Low Grade Gliomas

Part
01
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Part
01

Low Grade Glioma Prevalence

We could neither find nor estimate the number of people globally who suffer from low-grade gliomas. We did, however, find the overall glioma incidence rate for the U.S., as well as several additional data points about the prevalence of low-grade gliomas and other types of gliomas both in the U.S. and globally.

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:

After conducting thorough research, we concluded that there was insufficient information available from which to directly provide or triangulate the number of people globally who suffer from low-grade gliomas. We looked for that data in three different ways. First, we reviewed many medical research reports about low-grade gliomas published by highly credible industry sources, such as the National Center for Biotechnology Information. That strategy provided us with the U.S. incidence rate for low-grade gliomas, but not the global rate. Those medical research reports also contained insights about the prevalence of low-grade gliomas among certain populations, but information about the global incidence rate itself was not provided nor was there sufficient information to triangulate that value from.

Second, we looked for the global incidence rates for specific types of low-grade gliomas, which include oligondendrogliom and astrocytoma. We implemented that approach because we thought that the global incidence rates for those specific types of gliomas might be available, whereas the global incidence rate for low-grade gliomas as a whole was not. If that information had been available on a global scale, we would have added those values to calculate a triangulated answer to the number of people who suffer from low-grade gliomas. Instead, the information that we found from that approach was for some, but not all, specific types of gliomas, which were diffuse low-grade gliomas and glioblastomas. Since data for all of the types was not available, we couldn't provide a solid estimate of the number of people who suffer from low-grade gliomas based on that data.

As a third research method, we expanded the scope of our research to look for data about the global incidence rate for gliomas in general, instead of low-grade gliomas specifically. We did so because we thought that such data might be more readily available due to its broader scope. We reviewed articles from health industry sources and medical research reports in looking for that information, but the data we found from that approach was the brain tumor incidence rate worldwide, which we included above since it's related to this topic. Due to the limited data available about low-grade gliomas globally, we included the data points that we found about low-grade gliomas and other types of gliomas that we found throughout our research as a proxy. We did so to provide as much relevant information as we could on this topic, despite the limited data available on a global scale.
Part
02
of three
Part
02

Low Grade Gliomas: Overview

Low-grade 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 to any other body part. The different types of tumors are pilocytic astrocytomas, diffuse astrocytomas, oligodendrogliomas, gangliogliomas.

LOW-GRADE GLIOMAS: OVERVIEW

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


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:

To answer this request, we searched through trusted medical publications and health-related articles for information regarding an overview of low-grade gliomas, including what they are, how they're graded, how they're diagnosed, and generally how they're treated. The search was fruitful as we were able to find enough data regarding the topic. A significant amount of information was drawn from UptoDate's "Patient education: Low-grade glioma in adults (Beyond the Basics)" page. Our findings are outlined above.
Part
03
of three
Part
03

Low Grade Gliomas: Clinical Trials

In searching for clinical trials for low-grade gliomas, your research team was able to find three phase III studies that are currently being carried out. For the study that was looking into how tariquidar can affect multi-drug resistance in low grade gliomas, no key findings were found. A proper replacement was not found. The studies and research strategy are explained in greater detail below.

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

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

RESEARCH STRATEGY

Our research began by looking through clinical trial databases such as WHO's clinical trial database and clinicaltrial.gov. We ensured that the results we used were from studies that were active (actively recruiting or not), that they were phase III studies, and that they focused on low-grade gliomas, paying special attention not to include high-grade gliomas or glioblastomas. In this way, we were able to find the first two studies. We found some other studies but later found that it was not viable to include them because they recently began and either recently started or have not started at all. One example of this was the trial using a brand new drug by AstraZeneca called selumetinib. This drug was just given breakthrough status by the FDA, and the first trials are to begin in August. Because this strategy was not bringing up any more results, we switched strategy, and we only had two that we could use, we switched strategy.

Our next strategy was to look through medical news websites such as the Lancet for any mention of interim reports that were done on common drugs being tested such as temozolomide and carboplatin and PCV. We found that many of these studies were already done or were phase II trials. Finding information about PCV (procarbazine, CCNU, vincristine) revealed some key details about the first study we found, "Radiation Therapy With or Without Temozolomide in Treating Patients with Low-Grade Glioma". It showed that a previous study on PCV and temozolomide caused the NCI to temporarily suspend this study based on the results. We eventually found an article detailing interim results for a study on anaplastic glioma which we went ahead and included. While inputting key findings for all, we realized that we were coming short on the key findings for the Tariquidar study.

Our first strategy in finding information on the Tariquidar study was to look through the study itself for any results, but they did not update the trial with anything. Our next strategy to find this was then to search through news sites for any information as it relates to this study. We realized that this study was hardly mentioned anywhere. Our last strategy was to look through the website of Sigma-Aldrich, and while they had some great details on Tariquidar, there was hardly anything on the trial. Hence, we tried to replace this study with another one. So we changed strategy.

In this strategy, we looked through the websites of the makers of the drugs that were often mentioned in the past 10-15 years in studies, such as temozolomide, carboplatin, PCV and the individual drugs themselves, etc. We were finding information about the drugs, but we were finding a lot of completed studies, and nothing that we could use. A lot of the results focuse on temozolomide, and we thought it best to refrain from including another study on that drug because they seem to have similar goals by comparing its effectiveness against other methods such as radiotherapy. Hence, we completed our search.



Sources
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