Outcomes in Patients Treated with Laser Interstitial Thermal Therapy for Primary Brain Cancer and Brain Metastases

Laser interstitial thermal therapy (LITT) is a novel therapy for addressing radiation necrosis and local tumor progression. This article focuses on a possible noninvasive approache for assessing patients to establish an accurate diagnosis and guide optimal management.

Abstract

Laser interstitial thermal therapy (LITT) is an emerging modality to treat benign and malignant brain lesions. LITT is a minimally invasive method to ablate tissue using laser‐induced tissue heating and serves as both a diagnostic and therapeutic modality for progressive brain lesions. We completed a single‐center retrospective analysis of all patients with progressive brain lesions treated with LITT since its introduction at our center in August of 2015. Twelve patients have been treated for a total of 13 procedures, of which 10 patients had brain metastases and 2 patients had primary malignant gliomas. Biopsies were obtained immediately prior to laser‐induced tissue heating in 10 procedures (76.9%), of which seven biopsies showed treatment‐related changes without viable tumor. After laser ablation, two of three patients previously on steroids were successfully weaned on first attempt. The results of this analysis indicate that LITT is a well‐tolerated procedure enabling some patients to discontinue steroids that may be effective for diagnosing and treating radiation necrosis and tumor progression.

Introduction

Laser interstitial thermal therapy (LITT) is a minimally invasive neurosurgical method to ablate tissue using laser‐induced tissue heating and is an emerging diagnostic and therapeutic modality for progressive brain lesions. The risks of LITT include neurologic deficits related to ablation of eloquent tissues, treatment‐related edema, intracranial hemorrhage, and wound infection. Thin laser fiber probes allow for safe access to the lesion in question, and biopsies can be obtained to help establish a diagnosis intraoperatively. Several barriers prevented its use in the central nervous system (CNS), particularly the ability to accurately and efficiently place laser fiber probes into the brain to monitor rising tissue temperatures spatially. The development of image‐guidance platforms, including magnetic resonance imaging (MRI) thermography, allowed accurate targeting and monitoring of CNS lesions [1]. This thermography is crucial to allow heating of target neoplastic tissues to threshold temperatures for tissue death while limiting thermal injury to crucial CNS structures. This combination of surgical stereotactic laser fiber placement to thermally ablate tissues via LITT is a U.S. Food and Drug Administration‐approved minimally invasive procedure. LITT was introduced as a diagnostic and therapeutic option at the University of Michigan in August of 2015. Given the relative novelty of the procedure, there is a paucity of data on the patient characteristics, clinical outcomes, toxicities, and correlations between pathologic and radiologic features in patients with cancer who have undergone LITT for progressive brain lesions [2].

LITT provides a novel therapeutic opportunity for addressing both radiation necrosis and local tumor progression. Following focal high‐dose radiation, radiation‐related treatment effects or radiation necrosis may be observed, manifesting as enlargement of the treated, contrast‐enhancing lesion on standard MRI [3]. Treatment effects are difficult to distinguish from actual tumor progression, which has a similar appearance. The gold standard to distinguish between these two scenarios is biopsy; however, obtaining tissue previously required invasive craniotomy, for which a minority of patients are eligible. Therefore, there is a critically unmet need to identify noninvasive approaches for assessing patients with these imaging findings after treatment to establish an accurate diagnosis and guide optimal management.

Materials and Methods

We identified cancer patients who have undergone LITT when clinically indicated for treatment of progressive contrast‐enhancing lesions at the University of Michigan Rogel Comprehensive Cancer Center since the procedure was introduced in August 2015. Institutional review board approval was obtained. Demographic and clinical features were obtained for the study population.

Results

Twelve patients underwent LITT at our institution for a total of 13 procedures performed by two neurosurgeons (Table 1). One patient underwent two LITT ablations on separate dates approximately 7 months apart for anatomically distinct lesions and locations. Of these 12 patients, 10 had brain metastases from solid malignancies and 2 had glioblastoma multiforme. Non‐small cell lung cancer was the most commonly treated histology (6 patients, 50%). The median age of patients on the day of the LITT procedure was 58.4 years, and 66.7% of treated patients were female. All but one patient received focal radiation prior to LITT, and the majority of patients received multiple prior therapies. The most common site of LITT ablation was in the frontal cortex (7 procedures, 53.8%), and both supratentorial and infratentorial lesions were treated. Biopsy for intraoperative frozen section, followed by formal pathology review, was obtained in the majority of procedures (10 procedures, 76.9%) prior to laser‐induced tissue ablation. Pathology revealed treatment effect in seven cases and viable tumor in three cases.

Table 1. Clinical and demographic features of 12 patients treated with LITT for progressive brain lesions.

^a13 lesions treated in 12 patients.

^bMedian calculated for 12 procedures, as one patient was lost to follow‐up.

^cTreatment given for subsequent progression of disease during the course of follow‐up for this study.

Abbreviations: CNS, central nervous system; GBM, glioblastoma multiforme; LITT, laser interstitial thermal therapy; NSCLC, non‐small cell lung cancer.

Three patients were on steroids prior to LITT for a median duration of 70 days (range, 7–83). Of those, two (66.7%) were able to taper off steroids during the initial attempt. All nine additional patients were started on steroids after LITT per standard protocol, and six were successfully weaned on initial steroid taper. The median duration of post‐LITT steroids was 32 days, with a range of 6–300. One patient was lost to follow‐up and not included in this calculation. Reasons for failure of initial taper included seizure (grade 3) and worsening weakness (grade 2).

Focal motor weakness was the most common neurologic impairment after LITT in four patients, for which three patients required inpatient rehabilitation stays to regain function prior to discharge home. One of these patients had weakness prior to LITT and another had preceding ambulatory dysfunction. All four patients who developed weakness had lesions that were either in, immediately adjacent, or near the motor cortex or corticospinal motor tracts.

Of all patients who underwent LITT at our institution, four have subsequently died (33.3%), including one from unknown causes 8.1 months after LITT, one from pulmonary hemorrhage 27.4 months after LITT, and two from progression of intracranial disease 9.9 months and 19.4 months, respectively, after LITT (Table 2).

Table 2. Individual patient characteristics.

^aOne patient underwent 2 LITT ablations on separate dates approximately 7 months apart for anatomically distinct lesions and locations.

^bLost to follow‐up shortly after LITT procedure and declined further therapy.

^cBevacizumab used for systemic disease.

Abbreviations: B, bevacizumab; C, chemotherapy; CNS, central nervous system; Dex, dexamethasone; GBM, glioblastoma multiforme; I, immunotherapy; L, LITT; LITT, laser interstitial thermal therapy; N, none; N/A, not applicable; NSCLC, non‐small cell lung cancer; OS, overall survival; R, resection; SRS, stereotactic radiosurgery; Tx, treatment; X, radiation.

Discussion

Our findings indicate that LITT is a well‐tolerated procedure, allowing some patients to discontinue steroids, that may be effective for diagnosing and treating radiation necrosis and tumor progression. In the setting of suspected radiation necrosis, deciding between bevacizumab, LITT, or observation is complex. Patients selected for LITT were those for whom there was (a) increasing size of contrast enhancement, (b) diagnostic uncertainty between necrosis/treatment effects and recurrent tumor, (c) an increasing concern of the possibility of recurrence, and (d) progressive symptomatology.

Interpretation of post‐LITT imaging remains an area of active research. Contrast‐enhancing volume increases after LITT on the 3‐month postoperative MRI and then gradually starts to decrease over the 6‐month and 1‐year MRIs in patients who are responsive to LITT. Similarly, diffusion imaging shows initial increased diffusion restriction on diffusion weighted imaging in the center of the lesion, likely due to the central area of necrosis of the lesion, and then diminishes over time.

The analysis is limited by sample size and its retrospective, single‐institution design. Ultimately, well‐designed randomized trials comparing treatment modalities are needed to further elucidate the efficacy and safety of this novel therapy.

See http://www.TheOncologist.com for supplemental material available online.

Disclosures

Aki Morikawa: Novartis, Eli Lilly & Co, Takeda (RF); Jason Heth: Northwest Biotherapeutics, Tocagen (RF). The other authors indicated no financial relationships.

(C/A) Consulting/advisory relationship; (RF) Research funding; (E) Employment; (ET) Expert testimony; (H) Honoraria received; (OI) Ownership interests; (IP) Intellectual property rights/inventor/patent holder; (SAB) Scientific advisory board.