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For Your Patients-Neuro-Oncology
A Minimally Invasive Laser Thermal Therapy Is Effective for Glioblastoma with Smaller Tumors

ARTICLE IN BRIEF

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Researchers found that treating glioblastoma with a laser interstitial thermal therapy was safe and effective for treating glioblastoma.

A minimally invasive laser treatment for patients with glioblastoma (GBM) may be an optimal treatment for patients with recurrent GBM who can no longer tolerate open brain surgery to remove cancerous brain tissue, according to a descriptive report published ahead of print online on August 22 in Neurosurgery.

Laser Interstitial Thermal Therapy (LITT) involves drilling a hole in the skull and using a laser-tip probe that is guided through the brain into the tumor where it emits pulses of heat that burn the surrounding cancer cells. Real-time magnetic resonance imaging (MRI) thermometry allows for continuous monitoring of the ablation zone, and ablation can be stopped at any time.

During ablation, real-time MRI thermometry tracks the progress of the expanding ablation zone. The ablation zone is characterized by the yellow thermal damage threshold (TDT) line, signifying a dose equivalent of 43 degrees centigrade for two minutes, and by the blue TDT line, signifying a dose equivalent of 43 degrees centigrade for 10 minutes.

Complications of LITT include edema and swelling, and recovering patients typically receive steroids and antibiotics.

STUDY DETAILS, FINDINGS

Researchers at Siteman Cancer Center at Barnes-Jewish Hospital gathered data on patients with GBM who received LITT between 2010 and 2016. During that span of time, 54 patients between the ages of 35 and 78 years of age received 58 thermal laser treatments with the laser ablation system.

Of the 58 treatments with LITT, 17 were frontline for primary GBM as determined by biopsy, either previously or concurrently with LITT. Forty-one treatments were for recurrent GBM; the majority (33, or 80.4 percent) had surgical resection(s) and standard chemoradiation prior to LITT. Four patients had only chemoradiation prior to LITT. Four patients had prior LITT treatments; of these, three underwent repeat ablation for recurrence and one was the second stage of a planned two-stage procedure.

The majority of lesions were lobar, located in the frontal (n = 14), temporal (n = 8), parietal (n = 9), occipital (n = 1), or in multiple contiguous lobes (n = 8). Other locations included corpus callosum (n = 8), insular (n = 2), and thalamic (n = 8) GBMs.

Median tumor volume was 8.8 cm3. Overall, surgeons treated an average of 93 percent of tumor volume treatment within the yellow TDT line and 88 percent treatment with the blue TDT line, according to the study.

Nine incidents of complications resulted within a month of surgeons administering LITT to patients, which led to further procedures, readmission to the hospital, or transfer back to the ICU, according to the report. These complications involved cerebral edema (n = 3), seizures (n = 3), hydrocephalus (n = 1), hyponatremia (n = 1), and infection (n = 1).

Median overall survival after administration of LITT for the total cohort was 11.5 months (95 percent CI= 8.5 - 12.8 months, range 0 - 34.2 months), and median progression-free survival (PFS) was 6.6 months (95 percent CI= 4.3-7.7 months, range 0 - 32 months). Within these groups, there were 17 instances of primary GBMs treated with LITT as a frontline therapy: overall survival was 9.1 months (95 percent CI = 4.2- 14.2 months, range 0 - 25.4 months) and PFS was 3.6 months (95 percent CI= 0.37-7.67 months, range 0 -19.3 months).

Two of 17 patients in this cohort had no further therapy due to perioperative mortality and 15 had standard chemoradiation post-LITT. For recurrent GBMs (n = 41), overall survival was 11.8 months (95 percent CI= 8.6 -13.8 months, range 0 - 34.2 months) and PFS was 7.3 months (95 percent CI = 5.1 - 8.9 months, range 0 - 32 months; Of these, 36 patients had prior open craniotomy and all 41 had prior standard of care chemoradiation.

For frontline GBM treatment, median overall survival was 9.1 months, while for recurrent GBM treatment median overall was 11.8 months. Authors speculated that this difference may be in part due to patient selection for these groups. “Patients for whom LITT is chosen as a frontline therapy were not good candidates for craniotomy, due to deep-seated lesions, advanced age, poor functional status, or some combination thereof. Since these patients have a poorer prognosis from the start, it follows that overall survival in this group may be shorter,” they wrote.

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DR. PATRICK Y. WEN: “This study shows that it is relatively safe and feasible in experienced hands. However, it does not replace standard craniotomies for removal of tumors, especially for the larger tumors.”

The authors further noted that while LITT offers several advantages over craniotomy, a comparative study with matched groups would “directly compare the efficacy of the two treatments. Further studies examining LITT in this context will be useful.”

Lead investigator and author Eric C. Leuthardt, MD, told Neurology Today that the first FDA-approved case of LITT took place in 2011, and that he considers it “generally less risky than open (brain) surgery. Whether it is more effective is an active question being explored.”

Dr. Leuthardt, professor of neurosurgery at Washington University School of Medicine, noted that there are times when “the tumor is too large and causing mass effect, and in this case, a craniotomy and removal of tissue is the optimal solution.”

Further insights and care will be determined by conducting prospective studies and randomized controlled studies comparing LITT to the standard of care, he added.

EXPERT COMMENTARY

Shawn Hervey-Jumper, MD, associate professor of neurosurgery at University of California, San Francisco, told Neurology Today that “Dr. Leonhardt's lab did a great job of showing that LITT adds to the growing body of evidence showing that it is a viable treatment for patients with GBM”. Dr. Hervey-Jumper noted that prior descriptive studies of LITT on patients with GBM have focused on smaller samples, with only 10 to 20 patients.

Dr. Hervey-Jumper emphasized that LITT does not replace craniotomy in all patients and that it has also been associated with cerebral edema and swelling of brain tissue, which limits its utility in many situations. In addition, he said, LITT can be considered for patients with smaller brain tumors, noting that the mean volume of tumors in the study was 12.5 cm3.

He explained that the first time LITT was used to treat tumors was in 1972, and the technology continues to evolve and improve.

Justin T. Jordan, MD, MPH, clinical director for neuro-oncology at Massachusetts General Hospital, said the study suggests a new, potentially efficacious tool in the neurosurgical approach to glioblastoma care. “Survival data are preliminarily optimistic in this report for both recurrent glioblastoma and newly diagnosed, non-resectable glioblastoma, though the reported complications were not inconsequential, including 15.5 percent risk of severe complications and 3.4 percent risk of death,” he noted. “To better understand the risk-benefit ratio of this novel neurosurgical oncology therapy, the field will look forward to additional prospective clinical trial data which should be forthcoming.”

Patrick Y. Wen, MD, FAAN, professor of neurology at Harvard Medical School and director of the Center for Neuro-Oncology at the Dana-Farber Cancer Institute, told Neurology Today that “this study shows that it is relatively safe and feasible in experienced hands. However, it does not replace standard craniotomies for removal of tumors, especially for the larger tumors.”

Dr. Wen noted that since LITT is relatively non-invasive it can be used in patients who cannot tolerate a craniotomy. He added that “it also allows relatively non-invasive access to deep tumors or tumors in eloquent areas,” and that another potential use is in patients who develop symptomatic necrosis.

DISCLOSURES: Dr. Leuthardt consults for Monteris Medical. Dr. Jordan received consulting fees from the NF Network and royalties from Elsevier Publishers.

LINK UP FOR MORE INFORMATION:

• Kamath AA, Freidman DD, Akbari SH, et al. Glioblastoma treated with magnetic resonance imaging-guided laser interstitial thermal therapy: Safety, efficacy, and outcomes https://academic.oup.com/neurosurgery/advance-article/doi/10.1093/neuros/nyy375/5075992. Neurosurgery 2018; Epub 2018 Aug 22.