Glioblastoma, an incurable brain cancer, urgently needs new treatments. Why?

Glioblastoma, one of the incurable brain cancers, is an area with significant unmet medical needs despite surgery, chemotherapy, and radiation.

Even with surgery, chemo, and radiation, the average survival time for glioblastoma patients is only about 18 months, and the prognosis is very poor, with less than 30 percent of patients surviving for more than two years and less than 5 percent surviving for more than five years. Why is the prognosis for glioblastoma so poor?

“Despite a long course of treatment, including surgery, chemotherapy, and radiation therapy, the prognosis is known to be poor because cancer stem cells, which are known to be located in the center of the brain, are reactivated after a certain point and the disease progresses,” said Professor Stephen Ahn of the Department of Neurosurgery at the Catholic University of Korea Seoul St. Mary’s Hospital, on Seoul St. Mary’s Hospital TV.

Glioblastoma is considered a “malignant tumor” that is often difficult to treat.

“Most patients with glioblastoma often require urgent medical attention due to sudden neurological symptoms,” Ahn said. “We often experience difficulties conducting adequate testing and making surgical planning.”

Professor Ahn explained why it is difficult to treat glioblastoma.

“Benign tumors are mainly characterized by slow growth and poor infiltration into surrounding tissues. Only when there are clear symptoms or a large size is the criterion for surgical removal, and if the surgery goes well, there is no recurrence and a good prognosis,” he said. “Malignant tumors, on the other hand, grow very quickly and invade and destroy the brain. If left untreated, it can lead to neurological deterioration and death within a short period.”

Glioblastoma is one of the most common and aggressive brain cancers. While most cancers occur in older adults, glioblastoma is also relatively common among children and young adults compared to other cancers. Of course, the risk of glioblastoma increases with age, and because it can occur anywhere in the brain, it can cause various neurological symptoms, such as speech, movement, gait, and sensory perception problems, according to Professor Ahn.

“Because the brain has many different functions depending on its location, glioblastoma can cause a variety of neurological symptoms depending on where it is located,” Ahn said. “It can cause speech, movement, gait, sensory and cognitive impairment. In more advanced cases, it causes increased brain pressure, which can lead to severe headaches and even loss of consciousness.”

About 95 percent of glioblastomas can be diagnosed with an MRI scan.

“About 95 percent of glioblastomas can be diagnosed with MRI,” Ahn said. “However, there is a possibility that about 5 percent of glioblastomas may have tissue that is different from the MRI results. Because of the limitations of general MRI, it is essential to obtain accurate information about the tumor through a specialized brain tumor MRI using contrast agents.”

A brain tumor-specific MRI with a contrast agent is needed to pinpoint the location of glioblastoma, and a diffusion tensor imaging (DTI) scan is needed to identify and analyze the brain's neural pathways to understand how glioblastoma affects brain function. In addition, unlike other solid tumors, rehabilitation is evaluated before treatment, he explained.

“It is also important to carefully observe a glioblastoma patient's speech, motor, cognitive, and daily living functions through various rehabilitation assessments,” Ahn said. “This is an important basis for planning the scope of glioblastoma surgery and predicting the prognosis of the patient's neurological symptoms.”

Currently, surgery is considered the gold standard for glioblastoma treatment, and for good reasons.

“Glioblastoma treatment requires surgical removal accompanied by biopsy for accurate tissue identification,” Professor Ahn said. “Surgical removal is (currently) the only known way to improve prognosis.”

The key principle of surgery, the essential treatment for glioblastoma, is “maximally safe resection.”

“The goal is to remove as much of the tumor as possible while preserving as much of the vital brain function as possible,” Ahn said. “So, the primary goal is the balance between complete removal of the tumor and preservation of brain function.”

In glioblastoma, early rehabilitation after surgery is critical to a patient's quality of life. Since recovery is usually possible two to three days after surgery, Ahn emphasized the importance of maximizing the recovery of neurological function through early rehabilitation in case of residual disability.

Three to four weeks after surgery, a new round of treatment begins, including six weeks of chemotherapy and radiation.

“This treatment is usually done on an outpatient basis. However, if additional rehabilitation is needed, the patient may be admitted to the hospital,” Ahn said. “After the six weeks of chemo-radiation, the patient will receive six cycles of oral chemotherapy over six months.”

The oral chemotherapy drug used is Temodal, which is known to have relatively fewer side effects than other traditional chemotherapy drugs. There are still treatment options for glioblastoma patients who relapse despite surgery, chemotherapy, and radiation.

“If the disease recurs despite these treatments, the best option is to participate in a clinical trial,” Professor Ahn said. “If it does, reoperation may be considered. Reoperation may be the most effective option at this time, but it can be challenging because of the increased risk of neurologic complications and wound management. It may also have limited effectiveness if the tumor has spread to multiple locations, so it is only available in relatively limited cases.”

Another option is to return to Temodal for chemotherapy or try an injectable chemotherapy drug called Avastin. “The response to these treatments varies from patient to patient, so the choice of agent should be discussed with your doctor,” the neurosurgical specialist said.

So, what kind of new drug trials are currently available for glioblastoma patients in Korea?

In addition to new drug trials conducted by multinational pharmaceutical companies and domestic drug trials conducted by Korean doctors, advanced regenerative medicine and anticancer immunotherapy trials are currently in preparation.

“Recently, advanced regenerative medicine has emerged, and we are preparing to conduct clinical research on a treatment that directly cultures cancer-killing cells and injects them into patients. In addition, we are conducting various development studies to develop various anticancer immunotherapy drugs to enter clinical trials in line with the era of anticancer immunotherapy,” Professor Ahn said.