Challenges and opportunities for managing pediatric central nervous system tumors in China.

Central nervous system (CNS) tumors represent the most deadly cancer in pediatric age group. In China, thousands of children are diagnosed with CNS tumors every year. Despite the improving socioeconomic status and availability of medical expertise within the country, unique challenges remain for the delivery of pediatric neuro-oncology service. In this review, we discuss the existing hurdles for improving the outcome of children with CNS tumors in China. Need for precise disease burden estimation, lack of intra- and inter-hospital collaborative networks, high probability of treatment abandonment, along with financial toxicities from treatment represent the key challenges that Chinese healthcare providers encounter. The tremendous opportunities for advancing the status of pediatric neuro-oncology care in and beyond the country are explored.

Molecular grouping and outcomes of young children with newly diagnosed ependymoma treated on the multi-institutional SJYC07 trial.

BACKGROUND: This report documents the clinical characteristics, molecular grouping, and outcome of young children with ependymoma treated prospectively on a clinical trial. METHODS: Fifty-four children (aged ≤3 y) with newly diagnosed ependymoma were treated on the St Jude Young Children 07 (SJYC07) trial with maximal safe surgical resection, 4 cycles of systemic chemotherapy, consolidation therapy using focal conformal radiation therapy (RT) (5-mm clinical target volume), and 6 months of oral maintenance chemotherapy. Molecular groups were determined by tumor DNA methylation using Infinium Methylation EPIC BeadChip and profiled on the German Cancer Research Center/Molecular Neuropathology 2.0 classifier. RESULTS: One of the 54 study patients had metastases (cerebrospinal fluid positive) at diagnosis. Gross or near-total resection was achieved in 48 (89%) patients prior to RT. At a median follow-up of 4.4 years (range, 0.2-10.3 y), 4-year progression-free survival (PFS) was 75.1% ± 7.2%, and overall survival was 92.6% ± 4.4%. The molecular groups showed no significant difference in PFS (4-year estimates: posterior fossa ependymoma group A [PF-EPN-A; 42/54], 71.2% ± 8.3%; supratentorial ependymoma positive for v-rel avian reticuloendotheliosis viral oncogene homolog A [ST-EPN-RELA; 8/54], 83.3% ± 17.0%; and supratentorial ependymoma positive for Yes-associated protein [4/54], 100%, P = 0.22). Subtotal resection prior to RT was associated with an inferior PFS compared with gross or near-total resection (4-year PFS: 41.7% ± 22.5% vs 79.0% ± 7.1%, P = 0.024), as was PF-EPN-A group with 1q gain (P = 0.05). Histopathologic grading was not associated with outcomes (classic vs anaplastic; P = 0.89). CONCLUSIONS: In this prospectively treated cohort of young children with ependymoma, ST-EPN-RELA tumors had a more favorable outcome than reported from retrospective data. Histologic grade did not impact outcome. PF-EPN-A with 1q gain and subtotal resection were associated with inferior outcomes.

Marked functional recovery and imaging response of refractory optic pathway glioma to BRAFV600E inhibitor therapy: a report of two cases.

BACKGROUND: Despite appropriate therapeutic interventions, progressive optic pathway glioma (OPG) in children may result in loss of vision and other neurologic morbidities. Molecularly targeted therapy against the MAP kinase pathway holds promise in improving outcomes while resulting in lower treatment-related toxicities. We report two children with refractory OPG who had a substantial and early reversal of their neurologic deficits and an impressive imaging response of their tumor to BRAFV600E inhibition therapy. METHODS: Two children with OPG (BRAFV600E-mutated pilocytic astrocytoma) who did not respond to at least one frontline therapy were treated with the oral BRAFV600E inhibitor vemurafenib. RESULTS: Both children had substantial visual compromise before start of therapy, with one child additionally having motor deficits. Both had an early improvement in their vision, and the second child showed a demonstrable improvement in motor weakness. This was accompanied by a decrease in tumor size, which was sustained at 6 months from therapy. Neither child had significant toxicities except for mild skin sensitivity to vemurafenib. CONCLUSIONS: BRAFV600E inhibitor therapy can potentially reverse visual and neurologic decline associated with progressive OPG. The clinico-radiologic response appears to be prompt and marked. Ongoing clinical trials using BRAFV600E inhibitors can help confirm these early promising findings.

International telepharmacy education: another venue to improve cancer care in the developing world.

OBJECTIVE: In developed countries, pharmacists play a crucial role in designing and implementing cancer treatments as part of a multidisciplinary oncology team. However, developing countries have a shortage of pharmacists, and their role is generally limited to dispensing and selling drugs. The aim of this study was to investigate the feasibility of providing clinical pharmacy educational activities via international teleconferencing to improve cancer care in developing countries. MATERIALS AND METHODS: Meticulous preparation and intense promotion of the workshop were done in Egypt before the telepharmacy conferences began. Multiple connectivity tests were performed to resolve technical problems. Nine telepharmacy conferences were delivered during 3-h sessions that were held on three consecutive days. Talks were subsequently made available via Web streaming. Attendees were requested to complete a survey to measure their satisfaction with the sessions. RESULTS: The teleconference was attended by a total of 345 persons, and it was subsequently reviewed online via 456 log-in sessions from 10 countries. Technical issues (e.g., poor auditory quality) were resolved on the first day of the event. The rate of attendees' responses on the survey was 30.1%, and satisfaction with the event was generally good. CONCLUSIONS: Telecommunication is a relatively inexpensive approach that may improve pharmacy practices, especially those used to treat patients with cancer in developing countries. Special attention to patient-based telepharmacy education, including the use of cost-effective technology, should be considered.

Challenging issues in pediatric oncology.

Improvements in protocol-driven clinical trials and supportive care for children and adolescents with cancer have reduced mortality rates by more than 50% over the past three decades. Overall, the 5-year survival rate for patients with pediatric cancer has increased to approximately 80%. Recognition of the biological heterogeneity within specific subtypes of cancer, the discovery of genetic lesions that drive malignant transformation and cancer progression, and improved understanding of the basis of drug resistance will undoubtedly catalyze further advances in risk-directed treatments and the development of targeted therapies, boosting the cure rates further. Emerging new treatments include novel formulations of existing chemotherapeutic agents, monoclonal antibodies against cancer-associated antigens, and molecular therapies that target genetic lesions and their associated signaling pathways. Recent findings that link pharmacogenomic variations with drug exposure, adverse effects, and efficacy should accelerate efforts to develop personalized therapy for individual patients. Finally, palliative care should be included as an essential part of cancer management to prevent and relieve the suffering and to improve the quality of life of patients and their families.