Laser Thermal Therapy Effective for Brain Tumors, Epilepsy

Pauline Anderson

May 18, 2017

Laser interstitial thermotherapy (LITT) is safe and effective for treating both gliomas and metastatic brain tumors, including those that are recurrent or deep and inoperable, new research shows.

A study presented here at the recent American Association of Neurological Surgeons (AANS) 2017 Annual Meeting in Los Angeles, California, indicates that survival among patients undergoing LITT using the NeuroBlate System (Monteris Medical) for brain lesions was extended beyond what would be expected without treatment.

"LITT is a safe and effective way to treat deep and inoperable tumors of the brain, whether they be gliomas or brain metastases," Andrew Sloan, MD, director, Brain Tumor and NeuroOncology Center, University Hospitals Cleveland Medical Center, and professor and vice chair, Department of Neurosurgery, Case Western Reserve University School of Medicine, Ohio, told Medscape Medical News.

"It is also minimally invasive, has acceptable toxicity, and shows better than expected efficacy."

LITT technology is also being used to treat intractable epilepsy, according to research released at the recent American Academy of Neurology (AAN) 2017 Annual Meeting in Boston, Massachusetts.

A study in medically and surgically intractable epilepsy, presented at the meeting by Scheherazade Le, MD, clinical assistant professor, Stanford University, California, showed that the procedure — using similar technology but from a different company (Visualase, Medtronic) — is safe and well tolerated and offers most patients seizure freedom, at least in the short term. 

Tumor Ablation

For the NeuroBlate approach, the patient is prepared and put into an MRI scanner. After determining the correct trajectory or angle of entry for a robotic laser probe, and drilling a tiny hole through the skull, the surgeon remotely controls insertion, advancement, rotation, and firing of the probe to ablate the tumor.

The brain tumor studies included a total of 144 patients — 97 with glioma, many with glioblastoma (GBM), and 40 with metastatic tumors — treated at 9 centers between 2011 and 2015. The mean age of study patients was 54.7 years, and most were white (82.6%).

Just over half (54.9%) were current or past smokers, and 57.3% had other serious medical problems.

Most gliomas (93.8%) were located in the supratentorial region, with 3.1% each in the corpus callosum and thalamus. For the metastatic brain tumors, 90.4% were supratentorial, 7.2% were infratentorial, and 2.4% were thalamic.

About 70.0% of the metastatic tumors, and 51.5% of the gliomas, were recurrent. Fifty-eight percent of gliomas, and 32.5% of metastatic tumors, were considered inoperable.

"Most were cases that could not have been treated using conventional surgery because they were deep or there were other surgical contraindications," noted Dr Sloan.

The median lesion volume was significantly larger for gliomas than for metastatic brain tumors (12.9 mL vs 7.9 mL; P = .0083).

Neurologic Impairment

At baseline, 48.5% of patients with glioma had no neurologic impairment, 29.4% had mild impairment, 20.6% had moderate impairment, and 1.5% had severe impairment. At a month after intervention, there was a 12.4% decrease in the number of patients with no neurologic impairment, a 6% increase in mild impairment, and a 5% increase in severe impairment, while the moderate category changed only slightly.

For the patient with brain metastases, 46.9% had no impairment at baseline, which was reduced to 35.0% at 30 days, while the 9.4% with mild impairment was increased to 25%, the 43.8% with moderate impairment was decreased to 35%, and the 0% with severe impairment was increased to 5% (1 patient).

The median Karnofsky performance score went from 90 to 80 (out of 100) in patients with gliomas. "So they were still able to eat, sleep and take care of themselves," said Dr Sloan. "That's pretty impressive."

That same score went from a median of 80 to 60 for the patients with brain metastases undergoing treatment.

Dr Sloan pointed out that although there is no good comparator because this is a retrospective study, "if these patients were not treated, one would expect they would be worse."

The median survival in the glioma group was 564 days (about 18.5 months), which is "pretty phenomenal," said Dr Sloan. He noted that the median survival of a newly diagnosed GBM is about a year, and at the time of recurrence, about 6 to 9 months.

"Remember, almost 60% of this group were inoperable."

Again, Dr Sloan stressed that there is no good comparator. "It's hard to know what the reference should be, but clearly it should be less than a year."

In the metastatic brain tumor group, the median survival was 421 days or about 13.8 months. In the past, patients with a brain metastasis "would almost always die" of their brain tumor. The median survival with whole brain radiation was about 6 months.

"So these guys lived 2.5 times longer than that," said Dr Sloan.

He noted that today, patients with a brain metastasis typically die of their primary cancer.

Although the study didn't specifically address what treatments the patients received in addition to LITT. Dr Sloan noted that most patients did receive other therapies.

The LITT operation took 2 to 3 hours for patients in this series, but as the technology has evolved, the operation is now much speedier, said Dr Sloan.

To date, over 1200 patients have been treated with Monteris's LITT technology. It's available at 46 sites in the United States and 2 in Canada.

Obvious Strength

For a comment on the use of LITT in brain tumors, Medscape Medical News approached Edward Pan, MD, medical director, Annette G. Strauss Center for Neuro-Oncology, associate professor, Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, Texas, who is a member of the AAN.

Dr Pan described the study overall as "very interesting" and the safety results as "encouraging."

An "obvious strength" of the study was the number of patients it included, said Dr Pan. "Most reports are from individual centers and have small numbers, so nearly 150 patients is a pretty good number in terms of a study being valid."

But Dr Pan wanted more details on the study — including the breakdown of grades in the glioma group.

"If most of them were skewed as GBM, then this is good data; if most of them were skewed more toward grade IIs, then the survival of the glioma recurrence — 1.5 years — is less surprising."

When later asked for a breakdown, Dr Sloan said 71.1% of gliomas were GBM, 12.4% were grade III, and the rest were lower grades.

As well, Dr Pan wondered whether other treatments that the patients received after LITT may have affected survival.

Overall, said Dr Pan, while this treatment approach for brain tumors "is definitely interesting and worth studying," based on just this one study, "I don't think we can conclusively prove anything," especially since the study, while it was relatively large, was still retrospective.

"Going forward, we need a prospective study" as well as a "clean" study group of, for example, just GBMs.

Intractable Epilepsy

Dr Le and her colleagues prospectively tracked cases of medically intractable epilepsy in whom LITT was used from October 2014 to October 2016 at Stanford Health Care. Their study included 22 patients, all with mesial temporal ablations, ranging in age from 18 to 70 years, with an average follow-up of 13 months.

LITT targets included the right anterior hippocampus (n = 8) and left anterior hippocampus (n = 14).

One patient was lost to follow-up.

All 21 remaining patients had a greater than 50% reduction in baseline seizure frequency and 71% had a greater than 90% reduction in seizure frequency.

To date, 52% of the patients have achieved an Engel class I outcome (essentially seizure free); about a third (33%) achieved Engel class II (rare disabling seizures); 14% had Engel class III (worthwhile improvement); and no patients had an Engel class IV outcome (no worthwhile improvement).

Complications of the procedure were uncommon and largely transient.

About 24% of patients had perioperative seizures within the first 14 days after ablation.

"We sometimes give patients extra doses of medication around the time of surgery," Dr Le told Medscape Medical News. "Any surgical procedure can be stressful, and burning in the brain can cause inflammation, so seizures can sometimes get worse around the time of surgery. That doesn't necessarily mean patients won't eventually have good outcomes."

LITT has several advantages over conventional open surgery in patients with epilepsy, said Dr Le. For example, it "potentially has less cognitive deficits" and uses a much smaller incision (just 3 mm) requiring only one stitch to close.

As well, LITT involves a much shorter hospital stay. While most patients go home the next day, those undergoing conventional surgery stay in hospital 5 to 6 days and then need several weeks of recovery.

"I think it's just amazing that it's so minimally invasive," said Dr Le.

But in the end, Dr Le believes that the LITT technique "is probably less effective than traditional surgery" because surgeons can't take out as much brain tissue and aren't able to get enough tissue for a biopsy.

However, LITT might be considered as a "first step," said Dr Le. "And if it fails, you could still go to the traditional surgery."

A head-to-head comparison between LITT and conventional surgery isn't feasible because it would be impossible to blind such a study.

Although all patients in the current study had mesial temporal lobe seizures, the procedure is also being used for seizures arising from other areas of the brain, said Dr Le.

Dr Le and her team plan to follow these patients for 6 months to a year.

This LITT research in brain tumors was sponsored by Monteris Medical. Dr Sloan is a consultant for Monteris Medical. Dr Pan has disclosed no relevant financial relationships. The LITT study in epilepsy was not funded by the company. Dr Le has disclosed no relevant financial relationships.

American Association of Neurological Surgeons (AANS) 2017 Annual Meeting. Abstracts 905 and 2091. Presented April 26 and April 22, 2017, respectively.

American Academy of Neurology 2017 Annual Meeting (AAN). Abstract S34.003. Presented April 26, 2017.

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