Introduction
Despite remarkable advancements in the field of medicine, cancer remains
one of the most important diseases ever. Second cause of death in most
parts of the world, cancer is a disease that requires a fully dedicated
medical care as well as social support.1,2
One out of every 600 children under the age of 16 struggles with cancer
and it is estimated that 25% of these children have a central nervous
system (CNS) tumor which is the most prevalent cause of mortality in
children between the age of 3 and 7 years old. About 60 % of patients
who survive cancer face a life-threatening disability including
cognitive and neuroendocrine system disabilities.3-7
Brain tumors, especially malignant ones, are among the most paralyzing,
life threatening tumors because the patients not only suffer a definite
incurability but also deal with a high risk of mortality. These tumors
are categorized into 2 major types: primary and secondary. Primary
tumors initially originate from the brain while secondary tumors are
usually a metastasis of systemic malignancies. (2)
Pediatric Primary CNS tumors occur in 3.5-4.5 per 100000 persons with a
sex ratio of 1.14 in which the male percentage varies in a range of 53.3
to 57.7 in different epidemiological studies. This is almost 0.1 of its
incidences in adults. Conclusively, brain tumors are the most prevalent
tumors and second most common malignancy (after Hematopoietic and
lymphoid malignancies) in children with a generally higher incidence in
males than females.7-10
Data from multiple national cancer registries depict differences in
pediatric and adult brain tumor incidence. Overall, Medulloblastoma and
low-grade glioma are the most common tumors in children under the age of
15 while in adults, high grade glioma and meningioma occur most
often.3,11,12The most prevalent Primary CNS tumor in
children is Astrocytoma which includes low grade glioma, brainstem
glioma and non-brainstem high grade glioma. Low grade glioma is the most
common subdivision and responsible for 40% of pediatric brain tumors.
Medulloblastoma and ependymoma are respectively in 2nd and 3rd place
with regard to their incidence.8Supratentorial and
infratentorial tumors generally occur with an equal incidence; however,
supratentorial tumors are more common under the age of 2 while
infratentorial types have a higher incidence between the age of
4_10.5,13Suprasellar and epiphyseal regions are
typically potent areas for formation of supratentorial
tumors.8 In comparison with adults, pediatric
infratentorial tumors mainly form in the hind brain (Rhombencephalon)
and lower regions such as brainstem. Depending on their type, size and
anatomical location, as well as the age of onset, these tumors may have
a variety of different initial symptoms.
Based on tumor’s anatomical location, the most common initial symptoms
are increased intracranial pressure in supratentorial tumors, nausea and
vomiting in hind brain tumors (75%), headache in tumors of cerebral
hemispheres (49%) and backache in spinal tumors
(67%).4
Considering the increased occurrence of brain tumors in all age groups
and its significant mortality rate in children, an implementation of
highly accurate medical modalities such as surgery, radiotherapy and
chemotherapy is necessary for early diagnosis and treatment of the
disease. Since currently there is no complete cure for brain tumors, it
is of great importance to try to increase patients’ survival rates and
ameliorate their painful symptoms.2,5,14There are a
variety of treatment strategies based on the type, location,
removability, growth, relapse chances and clinical manifestations of the
tumor. In low grade glioma, which is completely removable by surgery,
the average 10-year survival rate after surgery is 90_100%. At the
same time, despite surgery and consequent radiotherapy in recurring or
irremovable high-grade tumors, treatment with available chemotherapy
regimens has little effect on increasing the Overall Survival rate. In
case of relapse, chemotherapy can only exert a restricted effect on
patients’ overall survival improvement.5,14-16
With the challenges mentioned above, there is an urge for focusing on
new pharmaceutical agents and novel therapeutic approaches to cancer
treatment among which is the life-saving chemotherapy regimen based on a
camptothecin derivative agent named Irinotecan which acts as a
topoisomerase-1 inhibitor. Irinotecan can be used mono-therapically or
in combination with other synergic agents such as Temozolomide or
Bevacizumab to overcome the resistance of tumor cells especially in
adults.14,17
Considering the fact that there isn’t, yet, an adequate number of
comprehensive studies about the synergistic effects of this new agent
and there are only a restricted number of clinical trials on this
subject, the aim of this study is to investigate the efficacy and
efficiency of Irinotecan based chemotherapy regimen in combination with
Bevacizumab in a target group of children.