New Therapies for Glioblastoma Multiforme

As reported in the recent Nature Outlook article on innovative therapies for glioblastoma multiforme, seven years ago, Kenneth Coughenour began to feel dizzy and strange. His doctor said that it could be the persistent effects of a sinus infection, but the sinus drugs did not work and a few days later the first episodes of hemiparesis started which eventually proved to be associated with a golf ball-sized non-operable glioblastoma. At the time, Kennet was 48 years old.

The Cleveland Clinic in Ohio confirmed that the tumor was not removable but could be destroyed using laser interstitial thermal therapy (LITT). You must use a hole in the shape of Coughenour’s skull, direct a laser beam into his brain and destroy the cancerous tissue using heat.

Kennet was operated few days later and the procedure went well. Kennet received then chemotherapy and radiotherapy. No one expected Kennet to survive long but 7 years have passed before a recurrence.

The brain cancer is notoriously difficult to treat, but there are new promising therapies such as LITT. The researchers are also trying to use lasers to activate cancer-fighting drugs. Often many of these therapies seem promising, researchers are still trying to determine their effectiveness and which patients can benefit from them. In the case of LITT it seems a way to treat tumors that cannot be operated.

To date, two LITT systems for neurosurgery are available, one sold by Medtronic and NeuroBlate sold by Monteris. The main advantage of LITT over conventional surgery is that it is minimally invasive. Instead of executing a craniotomy, the surgeon only needs to make a small hole. This shortens recovery times. But most neurosurgeons still prefer traditional therapy over which decades of data are present.

Since 2005, the standard of care for patients with glioblastoma is the Stupp protocol, a surgical procedure followed by 6 weeks of concomitant chemotherapy and radiotherapy, then 6-12 months of maintenance chemotherapy.

In the case of the application of LITT in the past, there have been some side effects associated with excessive heating of the probe and which have led to an improvement in the machines thanks to a brain mapping technique called resting-state magnetic resonance imaging. This is more accurate than functional magnetic resonance, allows neuroseurgeon to create a brain map before surgery and to use LITT to remove the tumors near important areas for language and other crucial cognitive functions through an automatic software-controlled procedure.

There are also new combined therapies. Lasers can destroy tumors, but they can also activate compounds or open pathways in inaccessible areas. LITT makes the blood-brain barrier more permeable for 4-6 weeks after surgery which could allow drugs that do not normally pass through the brain to penetrate. LITT could also improve the effectiveness of immunotherapies. The procedure leaves behind dead tissue, and because it creates a burn you can boost the body’s immune response to tumor antigens.

Another technique, photodynamic therapy (PDT), is based on a light-controlled drug called photosensitizer. These drugs accumulate disproportionately in tumors and, if exposed to a specific length of light, free radicals that destroy cells. The idea is to administer the photosensitizer a few days before surgery. Once the tumor is removed, the surgeon makes a laser shine in the cavity to kill all the malignant cells that remain. This technique is also being tested experimentally in the Lille University Hospital in France.

Some new therapies, however, treat the entire brain. Novocure has developed a system to provide alternating brain electric fields to curb cancer growth. The therapy, called Optune, consists of a series of electrodes that attach to the scalp. Electric fields interfere with the ability of microtubules to form and separate DNA and interrupt cell division. It seems that Optune has improved of about 40% patient life expectancy.

Optune received FDA approval in 2015 based on an analysis of phase III trial data. And in March 2018, the comprehensive national cancer network in the United States recommended Optune in combination with chemotherapy as a treatment option for patients with newly diagnosed glioblastoma.

Any progress that improves or extends the life of patients with brain cancer is great news. Kennet is optimistic and has started a new immunotherapy treatment in the hope that the treatment will extend his life waiting for new and better therapies.