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.