Stereotactic Laser Ablation of High-Grade Gliomas

Ammar H. Hawasli, M.D., Ph.D.; Albert H. Kim, M.D., Ph.D.; Gavin P. Dunn, M.D., Ph.D.; David D. Tran, M.D., Ph.D.; Eric C. Leuthardt, M.D.

Disclosures

Neurosurg Focus. 2014;37(6):e1 

In This Article

Results

Article Selection

The preliminary search for the use of laser therapy for brain tumors yielded 145 abstracts. After exclusion of nonhuman studies, expert opinions, and review articles lacking direct clinical data, 28 articles were identified. Each article was reviewed in detail and 10 were excluded for absence of HGGs, yielding a total of 18 eligible human clinical research publications on the use of laser ablation to treat HGGs ( Table 1 ). The studies published between 1990 and 2014 included a total of 230 patients and were case series and case reports without control cohorts. Although some patients were probably reported in more than one manuscript, duplication in data used between clinical studies was not easily ascertainable and could not be confirmed.

Treatment of HGGs With Stereotactic Laser Ablation

In the 18 eligible studies reviewed, 174 HGGs were reported to have been treated with LITT. The WHO grade was reported in 15 studies (Table 1). Glioblastomas (WHO Grade IV) and anaplastic gliomas/oligodendrogliomas (WHO Grade III) accounted for 106 (66%) and 55 (34%) patients, respectively. The number of patients with newly diagnosed versus recurrent tumors was available in 12 of 18 studies. Fifty-three patients (34%) were treated up front (de novo) for newly diagnosed HGGs, and 105 patients (66%) were treated with salvage therapy for recurrent HGGs. Twelve manuscripts reported tumor locations: 39 (38%), 16 (16%), and 15 (15%) of the 103 HGGs in which location was reported were located in the frontal, temporal, and parietal lobes, respectively. Twenty-one (20%) of these 103 HGGs were located in difficult to access locations, including 12 in the thalamus (12%), 5 in the corpus callosum (5%), 2 in the insula (2%), 1 in the basal ganglia (1%), and 1 in the midbrain (1%). Pretreatment tumor size measurements were either reported as maximum diameters or volumes in 11 studies. Maximum diameters ranged from 1 to 3.5 cm and volumes ranged from 0.37 to 68.9 cm3. Treatment times were reported as either laser times or total operative times (Table 2). Laser times ranged from 1.5 to 40 minutes and operative times ranged from 2 to 16 hours. Early publications subjectively reported that ablation covered the entire enhancing portion of the tumors. Recent reports have provided quantitative coverage data. Although thermal distribution data varied, recent authors reported treatment of tumor periphery at 42°C–45°C. Although there is probably some patient duplication among studies and some variation in laser technologies, laser wattages, intraoperative temperature monitoring, and other therapies received during the studies, the cumulative data offered valuable information about the potential use of LITT for the management of HGGs.

Radiographic Outcomes After Treatment of HGGs With Stereotactic Laser Ablation

The radiographic outcomes after LITT for HGGs were reported in 16 of 18 studies (Table 3 and Table 4). Not all reported patients who received LITT for HGG underwent follow-up imaging, and radiographic follow-up for each patient was difficult to assess. In 3 studies, only immediate radiographic outcomes were reported. Five studies reported the presence of central necrosis of the tumor after ablation in at least 53 patients, as demonstrated on T1- and T2-weighted MRI sequences. Gadolinium enhancement of the tumor periphery shortly after LITT was reported in 4 studies and 47 patients with HGG. Ten articles reported decreases in HGG size after ablation in at least 51 patients. Reduced tumor size on neuroimaging was reported 0.5–10 months after LITT.[7,13,62–65] Kahn et al. and Hawasli et al. reported 15%–87% and 67% decreases, respectively, in tumor size after LITT on follow-up imaging.[27,32] At least 22 patients showed no recurrence during the study duration. Sakai et al. and Reimer et al. reported radiographic recurrences at 15, 8, and 6 months post-LITT.[58,60] Hawasli et al. reported radiographic recurrences in 5 of 11 patients at a mean of 6.2 months post-LITT.[27] Mohammadi et al. reported radiographic progression in 23 patients with 5 central, 12 peripheral, and 6 distant recurrences.[44] Hence, immediate radiographic analyses generally showed initial treatment effects including central tumor necrosis and peripheral enhancement. Despite reporting variability, several studies showed a reduction in HGG size, ranging from within days of LITT to within 33 months. These radiographic findings suggested that laser ablation is a potential treatment option for patients with HGGs.

Clinical Outcomes After Treatment of All HGGs With Stereotactic Laser Ablation: Overall Analysis

Clinical outcomes after LITT for all HGGs (both newly diagnosed and recurrent HGGs) were reported in 12 of 18 studies reviewed. Some studies reported individual times until cancer progression, time until death, and time until neurological deterioration. Other articles provided overall median or mean values for their cohorts. Individual results were reported in 6 studies. In these, tumor progression for all HGGs was reported at 2.6–15 months after LITT. Times until death due to tumor progression were reported at 4.1–23 months after LITT (Table 3). The median or mean clinical outcome statistics were reported on LITT for HGG in 6 manuscripts. In patients with HGG treated with LITT, overall median or mean progression-free survival ranged from 1 to 17 months post-LITT. The median or mean overall survival post-LITT ranged from 6.9 to 30 months.[13,27,38,41,44,64,65,67] Most recently, Mohammadi et al. reported a 1-year estimated survival after LITT for mixed recurrent and newly diagnosed HGGs at 68% and overall progression-free survival at 5.1 months post-LITT.[44] Several authors have noted similar factors that contribute to better response to LITT. Consistent with traditional surgery, Mohammadi et al. found that a greater extent of ablation (i.e., gross-total ablation) increased progression-free survival from 4.6 to 9.7 months post-LITT.[44] In addition to greater extent of ablation, higher-dose LITT may also be associated with improved radiographic responses and clinical outcomes.[27,41,67]

Eleven studies reported a total of 52 complications, some more severe than others. For the most common complications in the overall cohort of 174 patients, there were 4 reports of cerebral edema (2%), which typically improved with time and steroid therapy; 30 reports (17%) of neurological deficits or injury (many transient); and 6 (3%) reports of infection. Karnofsky Performance Scale (KPS) data were reported in 9 studies (Table 5). Preoperative KPS scores ranged from 0 to 100 and, when reported, postoperative KPS scores ranged from 40 to 90.

The varying reporting measures, mixed patient cohorts, mix of newly diagnosed and recurrent tumors, often lower performance statuses, difficult tumor locations, and duplication undoubtedly make interpretation of these data difficult. These limitations are magnified by adjuvant therapies and their potential effects on outcomes and by varying times of total follow-up (Table 5). Nonetheless, outcome results from these heterogeneous studies with mixed recurrent and newly diagnosed WHO Grade IV HGGs highlight LITT as a potential treatment option for HGGs. Furthermore, when taken as a whole, the cumulative data suggest that gross-total LITT may provide some benefit for patients with HGG who do not qualify for traditional surgical options. Therefore, the current combined data show suggestions of clinical benefit and provide equipoise for better-controlled clinical investigations.

Stereotactic Laser Ablation for WHO Grade III Versus Grade IV HGGs

The LITT data for HGGs often included both Grades III and IV tumors as mixed cohorts. One-third of the tumors treated were Grade III. Given the differences in pathology and outcomes between grades, this mixture makes interpretation of data somewhat difficult. Fortunately, several authors have reported separate outcome measures for the 2 grades or have only included WHO Grade IV tumors in their case series. Lumenta et al. and Leonardi and Lumenta reported that median progression-free survival for WHO III HGGs was 17 and 10 months post-LITT, respectively.[38,41] Leonardi and Lumenta found that overall survival for WHO Grade III tumors was 20 months post-LITT.[38] Several authors reported WHO Grade IV–specific outcome data.[13,38,41,64,65,67] Progression-free survival for WHO Grade IV HGGs ranged from 1 to 5 months post-LITT. Overall survival post-LITT ranged from 7 to 15 months.

Stereotactic Laser Ablation as a Salvage Therapy for Recurrent HGG: Subgroup Review

Repeat resection plus chemotherapy increases survival for patients with recurrent HGGs from 6 months to 9 months when compared with chemotherapy alone.[5] Unfortunately, not all patients are candidates for open surgery. For these individuals, several groups have enrolled patients in clinical trials to evaluate whether adding minimally invasive LITT could improve outcomes when compared with chemotherapy alone. Twelve articles reported the use of LITT for 106 patients with recurrent HGGs (Table 6). Eight articles reported outcomes for salvage-specific HGG treatments and 4 did not. In 6 articles, only patients with recurrent HGGs were reported. Among the largest cohorts, Leonardi and Lumenta reported results on recurrent HGGs and stratified by tumor grade. Leonardi and Lumenta report that the mean progression-free survival for recurrent Grade III and IV HGGs was 10 and 4 months, respectively.[38] The mean overall survival for recurrent Grade III and IV HGGs was 30 and 9 months, respectively.[38] Schwarzmaier et al. reported that the overall survival of 16 patients with recurrent HGG after LITT was 11.2 months.[65] Carpentier et al. reported that overall survival among 4 patients with HGGs was 10 months after LITT.[13] Most recently, Sloan et al. reported that survival in patients treated with salvage high-dose LITT was 15.2 months.[67] Hence, subgroup analysis of recurrent HGGs found that treatment with LITT may lead to an overall survival of 9–15.2 months after treatment. Although adjuvant therapies are probably contributing to this promising outcome, it appears to be similar to previously published survival rates seen with traditional open surgery and chemotherapy. These data suggest that LITT may serve as a viable salvage treatment.

De Novo Stereotactic Laser Ablation for Newly Diagnosed HGGs: Subgroup Review

Retrospective data suggest that GTR of newly diagnosed HGGs increases median survival from 8 to 13 months.[12] This has been corroborated by prospective Level II evidence that greater extent of resection of HGGs improves both quality of life and length of survival.[11] Unfortunately, not all patients with HGGs are candidates for a craniotomy for tumor resection. In 5 studies, authors reported treating a total of 40 patients with newly diagnosed HGGs (de novo therapy; i.e., first-time therapy). Although it was not consistently reported, most were treated with LITT rather than open traditional resection due to tumor location or patient factors preventing open resection. Reporting of de novo–specific therapy outcomes is even more sparse and difficult to interpret than for recurrent lesions. Sakai et al. treated a parietal newly diagnosed de novo tumor and reported no evidence of progression or recurrence at 12 months post-LITT (Table 3).[60] Hawasli et al. reported recurrence at 2.6 and 3.2 months in 2 of 7 patients with de novo lesions, but had a short study window for 3 of 7 patients.[27] One of 7 patients died at 4.1 months due to tumor progression. Despite the data available for all HGGs, outcome data on de novo–treated HGGs is very sparse. Therefore, without additional clinical experience, it is difficult to draw any specific conclusions about this subset of patients.

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