Introduction
The burden of pediatric cancer worldwide is estimated to be at nearly 160,000 new cases each year 1, 2. Advances in the understanding of the molecular and cellular biology of pediatric malignancies, as well as advances in diagnosis, treatment, and supportive care have increased the total cure rate for children in high-income countries (HIC) to 80% 3. However, 80% of children with cancer worldwide live in low-to middle-income countries (LMIC) and do not have access to the same level of care, leading to inferior outcomes 1, 2.
As the rates of communicable diseases and other causes of early childhood mortality have decreased in LMIC due to improving healthcare infrastructure, it is imperative to undertake the mission of providing today’s advances in cancer care to all children worldwide. Several consortia formed between institutions in North America and Europe and institutions in LMIC have demonstrated the positive impact that global cooperative efforts can have on improving outcomes for pediatric cancer patients in LMIC 1, 4. Acute lymphoblastic leukemia is one such example where international efforts have improved outcomes5. In Recife, Brazil, creating standardized regimens for treatment and supportive care increased the 5-year event free survival (EFS) from 32% to 63% over a 20-year period6. While outcomes have begun to improve for hematologic malignancies in LMIC, survival for patients with solid tumors such as PBT have relatively poor outcomes in LMIC compared to HIC7-10. Given the discrepancy in survival rates for children with brain tumors in LMIC compared to HIC, it is important to study the factors affecting those outcomes in LMIC so that interventions can be made to improve survival.
Medulloblastoma is the most common malignant brain tumor of childhood and is an embryonal tumor of the posterior fossa that arises from transformed progenitor cells within the developing cerebellum11, 12. It can arise at any age with the most frequent age at presentation being between 5-9 years 13. The current management of medulloblastoma for children greater than three years of age involves maximum resection of the primary tumor followed by risk-adapted craniospinal radiation (CSI) with boost to tumor bed (total radiation dose of 54-60Gy) and maintenance chemotherapy13, 14. Radiation (CSI dose 23.4Gy) plus adjuvant chemotherapy can be used in standard-risk patients with excellent outcomes and radiation (with CSI dose of 36Gy) plus adjuvant chemotherapy improves survival in high-risk patients15-17. While the next generation of clinical trials are using molecular data to classify and risk stratify patients based on seminal work by Michael Taylor and colleagues, for the last several decades, risk stratification in patients over three years of age with medulloblastoma has relied primarily on two clinical variables, extent of residual tumor after surgery and presence of metastatic disease at diagnosis as graded by Chang criteria. Patients considered to be high-risk have residual tumor area greater than 1.5cm2 and/or evidence of dissemination in cerebrospinal fluid, leptomeninges, or extracranial sites at time of diagnosis 18-20.
In order to help improve outcomes for children with medulloblastoma in LMIC, we must first gain an understanding of the current resources, barriers, and outcomes. Therefore, we performed a retrospective analysis of the clinical, histological, and survival characteristics of children greater than three years of age diagnosed with medulloblastoma and treated at The National Institute for Neoplastic Disease (INEN) the largest National referral center, treating 65% of all Pediatric Cancer in Peru. Our primary objectives were to: 1) describe the demographics, clinical characteristics, and management of children with medulloblastoma in Peru, 2) quantify survival outcomes of children with medulloblastoma in Peru, and 3) compare survival outcomes between groups to identify factors that may affect outcomes in Peru.