Laser Interstitial Thermal Therapy Induces Robust Local Immune Response for Newly Diagnosed Glioblastoma With Long-term Survival and Disease Control.

Laser interstitial thermal therapy (LITT) is a minimally invasive neurosurgical technique used to ablate intra-axial brain tumors. The impact of LITT on the tumor microenvironment is scarcely reported. Nonablative LITT-induced hyperthermia (33-43˚C) increases intra-tumoral mutational burden and neoantigen production, promoting immunogenic cell death. To understand the local immune response post-LITT, we performed longitudinal molecular profiling in a newly diagnosed glioblastoma and conducted a systematic review of anti-tumoral immune responses after LITT. A 51-year-old male presented after a fall with progressive dizziness, ataxia, and worsening headaches with a small, frontal ring-enhancing lesion. After clinical and radiographic progression, the patient underwent stereotactic needle biopsy, confirming an IDH-WT World Health Organization Grade IV Glioblastoma, followed by LITT. The patient was subsequently started on adjuvant temozolomide, and 60 Gy fractionated radiotherapy to the post-LITT tumor volume. After 3 months, surgical debulking was conducted due to perilesional vasogenic edema and cognitive decline, with H&E staining demonstrating perivascular lymphocytic infiltration. Postoperative serial imaging over 3 years showed no evidence of tumor recurrence. The patient is currently alive 9 years after diagnosis. Multiplex immunofluorescence imaging of pre-LITT and post-LITT biopsies showed increased CD8 and activated macrophage infiltration and programmed death ligand 1 expression. This is the first depiction of the in-situ immune response to LITT and the first human clinical presentation of increased CD8 infiltration and programmed death ligand 1 expression in post-LITT tissue. Our findings point to LITT as a treatment approach with the potential for long-term delay of recurrence and improving response to immunotherapy.

Towards the definition of progressive disease in brain metastasis treated with laser ablation: an evidence-based study.

PURPOSE: The postoperative period after laser interstitial thermal therapy (LITT) is marked by a temporary increase in volume, which can impact the accuracy of radiographic assessment. The current criteria for progressive disease (PD) suggest that a 20% increase in size of brain metastasis (BM) assessed in 6-12 weeks intervals should be considered as local progression (LP). However, there is no agreement on how LP should be defined in this context. In this study, we aimed to statistically analyze which tumor volume variations were associated with LP. METHODS: We analyzed 40 BM that underwent LITT between 2013 and 2022. For this study, LP was defined following radiographic features. A ROC curve was generated to evaluate volume change as a predictor of LP and find the optimal cutoff point. A logistic regression analysis and Kaplan Meier curves were performed to assess the impact of various clinical variables on LP. RESULTS: Out of 40 lesions, 12 (30%) had LP. An increase in volume of 25.6% from baseline within 120-180 days after LITT presented a 70% sensitivity and 88.9% specificity for predicting LP (AUC: 0.78, p = 0.041). The multivariate analysis showed a 25% increase in volume between 120 and 180 days as a negative predictive factor (p = 0.02). Volumetric changes within 60-90 days after LITT did not predict LP (AUC: 0.57; p = 0.61). CONCLUSION: Volume changes within the first 120 days after the procedure are not independent indicators of LP of metastatic brain lesions treated with LITT.

Surgical Approaches to Thalamic Gliomas: A Systematic Review.

BACKGROUND: Adult thalamic gliomas (ATGs) present a surgical challenge given their depth and proximity to eloquent brain regions. Choosing a surgical approach relies on different clinical variables such as anatomical location and size of the tumor. However, conclusive data regarding how these variables influence the balance between extent of resection and complications are lacking. We aim to systematically review the literature to describe the current surgical outcomes of ATG and to provide tools that may improve the decision-making process. METHODS: Literature regarding the surgical management of ATG patients was reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Four databases were queried and a description of clinical characteristics and survival analysis were performed. An individual patient data analysis was conducted when feasible. RESULTS: A total of 462 patients were included from 13 studies. The mean age was 39.8 years with a median preoperative Karnofsky performance scale of 70. The lateral approaches were most frequently used (74.9%), followed by the interhemispheric (24.2%). Gross total and subtotal/partial resections were achieved in 81%, and 19% of all cases, respectively. New permanent neurological deficits were observed in 51/433 patients (11.8%). individual patient data was pooled from 5 studies (n = 71). In the multivariate analysis, tumors located within the posterior thalamus had worse median overall survival compared to anterior gliomas (14.5 vs. 27 months, P = 0.003). CONCLUSIONS: Surgical resection of ATGs can increase survival but at the risk of operative morbidity. Knowing which factors impact survival may allow neurosurgeons to propose a more evidence-based treatment to their patients.