Abstract OBJECTIVE Laser interstitial thermal therapy (LITT) is a minimally invasive option for the management of intracranial pathologies, including radiographically progressive tumors following stereotactic radiosurgery. Although LITT has been increasingly accepted in recent years, little is known regarding presentation and outcomes of patients with diverse backgrounds, particularly for centers specializing in central nervous system (CNS) metastases. METHODS All patients receiving their index LITT for brain metastasis at a single center from 2015 – 2023 were retrospectively reviewed. Patient demographics and geospatial data was used to compare differences in receipt of LITT by race/ethnicity, survival outcomes, and clinical trial enrollment. RESULTS From 2015-2023, 137 patients presented for LITT to 146 intracranial lesions. One hundred and six patients (77.3%) were non-Hispanic White (NHW), 25 (18.2%) were Black or African American, 5 (3.6%) were Asian American/Pacific Islander, and 1 (0.7%) was Hispanic or Latino (Hispanic or non-White, HNW). Among HNW patients, women more frequently received LITT (P = 0.022), with skin cancers being a more frequent indication among NHW patients (P = 0.019). NHW patients traveled a median of 62.0 (6.2 – 1045.9) miles to receive LITT vs 25.9 (1.31 – 238.3) miles for HNW patients (p = 0.001). In multivariate analyses, post-LITT overall survival was predicted by pre-LITT KPS (P = 0.0007) and recurrent tumor on biopsy (P = 0.0002), while probability of clinical trial enrollment was lower among those of female sex (P = 0.049), HNW race/ethnicity (P = 0.041), or external referral status (P = 0.035). CONCLUSION Patient sex, systemic disease histology, and distance from a treating center may differentially influence presentation for LITT according to underlying racial/ethnic identity. However, patients successfully treated in multidisciplinary CNS metastasis centers experience excellent post-procedural outcomes. Such centers should enact measures to ensure equitable clinical trial enrollment.

INTRODUCTION: Immune checkpoint blockade (ICB) has gained acceptance as a life-extending therapy in a variety of solid tumor types. For patients with brain metastases, combination stereotactic radiosurgery (SRS) and ICB remains an area of clinical equipoise. Similarly, for recurrent or difficult-to-access intracranial lesions, safety and synergy of laser interstitial thermal therapy (LITT) and ICB has yet to be explored. METHODS: In accordance with an IRB-approved protocol, all patients undergoing LITT at a tertiary center from 2015-2022 were retrospectively reviewed. Patients who received ICB within 6 weeks of LITT were included in the LITT + ICB cohort. Demographic, clinical, and survival data were collected. RESULTS: Combination LITT and ICB occurred in 25 patients with clinically recurrent tumors. The median cohort age was 62 (40-78) and 12 (48%) were female. The median KPS was 80 (50-100). The most common primary pathology was non-small cell lung cancer (NSCLC) in 15 patients (60%), followed by melanoma in 3 (12%); two high-grade gliomas were additionally treated. The majority of the cohort (24 patients, 96%) recieved single agent ICB in combination with LITT, with pembrolizumab (12, 48%) and nivolumab (6, 24%) most common. Median duration between ICB dosing and LITT was 2.85 (0.85-5.84) weeks. Ten patients (40%) had evidence of immune-related adverse events attributable to ICB, with only 1 event > grade 3 according to Common Terminology Criteria; 17 (68%) had a pre-LITT steroid requirement. Intracranial adverse events related to LITT were rare, with median overall survival for the cohort of 8.6 months (1.4-26.4 months). CONCLUSIONS: Combination LITT and ICB appears safe and feasible. No prospective studies have compared cytoreduction with LITT to LITT + ICB; construction of a matched NSCLC cohort is ongoing. Exploration of the immune consequences of LITT + ICB is needed.

1614 Background: Despite the unique ability of machine learning (ML) techniques to uncover complex interactive effects in datasets, studies exploring predictors of clinical trial enrollment have largely used standard statistical methods to discern associations. Furthermore, there have been limited applications of ML to close existing disparities in clinical trial enrollment of underrepresented patients in neuro-oncology. This study aims to use supervised machine learning to define and validate primary contributors of therapeutic clinical trial enrollment for a) all patients, b) women and c) NIH-designated minority patients with low- and high-grade glioma. Methods: Adult glioma patients who received care from the UCSF Brain Tumor Center between 1997- 2017 were identified in a prospective registry. Bootstrap forest (BF) and Recursive Partitioning (RP) models were created by randomly dividing patients in a 70/30 split into development (DEV) and validation (VAL) cohorts among all patients, women, and NIH-designated minority patients, separately. Model performance was assessed using the area under the curve (AUC) in the DEV and VAL cohorts. Results: Among 1042 patients, 350 patients (33.6%) enrolled in a therapeutic clinical trial. There were 445 women (42.7%), of which 144 (32.4%) enrolled, and 141 minority patients (13.5%), of which 39 (27.7%) enrolled. For all patients, in order of decreasing influence, the BF model selected median neighborhood household income, age, neighborhood poverty level, distance from hospital, tumor location, tumor volume, treatment with chemotherapy, occupation, KPS, insurance status, employment status, seizure at presentation, and volumetric extent of resection (EOR) to predict trial enrollment (DEV AUC: 0.984; VAL AUC: 0.746). For women, the BF model selected distance from hospital, age, household income, neighborhood poverty level, tumor location, treatment with chemotherapy, and KPS for trial prediction (DEV AUC: 0.972; VAL AUC: 0.746), whereas for minority patients, the BF model selected neighborhood poverty level, age, occupation, distance from hospital, tumor volume, insurance status, employment status, and EOR to predict trial enrollment (DEV AUC: 0.9830; VAL AUC: 0.769). The RP model for women designated those with non-White race as less likely to enroll (DEV AUC: 0.735; VAL AUC: 0.665) while the RP model for minority patients characterized those who preferred a non-English language or who were divorced or widowed as less likely to enroll (DEV AUC: 0.775; VAL AUC: 0.601). Conclusions: Supervised machine learning models achieved similar predictive performance among patient subgroups, while uncovering interactions between gender identity, minority status, and sociodemographic variables. These findings can guide targeted recruiting efforts to advance equitable trial enrollment for women and minorities.

Abstract BACKGROUND For brain metastases (BM), resection remains a mainstay for the upfront management of large, symptomatic lesions, while laser interstitial thermal therapy (LITT) has become a key treatment for radiographically progressive BM following stereotactic radiosurgery (SRS). Compared to LITT, resection-associated morbidity may delay systemic therapies. We evaluated functional outcomes for resection versus LITT to primary motor cortex (PMC)-associated metastases. METHODS Patients receiving resection or LITT for BM radiographically associated with the PMC from 2015-2023 were retrospectively reviewed. Demographic and survival data were collected, with patient Karnofsky Performance Status (KPS) or modified Rankin Scale (mRS) scores assessed out to 1-year by independent raters. RESULTS Forty-one patients underwent resection and 30 underwent LITT to a PMC-associated lesion. Median age was 67 (range 38 – 80) vs 65 (44 – 80) for resection vs LITT; median pre-operative KPS (70 vs 80, P = 0.1) or mRS (2 vs 2, P = 0.66) did not differ between groups. Lung was the most common primary (56.1% resections vs 56.7% LITTs). Resected lesions were of larger median diameter than LITT, 2.8 vs 1.9 cm, P = 0.0001. For resections, length of stay was longer, median 2 vs 1 day, P = 0.0002, and ICU use more frequent (75.6% versus 20.0%, P < 0.0001). At 1-month post-op, 66.7% of resection patients and 51.7% of LITT patients had stable or improved symptoms from pre-op, P = 0.21, with parity at 3-months (65.7% vs 62.9%) and therafter. Further, there was no significant decrement in KPS or mRS score out to a year for either intervention. CONCLUSIONS While there is a short-term increased risk of post-operative neurologic worsening due to LITT-associated edema, our data shows that, relative to resection, this is a transient and clinically limited phenomenon. With careful patient selection, LITT to lesions involving the PMC is feasible.

Abstract Stereotactic radiosurgery (SRS) is the standard of care for initial management of brain metastases (BM) and provides excellent local control with reduced incidence of adverse neurocognitive effects. However, radiographically progressive lesions post-SRS pose a key clinical challenge, as imaging characteristics cannot effectively distinguish between local recurrence (LR) and radiation necrosis (RN). A retrospective analysis was performed on patients receiving SRS treatment for BM between 2011-2022 and who subsequently underwent biopsy alone or in combination with laser interstitial thermal therapy for suspicion of LR vs RN on imaging. Patient demographics, clinicopathologic characteristics, SRS treatment parameters, and biopsy results were collected. The study included 145 patients with 151 progressive lesions biopsied after SRS treatment. The median age at biopsy was 62 (range: 27-92), with lung being the most prevalent primary site (84 cases, 57.9%). Post-SRS biopsy confirmed 92 lesions (61.3%) with RN, 58 (38.7%) with LR, and 1 biopsy result was missing. The median duration from SRS to biopsy was 13 months (range: 3-81), with a median prescribed SRS dose of 20.0 (range: 14.0-30.0) Gy. Of the lesions, 70.3% received unfractionated SRS, while 29.7% received fractionated SRS. Univariate analyses demonstrated that breast primary (vs. lung, P = 0.027, vs. skin, P = 0.012) and receipt of biopsy ≥ 9 months following SRS (P = 0.0062) were associated with lower odds of LR, while fractionation or prescribed SRS dose were not predictive. The association of biopsy timing ≥ 9 months with lower odds of LR remained significant on multivariate analyses (P = 0.0065). The natural history of LR and RN differ such that for patients presenting with an enlarging lesion ≥ 9 months post-SRS, radiation necrosis should be suspected over local tumor recurrence. Multi-disciplinary oncology teams should consider adjusting treatment for lesions progressing prior to this timepoint.

Abstract BACKGROUND Laser interstitial thermal therapy (LITT) is a minimally invasive option for tissue diagnosis, cytoreduction, and rapid post-operative return to systemic therapies for patients with brain tumors or radiation necrosis. As ablated tissue remains in situ, post-LITT edema may be associated with apparent increased lesion size and transient clinical worsening, complicating assessment of progression. METHODS All patients receiving LITT at a single center for tumors or radiation necrosis from 2015 – 2023 with ≥ 9 months of MRI follow-up were retrospectively reviewed. A 3D U-net segmentation model implemented in nnU-Net was developed for automated segmentation of Contrast-enhancing Lesion Volume (CeLV) of LITT-treated lesions on T1-weighted post-contrast MR images. CeLVs were analyzed to establish volumetric post-LITT response assessments. RESULTS Across 384 unique MRI exams, 61LITT-treated lesions and 6 control cases of medically-managed radiation necrosis were analyzed. Automated segmentation was qualitatively accurate in 367/384 (95.6%) images. CeLV increased to a median of 68.3% (IQR 35.1 – 109.2%) from baseline at 1 – 3 months from LITT (P = 0.0012) and returned to baseline thereafter. Based on established criteria, volumetric disease progression was defined as lesion expansion 40% from volumetric nadir or baseline. Twenty-one of 56 (37.5%) patients experienced volumetric progression with a progression-free survival of 21.4 (6.0 – 93.4) months. Patients experiencing volumetric progression had lower mOS (17.3 vs 62.1 months, P = 0.0015). CONCLUSIONS We observed a stereotyped increase in CeLV at 1 – 3 months post-LITT, which resolved within 6 months of the procedure. Post-LITT disease response can be reliably and feasibly assessed with criteria that account for this transient CeLV expansion. Automated lesion segmentation may speed adoption of volumetric response assessment criteria to clinical practice.

Abstract BACKGROUND Laser interstitial thermal therapy (LITT) allows for definitive tissue diagnosis, surgical cytoreduction, and faster post-operative return to systemic therapies for patients with brain tumors or radiation necrosis. Ablated tissue remains in situ following LITT, resulting in characteristic post-LITT lesion expansion. Post-LITT edema may be associated with transient clinical worsening and complicates subsequent response assessment. METHODS All patients receiving LITT at a single center for tumors or radiation necrosis from 2015 – 2023 with ≥ 9 months of MRI follow-up were retrospectively reviewed. A 3D U-net segmentation model implemented in nnU-Net was developed for automated segmentation of Contrast-enhancing Lesion Volume (CeLV) of LITT-treated lesions on T1-weighted post-contrast MR images. CeLVs were analyzed to establish volumetric post-LITT response assessments. RESULTS Sixty-one LITT-treated lesions and 6 control cases of medically-managed radiation necrosis were analyzed across 384 unique MRI exams. Automated segmentation was qualitatively accurate in 367/384 (95.6%) images. CeLV increased to a median of 68.3% (IQR 35.1 – 109.2%) from baseline at 1 – 3 months from LITT (P = 0.0012) and subsequently returned to baseline. Median overall survival (mOS) for LITT-treated patients was 39.1 (9.2 – 93.4) months. Using previously established volumetric thresholds, volumetric disease progression was defined as lesion expansion ≥ 40% from volumetric nadir or baseline. Twenty-one of 56 (37.5%) patients experienced volumetric progression with a progression-free survival of 21.4 (6.0 – 93.4) months. Patients with volumetric progression had lower mOS (17.3 vs 62.1 months, P = 0.0015). CONCLUSION We observed a nearly 70% increase in CeLV at 1 – 3 months post-LITT, which characteristically resolved within 6 months of the procedure. Development of response assessment criteria that account for transient post-LITT lesion expansion is feasible and should be considered for clinical trials. Automated lesion segmentation may facilitate adoption of volumetric response assessment into clinical practice.

Abstract Glioblastoma (GBM) remains among the most fatal cancers with few treatment modalities and resistance to modern immunotherapeutic treatment paradigms including immune checkpoint inhibitors (ICI). ICIs neutralize the regulatory signals that disable T cells and have demonstrated remarkable efficacy against a variety of cancers, though not in GBM. The impotence of ICI in GBM has been linked to the tumor’s remarkable capacity to elicit T cell exhaustion, though the mechanism remains poorly understood. Chronic interferon (IFN) cytokine signaling is known to promote immunosuppression and Tex in several cancer types as well as resistance to ICI. However, the role of IFN in GBM has not been investigated despite evidence that IFN signatures exist within clinical samples of GBM. Syngeneic murine GBM cell lines CT2A and SB28 were utilized for in vivo and in vitro studies. Anti-mouse PD-1 and CD8 antibodies or PBS control were injected intraperitoneally. CRISPR editing was used to create validated knockouts (KO) of the type I IFN receptor (IFNAR1) in CT2A. Mice bearing IFNAR1 KO intracranial tumors have improved median survival (p < 0.05) and are exquisitely sensitive to checkpoint anti-PD-1 blockade (p < 0.05) with the majority of mice surviving. Furthermore, surviving mice reject the subsequent intracranial re-challenge with parental CT2A tumors compared to controls (p <0.05) suggesting central memory responses mediating rejection. We conclude that abrogation of Type I IFN signaling is sufficient to extend survival which is further enhanced by ICI. Work is ongoing to further elucidate the precise mechanism that mediates this response and to identify a therapeutic intervention that enables tumor-specific inhibition of the IFN pathway with preliminary work suggesting a CD8 T cell mediated response and reversal of the T cell exhaustion phenotype.

Abstract BACKGROUND Laser interstitial thermal therapy (LITT) has clinical utility in treating radiographically progressive brain metastases (BM) following stereotactic radiosurgery (SRS), while resection has been reserved for large, symptomatic lesions in the upfront setting. Resection-associated morbidity in eloquently-located metastases may hinder definitive management. METHODS Patients receiving resection or LITT for BM radiographically associated with the primary motor cortex (PMC) from 2015-2023 were retrospectively reviewed. Clinicodemographic and survival data were collected, with patient Karnofsky Performance Status (KPS) or modified Rankin Scale (mRS) scores assessed out to 1-year by independent raters. RESULTS Forty-one patients underwent resection and 30 underwent LITT to a PMC-associated lesion. Median age was 67 (range 38 – 80) vs 65 (44 – 80) for resection vs LITT; median pre-operative KPS (70 vs 80, P = 0.1) or mRS (2 vs 2, P = 0.66) did not differ between groups. Lung was the most common primary site (56.1% resections vs 56.7% LITTs). Resected lesions were of larger median diameter than LITT, 2.8 vs 1.9 cm, P = 0.0001. For resections, length of stay was longer, median 2 vs 1 day, P = 0.0002, and ICU use more frequent (75.6% versus 20.0%, P < 0.0001). At 1-month post-op, 66.7% of resection patients and 51.7% of LITT patients had stable or improved symptoms from pre-op, P = 0.21, with parity at 3-months (65.7% vs 62.9%). Further, there was no significant decrement in KPS or mRS score out to a year for either intervention. CONCLUSION While LITT-induced edema may slightly increase the risk of post-operative neurologic deficits, this is a transient and clinically insignificant phenomenon. Reduced operative footprint in the context of LITT may allow for faster definitive management of BM. For carefully selected lesions, LITT adjacent to eloquent cortex is feasible.

Abstract BACKGROUND Laser interstitial thermal therapy (LITT) is a minimally invasive surgical treatment being employed frequently for radiographically progressive brain metastases (BM). Considerable interest exists in combining LITT-mediated in situ vaccination to license immune checkpoint blockade (ICB) and activate an anti-tumor immune response. However, LITT also disrupts the blood-brain barrier, causing transient peritumoral edema. Accordingly, information on safety and feasibility of this combination in BM is needed. METHODS All patients receiving LITT for radiographically progressive non-small cell lung carcinoma (NSCLC) BM at a single center from 2015 – 2023 were retrospectively reviewed. Combination therapy was defined as ICB within 6 weeks of LITT. Clinical data, post-LITT freedom from local progression (FFLP), and overall survival (OS) were collected. Adverse events (AEs) were evaluated according to Common Terminology Criteria. RESULTS Eighteen patients received LITT + ICB to a total of 19 lesions. Median time between therapies was 2.29 weeks (range 0.85 – 5.98). In comparison to NSCLC patients receiving LITT alone (n = 25), there was no decrement in % ablation (98 vs 95%, P = 0.1), length of stay (1 vs 1 days, P = 0.91), home discharge (100 vs 92%, P = 0.5), or 30-day readmissions (15.8 vs 16%, P = 0.99). Despite decreased preoperative steroid use (P = 0.0098), patients receiving LITT + ICB discontinued steroids at a median of 11 (4 – 147) days post-LITT vs. 24 (3 – 242) days for patients receiving LITT alone (P = 0.62). At study cutoff, 18/19 (94.7%) lesions in the LITT + ICB group and 22/25 (88.0%) in the LITT only group were locally controlled. There were 3 and 5 AEs ≥ Grade 3 in the LITT + ICB and LITT alone group, respectively. CONCLUSIONS Combination LITT and ICB does not compromise procedural outcomes and may favorably impact local control in NSCLC. Prospective studies are needed to assess biomarkers of immune response.

Abstract BACKGROUND Tumor-related epilepsy is a common sequela of both primary and metastatic brain tumors, as well as radiation necrosis (RN). Laser interstitial thermal therapy (LITT) is an effective option for lesional cytoreduction but induces transient peritumoral edema that typically resolves within 3 months of the procedure. Accordingly, we quantified the risk of seizure development early post-LITT in patients with tumors or RN of diverse histologies. METHODS Patients treated with LITT for brain tumors or radiation necrosis at a high-volume center from 2015 – 2021 with at least 3 months of clinical follow-up were evaluated for seizure risk and time to discontinuation of anti-epileptic drugs (AEDs) for at least 4 weeks, with censoring at death or last follow-up. RESULTS One-hundred and seventeen patients met inclusion criteria, and 22 (19%) experienced a post-LITT seizure within 3 months of surgery. Those with pre-LITT seizures (P = 0.03), prior whole-brain radiation (WBRT) (P = 0.0099), or lower pre-operative KPS (P = 0.04) were more likely to have a post-LITT seizure. Frontal lobe tumors appeared to be more frequently associated with seizures (68% vs 45%, P = 0.06). Prior WBRT, odds ratio (OR) 4.27 (95% CI 1.01 – 18.55), P = 0.047 and pre-LITT seizure, OR 5.39 (95% CI 1.87 – 16.31), P = 0.002 remained predictive on multivariate analyses. Successful AED weaning occurred at a median of 1.68 months (no seizure within 3-months group) versus undefined for patients experiencing seizures (P = 0.015). Post-LITT seizures within 3 months were associated with worsened post-LITT overall survival, 5.95 vs 17.2 months, P < 0.0001. DISCUSSION Prior seizure history or previous WBRT pose a risk of breakthrough seizures following laser ablation. Neurosurgeons should consider extended AED treatment or referral for management of tumor-related epilepsy in patients with these neurologic risk factors.

Abstract The long-accepted paradigm for both cellular and antitumor immunity relies upon tumor cell kill by CD8+ T cells recognizing cognate antigens presented in the context of target cell major histocompatibility complex class I (MHC I) molecules. Likewise, a classically described mechanism of tumor immune escape is tumor MHC-I downregulation. Here, in contrast to the decades old model of T cell immunity, we instead report that CD8+ T cells maintain the capacity to kill tumor cells that are entirely devoid of MHC-I expression. This capacity proves to be dependent instead on interactions between T cell NKG2D and tumor NKG2D ligands (NKG2DL), the latter of which are highly expressed on MHC-loss variants. Necessarily, tumor cell kill in these instances is antigen-independent, although prior T cell antigen-specific activation is required and can be furnished by myeloid cells or even neighboring MHC-replete tumor cells. In this manner, adaptive priming can beget innate killing. These mechanisms are active in vivo in mice, as well as in vitro in human tumor systems, and are obviated by NKG2D knockout or blockade. These studies challenge the long-advanced notion that downregulation of MHC-I is a viable means of tumor immune escape, and instead identify the NKG2D/NKG2DL axis as a therapeutic target for enhancing T cell-dependent anti-tumor immunity against MHC loss variants.

Abstract BACKGROUND Laser interstitial thermal therapy (LITT) is a surgical treatment for progressive brain metastases (BM) following stereotactic radiosurgery (SRS). Although LITT has been increasingly accepted, little is known regarding factors influencing presentation and outcomes of patients with diverse backgrounds. METHODS Retrospective review of all patients receiving their index LITT treatment for BM at a single center from 2015 – 2023. Patient demographics and geospatial data was used to compare differences in receipt of LITT by race or ethnicity, survival outcomes, and clinical trial enrollment. RESULTS From 2015-2023, 137 patients presented for LITT to 146 intracranial lesions. One hundred and six patients (77.3%) were non-Hispanic White (NHW), while among Hispanic or non-White (HNW) patients, 25 (18.2%) were Black or African American, 5 (3.6%) were Asian American, and 1 (0.7%) was Hispanic/Latino. Among HNW patients, women more frequently received LITT (p = 0.022), with skin cancers being a more frequent indication among NHW patients (P = 0.019). NHW patients traveled a median of 62.0 (6.2 – 1045.9) miles to receive LITT vs 25.9 (1.31 – 238.3) miles for HNW patients (p = 0.001). Length of stay, discharge location, or readmission rates did not differ between groups. In multivariate analyses, probability of clinical trial enrollment was less among those of female sex (P = 0.049), HNW race/ethnicity (P = 0.041), or external referral status (P = 0.035), while post-LITT overall survival was predicted by pre-LITT KPS (P = 0.0007) and recurrent tumor on biopsy (P = 0.0002). CONCLUSIONS Differences in presentation for LITT by race or ethnicity may be influenced by underlying patient factors, including sex, systemic disease histology, and distance from a treating center, which do not influence post-LITT procedural outcomes or survival. Accordingly, clinical trial enrollment should be prioritized for vulnerable patient populations to realize the full benefits of laser ablation.

Abstract INTRODUCTION Treatment of intracranial lesions with laser interstitial thermal therapy (LITT) allows for simultaneous cytoreduction and the potential to generate an anti-tumor immune response. The safety and efficacy of combination immune checkpoint blockade (ICB) and LITT has not been determined. METHODS All patients who received LITT for neuro-oncologic indications at a single NCI-designated cancer center from 2015 – 2022 were included. Simultaneous ICB was defined as receipt of therapy within 6 weeks of LITT. Demographic, clinical, and survival data were collected. Immune-related and intracranial adverse events (iRAEs and IAEs) were graded according to Common Terminology Criteria. RESULTS Twenty-four patients received simultaneous LITT and ICB. Median age was 62 (range 40 - 78) and 12 (48%) were female. Median KPS was 80 (50 – 100). Use of ICB increased during the study period (r = 0.69). The most common pathology was non-small cell lung cancer (15 patients, 62.5%), followed by melanoma in 3 (12.5%) and 2 (8.3%) patients each with renal cell carcinoma or high-grade glioma. Twenty-three (96%) patients received single agent ICB, with pembrolizumab most common (12, 50%), followed by nivolumab (6, 25%). The median interval between LITT and ICB was 2.56 (0.85 – 4.98) weeks. The most common iRAE was hypothyroidism in 4 (16.6%) patients, with grade 3 pneumonitis in one patient. The most common IAE was seizures in 4 (16.6%) patients. Local progression was seen in 4 patients (16.6%), with a post-LITT overall survival of 20.6 (1.0 – 36.1) months for the cohort. CONCLUSIONS Combination LITT and ICB appears safe and effective, with iRAEs commensurate with trials of checkpoint inhibition. High-grade intracranial toxicity was rare. Prospective studies of combinatorial LITT + ICB are needed to establish biomarkers and optimal timing.

Laser interstitial thermal therapy (LITT) is a growing minimally-invasive approach for treatment of intracranial tumors. Stereotactic placement of the laser catheter within the target lesion carries a theoretical risk of tract seeding, which could lead to disease progression. A retrospective analysis of patients treated with LITT for biopsy-confirmed tumor from 2016-2020 was conducted to characterize the risk of post-LITT tract seeding. Forty-two patients met inclusion criteria, of whom 23 (54.7%) had primary brain tumors and 19 (45.3%) metastases. Thirty-three (78.6%) lesions were recurrent disease at the time of LITT. On follow-up MRI, 3 patients (7.1%) were identified to have had tumor seeding along the LITT tract resulting in progressing disease. There were no significant differences in tumor histology, pre-operative maximum lesion diameter, number of LITT trajectories, rounds of lasing, or post-LITT radiotherapy or surgery between patients with and without tract seeding. All patients with tract seeding were treated for periventricular lesions (<1cm). Patients with tract seeding were also more likely to have received LITT ablations administered from the superficial to deepest elements of the lesion (p=0.05). The median time to progression post-LITT for patients with tract seeding was significantly shorter than those without (1.1 vs 5.9 months, p=0.02). Additional analyses revealed trends towards longer median tract length (4.0 vs. 2.2 cm, p=0.23) and shorter overall survival (5.4 vs. 14.2 months, p=0.17) in the tract seeding cohort. In summary, tract seeding is an infrequent complication associated with both LITT and traditional biopsy. In LITT, tract seeding progression occurs significantly faster than at the treated site, which may be associated with a worse overall prognosis. Prophylactic stereotactic radiosurgery to the LITT tract could be of benefit, however this may pose further risk to patients given the low overall frequency. More frequent monitoring may be necessary lesions in periventricular or difficult to ablate regions, or with longer LITT tracts.