Laser interstitial thermal therapy (LITT) has emerged as a potential tool in the armamentarium of neurosurgeons managing patients with deep-seated and difficult-to-access brain tumors. Advances in stereotactic neurosurgery coupled with neuroimaging tools have led to the resurgence of interest in laser therapy for a variety of neurosurgical indications. Stereotactic placement of laser probe using minimally invasive techniques and the ability to monitor the tissue ablation in real time using MR thermometry are two distinct advantages of LITT. Patients with recurrent gliobastoma multiforme (GBM) or newly diagnosed gliomas with significant medical comorbidities, radiation necrosis, radiosurgery-resistant brain metastasis and cancer-related pain pose significant challenges in the field of neuro-oncology. LITT offers an opportunity to obtain stereotactic biopsy and cytoreduction in a minimally invasive nature. In this chapter, we have described the current applications of LITT in neuro-oncology, including malignant gliomas, brain metastatic disease, radiation necrosis and other indications such as cancer-related pain and epilepsy. We have also described the principles, technical nuances and LITT systems currently available in the clinical practice. With growing interest and acceptance of LITT in neuro-oncology, we are likely to obtain high-quality evidence supporting the utility of this modality in patients with a variety of neuro-oncological conditions in the near future.
- laser therapy
- thermal therapy
- radiation necrosis
- brain metastasis
- cancer pain
Laser interstitial thermal therapy (LITT) has established itself as a new treatment modality in neurosurgery due to its minimally invasiveness nature, safety and efficacy. Nowadays, LITT has become a reality in the world of neuro-oncology [1–4], epilepsy surgery [5–7], and is also emerging as an attractive option in the fields of spine surgery [8–10] and chronic pain syndromes[10–12]. In neuro-oncology, LITT has emerged as an option for malignant gliomas, refractory brain metastatic disease and radiation necrosis. LITT is best suited, but not limited, for patients with tumors located in deep-seated, difficult-to-access areas that could develop significant postoperative neurological deficits and poor performance status with traditional microsurgical resection. It is a FDA-approved treatment option for intracranial lesions including recurrent glioblastomas . Concerning brain metastatic disease, although stereotactic radiosurgery (SRS) has become the standard of care for most patients, the failure rate associated with SRS is up to 23% [13–15]. Additionally, the potential risk of developing radiation necrosis following SRS can vary from 1.4 to 24% [16–18], and this complication can be refractory to standard therapeutic options like steroids and Bevacizumab. LITT has been effective in managing both radiosurgery-resistant brain metastasis [2, 3, 19–22] and radiation necrosis [3, 21–24].
The surgical applications of lasers are represented by three distinct functionalities of this technology: photocoagulation, photovaporization and photosensitization . LITT is referred to the first one, photocoagulation, which implies tissue damage by thermal energy provided by a source of constant and continuous laser delivery to a planned target volume. It was first introduced in 1983 by Bown and colleagues , who used a neodymium-doped yttrium aluminum garnet (Nd:YAG) laser and achieved focal tissue coagulation in an experimental brain tumor model without tissue vaporization. Research using experimental animal models demonstrated the brain tissue changes in response to hyperthermia and confirmed that coagulation necrosis could result from the application of thermal energy to brain tissue [27–30]. However, the inability to monitor and control the laser-induced thermal effects limited the widespread application of this technology. Recent advances in magnetic resonance (MR) thermography  allowed real-time image feedback of laser thermal energy delivery, making it possible to predict the thermal damage of a planned target in the brain.
In the present chapter, the authors describe the current applications of LITT in neuro-oncology, including malignant gliomas, brain metastatic disease and radiation necrosis together with the basic principles and technical nuances related to the surgical procedure and the current LITT systems available in clinical practice. We also touched upon other applications of LITT such as cancer-related refractory pain and epilepsy. Future directions are also discussed in this chapter.
2. Laser interstitial thermal therapy: principles and rationale
Treating cancers with heat energy dates back to 1960s when Rosomoff et al.  first reported the application of ruby pulsed laser beam in two patients with GBM and in experimental animals. They reported that in normal brains of experimental animals, laser application was associated with total cellular destruction with vacuolization secondary to vaporization and hemorrhage. The sensitivity to laser can be increased by Cardio-green and Evans blue injections. Whereas on brain tumors in patients with GBM, laser therapy induced cellular necrosis without hemorrhage and inflammation. Laser bursts were given at 2 min interval at estimated 3 cm depth from the cortical surface, followed by progressive 1 cm depth till approximately 9 cm depth from the surface was reached. Differential susceptibility of normal and tumor to laser application was noted in this study. However, given that the precise application and delivery of laser energy were not feasible at that time, this therapy has fallen out of favor and did not get acceptance in routine clinical practice. In 1985, Winter et al.  used microwave hyperthermia for treating brain tumors. Later, brain tumors were treated with focused ultrasound by Britt and coworkers . Following these reports, another study  investigated the use of interstitial hyperthermia and iridium brachytherapy in malignant gliomas.
Without the availability of technology to safely monitor the extent of hyperthermia, these techniques remained largely experimental and were unable to be integrated in mainstream clinical practice. When the technological advancements overcome these limitations, thermal ablation using LITT was considered as a more viable, practical and cost-effective approach in treating brain tumors in selected patients. Using LITT, otherwise surgically inaccessible tumors were made amenable to surgical ablation with good outcomes [36, 37]. Though earlier generation probes like Nd-YAG lasers had limitations such as charring of adjacent tissue, thus limiting energy penetration and uncertainties in the extent of tissue ablation [37, 38], new-generation probes have protective mechanisms to prevent charring and also use real-time MR imaging (MR thermometry) to monitor the extent of ablation for minimizing thermal damage to normal surrounding brain parenchyma.
3. Histopathological and biological effects of LITT
Delivering thermal injury with LITT causes some major biological changes in the tissues . Laser photons in the near-infrared range, when directed to the target tissue, get absorbed and converted to heat energy. Aided by abundant blood flow, conduction, convection and refraction all play a significant role in distributing the heat energy around the target tissue . The inherent biology of the surrounding structures and the physical properties of the laser determine the uniformity in the distribution of the heat applied. Ablation of the entire target lesion is the primary aim of using LITT .
Cellular homeostasis is usually not disturbed with mild elevation in temperature to approximately 40°C. However, when the temperature is increased in the range of 42 to 45°C (hyperthermia), there is a substantial increase in susceptibility to cellular damage [40, 41]. When the temperature is increased from 46 to 60°C, marked cytotoxicity and cell death ensue with considerably decreased time needed to kill the cells [42, 43]. Above 60°C, there is substantial damage to the mitochondrial enzymes, cytosol and the nucleic acid proteins that culminate to coagulation necrosis . Super boiling temperatures like 105°C results in charring, tissue boiling, vaporization, and carbonization which if not released immediately might culminate in increased intracranial pressure. Apart from the true values of the temperature used, the time of exposure to such temperatures is also important. For example, 43°C for 2 min causes reversible damage to the tissue, while the same temperature for 10 min causes permanent tissue damage and for 60 min causes coagulative necrosis [22, 45]. Based upon the Arrhenius equation, only shorter intervals are needed when using high temperatures to get the same results .
The target lesion usually undergoes central coagulation necrosis following LITT therapy, surrounded by a zone of edema next to the undamaged tissue . By the end of 1st week, granulation tissue gradually replaces the zone of necrosis. The targeted lesion then develops into a cystic lesion with remnant necrotic debris surrounded by reactive gliosis with mesenchymal deposits [47, 48].
Three distinct zones can be identified on MRI following LITT. The first central zone represents the zone of coagulation necrosis and if the temperature inadvertently exceeds 100°C, then there is a chance of charring and vaporization followed by a pseudo cavity formation. Just outside the core area lays a non-viable part with increased interstitial fluid called the intermediate zone. The outermost marginal zone is viable consisting of edematous viable surrounding brain parenchyma following thermal exposure and sharply delineates itself from the inner two zones. The ultra-structure of the inner two zones of thermal injury show disrupted organelles and evidence of apoptosis, whereas the outer zone shows only axonal swelling, neuronal shrinkage and hypertrophied endothelial cells with no evidence of vessel thrombosis [4, 49–51]. Following LITT therapy, the target lesions might exhibit an increase in size due to necrosis and perilesional edema, but eventually will shrink and form a rim of granulation tissue.
4. Technical aspects and commercially available components of LITT
4.1. MR thermometry
After numerous attempts of measuring the thermal energy delivery to the target tissue during LITT, including the use of skin thermometers, subcutaneous and interstitial probes, infrared detectors and thermographic cameras [28, 29, 52–56], it was the addition of MR thermometer that played the most significant role in allowing real-time monitoring and quantification of thermal energy delivery leading to thermal ablation . MR thermography based on the temperature-dependent water proton resonance frequency (PRF) is capable of providing visual imaging together with a quantification model of thermal deposition with accurate temporal and spatial resolution. The theory behind PRF is based on the fact that as temperature increases during LITT, the number of free H2O molecules also increases due to breakage of hydrogen bonds between H2O molecules. The hydrogen nuclei (proton) are mobilized more efficiently within the gradient field when in the free H2O molecule state, producing real-time imaging that can be interpreted and visualized using the proper computer software in the treatment workstation [57, 58].
4.2. Lasers and probes used for LITT
The two most common types of lasers used for LITT are the continuous-wave neodymium-doped yttrium aluminum garnet (Nd:YAG), with a wavelength of 1064 nm, and diode lasers with wavelengths between 800–980 nm, which operate at a wide range of powers [1, 59, 60]. Nd:YAG lasers are capable to achieve deeper tissue penetration compared to diode lasers, especially in soft tissues with high blood perfusion at wavelengths between 1000–1100 nm [59, 61]. Diode lasers have the advantage of producing lesions faster, but typically with less penetration .
LITT probes have three main components: an optical fiber with a 600 μm diameter, a heat-resistant terminal tip made of sapphire or quartz, measuring around 10 mm  and a cooling system, which is required to avoid overheating, tissue carbonization and optical fiber damage . The current cooling mechanisms use either a cooled gas system (CO2) or a constant stream of fluid (water or saline) delivered to the tip of the probe through a sheath associated to the optic fiber [60, 62]. The thermal energy delivery at the probe tip has been classically described as a symmetrical ellipsoid shape centered along the axis of the probe. Recent advances in probe design, most specifically by the NeuroBlate® System (Monteris Medical Corporation, Plymouth, MN, USA), also led to the development of side firing laser probes, which allows the surgeon to control the laser ablation of complex shaped tumors in a real-time fashion.
4.3. Commercially available LITT systems used in neurosurgery
Currently, there are two commercially available FDA-cleared LITT systems for neurosurgery in the United States: the NeuroBlate® System (Monteris Medical Corporation, Plymouth, MN, USA) and the Visualase Thermal Therapy System (Medtronic Inc., Minneapolis, MN, USA).
5. Animal models and preclinical studies
Various canine [32, 64, 65] and murine [48, 66–68] animal models of brain tumors have been used to investigate the efficacy of laser thermal therapy on tumors and surrounding brain tissue, as well as to evaluate the thermal dose models. First, animal experiments evaluating the impact of laser energy on normal murine brains can be dated back to 1960s. Fine et al.  used ruby pulsed laser delivering 100 J of energy to the forehead of mice, which resulted in a mortality rate of 75% within a day of exposure. Later, Earle et al.  showed that 20–40 J of energy delivered using ruby laser was not lethal and resulted in sub-arachnoid and intracerebral hemorrhage with minimal neurological effects. Later, Rosomoff et al.  reported similar findings using 8 J ruby laser in a rat and dog experiment models. They also reported that the sensitivity to laser could be increased by Cardio-green and Evans blue injections. Kangasniemi et al.  reported the feasibility and utility of MR-guided laser (980 nm diode) ablation of tumors (transmissible venereal tumors) in seven canines. Utility of LITT was studied in Lewis mice implanted with glioma cells  and neoplastic lesion was monitored using MRI. In addition, proliferation of implanted tumor cells, gliosis and apoptosis was monitored using immunohistological techniques. LITT caused necrosis of neoplastic cells; however, apoptosis of residual tumor cells at the margin (more vascularized compared to pre-treatment) was noted following LITT . Canine models have also been used to establish various thermal dose models, so as to reliably predict post-LITT tissue damage as well as to monitor tissue ablation in real time . Localized interstitial thermal therapy using magnetic nanoparticles (dextran- or aminosilane-coated iron-oxide nanoparticles) have been described in a rat model of GBM . Interestingly, rats treated with aminosilane-coated nanoparticles showed improvement in survival (4.5 times prolongation), whereas those treated with dextran-coated particles did not show any difference in survival compared to controls. These animal experiments paved a way to the development of LITT and future therapeutic options for gliomas.
6. Use of LITT in gliomas
High-grade glioma or glioblastoma multiforme (GBM, WHO grade IV), in particular, is a significant clinical challenge in the field of neuro-oncology with a high rate of morbidity and mortality. GBM constitutes approximately 45% of all malignant primary glial neoplasms . Gross total surgical resection with concurrent chemo-radiotherapy is the mainstay treatment modality for this aggressive tumor . However, even with the best available treatment options, 5-year overall survival (OS), progression-free survival (PFS) and median survival have been reported to be 9.9%, 6.9 months and 14.6 months, respectively [59, 71, 72]. The median survival decreases to 12.1 months with post-resection radiotherapy alone instead of concurrent chemo-radiotherapy and to 6.2 months in patients with progressive disease following standard treatment regimen [71, 72]. There is controversial data regarding optimal management (surgical vs. medical) in patients with recurrent GBM. Extent of resection greater than 80% has been shown to have improved overall survival in carefully selected patients with recurrent GBM [73–75]. Young patients with good performance status have been shown to have improved overall survival following surgical resection for recurrent GBM [76, 77]; however, after adjusting for age, no significant benefit was achieved following repeat surgery . In addition, redo craniotomy for progressive GBM is associated with increased risk of per-operative complications including neurological deficits (18–22%) [78, 79]. Also, there is a cumulative risk of these complications following each craniotomy with maximum risk between first and second procedures . There is insufficient evidence supporting the role of radiosurgery, stereotactic fractionated radiation therapy or interstitial brachytherapy in patients with recurrent GBM [81, 82]. Of note, radiosurgery has also been shown to be associated with increased toxicity in patients with recurrent disease . Survival benefit of 9.3 months have been reported in patients (good performance status) receiving interstitial brachytherapy for recurrent GBM . Given a high incidence of this primary brain tumor with lack of effective therapies and dismal outcome, significant research is directed toward developing effective medical and surgical treatment modalities to improve overall and progression free survival. Laser interstitial thermal therapy (LITT) is one of the advancements in the surgical management of these tumors. LITT is a minimally invasive procedure, which involves stereotactic-guided placement of laser probe and utilizes thermal energy to cause protein coagulation and cell death [83, 84]. Advances in neuroimaging coupled with stereotactic techniques have led to the resurgence of interest in the utility of laser thermacoagulation in patients with brain tumors. In addition, integration of MR thermography to LITT made it possible to deliver thermal energy under real-time monitoring, thus avoiding injury to surrounding normal brain tissue . Given these advantages of LITT, this technique has been utilized for a variety of neurosurgical indications such as deep-seated gliomas [1, 4, 86, 87], epilepsy [20, 88], brain metastasis with radiation necrosis [19, 23, 24, 49] and cingulotomy for intractable pain [12, 89].
First report of utilization of Nd-YAG laser thermal therapy in five patients with deep-seated brain tumors was published in 1990 . Later, several studies with a smaller (
Although there is no Class 1 evidence supporting the efficacy of LITT in patients with high-grade gliomas, there is also paucity of high-quality data supporting the role of craniotomy and surgical resection in such patients . Given the minimally invasive nature of LITT coupled with advances in neuroimaging stereotactic techniques and thermography, LITT can be a useful treatment modality in patients with poor performance status or medical comorbidities and high-grade glioma. The advantages of LITT have led to the exploration of this technique for a variety of intracranial tumors. LITT has been investigated in various prospective case-controlled studies and there is a likelihood to have Class 2 evidence data in the next couple of years.
7. Use of LITT in brain metastasis and radiation necrosis
Brain metastasis is a common and challenging clinical scenario affecting up to 40% of patients with systemic malignancies [100–102]. Lung carcinoma (16–19%) is the leading systemic cause of brain metastasis followed by renal (6–9%), melanoma (7–7.4%), breast (5%) and colorectal cancers (1.2–1.8%) [103, 104]. Prognosis in patients with brain metastasis is often dismal, due to limited therapeutic options. Majority of chemotherapeutic agents and targeted immunotherapies do not cross the blood brain barrier, hence limited applicability of these agents in management of patients with brain metastasis. Stereotactic radiosurgery (SRS) has emerged as a primary therapeutic modality in patients with single or multiple brain metastases with an improvement in overall survival and quality of life [13, 14, 105, 106]. However, there is a subset of patients (up to 23%) who fail SRS with progression of metastatic disease and subsequent mortality [13, 15]. Brain metastasis from radio-resistant systemic tumors such as renal cell carcinoma, sarcoma, melanoma and triple negative breast carcinoma carries a worse prognosis, despite better control rates with SRS as compared to conventional radiotherapy . Stereotactic radiosurgery is also associated with adverse radiation effects (AREs) with a 1-year cumulative incidence of 13–14%, which increases with size and volume of the tumor [108–111]. Of these adverse radiation effects, radiation necrosis (RN) is the most challenging in terms of diagnosis and management with a reported incidence ranging between 1.4% and 25% [16–18, 112]. Imaging modalities such as MR perfusion, MR spectroscopy, 6-[(18)F]-fluoro-L-3,4-dihydroxyphenylalanine (F-DOPA)/FDG PET, l-methyl-(11)C-methionine ((11)C-MET) and SPECT scan have been shown to be useful in differentiating radiation necrosis from recurrent metastasis or tumor [113–116]. The sensitivity, specificity, accuracy of perfusion MRI and F-DOPA PET have been reported to be 86.7, 68.2, 75.6 and 90, 92.3, 91.3%, respectively . SPECT scan has been shown to have the highest specificity of 97.8% (sensitivity 87.6%) for differentiating tumor progression and radiation necrosis and may be preferred over other imaging modalities . Medical therapeutic options for RN include corticosteroids, Bevacizumab, hyperbaric oxygen therapy, anticoagulation (heparin or warfarin) or vitamin E [117–125]. Surgical resection of RN can be considered in symptomatic patients with mass effect in accessible areas . Therefore, there is always a scope for newer treatment strategies in the management of patients with brain metastasis to improve the clinical outcomes. LITT is a minimally invasive technique that offers an alternative therapeutic option in patients with either SRS-failed or radio-resistant brain metastasis. LITT also offers an opportunity to have a histological diagnosis before laser ablation in cases of suspicion between recurrence of metastasis and radiation-related changes. The minimally invasive nature of this technology permits its utility in patients with multiple medical comorbidities with poor Karnofsky performance status (KPS) and tumors in difficult-to-access locations.
First use of laser therapy for brain metastasis was reported in 1986, with successful-laser assisted ablation of a midbrain metastasis from primary lung adenocarcinoma . In 1990, Sugiyama et al.  reported the utility of laser in patients with deep-seated tumors including metastasis. Later, Schulze et al.  studied the histological effects of laser thermotherapy in seven patients with brain metastasis and eight patients with glial tumors. In this study, authors reported that laser therapy created a unique pattern of architectural changes at the histological level with central zone of necrosis surrounded by edematous tissue. This surrounding edematous tissue tends to undergo cystic changes following regenerative and resorptive changes . In addition to thermal coagulation, laser-induced tumor damage is caused by disruption of cellular membranes and organelles. Authors advocated this technique in older patients with significant medical comorbidities and brain tumors. First pilot clinical trial investigating the safety and feasibility of LITT in patients with resistant focal metastatic brain tumors was reported in 2008 . Four patients with six metastatic brain tumors (temporal lobe,
Another study reported progression-free and overall median survival of 5.8 months each following LITT in five patients with metastasis (non-small cell lung carcinoma,
Torres-Reveron et al.  reported the utility of LITT in six patients with progressive brain metastatic tumors (non-small cell lung cancer,
A recent study reported delayed failure in two patients who underwent LITT following tumor progression and refractory cerebral edema after SRS [23, 49]. LITT was performed 7 months (breast adenocarcinoma) and 14 weeks (lung adenocarcinoma) after stereotactic radiosurgery. Patient with lung adenocarcinoma metastasis to the external capsule had significant perilesional edema following radiosurgery and also experienced severe side effects secondary to steroid therapy (refractory hyperglycemia, weight gain and bilateral proximal muscle weakness), therefore LITT was considered 14 weeks after SRS . This patient had significant clinical improvement and steroid was weaned off in 2 weeks following ablation therapy. However, first patient with parietal metastasis and second patient with external capsule metastasis demonstrated tumor recurrence at 6 and 11 months, respectively, which was histologically confirmed following surgical resection . A recent review based on pooled 25 patients with brain metastasis who were treated with LITT reported a median overall survival (OS) of 12.6 months (range 9.0–19.8 months) and progression-free survival (PFS) to vary between 3.8–8.5 months . Severe complication rate was reported to be 8% and included events such as perioperative hemorrhage (non-surgical) and blood suffusion. Intracranial progression of disease (excluding local progression, 8%) and extra cranial progression as the etiology of mortality was reported in 36 and 55% of patients respectively following LITT for brain metastasis. Median survival time (9.0–19.8 months) and severe complication rate of 8% following LITT are similar to 1.4–16.1 months and 6–19%, respectively, following surgical management of brain metastasis . Given these comparable outcomes, LITT is an effective therapeutic option for patients with resistant brain metastasis in difficult-to-access areas. There is a paucity of literature on the utility of LITT in patients with radiation necrosis (RN). It is often difficult to distinguish patients with radiation necrosis and those with tumor recurrence following stereotactic radiosurgery. Therefore, the majority of reported cases could represent a mixture of these clinical conditions, even following stereotactic biopsy. In an anecdotal report, LITT was used for diagnosed RN following stereotactic biopsy (may represent a mixed lesion), as patient was refractory and not able to tolerate standard medical management (steroids and bevacizumab) for suspected RN . Patient developed several steroid-related complications along with several medical comorbidities. In light of these facts and the presence of a lesion in a difficult-to-access area (left centrum semiovale), LITT was considered in this patient with RN following SRS for brain metastasis (non-small cell lung carcinoma). As demonstrated in earlier reports, there was a significant improvement in clinical symptoms following LITT and patient was weaned off the steroid in 2 weeks after the procedure. However, there was a mild increase in size of lesion with no significant FLAIR signal changes at 7 weeks postoperative MRI, which was consistent with the literature.
Patel et al.  reported the utility of LITT in patients with a variety of intracranial pathologies including patients with recurrent metastasis or radiation necrosis (
LITT has shown initial promising results in patients with recurrent brain metastasis and RN (to some extent) following SRS. However, long-term prospective randomized controlled studies are warranted and required to validate the efficacy of LITT for these clinical indications.
8. Use of LITT in other intracranial tumors
Jethwa et al.  reported the application of Visualase laser system in 20 patients (33 procedures) with a variety of intracranial tumors over a period of 1 year. GBM was the most common pathology treated (
9. Use of LITT in cancer-related pain
Cancer-related pain is a significant clinical problem affecting up to 60–90% of patients with cancer in terminal stages . The first line of management in such patients is pharmacological including opioids; however, 10–20% of such patients are refractory to medical line of management and thus requires intervention for pain management [131–133]. Various neuromodulation and ablative procedures such as intrathecal morphine, myelotomy, cordotomy, DREZotomy, sympathetic blocks, paravertebral blocks and cingulotomy have been described for pharmacological-resistant, cancer-related and various refractory pain syndromes [131–137]. Ablative cingulotomy using radiofrequency  and neuromodulation using DBS  has been described in patients with various refractory pain syndromes. With the advances in neuroimaging and stereotactic techniques and introduction of LITT, this technique has been explored in patients with pharmacoresistant cancer-related pain [12, 98]. Patel et al.  describe the feasibility of MRgLITT in three patients (four procedures) with cancer-related pain. Ablation coordinates used in patients who underwent first-time ablation includes
Another recent study reported the utility of LITT in five patients with chronic pain syndrome . Total operative time and ablation time were 2.9±0.3 h and 4.3±0.6 mins, respectively. No postoperative complications were noted following LITT in patients with chronic pain . Outcomes in terms of pain control was not reported in this study .
10. Use of LITT in epilepsy
Pharmacoresistant or drug-resistant epilepsy (DRE) is a significant clinical challenge with prevalence of approximately 28 to 40% in patients with epilepsy [139, 140]. In addition, approximately 10% of pediatric patients with epilepsy meet the criterion of DRE within 18 months of diagnosis . Epilepsy surgery has been shown to have beneficial long-term effects in terms of seizure control (seizure free outcome rate of 67 and 26% at 5 and 15 years follow-up, respectively) and psychosocial outcomes in patients with DRE [141–143]. Based on a recent meta-analysis, the incidence of neurological deficits, permanent neurological deficits, wound infection/meningitis following temporal lobectomy with/without amygdalohippocampectomy and extratemporal lobar/multilobar resections have been reported to be 5.2, 0.8, 1.1 and 19.5, 3.2, 1.9%, respectively . The complication rates have been shown to increase from 10% during first resective surgery in pediatric patients with complex refractory epilepsy to 50% during second respective surgery . Given this success of epilepsy surgery in controlling seizures with associated morbidity in patients with DRE, there is always a need to improvise on surgical techniques so as to reduce the morbidity while improving the outcomes. Introduction of MRI-guided LITT in neurosurgery over the past decades have paved a way to exploration of this technique in patients with DRE. MRgLITT is a minimally invasive stereotactic technique that can be used to ablate the epileptogenic zone and associate fibers so as to simulate the resection and disconnection procedures, respectively. FDA approved Auto LITT in 2009, following a successful Phase 1 multicenter trial investigating the safety of this system in patients with recurrent GBM. In 2012, Curry et al.  first reported the use of MRI-guided (1.5T) LITT (Visualase thermal system) in five patents with DRE. In this study, they ablated six epileptic zones (cingulate tuber
11. Future trends
FDA approved AutoLITT in 2009, following a multicenter trial investigating the efficacy of this modality in patients with recurrent GBM. Laser ablation has currently been investigated as a potential treatment modality in patients with failed stereotactic radiosurgery for brain metastasis (NCT01651078, Laser Ablation after Stereotactic Radiosurgery, LAASR study). Following these results, LITT is likely to be explored in other areas of neuro-oncology.
12. Our experience
At Cleveland clinic we have an experience of about 150 patients, who underwent LITT for a variety of indications since 2011. At our center, we use NeuroBlate® System (Monteris Medical Corporation, Plymouth, MN, USA) with a side firing probes (Figure 1). Regarding intra-axial tumors, we have used LITT in 30 patients with de novo GBM, 24 patients with recurrent GBM (following standard treatment), 22 patients with recurrent anaplastic tumors, upfront in 10 patients with anaplastic tumors, 24 patients with low-grade gliomas (7 upfront and 17 recurrent). We have also used this modality in 17 patients with radiation necrosis and 15 patients with metastasis. We are also participating in a multi-institutional study investigating the role of this modality in patients with failed SRS (LAASR study). We have also utilized this therapy in patients with recurrent meningioma (
LITT is a stereotactic minimally invasive technique that involves ablation of pathological tissue using laser energy. This technique has shown promising results in a variety of neuro-oncological conditions such as recurrent GBM, upfront deep-seated GBM, recurrent metastasis following SRS, radiation necrosis and cancer-related pain. LITT was approved by FDA in 2009 for unlimited intracranial usage. Minimally invasive nature of the therapy coupled with real-time monitoring of thermal ablation are distinct advantages of LITT over traditional surgical approaches, especially for deep-seated tumors in patients with significant co-morbidities. Currently, there is Level III /Level IV evidence in the literature supporting the role of LITT in patients with recurrent GBM/high-grade gliomas, metastasis and radiation necrosis. There is a paucity of data regarding other indications of LITT. However, trials are underway and are likely to provide significant level of evidence supporting the efficacy of LITT in a variety of the above-mentioned indications in coming years.
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