Prolonged survival after laser interstitial thermal therapy in glioblastoma

INTRODUCTION

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults with an age-adjusted annual incidence of 3.22/100,000 population.[12] GBM is defined pathologically as a glial tumor with an abundance of mitoses, necrosis, and neovascularization.[6] The standard management of these tumors is maximal safe resection followed by concurrent chemoradiation with subsequent adjuvant chemotherapy.[15,17] Prognosis remains poor with median survival of 14 months.[15,17] Extent of surgical resection is an important treatment factor for this disease.[13] Deep seated or eloquent tumor locations pose increased risk of surgical morbidity. Depending on tumor location, even subtotal resection may not be safely possible.

Laser interstitial thermal therapy (LITT) is a technique used to thermally ablate tumors in a minimally invasive fashion. The use of laser-mediated interstitial thermal ablation was first demonstrated in 1983, and the clinical utility of this technology was improved by the development of magnetic resonance (MR) thermography.[1,2] The main mechanism of LITT is to impart thermal damage on local tissue.[14] Irreversible heat-induced necrosis occurs at or above 46°C.[8] LITT has been utilized in diverse disease processes in neurological surgery.[9] As of yet, no randomized controlled trials have been performed regarding intracranial LITT, but retrospective series show positive results for LITT.[16,18] Given its minimally invasive nature, LITT offers a surgical option for GBM located in areas of high surgical risk. Here, we report a case of prolonged survival in a patient with a thalamic GBM treated with LITT, which serves to highlight the potentially durable nature of LITT treatment for this disease.

CLINICAL CASE

A previously healthy 32-year-old man presented to our institution for a second opinion after undergoing biopsy of a left thalamic lesion which revealed GBM. He initially presented to an outside hospital with a complaint of progressive clumsiness of the right hand and foot. MRI of the brain revealed a solitary ring-enhancing lesion with associated increased FLAIR signal in the left thalamopeduncular region [Figure 1a]. Stereotactic biopsy of the lesion was performed at the outside institution, and neuropathology analysis revealed the WHO Grade IV GBM. Immunohistochemistry showed no mutation in IDH1, ATRX, or BRAF genes. Subsequent molecular analyses showed indeterminate O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation and no mutation or copy number alteration in IDH1, IDH2, EGFR, or PDGFR. Histone H3F3 (H3K27M) mutation was absent, and H3K27me3 shows retained trimethylation mark. He presented to our institution for a second opinion. At that time, he had a normal neurologic examination. Given the deep-seated location of the tumor and eloquence of surrounding structures, we elected for LITT followed by radiation alone and adjuvant temozolomide. The patient continues to do well at last follow-up [Figure 1b].

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Figure 1:: Pre and postoperative MRI. (a) Representative preoperative T1 contrast enhanced (left) and FLAIR (right) images. (b) Representative 46.9-month post-LITT T1 contrast enhanced (left) and FLAIR (right) images.

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The LITT procedure was performed in our intraoperative MRI suite using image-guided stereotactic lead placement using the ClearPoint system (Clearpoint Neuro). For the ablation, we utilized the NeuroBlate system (Monteris). The laser ablation was carried out under real-time MR thermography [Figure 2a]. We began thermal lesioning 5 mm superior to target along our trajectory following the long axis of the tumor, advancing 5 mm at a time until the entire lesion was affected by adequate thermal damage. Total laser on time was approximately 7 min. Nearly, total ablation of the tumor was achieved with the vast majority of the tumor. There was a sharp drop in temperature across the enhancing surface of the tumor, allowing adequate tumor ablation without damaging the corticospinal tracts. Immediate postoperative MRI showed diffusion restriction within the tumor and increased enhancement within the necrotic core [Figure 2b]. He was given a short course of dexamethasone to prevent postoperative perilesional edema and discharged home on postoperative day 1 with no neurologic deterioration.

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Figure 2:: Intraoperative and immediate postoperative MRI. (a) Intraoperative MRI demonstrating laser probe position. (b) Immediate postoperative T1-weighterd post-contrast and diffusion-weighted images.

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Postoperatively, the patient received intensity-modulated radiation therapy to the resection cavity with a total dose of 60 Gy in 30 fractions starting on postoperative day 13. He did not receive concurrent chemotherapy. Thereafter, he was given adjuvant temozolomide at 200 mg/m²/day, days 1–5 every 28-day cycle, for 12 cycles. Most recently, his MRI from 47.5 months after initial biopsy and 46.9 months after LITT showed only a small cavitation with minimal enhancement and FLAIR signal, likely as a result of LITT [Figure 1b]. His neurologic examination remains normal at 51 months after initial biopsy.

DISCUSSION

CONCLUSION

In summary, we report a unique case of prolonged survival and excellent radiographic response using LITT to treat a thalamic GBM. GBM in deep-seated locations remains challenging neuro-oncological problems as resection is often not possible. The published data regarding LITT are sparse with mixed result. This case highlights the need for higher quality research regarding LITT in GBM. Moreover, this report suggests that LITT treatment in GBM may offer durable treatment response beyond the current standard of care.