CHILDHOOD BRAIN TUMORS

Authors: Darshini Muthukumar, Dr. Lopamudra Das Roy

Published 2021

ABSTRACT

Pediatric brain tumors (ages 0-14) occur when cells within a child’s brain and its tissues grow uncontrollably and form a malignant (or cancerous) mass. Cancer occurs when the child’s natural mechanism to produce new cells upon the death of old or damaged cells is impaired, and the cells multiply and band together to form a tumor. The aim of this research is to provide a brief description of various kinds of pediatric brain tumors as well as their symptoms (as they are not always obvious and evident) and compare diagnosis statistics across countries. I referred to various PubMed articles as well as other certified medical institutions and resources for information about classifications and specific tumors, as well as diagnosis statistics. My research concluded that brain tumors do not have a clear underlying cause, and one of the only risk factors associated with this cancer is ionizing radiation. Additionally, I found there are large disparities between the 5 year survival rate in developed nations and developing (low income) nations, often caused by late, inaccurate diagnosis and inaccessibility to a treatment plan. This paper will cover the symptoms, diagnostic procedures, and expected survival rates for different types of pediatric brain tumors.

INTRODUCTION: About Childhood Brain Tumors

The human body has a natural mechanism to produce new cells upon the death of old or damaged cells. Cancer occurs when this mechanism is impaired and the cells multiply and band together to form a tumor. In patients of younger ages, symptoms of brain tumors may be harder to detect and can be mistaken for other syndromes. A tumor is classified as a brain tumor when it occurs in the Central Nervous System, or CNS.

CAUSES

Due to the variety of brain cancers and locations of the tumor, the exact cause of the tumor is unknown. These tumors start with a mutation of the cells’ DNA, which causes it to divide and reproduce in unhealthy numbers [1]. These cells grow unhealthy and abnormal and eventually form a tumor which impairs the tissue’s/ organ’s normal functions, disrupting homeostasis within the body. Different kinds of brain tumors involve different genes that undergo changes and develop a tumor. Not all brain tumors have research that has identified which gene and what changes were involved to cause it. It is difficult to pinpoint the exact cause at a cellular level, as many acquired gene changes occur due to random events [2].

RISK FACTORS

Certain brain tumors (ependymoma, medulloblastoma) are more common in children. The risk of the child developing a brain tumor may be increased if the family has a history of brain tumors or genetic syndromes [1]. Additionally, children born to women over age 40 are at a higher risk for astrocytomas and ependymomas [3].

GENETICS AND FAMILY HISTORY

Certain inherited syndromes such as neurofibromatosis and tuberous sclerosis can cause a higher risk of brain tumors [4].

Tumors can also be tested for certain genes and its changes to determine the prognosis of the cancer. For instance, gliomas have a better survival rate if they possess IDH1/ IDH2 mutations.

Similarly, oligodendrogliomas have a better chance of successful chemotherapy if parts of certain chromosomes are not present (1p19q co-deletion) [6].

TYPES OF BRAIN TUMORS

Tumors are classified based on what type of cell it originated from, the grade, gene changes, and its location [7]. General groups of tumors that originate from glial cells are known as gliomas. These include oligodendrogliomas, astrocytomas, optic gliomas, and brain stem gliomas. Gliomas account for ½ of brain tumors found in children. The severity of the tumor is measured in grades from I to IV (I: Pilocytic, II: Fibrillary, III: Anaplastic, and IV: GBM) [8]. Astrocytomas originate in astrocytes and can be hard to remove surgically after they spread into brain tissue and along CSF pathways [7, 9]. Low grade astrocytomas include pilocytic astrocytomas, subependymal giant cell astrocytomas, diffuse astrocytomas, pleomorphic xanthoastrocytomas, and optic gliomas. High grade astrocytomas include glioblastoma multiforme and anaplastic astrocytomas [9].

COMMON PEDIATRIC BRAIN TUMORS

SYMPTOMS

The most common symptoms in children with brain tumors are headaches, nausea and vomiting, and double vision [1]. Children also report intracranial pressure, which is created in the brain when the tumor and surrounding tissues expand and swell [10]. Balance problems, drowsiness, and seizures are also common symptoms [1]. Other symptoms dependent on location are slurred speech, difficult swallowing, drooping on one side of the face, memory issues, and loss of appetite [1].

PREVENTION

Since exposure to radiation is the only proven environmental risk factor, there isn’t a guaranteed way to prevent brain tumors. More often than not, the benefits of low dose radiation therapy outweigh the risk of developing tumors later on in life. Radiation given through X-Rays/ CT Scans at birth and early childhood use much lower doses than cancer treatment and should not pose a risk [12].

DIAGNOSIS/ SCREENING

If a child has a suspected tumor, the physician/neurologist will conduct an exam in which they test vision, balance, coordination, reflexes, strength, and hearing. If the child struggles with certain motor functions, this can indicate which parts of the brain may be impaired and needs further testing [1]. Further testing is conducted through MRI, CT, and PET scans to pinpoint the location and size of the tumor. A biopsy can also be performed to assess the kinds of cells found in the suspicious area. To minimize damage and invasiveness, the surgeon may drill a small hole and use a needle to draw a small sample of the tissue from the patient’s skull [1]. After conducting an imaging scan, the neurosurgeon removes pieces of the tumor for further testing. This is then sent to the pathologist to determine what kind of tumor the child has and if it is malignant [6]. If surgery can be used to treat the tumor, the neurosurgeon will remove most of it through a process called debulking in a craniotomy. If the doctor finds that further surgery is not advised while performing the procedure, the child will receive a final diagnosis and an altered treatment plan [6]. More aggressive cancers, such as medulloblastomas can spread past the brain so bone marrow is tested through a bone marrow aspiration to observe if the cancer has become metastatic. A hollow needle is inserted into the child’s pelvic bone to extract bone marrow [6]. In the case that the child’s tumor has become metastatic, further testing may be conducted to determine the extent of the cancer and assess which organs and structures are now affected.

Along with postnatal tumors, congenital brain tumors can be spotted in 2nd/3rd trimester ultrasounds along with hydrocephalus and intracranial mass. Fetal MRI can be used to properly diagnose suspected neurological tumors [13].

TREATMENT

SURGERY

If the tumor is easily accessible and is not located in a sensitive area of the brain that is prone to damage, the pediatric neurosurgeon will surgically remove as much of the tumor as possible. This is not always an option as the tumor may be too large to remove without affecting the child’s brain functions such as vision and memory. Surgery is considered a viable option if the tumor can be resected completely in Grade 1 tumors [1, 10].

RADIATION THERAPY

Other options include radiation therapy, proton beam therapy, radiosurgery, chemotherapy, and targeted drug therapy. During radiation therapy, high-energy rays (Protons, X-rays) are used to kill cancer cells. The type of radiation can vary from whole-brain radiation, which is usually used to treat types of metastatic cancer or external beam radiation that focuses solely on the affected area of the brain [1].

PROTON BEAM THERAPY

Proton beam therapy is programmed to deliver more precise doses of radiation without exposing the rest of the body to the rays, thus reducing effects of traditional radiation [1].

RADIOSURGERY

During radiosurgery, different beams of radiation meet at one point and deliver a highly focused dose to kill the tumor. The technology used to deliver these doses are Gamma Knives and LINACs (Linear Accelerators) [1, 10].

CHEMOTHERAPY

Chemotherapy is administered intravenously to kill cancer cells, and specific drugs are administered to treat abnormalities in targeted drug therapy if testing reveals the presence of a specific molecule [1, 10].

Even after treatment and remission, tumors may affect a child’s motor skills, vision, memory, or critical thinking so it is important to immerse the patient in physical/occupational/speech therapy upon recovery to regain and strengthen these functions [1].

GRADES

Brain tumors impair functions of the brain such as speech and cognitive abilities, instead of impairing other organs. They are classified under a grade system (from WHO) based on the aggressiveness of the mass. The factors used to classify them are their size, location, ability to be removed through surgery, and its spread within the brain. There are 4 grades along with brain metastasis in which cancer has spread to the brain from another organ [15, 16].

PROGNOSIS

There are many factors that determine a child’s prognosis and survival, such as the type and grade of the tumor, size and location, resectability, presence or absence of certain gene mutations, spread of the tumor beyond the CNS, and the child’s ability to function 14. Prognosis is better for low grade gliomas [17].

AMERICAN STATISTICS

In America, brain tumors are the second most common form of pediatric cancer. More than 4,000 brain and spinal cord tumors are diagnosed annually. Three out of four children survive past 5 years of their diagnosis [18].

Since 5 year survival rates date back to cases diagnosed 5 years prior, we have compiled the latest data available. Statistics will be updated as made available to the public.

The incidence rates for childhood brain cancer (ages 0-14) within the U.S. from 2013-2017 was 3.6 per 100,000 people [20]. The death rates for the same demographic from 2014-2018 was 0.7 per 100,000 people [21]. The 5-year relative survival rate for childhood brain cancer from 2010-2016 was 73% [22], and this number grew to 74.9% from 2011-2017 [17]. The age group that faces the highest deaths from childhood brain tumors are ages 5-9 [17]. There are an estimated 3460 cases of new childhood brain tumors in 2021 [23].

GLOBAL SCENARIO

STATISTICS AND ETHNICITY

The world-standardized incidence rate of pediatric brain tumors in 2018 was 12 cases per million [24]. The world-standardized mortality rate in 2018 was 0.7 deaths per million [24]. Pediatric brain tumors have shown to be more common in White and Asian/Pacific Islanders than Blacks and American Indians. Incidence is also higher in Non-Hispanics compared to Hispanics [25]. Additionally, Non-Hispanic Males (3.7) and White Males (3.6) have the highest rate of new cases per 100,000 people (Ages 0-14) (2014-2018) [17].

SCREENING AND DETECTION RATE

From data compiled from 2011-2017, 79% of cases were detected when localized, 10% were detected when it had spread to regional lymph nodes, 6% were detected when the cancer had metastasized, and 5% were detected at an unknown stage 17. 4.3% of all brain tumors diagnosed occur from ages 0-14 [23].

ROLE OF LIFESTYLE AND ENVIRONMENT

Unlike other forms of cancer that can be caused by increased tobacco usage or an unhealthy lifestyle, pediatric brain tumors are not highly affected by a child’s surrounding environment. The only two proven causes of brain tumors are ionizing radiation and presence of certain genetic conditions.

EARLY/ LATE DETECTION THROUGHOUT COUNTRIES

The prognosis for a child with a brain tumor depends more on the location and type than how early it was detected [25]. Nevertheless, localized tumors that were detected early from 2011-2017 had a 77.6% 5-year relative survival rate, as opposed to metastasized distant tumors with 55.0% 17. Five-year survival rates have increased throughout the 2000s due to an improvement in the prognosis of patients with medulloblastomas [24].

In high income countries, 80% of children survive cancer but in low income countries, only 15-45% do 26. This is due to late or inaccurate diagnosis, lack of access to therapy and treatment, death from side effects, and relapse [26]. Five-year survival rates ranged from 29% in Brazil to 80% in European countries due to obstacles such as lack of access to surgery and treatment [24].

CONCLUSION

My conclusion is that early imaging and screening in developing nations would increase a child’s survival rates if the child exhibits more common symptoms and signs of brain tumors. Additionally, more updated diagnostic statistics from low-income countries could help neurologists and oncologists better predict trends in survival rates and provide a more customized treatment plan to each affected individual. Researchers and doctors in countries that do not have widely accessible statistics must work together to provide numbers to the public and update outdated data. This would enable professionals to better combat the spread of brain tumors, raise awareness, and raise survival rates.

References

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2. https://www.cancer.org/cancer/brain-spinal-cord-tumors-children/causes-risks-prevention/what-causes.html

3. Subramanian, Surabhi. “Childhood Brain Tumors.” StatPearls [Internet]., U.S. National Library of Medicine, 4 Dec. 2020, www.ncbi.nlm.nih.gov/books/NBK535415/.

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13. Johnson, Kimberly J, et al. “Childhood Brain Tumor Epidemiology: A Brain Tumor Epidemiology Consortium Review.” Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology, U.S. National Library of Medicine, Dec. 2014, www.ncbi.nlm.nih.gov/pmc/articles/PMC4257885/.

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24. Girardi, Fabio, et al. “Worldwide Trends in Survival from Common Childhood Brain Tumors: A Systematic Review.” Journal of Global Oncology, American Society of Clinical Oncology, Oct. 2019, www.ncbi.nlm.nih.gov/pmc/articles/PMC6882508/.

25. https://www.cancer.org/cancer/brain-spinal-cord-tumors-children/causes-risks-prevention/prevention.html

26. https://www.who.int/news-room/fact-sheets/detail/cancer-in-children

Childhood Brain Cancer

CHILDHOOD BRAIN TUMORS