviations in the radiotherapy procedure. RESULTS: Of 160 patients who were fully evaluable for all treatment quality parameters, 91 (57%) had 1 or more major deviations in their treatment schedule. Major deviations by treatment site were brain (26%), spinal (7%), posterior fossa (40%), and primary tumor bed (17%). Major treatment volume or total dose deviations did not significantly influence overall and event-free survival. CONCLUSIONS: Despite major treatment deviations in more than half of fully evaluable patients, underdosage or treatment volume misses were not associated with a worse event-free or overall survival.

Value of surveillance imaging in the management of medulloblastoma.

BACKGROUND: To investigate the value of surveillance scanning for the detection of recurrences in medulloblastoma. PROCEDURE: The charts of 95 patients with medulloblastoma were retrospectively reviewed. Information regarding the patient characteristics, treatment modalities, dates, types and results of CT and MRI studies, the frequency with which recurrences were identified on surveillance images, changes in patient management, outcome of the patients following recurrences, and survival data were analyzed. RESULTS: Thirty-one patients had a recurrence of tumor in the central nervous system; none experienced extraneural relapses. Of all recurrences, 21 were symptomatic and 10 were discovered by surveillance scans asymptomatically. None of the patients with a recurrence survived. For all 95 patients, 5-year overall and event-free survival rates were 47.1 and 49.8%, respectively. In patients with symptomatic and asymptomatic recurrences, the mean time to recurrence since initial diagnosis, the mean duration of survival post-recurrence, and the mean duration of overall follow-up were 19.2 and 26.1 months, 3.6 and 8.0 months, and 22.8 and 34.1 months, respectively. For 95 patients, 468 surveillance and 38 symptomatic images were reviewed as 313 CTs and 193 MRIs. Rate of diagnosis of recurrence per surveillance image was 2.1% (10/468). CONCLUSIONS: In our study, surveillance scanning brought no survival advantage since it detected a minority of recurrences. Longer survival achieved by early detection of recurrences might be a reflection of lead-time and length biases. Surveillance procedures will gain more importance as new effective therapeutic options are developed for recurrent medulloblastoma.

Brain tumours under the age of three. The price of survival. A retrospective study of 20 long-term survivors.

Between 1975 and 1989, 98 children with brain tumours under the age of three at time of diagnosis were entered into a retrospective study. Twenty of them are alive and free of tumour more than five years after treatment and were evaluated in this study. Thirteen tumour localizations were infratentorial and 7 were supratentorial. A histological examination was performed in 15 patients: 5 ependymomas, 6 medulloblastomas and 4 astrocytomas were identified. Fifteen patients underwent surgical removal of tumour, all but one received radiotherapy and 8 were given chemotherapy. Only two children have not late effects. Analysis of long-term sequelae in survivors showed central endocrinopathies in 14 (70%), a neurological handicap in 13 (65%) and impaired cognitive functions in 17 (85%). Irradiation was clearly responsible for mental sequelae in 7 patients and endocrinopathies in 6 patients. The other possible causes are tumour injury, hydrocephalus or surgery. The risks incurred with radiotherapy and advances in infant brain tumour therapy are discussed.