Advances in Brain Tumor Treatment—2017 and 2018

In adults, primary brain tumorsmost commonly consist of glioblastoma multiforme (GBM). Brain tumors originate in the brain's main supporting cells, which also help nerve cells carry out their functions, glial cells.

Classification of brain tumors:

Low-grade tumors

are called grade I and II glial tumors.

High-grade tumors

• Grade III tumors: Anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, anaplastic ependymoma 
• Grade IV tumors: Glioblastoma (GBM or GBM-IV ), as classified.

Standard treatment for newly diagnosed GBM is brain tumor surgery removing as much tumor as possible, followed by adjuvant (preventive) radiotherapy and chemotherapy. Although chemotherapy and radiotherapy prolong survival in GBM, in most patients, cancer recurs after initial treatment. Despite current treatments, desired success has not been achieved in recurrent GBM.

Looking at recent studies on high-grade tumors in these patients:

1. Alternating Electric Field Treatment Provides an Important Benefit in Newly Diagnosed Glioblastoma (January 2018)

The device delivering electric field treatment, Optune , received in October 2015 FDA approval. Optune inhibits cancer cell proliferation in the brain (anti-mitotic) and causes their death without harming healthy brain tissue. It is a portable, noninvasive device delivering low-intensity, intermediate-frequency alternating electrical current. Electrodes are placed directly on the skull to target the tumor, with placement determined by each patient's MRI results to maximize the effect.

Postoperative preventive treatment for GBM consists of the chemotherapy pill temozolomide together with radiotherapy . In a study, adding Optune for some patients receiving this standard treatment provided an additional 5 months of overall survival.

Although adding Optune to standard GBM treatment provides a significant benefit, wearing the device continuously throughout treatment, its limited availability in our country and considerable cost may not be acceptable for every patient.

2. The Antiangiogenic Drug Bevacizumab Alone Is Sufficient in Recurrent Glioblastoma (December 2017)

One of our most important drugs for recurrent GBM is a targeted drug that inhibits tumor blood vessel formation (antiangiogenic), bevacizumab (brand name Altuzan). Using it with the chemotherapy drug irinotecan is our standard approach. Lomustine is another chemotherapy used in these patients. It disrupts cancer cells' DNA and belongs to the group called alkylating agents. A phase-II clinical studycombining it with bevacizumab was promising, but a phase-III study enrolling 400 patients showed that the combination was not superior to use alone.

For GBM recurring during treatment, we believe new treatment choices should be individualized according to the patient's general condition, previous treatments and drug side effect profiles.

3. Aminolevulinic Acid, Which Facilitates Brain Tumor Surgery, Receives FDA Approval

Good surgery is the most important treatment for brain tumors, and identifying remaining cancerous tissue is crucial. Aminolevulinic acid hydrochloride (Gleolan), after oral intake, is absorbed by cells and converted into fluorescent chemicals, particularly protoporphyrin IX (PPIX). Glioma cells absorb it intensely and convert it to PPIX protein. Under blue light of a particular wavelength, healthy brain tissue appears blue while tumor PPIX glows intensely red. This allows the surgeon to see the tumor more clearly and remove it more accurately while preserving healthy brain tissue. After clinical studies demonstrated efficacy, particularly in high-grade brain tumors, it received FDA approval and entered clinical use.

- Study details: Aminolevulinic Acid, Which Facilitates Brain Tumor Surgery, Receives FDA Approval

4. Immunotherapies Show Promise in Brain Tumors (September 2017)

By removing suppression of the immune system, immunotherapies have shown efficacy in many cancers and entered clinical use. Studies are also being conducted in high-grade brain tumors.

A study of nivolumab (brand name Opdivo) did not achieve the desired response, while a pembrolizumab (brand name Keytruda) study after second- or third-line chemotherapy found disease control (progression-free survival) at 6 months to be %45. A durvalumab study in similar patients found 1-year survival of %44.

Studies of these drugs continue. The main challenge is identifying which high-grade brain tumor patients benefit most from immunotherapy. We know individualized treatments will benefit patients.

- Related topic: A New Target for Aggressive Brain Tumor Glioblastoma Treatment: Telomere Proteins!

5. A Newly Developed Cancer Vaccine Called pp65 Shows Promise for Glioblastoma (May 2017)

Recent advances in immunotherapies—treatments activating the body's defenses against cancer—have been breathtaking. They may remove braking mechanisms on immune cells or take the form of vaccines specific to a person's cancer.

Recent studies showed that a protein called pp65 is also produced by human cytomegalovirus (CMV) and prevents the immune system from reacting to CMV. It is also produced in %90 of glioblastoma cells. Researchers used pp65 to develop a dendritic cell vaccine for GBM. This phase I study of 11 patients prolonged both time to recurrence and survival.

Before clinical use, further studies must be awaited, because this study is still at phase-I and evaluated only a small number of patients. 

- Study details: New Hope for Glioblastoma Brain Tumor Treatment: The pp65 Cancer Vaccine