Findings

1. Incidence Rates — U.S. & North America

• Per research published by the National Center for Biotechnology Information, there are 20,000 glioma diagnoses in the U.S. annually.
• Gliomas account for approximately 25% of the estimated 80,000 "primary brain tumor" diagnoses in the U.S. annually.
• As one of two types of low-grade gliomas, "[l]ow-grade astrocytomas are relatively uncommon tumors when compared to their higher-grade counterparts . . . [as] about 1,500 are believed to occur in North America each year."
• The diagnosis prevalence for a specific type of gliomas, glioblastomas, is about 12,000 per year in the U.S., which accounts for about 15% of new brain tumor diagnoses in the country annually.
• Among U.S. individuals ages 20-34, "gliomas account for 32% of all primary CNS [central nervous system] tumors, 17% of which are astrocytic tumors; 28% of these are glioblastomas."
• Among U.S. individuals ages 15-39, "[g]liomas account for 29%–35% of the CNS tumors . . ., with approximately two-thirds being low-grade glioma (LGG) and the remaining being high-grade glioma (HGG)."

2. Global Incidence Rate

• We could not find Information about the global incidence rate for low-grade gliomas. One likely reason for that is illustrated in the following statement from the medical industry source Annals of Translational Medicine: "[P]recise information on brain tumors’ epidemiology is poor, since the registration is not mandatory in many countries worldwide. Moreover, brain tumor recording is often limited to malignant tumors, thus excluding non-malignant or borderline ones."
• The incidence rate for a form of low-grade gliomas, diffuse low-grade gliomas, ranges between "3–15% of all brain tumors."
• Diffuse low-grade gliomas account for "15% of gliomas."
• Medical research studies conducted in Europe and America have estimated the brain tumor incidence rate at between 17.6-22 per 100,000 people.
• Another type of glioma is glioblastoma, which "is the most common type of glioma." Glioblastomas "account[] for 52 percent of all primary brain tumors."
• The annual, global incidence rate for glioblastomas is "2–3 new cases per 100,000 people."

Your research team applied the following strategy:

LOW-GRADE GLIOMAS: OVERVIEW

• Gliomas are generally, primary brain tumors (cancers) that originate in the brain.
• They are referred to as primary because they originated in the brain and are different from secondary tumors which originate in other parts of the body before spreading.
• These primary brain tumors develop from glial cells, a cell that provides the brain with its structural backbone and also supports the function of the neurons (nerve cells).
• The different types of glial cells arise from a common brain stem cell from which gliomas form when these immature stem cells mutate and grow out of control.
• The different types of are named based on the type of cells from which they emanate.
•  Types of low-grade gliomas include pilocytic astrocytomas, diffuse astrocytomas, oligodendrogliomas, gangliogliomas.
• Glioblastoma is the most dangerous type, while pilocytic astrocytomas are the least malignant brain tumors.
• These tumors tend to grow and penetrate the normal brain tissue, making surgical removal very difficult.
• Gliomas can also occur in the spinal cord.
• The most common symptoms of the tumor include headaches, confusion, nausea and/or vomiting, seizures, change in speech or language, personality changes, memory loss, weakness on one side of the body, difficulty with walking or balance, and vision loss or blurred/double vision.
• Other risk factors of the illness include age bracket, exposure to radiation, and family history.
• Most gliomas that occur in children are low grade.

GRADING

• Low-grade gliomas are categorized based on the microscopic appearance of the tumor and several other important genetic variations.
• They are classified into four grades (I, II, III, and IV) and the treatment grade and prognosis depend on the tumor's classification.
• According to UpToDate's patient education page, "Patient education: Low-grade glioma in adults (Beyond the Basics)," "Grade I or II tumors are termed low-grade gliomas."
• To analyze and grade the tumor, the following questions are asked: (1) from what type of brain cell did the tumor arise and (2) whether there are signs of rapid growth in the tumor cells.
• The different types of low-grade gliomas are determined depending on the tumor's grading.
• Pilocytic astrocytomas occur almost exclusively in people who are younger than 25 years of age and tend to progress very slowly.
•  Diffuse astrocytomas are the most common type of low-grade glioma and are usually seen in individuals in their late thirties.
• UpToDate also notes that "they are subdivided based upon whether they have a mutation in the isocitrate dehydrogenase (IDH) gene. "
• Oligodendrogliomas also tend to progress slowly and contain a mutation in the IDH gene and are missing pieces of two chromosomes (1p and 19q), which separates them from other low-grade gliomas.
• Gangliogliomas are tumors that have characteristics of both gliomas and tumors arising from neurons and also tend to grow very slowly.

DIAGNOSIS

• Gliomas are often diagnosed in older adults, depending on the different types.
• They are slightly more likely to be diagnosed in males than in females.
• There are 6 cases of gliomas diagnosed per 100,000 people yearly in the United States.
• According to the American Brain Tumor Association, there are more than 79,000 new cases of brain tumors yearly.
• The symptoms of the tumor may vary depending on which part of the brain it originated and they usually come on gradually from days to months.
• When a brain tumor is suspected, a test is carried out which includes a CT scan, MRI, or both.
•  Neurological examinations can be performed by the doctor to check vision, balance, hearing, coordination, reflexes, and strength.
•  A biopsy may be performed for diagnosis if the scan results suggest a brain tumor. The biopsy may be carried out as a separate procedure or concurrently with surgical removal. A sample is removed from the tumor by stereotactic needle biopsy using x-ray guidance, a process with the potential to cause brain damage or complications. The biopsy may be delayed until symptoms worsen or the tumor becomes more aggressive for the sake of certainty and reduced biopsy risks.

TREATMENT

• The treatment process normally involves the best way to manage symptoms and remove or reduce the tumor.
• The decision to treat the tumor must match the benefits of the process against the potential for treatment-related complications.
• The major symptoms that can be managed are obstructive hydrocephalus (pressure build up in the brain), seizures, and cerebral edema (swelling in the brain around the tumor).
•  Some symptoms-management methods include epilepsy medication (to manage the seizures), the use of steroids (dexamethasone/Decadron) to control cerebral edema, and lastly, surgery, to treat obstructive hydrocephalus and lower brain pressure due to the tumor.
• Surgery, chemotherapy, and radiation therapy may be used to treat a low-grade glioma, either separately or collectively.
• Surgery is normally the first approach performed to remove as much of the tumor as possible.
•  Radiation therapy normally follows surgery in the treatment of glioma, especially high-grade gliomas. Radiation therapy processes include using computers to pinpoint delivery, using protons, and using multiple beams of radiation to locate and kill tumor cells.
•  Chemotherapy involves the use of medication which kills cancerous cells whether in a pill form or a liquid that is given through an IV into the bloodstream.

EXPERT OPINION

•  Nancy Ann Oberheim Bush, MD, Ph.D., is an Assistant Professor of Neurological Surgery at the University of California, San Francisco (UCSF) and a member of the Division of Neuro-Oncology at UCSF who has been involved in investigator-initiated, sponsored, and multi-institutional consortium studies.
• Her research interests center on the development of phase I clinical trials testing novel treatment strategies for patients with brain tumors.
• She suggests that "the risk-benefit ratio of adjuvant treatment must be weighed for each individual."

RESEARCH STRATEGY:

STUDIES

Radiation Therapy With or Without Temozolomide in Treating Patients With Low-Grade Glioma

• ID: ECOG-E3F05 
• Drug: Temozolomide 
• Manufacturer: Merck 
• Key Findings:
• The study was suspended in early 2014 and updates on the potential benefit of temozolomide treatment with radiation therapy should be released soon.
• The suspension came from the NCI as a result of the outcome of RTOG 9802 which showed significant improvement for the overall survival and progression-free survival of the patients, but also showed no difference effects of radiotherapy or temozolomide on health-related quality of life.

Assessment of Multidrug Resistance in Breast Cancer and Low Grade Glioma Patients with Tariquidar Pem. A Pilot Study

• ID: EUCTR2011-004189-13-AT 
• Drug: Tariquidar 
• Manufacturer: Sigma-Aldrich 
• Key Findings:
• N/A

Phase III Trial of Anaplastic Glioma Without 1p/19q LOH (CATNON)

• ID: EORTC-26053-22054 
• Drug: Temozolomide 
• Manufacturer: Merck 
• Key Findings:
• With the use of adjuvant temozolomide, it was found that the hazard ratio of the 745 patients was 0·65 (99·145% CI 0·45–0·93).
• At five years, the overall survival rate was 55·9% (95% CI 47·2–63·8) with adjuvant temozolomide and 44·1% (36·3–51·6) without adjuvant temozolomide.
• Grade 3-4 adverse events were observed in 8-12% of 549 patients that were given temozolomide, but these events were hematological in nature and were reversible.

RESEARCH STRATEGY