Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.
Eyes front and ears open. Class is now in session.
The disease that we will be learning about today is:
Glioblastoma Multiforme
Also known as glioblastoma or grade IV astrocytoma.
What is Glioblastoma?
- GBM arises from the astrocytes – star-shaped cells that make up the supportive tissue of the brain
- Most common and aggressive malignant primary brain tumor
- Mean survival time without treatment is 3 months
- GBM was selected as the first brain tumor to be sequenced as part of The Cancer Genome Atlas, a national effort to map the genomes of the many types of cancer. In this effort, researchers discovered that GBM has four distinct genetic subtypes that respond differently to aggressive therapies.
- Very difficult to treat:
- Tumor cells are resistant to conventional therapies
- The brain is susceptible to damage due to conventional therapy
- The brain has a limited capacity to repair itself
- Many drugs cannot cross the blood-brain barrier to act on the tumor
- Usually found in the cerebral hemispheres of the brain, but can be found anywhere in the brain or spinal cord
- Usually contains a mix of cell types – cystic mineral, calcium deposits, blood vessels, or a mixed grade of cells
- The cancer cells grow quickly and are nourished by an ample blood supply
- Rarely spreads elsewhere in the body
- Two types of glioblastomas:
- Primary, or de novo: Most common form – very aggressive
- Secondary: Have a longer, somewhat slower growth history, but still are very aggressive. Represent about 10% of glioblastomas
- 12,000-14,000 people are diagnosed with GBM in the US each year
- GBM accounts for 12-15% of all intracranial tumors and 50-60% of all astrocytic tumors
- Only about 3% of childhood brain tumors are glioblastomas
- There are nearly 700,000 people in the U.S. living with some type of brain tumor
- This year, nearly 14,000 people will lose their battle with a brain tumor
How Do You Get It?
- Exact cause is unknown
- More common in males
- More common in those over 50
- More common in Caucasian and Asian ethnicity
- One of the only risk factors known is radiation exposure
- Some studies suggest increased risk with:
- Alcohol consumption
- Exposure to PVC
- Lead exposure
- Having a lower grade astrocytoma can often develop into a higher grade tumor including glioblastoma
What Are The Symptoms?
- Symptoms in patients with GBM have typically been occurring for less than 3 months and may include:
- Motor weakness
- Headache
- Nausea and vomiting
- Cognitive impairment
- Seizures
- Personality changes
- Weakness on one side of body (hemiparesis)
- Sensory loss
- Visual loss
- Aphasia
- Drowsiness
How Is It Treated?
- GBM is challenging to treat because the cells within the tumor are very resistant to most types of treatments. As a result, doctors may draw upon a variety of treatments to try to slow tumor growth. In addition, these tumors tend to have a tentacle-like structure, so it can be difficult to fully remove the tumor though surgery.
- Median survival for those treated for glioblastoma is 14.6 months
- Two year survival is 30%
- A 2009 study reported that 10% of patients with GBM will live 5 years or longer
- Those over 60 years old have a poorer prognosis
- UCLA Neuro-Oncology publishes real-time data on how patients treated at their institution fare. The data shows:
- Age range 18-34: Survival – 36.45 months
- Age range 35-50: Survival – 20.81 months
- Age range 50-70: Survival – 598.5 days
- Age range 70-93: Survival – 19.66 months
- For all groups combined: Survival 20.12 – months
- Treatment for glioblastoma includes:
- First step: Craniotomy/biopsy and or resection to clarify and confirm the pathologic diagnosis in order to create treatment plan
- Make sure the pathologic diagnosis matches what is seen on the MRI and the symptoms the patient is experiencing
- Initial treatment
- Standard treatment for those newly diagnosed following surgery consists of 6 weeks of external beam radiation 5 times a week plus oral temozolomide daily
- After the 6 weeks of combined radiation therapy and chemotherapy, patients continue to receive temozolomide daily for 5 consecutive days in 28-day cycles for 1 year
- Following initial treatment it has been found that treatment-induced damage to healthy tissue makes it difficult to correctly diagnose recurrence
- Further surgery may be used to remove as much of the tumor as possible. However, it may not be recommended in all cases
- Not surgically curable, but the more tumor that can be removed the better the prognosis
- The three surgical procedures that are performed on patients with glioblastoma multiforme include:
- Surgical biopsy
- Most cases can be biopsied easily
- Resection (removal)
- The goal of the surgery is to remove as much of the tumor as possible without damaging healthy brain tissue
- Shunt placement/revision
- A temporary drain that is placed, called a ventriculostomy or external ventricular drain (EVD), to relieve pressure in the brain. A revision repositions the drain so it continues to drain effectively.
- Surgical goals include:
- Establishing a pathological diagnosis
- Relieve the effects of the tumor’s mass
- Achieve a total resection to facilitate adjuvant therapy
- Surgery is typically followed by radiation and chemotherapy
- Radiation Therapy
- May help control the growth of the tumor and kill cancer cells left behind after surgery
- Can also be used as an alternative to surgery if surgery is not advisable
- Has been shown to prolong survival compared to surgery alone
- Has been shown to increase survival from 3-4 months to 7-12 months
- Responsiveness to radiation varies – it can induce a period of remission. Even with a response to radiation, the effect is limited and the tumor typically recurs within 1 year.
- Stereotactic radiosurgery can also be used
- Highly focused beams of radiation aimed at a tumor from multiple angles
- Commonly known as CyberKnife, Gamma Knife, or LINAC
- Combination therapy of Radiation and Chemotherapy
- Combination therapy of Radiation and Chemotherapy followed by additional Chemotherapy
- Chemotherapy
- Used to help shrink a tumor, or as follow-up after surgery to kill off any cancer cells left behind
- Studies have suggested that more than 25% of patients obtain a significant survival benefit from adjuvant chemotherapy
- Adjuvant chemotherapy results in a 6-10% increase in 1-year survival rate according to studies
- Temozolomide (Temodar – Merck), approved in 2005, is a standard first-line treatment for those newly diagnosed with GBM
- Adjuvant and concomitant temozolomide with radiation was associated with significant improvements in median progression-free survival over radiation alone (6.9 vs 5 mo), overall survival (14.6 vs 12.1 mo), and the likelihood of being alive in 2 years (26% vs 10%)
- Carmustine (BCNU) (Gliadel Wafers) are sometimes implanted during surgery to deliver chemotherapy directly to the tumor site
- A major hindrance to the use of chemotherapy for brain tumors is the fact that the drugs cannot cross the blood-brain barrier
- Optune™ TTF therapy alone or in combination with other modalities
- Optune™ is currently indicated for adult patients with a recurrence of GBM in the supra-tentorial region of the brain after receiving chemotherapy. It is intended to be used as an alternative to standard medical therapy after surgical and radiation options have been exhausted
- Recurrence
- Most patients will have a recurrence of glioblastoma within 2 years of their original diagnosis
- There is no standard therapy for recurrence
- If a patient has a recurrence, a limited number of treatments are available. After recurrence, options include:
- A second surgery can be performed in some cases
- A second course of radiation therapy if the cancer recurs in a different area of the brain
- A variety of chemotherapy regimes:
- Bevacizumab (Avastin – Genentech) was approved in 2009 for the treatment of recurrent glioblastoma
- Others can include: nitrosoureas, platinoids, etoposide, irinotecan, procarbazine and vincristine and tamoxifen
Where Can I Learn More???
- Check out our cornerstone on this disease here.
- Learn more about this disease from the National Brain Tumor Society.
