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.