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Laser Interstitial Thermal Therapy for Posterior Fossa Lesions: History
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Subjects: Neurosciences
Contributor: Hamid Borghei-Razavi

Laser interstitial thermal therapy (LITT), a minimally invasive stereotactic treatment option, is emerging as a viable treatment option for deep-seated primary and metastatic brain lesions due to the use of real-time magnetic resonance thermography. LITT has been used with good outcomes for a variety of brain lesions. The use of LITT for the treatment of posterior fossa lesions continues to show promise. LITT is a feasible method for the treatment of deep-seated lesions of the posterior fossa.

  • laser interstitial thermal therapy
  • LITT
  • neuro-oncology
  • posterior fossa

1. Introduction

Neurosurgeons and neuro-oncologists have considerable difficulties when it comes to surgical treatment of deep or difficult-to-access lesions in both pediatrics and adults. Approaching deep subcortical disorder has a high morbidity rate, which is a critical issue in different types of surgeries, including epilepsy surgery, vascular surgery, and tumor surgery [1].
Laser interstitial thermal therapy (LITT), a minimally invasive stereotactic treatment option, first introduced in 1983, is emerging as a viable treatment option for deep-seated primary and metastatic brain lesions due to the use of real-time magnetic resonance (MR) thermography [2]. The therapy involves the insertion of a laser catheter, which is subsequently heated to destroy pathologic tissue [3]. Real-time MR guidance focuses the laser treatment to decrease damage to surrounding structures [4]. LITT has been used for epilepsy treatment, which is not treatable with stereotactic radiosurgery (SRS), and also radiation necrosis (RN), which does not respond to SRS or surgery [5].
In addition, LITT is of particular interest to surgical neuro-oncologists since there is evidence supporting additional LITT effects that can be used to augment adjuvant therapies, such as disruption of the blood–brain barrier (BBB), which facilitates the dissemination of chemotherapeutics [6][7].
However, LITT for posterior fossa lesions remains understudied. The posterior fossa is a small cranial compartment, and anatomical challenges require significant surgical consideration [8]. Currently, there are no treatment recommendations for LITT of the posterior fossa due to a limited pool of data.

2. Laser Interstitial Thermal Therapy for Posterior Fossa Lesions

Eleven articles specifically examine the use of LITT on posterior fossa lesions. Among them, Tan et al. [9], Chan et al. [10], Eliyas et al. [11], Kozlowski et al. [12], and Lawrence et al. [13] each reported only 1 patient who underwent LITT for their posterior fossa lesions, which primarily originated from unresectable intrahepatic cholangiocarcinoma [9], anaplastic astrocytoma [10], pulmonary adenocarcinoma with recurrent metastasis [11], poorly differentiated carcinoma consistent with gastrointestinal versus pulmonary metastasis [12], and hemorrhagic pontine cavernoma [13], respectively. With the exception of the last case, which developed diplopia secondary to Abducens’ palsy [13], none of the aforementioned studies developed post-LITT complications [9][10][11]. Gamboa et al. reported MR-thermography-guided LITT for 2 brainstem cavernous malformations [14]. Both patients demonstrated remarkable symptomatic improvement and were hemorrhage-free at 12- and 6-month follow-up, respectively.

In addition to the items mentioned in Table 1, Ashraf et al. reported that an 84% overall local control rate was achieved at 9.5-month median follow-up [15]. No mortality was associated with the procedure in three studies [16][17][18], while there was 1 procedure-related death in the Ashraf et al. study [15]. The median volume of the ablation cavity and perilesional edema gradually decreased in follow-ups [16][17]. Luther et al. stated that radical ablations are both possible and safe in the posterior fossa. Immediately after surgery and at the time of the final follow-up, radical ablations may result in higher reductions in perilesional edema and an enhanced functional status [19].

Table 1. LITT on posterior fossa tumors.
Author, Year, (Ref.) Sample Size Mean Age Histology Location Prior Treatment Volume (Mean ± SD) Complications KPS
Pre-LITT Tumor Volume Post-LITT Cavity Volume Tumor Volume at Last Follow-Up Pre-LITT Post-LITT
Traylor, 2019, [17] 13 58 RN: 5, breast: 4, lung †: 2, kidney and GI ‡: 2 NR SRS: 8, RT: 1, Co $:4 4.63 ± 2.85 cm3 6.90 ± 3.42 cm3 3.14 ± 1.39 cm3 CN7&8 palsy: 1 90 80
Borghei-Razavi, 2018, [16] 8 53.87 RN: 2, brain *: 3, lung †: 1, others §: 2 Cerebellum: 6
Cerebellar peduncle: 2		 Res:1, SRS: 2, N: 5 5.58 ± 5.27 cm3 9.64 ± 7.33 cm3 5.67 ± 8.39 cm3 Wound infection: 1,
ataxia and hydrocephalus: 1, and
CN6 palsy: 1		 90 80
Eichberg, 2017, [18] 4 54.25 Breast: 3, others §: 1 Cerebellum: 4 SRS: 1, Co $: 3 3.35 ± 2.72 cm3 NR NR Diplopia: 1,dysarthria due to a new lesion: 1 NR NR
Ashraf, 2020, [15] 58 56.4 Breast: 19 #, brain *: 16, lung †: 17, kidney and GI ‡: 2, others §: 6 Cerebellum: 52
Brain stem: 7
Pineal region: 1		 Res: 6, SRS: 34, RT: 1, Co $: 12, N: 4 2.24 ± 0.21 cm3 3.92 ± 0.28 cm3 NR Hemiparesis: 1, CN7 palsy: 1, facial droop and hemiparesis: 2, arm weakness: 1, dysmetria and slurred speech: 2, diplopia: 1, refractory cerebral edema: 1, hearing loss: 2, truncal ataxia and scanning speech: 1, and death: 1 NR NR
Luther, 2021, [19] 17 57.9 Breast: 8, brain *: 3, lung †: 1, kidney and GI ‡: 2, others §: 3 Cerebellum: 16
Vermis: 1		 Res: 1, SRS: 10, Co $: 5, N: 1 2.0 ± 1.5 cm3 4.8 ± 2.2 cm3 1.7 ± 0.9 cm3 Diplopia: 1 and
speech impairment: 1		 91.2 NS
Gamboa, 2020, [14] 2 57.5 Brain *: 2 Brain stem: 2 Res: 2 1.8 and 1.6 cm NR NR Left-sided weakness and ataxia: 1 NR NR
Tan, 2020, [9] 1 71 Kidney and GI ‡: 1 Cerebellum: 1 N: 1 0.7 cm3 NR Resolve NR NR NR
Chan, 2016, [10] 1 60 Brain *: 1 Cerebellar peduncle: 1 SRS: 1 2.4 × 2.7 (cm2) NR Resolve NR NR NR
Eliyas, 2014, [11] 1 67 Lung †: 1 Cerebellum: 1 N: 1 3.23 cm3 NR NR NR NR NR
Lawrence, 2021, [13] 1 20 Brain *: 1 Brain stem: 1 N: 1 2.4 × 2.6 (cm2) NR 1.3 × 1.2 (cm2) Diplopia secondary to CN6 palsy: 1 NR NR
Kozlowski, 2021, [12] 1 75 Others §: 1 Cerebellum: 1 Co $: 1 NR NR NR NR NR NR
Dadey, 2016, [20] 2 45.5 Brain *: 2 Cerebellum: 1
Brain stem: 1		 N: 2 12.85 ± 5.8 cm3 NR NR Internuclear ophthalmoplegia, right eye ophthalmoplegia, dysarthria, and reduced sensation on left side: 1 NR NR
Beechar, 2018, [21] 4 NS NS Cerebellum: 4 SRS: 4 NS NS NS Neurological complication: 2 NS NS
Ahluwali, 2019, [22] 6 NS NS Cerebellum: 6 NS NS NS NS NS NS NS
Kaye, 2020, [23] 22 NS NS Cerebellum: 20
Brain stem: 2		 SRS: 22 NS NS NS Neurologic death: 8
Non-neurologic death: 10		 NS NS
Shao, 2020, [24] 9 NS NS NS NS NS NS NS NS NS NS
* Brain consists of low-grade glioma (pilocytic astrocytoma, ganglioglioma, etc.), anaplastic astrocytoma, high-grade glioma (glioblastoma), ependymoma, hemangioblastoma, neuroendocrine tumor, pineal parenchymal tumor, epilepsy focus, and cavernous malformations. † Lung consists of small-cell lung carcinoma (SCLS), non-small-cell lung carcinoma (NSCLC), and pulmonary adenocarcinoma. ‡ Kidney and GI consists of renal cell carcinoma (RCC), colon cancer, and cholangiocarcinoma. § Others consists of ovarian cancer, cervical cancer, melanoma, parotid adenoid cystic carcinoma, unknown origin, and metastatic adenocarcinoma. $ Co (combination) includes radiotherapy + SRS, resection + SRS, resection + SRS + radiotherapy, or radiotherapy + resection. There were 58 patients with 60 tumors. # Including one case of untreated metastatic breast cancer. Abbreviations: M: male, F: female, GI: gastrointestinal, CN: cranial nerve, RN: radiation necrosis, Res: surgical resection, RT: radiotherapy, Co: combination therapy, N: none, NR: not reported, NS: not specified.
In terms of LITT complication, thermal-ablation-related complication (hyperthermia, post-ablation edema, or ablation-induced bleeding) and laser-insertion-related complication are the two types of postoperative complications associated with LITT [25][26][27]. In this systematic review, death attributed to treatment failure, disease progression, recurrence, or postoperative complications occurred in approximately 6.8% (9/131) of the pooled sample. Procedure-related complications, including new neurologic deficits, occurred in approximately 14.5% (19/131) of the pooled sample.
In comparison to other therapeutic modalities in the posterior fossa, LITT seems to be safe and less complicated. Surgical complications were seen in 38.5% of patients with giant solid hemangioblastomas in the posterior fossa according to the Jeon et al. study [28]. Siomin et al. reported leptomeningeal disease after surgical removal of posterior fossa metastases in 50% of patients, whereas leptomeningeal disease occurred after SRS in 6.5% of patients [29]. However, no case of leptomeningeal disease has been observed after LITT for posterior fossa metastasis.
The higher rate of neurologic mortality in patients who had lesions on the brainstem was not an unexpected finding since the risk of any intervention in these deep and eloquent locations remains high. The difference in the rate of tumor volume reduction after LITT depends more on the underlying histopathology of the tumor than on the size and location of the tumor [15].
Traylor et al. discovered a remarkable correlation between patients who received adjuvant chemotherapy (targeted and systemic) after LITT and a prolonged time to local development, suggesting that systemically administrated chemotherapeutic drugs have restricted penetration of the BBB [17]. This is due to LITT’s hyperthermic disruption of the BBB, which is comparable to a mechanism reported previously that may improve chemotherapeutic drug delivery to the central nervous system (CNS) [6]. These data imply that combining chemotherapy with LITT for the treatment of posterior fossa lesions might be a potential therapeutic approach.
Khan et al. reported that 34% of their medulloblastoma patients who received surgical resection had PFS. They further assessed their patients once they finished craniospinal radiotherapy and every 3–6 months after that [30]. At 1 year, 14.8% and 7.7% of children with PFS1 and PFS2 had severe dysarthria, respectively [30]. Gentile et al. reported that 23.1% of patients with posterior fossa tumor who underwent proton beam therapy demonstrated PFS [31]. In comparison with these two mentioned studies, LITT has less probability (4.5%) of evoking PFS and thus seems to be a safer therapeutic modality.
The study highlights a number of the difficulties that are faced for LITT of the posterior fossa due to its delicate anatomical area. Because of the close proximity to the dural venous sinuses, the brain stem, and the fourth ventricle, meticulous trajectory planning is required to ensure appropriate ablation coverage. As a result, in some studies, certain lesions were not susceptible to full ablation and caused metastasis or recurred.
Overall, reported morbidity, mortality, and disease progression rates were low for LITT of the posterior fossa.

This entry is adapted from the peer-reviewed paper 10.3390/cancers14020456

References

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