Laser interstitial thermal therapy (LITT) is a neurosurgical technique that is becoming increasingly popular in the pediatric population2,3. PLGGs commonly involve deep and eloquent regions; such as thalamic or thalamo-peduncular, periventricular, and other subcortical locations. The approach to these locations may necessitate crossing functional pathways. The ability to approach these lesions in a minimally destructive manner using an optic fiber to ablate the lesion is appealing. A recent review of LITT in the pediatric population, including 303 pediatric LITT procedures across 35 studies, found that brain tumors were the 2nd most common indication for LITT after epilepsy2. LITT was used mainly for deep-seated PLGG, in the periventricular zone or in the thalamus2. The largest series published on LITT for pediatric brain tumors, by Arocho-Quinones et al, reported multi-center results on 86 pediatric patients8, most of them with low-grade (WHO grade I or II) histology8. 83% of the low-grade tumors demonstrated volume reduction at the latest follow-up, suggesting LITT is effective in the management of pediatric low-grade tumors8.
Complications:
Although LITT is a minimally invasive procedure, it still carries a risk of complications. The exact rate of complications varies between different studies, but one recent analysis of a US national inpatient sample database found a complication rate of 13% and a mortality rate of 2.5%9. Similarly, a review of LITT in the pediatric population by Zeller et al. found an overall complication rate of 15.8%, with a 19.1% complication rate in the pediatric tumor subgroup2. Arocho-Quinones et al. reported a higher complication rate of 26.7%, most of which were temporary8. The mortality rate in their study was 2.3%, with 2 out of 86 cases resulting in death8. These complication rates are comparable to the reported complication rate in adult LITT series10–12.
Complications during tumor ablation can be categorized into three main groups. The first category includes surgical approach-related complications, such as intracranial hemorrhage or suboptimal catheter placement, which can lead to incomplete tumor ablation. The second category comprises hyperthermia-related neurological injuries that can occur during the ablation process. The extent of these injuries depends on the location of the tumor and relation to eloquent areas and the surgeon's experience. This category also includes temporary neurological deficits due to post-ablation edema that resolves within a few weeks. The final category includes technical complications related to the laser system2,13.
Extent of resection vs. ablation
The advantages of LITT should be weighed against the ability to achieve complete ablation of the lesion, which depends on several factors, such as the size and shape of the lesion, location, and consistency (heat conductance) (table 3). It has been repeatedly shown in PLGG that the long-term oncological outcomes are superior with GTR compared to STR14. When considering LITT, it is assumed that complete ablation of a tumor is equivalent in terms of local control to resection. A limitation of LITT is that it relies on a statistical thermal damage estimation (TDE) model to predict the area of ablated tissue and intact tumor cells that might be left in the periphery of the ablated zone15. Due to the energy absorption/penetration properties of brain tissue at the used laser wavelength (980nm with Visualase or 1060nm with Neuroblate), the maximal diameter that can be ablated around a single fiber is up to 18 mm using the Visualase (Medtronic) probe and up to 3cm using the Neuroblate (Monteris) probe. By using serial ablations along the fiber tract, an elongated cylinder of ablated tissue can be created. Large and irregularly shaped lesions can also be targeted using multiple fibers, however, this adds both risks and cost, which in some countries might be a significant limiting factor13. Cystic lesions may be less favorable as the fluid in the cyst serves as a heat sink and dumps the effect of the ablation beyond it.
It should also be kept in mind that in contrast to resective surgery, the ablated tissue is left in situ, often transiently expanding in volume after ablation, and might cause increased mass effect and neurological morbidity16,17. This is especially critical near eloquent areas, in closed compartments like the posterior fossa, or near CSF pathways17,18. Staging the ablation for large tumors might lower the risk of edema and hydrocephalus as demonstrated in case #2.
Location near eloquent cortex or subcortical fibers poses specific challenges to LITT13,16. Careful trajectory planning, taking into account tractography and using low power to understand where and how the heat spreads across the lesion and/or small diffusing tip as necessary might mitigate the risks. However, real-time motor and language mapping using stimulation cannot be performed during the ablation inside the MRI. Awake LITT has been used in adults to mitigate these risks19; however, monitoring in the MRI is challenging, and the ablation is stopped only after a mild deficit has already occurred. Open resection, on the other hand, will allow both cortical and subcortical motor mapping, while awake open surgery (even in selected children) will enable the performance of linguistic mapping.
Therefore, choosing appropriate candidates who may benefit from LITT requires careful consideration of the lesion's specific characteristics and the procedure's limitations.
Table 3: Lesion variables and preferred treatment manner
|
Favors LITT
|
Favors open surgery
|
Size
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<2cm
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>2cm
|
Location
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Deep
Not abating eloquent regions
|
Superficial
Near eloquent regions
|
Consistency
|
Solid
|
Cystic
|
Associated epilepsy
|
|
LEAT*
|
* Long-term epilepsy-associated tumors (LEAT)
Biopsy
The role of tissue diagnosis is multifactorial, the first is to verify the tumor histology as opposed to other pathologies. Second, beyond histopathological diagnosis, adequate tissue sampling is critical to allow molecular profiling that helps determine prognosis and guide systemic therapies.
For example, BRAF antagonists and MEK inhibitors are the cornerstone biological treatments for specific pLGG 20, while chemotherapeutic regimens are the primary treatment, especially for chiasmatic hypothalamic tumors in infants21. While biopsy sampling is possible during LITT procedure, concerns have been raised by several groups that it may lead to a suboptimal effect of the LITT due to small air bubbles or small bleeds7,22. In addition, tissue sampling is limited and can be non-diagnostic as in case #3, and after ablation is performed there might not be diagnostic tissue to sample from. On the other hand, performing LITT in a separate setting necessitates an additional general anesthesia procedure for the child. In Arocho-Quinones series only 74.4% of the cases were proven by biopsy. In 25.6% of the cases, no biopsy was obtained during the LITT procedure and the diagnosis was presumed based on clinical history and imaging characteristics8.
In this aspect, the advantage of open resection is that sufficient pathological material is available for histopathology and molecular profiling. Since modern treatments and prognosis are highly dependent on appropriate adjuvant treatment, this should be an important factor when deciding between LITT and open resection in newly diagnosed tumors. This may make any future biopsies of the lesion or its surroundings, that were previously treated by LITT, to express tissue changes that are not tumoral, potentially leading to a tissue sampling error.
Epilepsy associated tumors
Long-term epilepsy-associated tumors (LEAT) are a subgroup of PLGG that cause epilepsy in children23. Most tumors are gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNET), which in 50-80% have an associated cortical dysplasia. Thus, treatment often includes not only the lesion (lesionectomy), but also associated dysplasia, often guided by electrocorticography (ECOG). These considerations cannot be addressed using LITT.
Imaging changes due to BBB opening and therapeutic implications:
It is important to be aware of the unique time-dependent imaging changes that occur following LITT. Immediately after the procedure, several tissue zones around the ablation area can be observed (Figure 2E,G). A central necrosis zone surrounds the optic fiber at the center of the ablation area. This coagulated area where cellular and subcellular membranes are disrupted is characterized on MRI by hyperintensity on T1-weighted images. Around the central necrotic area is a peripheral zone of necrotizing edema, where although irreversible cell damage has occurred, characterized by intra-cellular edema, the initial structural tissue damage is minimal, becoming apparent in the first 48-72 hours post-ablation. This area is characterized by hypointensity on T1-weighted images. A 1-3mm enhancing rim, seen in the post-ablation MRI, at the margin of the peripheral zone defines the total volume of thermally induced cell damage.
Beyond that, the damage to the surrounding cells is usually reversible, containing viable cells and reactive perilesional edema. It has been shown that LITT temporarily and locally disrupts the tight junctions that form a major part of the BBB while minimizing collateral damage to the surrounding neuronal tissue24. The peak of the increased permeability of the BBB and resulting edema occur 1–2 weeks after laser ablation, extend up to 1-2 cm from the enhancing rim, and usually resolve by 4–6 weeks. The BBB-opening effect has been investigated for its potential to enhance the delivery and response to adjuvant chemotherapy in viable tumor cells that may remain around the ablated area following LITT.
On follow-up imaging, lesions’ volume usually transiently increases in the first 2-4 weeks after the procedure and then gradually decreases, returning to pre-ablation volumes around 3 months after the procedure25. This pseudo-progression effect is thought to be mediated by post-ablation inflammatory processes due to thermal necrosis, which, like other ischemic processes, leads to increased vascular permeability and, consequently, increased contrast enhancement26. Lesions continue to decrease in volume over time, but it is not uncommon for a small residual enhancing lesion to remain even 6-12 months after the ablation (Figure 1F,G), without evidence of regrowth. This pseudo-progression might be challenging to differentiate from tumor recurrence and requires serial imaging surveillance.