bluuebunny/crossref_metadata_2025 huggingface dataset:
RBIO-01. CHARACTERIZING THE TEMPORAL EVOLUTION OF BRAIN ARCHITECTURE DURING RADIOTHERAPY FOR GLIOBLASTOMA USING NONLINEAR IMAGE REGISTRATION
Authors: DeWalt Nicholas , Xu Yuanguang , Wang Tony , Grinband Jack
Published: November 2024

BACKGROUND

Previous serial MRI studies following glioblastoma (GBM) resection reveal dynamic changes in the tumor cavity and surrounding tissue. However, the time course of these dynamics is unclear, especially in the immediate postoperative period.

METHODS

GBM patients (n=8) received three MRIs: within 72 hours post-resection, immediately preceding RT (RTstart), and at the RT midpoint (RTmid). The radiation field (RF) was based on the resection cavity (RC) and surrounding T2-FLAIR hyperintensities at the 72 hour MRI. Nonlinear image registration was performed across the two time intervals, allowing comparison between the intended radiation targets and the actual irradiated tissue. Dice coefficients (DRF and DRC), the relative volume of the RC (RCvol), and the volume of unintended iatrogenic radiation (IRvol) were measured at each timepoint, and IRvol was fitted to an exponential decay.

RESULTS

DRF showed modest reduction, with mean±SD of 0.97±0.02 at both RTstart and RTmid. In contrast, the RC showed more change, with mean DRC 0.63±0.13 and 0.60±0.12, and mean RCvol of 0.74±0.27 and 0.72±0.25 at RTstart and RTmid, respectively. DRF, DRC, and RCvol showed greater change during the first interval than the second (p=3.5x10-4, 4.1x10-4, and 0.1, respectively). The mean IRvol was 16.7±12.6 at RTstart and 21.7±12.8 at RTmid, with a time constant of -0.031 (95% CI=[-0.017, -0.060]), indicating that 80% of all voxels that receive unintended iatrogenic radiation moved into the radiation field by postoperative day 57, and 95% will have moved in by day 125.

CONCLUSIONS

Nonlinear registration demonstrated significant postoperative architectural changes, with most occurring in the first two months after surgery near the RC. This potentially suggests a role for adaptive planning during RT, particularly for protocols that focus on the RC rather than T2-FLAIR hyperintensities. Future prospective studies are needed to assess the role of adaptive radiotherapy for GBM.
RBIO-04. OUTCOMES OF RADIOSURGERY FOR WHO GRADE 2 MENINGIOMAS: THE ROLE OF KI-67 INDEX IN GUIDING THE TUMOR MARGIN DOSE
Authors: Meng Ying , Bernstein Kenneth , Mashiach Elad , Santhumayor Brandon , Kannapadi Nivedha , Gurewitz Jason , Snuderl Matija , Pacione Donato , Sen Chandra , Donahue Bernadine , Silverman Joshua , Sulman Erik , Golfinos John , Kondziolka Douglas
Published: November 2024

The management of WHO grade 2 meningiomas is complicated by their diverse clinical behaviors. Stereotactic radiosurgery (SRS) can be an effective management option. Literature on SRS dose selection is limited, but suggests a higher dose is better for tumor control. We aimed to characterize the predictors of post-SRS outcomes that can help guide planning and management. We reviewed a cohort of consecutive patients with pathologically-proven WHO grade 2 meningiomas who underwent SRS at a single institution between 2011 and 2023. Ninety-nine patients (median age 62 years) underwent SRS, eleven of whom received hypofractionated SRS in 5 fractions. Twenty-two patients had received prior irradiation. The median follow-up was 49 months. The median overall survival (OS) was 119 months (95%CI 92–NA) with estimated 5- and 10-year survival of 83% and 27% respectively. The median progression-free survival (PFS) was 40 months (95%CI 32–62) with 3- and 5-year rates at 54% and 35% respectively. The median locomarginal PFS was 63 months (95%CI 51.8-NA) with 3- and 5-year rates at 65% and 52%. Nine (9%) patients experienced adverse events, 2 CTCAE grade 3 and 7 grade 2, consisting of worsening neurologic deficit from edema. In the single-session SRS cohort, Ki-67 was a significant predictor of both OS and intracranial PFS. Tumors with Ki-67 >10% had ~10 times risk of locomarginal progression compared to Ki-67 ≤10% (p<0.001). In tumors with Ki-67 >10%, margin dose ≥14 Gy was associated with significantly better tumor control, but not for tumors with Ki-67 ≤ 10%. Other significant predictors of tumor control were prescription dose, tumor volume, and location. The management of WHO grade 2 meningiomas requires a multi-modality approach. This study demonstrated the value of a targeted SRS approach in patients with limited disease, and further establish predictive biomarkers that can guide planning through a personalized approach.
RBIO-05. IPAX-2: PHASE 1 SAFETY AND DOSE FINDING STUDY OF [131I]IPA PLUS STANDARD OF CARE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Gan Hui , Cerqueira Brenda , Divlianska Daniela , Cade David
Published: November 2024

BACKGROUND

Glioblastoma (GBM) overexpresses the L-type amino transporter (LAT) 1 & 2, which supports internalization of the therapeutic small-molecule amino acid derivative, 4-L-[131I] iodo-phenylalanine ([131I]IPA) and its companion diagnostic, 18F-FET. Previous studies of [123I]IPA SPECT have shown uptake by >85% of gliomas. Results from a phase 1 trial (IPAX-1) that explored [131I]IPA + radiotherapy in patients with recurrent GBM demonstrated a favorable safety and tolerability profile and promising efficacy. The objective of IPAX-2 (NCT05450744) is to evaluate the safety and tolerability of [131I]IPA in patients newly diagnosed with GBM.

METHODS

IPAX-2 is a phase 1, multicenter, open-label, single-arm, parallel-group, dose-finding study to evaluate the safety of ascending radioactive dose levels of [131I]IPA + best standard of care in newly diagnosed patients with GBM. Eligible participants (N=12) will be 18-65 years of age with histologically-confirmed intracranial GBM following surgical resection; no prior systemic therapy or radiation for GBM; a Karnofsky Performance Status ≥70; a plan to begin chemoradiation 3-6 weeks after surgical resection with Stupp regimen; adequate organ function; and adequate tissue samples previously archived. Four cohorts will encompass a 3 + 3 dose escalation, with [131I]IPA administered in 2 fractions corresponding to ½ of full dose activity via intravenous infusion (2x3.0 GBq, 2x4 GBq, 2x5 GBq, 2x6 GBq). Dose 1 will be administered prior to external beam radiation therapy (EBRT), and Dose 2 will be administered following completion of EBRT. 18F-FET PET will be used to identify suitable candidates with LAT1/2 overexpression, establish a baseline, and provide quantitative follow-up information. Primary outcome measures are 1) incidence rate treatment-emergent adverse events and 2) safety and tolerability by determining the dose-limiting toxicity, maximum tolerated dose, and recommended phase 2 dose. DISCLOSURES: Telix Pharmaceuticals is the sponsor of this study.
RBIO-07. IMMUNOMODULATORY PATHWAYS MEDIATE RADIOTHERAPY RESPONSE IN MALIGNANT PERIPHERAL NERVE SHEATH TUMORS
Authors: Zhu Iowis , Chien Julian , Mirchia Kanish , Miller Kaeli , Payne Emily , Pak Joanna , Monga Varun , Braunstein Steve , Jacques Line , Pekmezci Melike , Liu John , Vasudevan Harish
Published: November 2024

PURPOSE

Malignant peripheral nerve sheath tumors (MPNSTs) are the most common cause of death in neurofibromatosis type 1 (NF-1) and are resistant to radiation therapy (RT), yet the mechanisms underlying RT response are poorly understood. Here, we elucidate mechanisms of RT response in NF-1 associated peripheral nerve sheath tumors through genome-wide CRISPRi screens, genomic analysis of mouse models, and molecular analysis of patient-derived tumor specimens.

METHODS

Patient derived NF1 mutant plexiform neurofibroma (pNF) cells (NF9511b, NF95.6), and MPNST cells (ST88-14; JH2-002) were used to measure RT responses by cell counts and flow cytometry. Genome-wide CRISPRi screens were used to identify functional modifiers of RT response in ST88-14 and JH2-002 MPNST cells. Nf1-/-; Tp53-/- mouse MPNSTs were subcutaneously implanted in immunocompetent C57/B6 mice, irradiated (2Gyx5), and dissociated for single-cell RNA sequencing (scRNA-seq) using 10x Genomics. Human MPNST tumor specimens (n=45) were analyzed with targeted DNA mutation sequencing and methylation arrays for cell type deconvolution.

RESULTS

Radiation single-dose response curves revealed MPNST cells (IC50 6.85Gy) were radioresistant compared to pNF cells (IC50 3.13Gy). Genome wide CRISPRi screens in ST88-14 and JH2-002 MPNST cells converged on cell cycle, DNA repair, and immunomodulatory gene sets mediating RT sensitivity. Irradiation of subcutaneous mouse Nf1-/-; Tp53-/- MPNSTs significantly decreased tumor growth (p=0.01, t-test). scRNA-seq of 32,763 cells from 4 irradiated and 3 unirradiated mouse Nf1-/-; Tp53-/- MPNSTs identified 8 tumor clusters and 7 non-tumor clusters. Irradiation demonstrated a pro-inflammatory effect with increased T-cell presence (5.8% versus 3.3%, p=0.04, t-test) and greater activation of immunostimulatory genes (Cxcl10, Stat1, Irf7) in T cells. In human MPNSTs, CDKN2A/B deletion (p=0.04, log-rank test) and decreased immune cell composition (p=0.03, log-rank test) were associated with significantly worse overall survival in response to RT.

CONCLUSION

MPNST RT responses may depend on immunomodulatory mechanisms that could be leveraged to improve clinical RT response.
RBIO-09. EFFECTS OF RADIATION ON THE HIPPOCAMPUS AND HIPPOCAMPAL NEUROGENESIS: A SYSTEMATIC REVIEW OF INJURY MECHANISMS AND INTERVENTION STRATEGIES
Authors: Leskinen Sandra , Alsalek Samir , Wernicke A Gabriella
Published: November 2024

PURPOSE

To understand how radiation affects the hippocampus and hippocampal neurogenesis. Radiotherapy is a common modality in the treatment of brain tumors that targets malignant cells with radiation. However, unintended iatrogenic injury may extend to adjacent healthy cells. The hippocampus is a particular area of concern, given its vital role in memory and learning and capacity for neurogenesis.

METHODS

We searched the PubMed, Embase, and Web of Science databases for studies assessing the effects of radiation on the hippocampus and hippocampal neurogenesis, adhering to PRISMA guidelines. Animal studies were evaluated according to the ARRIVE guidelines for pre-clinical studies. The SYRCLE risk of bias tool was utilized to examine potential bias among studies. Study characteristics, including study design, sample size, experimental methods, radiation dose, and results were collected and synthesized.

RESULTS

Ninety-two studies met inclusion criteria, and the majority of studies investigated rat and/or mouse models (n = 91, 98.9%). Across studies, cranial irradiation was consistently found to be associated with detrimental effects on hippocampal function and structure through molecular alterations to gene and protein expression, neuronal cell apoptosis, disruption of dendritic spines, and initiation of pro-inflammatory processes. The consequences for neurogenesis were mostly focused on the dentate gyrus of the hippocampus. These effects manifested as cognitive deficits in hippocampus-dependent tasks such as memory and learning. Behavioral (e.g., running) and pharmacological (e.g., PPARα agonists) interventions against the deleterious effects of radiation suggest the potential to address radiation-induced hippocampal disruption and cognitive deficits. The majority of studies were found to have an unclear risk of bias.

CONCLUSIONS

This systematic review highlights the effects of cranial radiation on hippocampal neurogenesis and their association with disruptions in memory and learning. Future research should continue to focus on delivering radiotherapy that spares susceptible regions in the brain, preserving patients’ cognitive function and quality of life.
RTID-03. A MULTICENTER, RANDOMIZED, CONTROLLED TRIAL OF FOCUSED-ULTRASOUND-MEDIATED BLOOD-BRAIN BARRIER DISRUPTION PLUS SYSTEMIC PEMBROLIZUMAB FOR PATIENTS WITH NSCLC BRAIN METASTASES (LIMITLESS)
Authors: Ahluwalia Manmeet , Ozair Ahmad , Sahni K Singh , Sanai Nader , Sahgal Arjun , McDermott Michael , Nwaogu Kingsley , Dye Lisa , Woodworth Graeme , Lipsman Nir
Published: November 2024

BACKGROUND

Systemic therapy for brain metastases (BM) is hindered by blood-brain barrier (BBB). Low-intensity focused ultrasound (LIFU), combined with IV microbubble oscillators, leads to non-invasive BBB disruption, which could enhance intracranial delivery of systemic immune checkpoint inhibitors. This randomized controlled trial (RCT) aims to evaluate safety and efficacy of LIFU-mediated BBB disruption plus systemic pembrolizumab for NSCLC BM.

METHODS

LIMITLESS (NCT05317858) is an ongoing, multicenter, parallel-arm, open-label RCT that randomizes NSCLC BM patients on standard-of-care pembrolizumab monotherapy to LIFU plus pembrolizumab (arm 1) or pembrolizumab alone (arm 2) in a 2:1 ratio. Included patients have age ≥18 years, normal organ function, KPS ≥70, EGFR- and ALK-negative primary tumor, and ≤3 BM with ≥1 BM meeting RANO-BM measurable disease criteria. All patients receive standard-of-care therapy, while those on arm 1 undergo LIFU before each pembrolizumab dose (200mg IV q3weeks). Patients undergo pre-treatment brain MRI, followed by IV microbubbles for enhanced sonication effects. MR-guided BBB disruption is performed using transcranial 220kHz LIFU device with real-time acoustic-feedback-based power control for maintaining effective microbubble activation. Pembrolizumab is infused immediately after sonication, and repeat MRI is done 24-48 hours later to assess treatment effects. Primary study outcome is overall objective response rate (ORR) at 6 months as assessed using RANO-BM. Using Bayesian design for power analysis, a superior ORR of 60% is assumed for LIFU arm versus 30% for control arm for total sample size of N=96 (64 participants in LIFU and 32 in control arm), for 80% power using two-sided chi-square test with alpha=0.05. For upper-bound estimate, ORR of 45% in LIFU arm and 30% in control arm, the study needs N=369 participants (246 in LIFU arm and 123 in control arm). Secondary outcomes are best ORR and median time-to-response. Exploratory outcomes are median progression-free survival (PFS), overall survival (OS), median intracranial PFS, median extracranial PFS, and quality of life. Patient enrollment commenced in 2022 and remains ongoing.
SURG-07. QUANTIFYING THE RISK OF SHORT TERM SEIZURES FOLLOWING LASER INTERSTITIAL THERMAL THERAPY
Authors: Srinivasan Ethan , Flusche Ann Marie , Haskell-Mendoza Aden , Woo Joshua , Gonzalez Ariel , Reason Ellery , Jackson Joshua , Lerner Emily , Edwards Ryan , Schwalb Allison , Fecci Peter
Published: November 2024

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.
SURG-10. SUPRATOTAL RESECTION: AN EMERGING CONCEPT OF GLIOBLASTOMA MULTIFORME SURGERY—SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Aziz Peer , Memon Salma , Mubarak Hussain , Memon A , Abbas Kiran , Qazi Shurjeel , Memon Riaz , Qambrani Kanwal , Taj Osama , Ghazanfar Shamas , Ellahi Aayat , Ahmed Moiz
Published: November 2024

The severe neurologic tumor known as glioblastoma (GBM), also referred to as a grade IV astrocytoma, is rapidly progressive and debilitating. Supratotal resection (SpTR) is an emerging concept within glioma surgery, which aims to achieve a more extensive resection of the tumor than is possible with conventional techniques. We performed a language-independent search of PubMed, Scopus, and Cochrane CENTRAL to identify all available literature up to August 2022 of patients undergoing SpTR assessing survival outcomes in comparison to other surgical modalities. After screening for exclusion, a total of 13 studies, all retrospective in design, were identified and included in our meta-analysis. SpTR was associated with significantly increased overall survival (hazard ratio 0.77, 95% CI 0.71–0.84; P < 0.01, I2 = 96%) and progression-free survival (hazard ratio 0.2, 95% CI 0.07–0.56; P = 0.002, I2 = 88%). SpTR is associated with greater overall survival and PFS when compared with other glioblastoma surgeries like GTR or SubTR.
SURG-12. CLINICAL OUTCOMES OF AWAKE SURGERY WITH INTRAOPERATIVE MRI FOR INSULAR GLIOMA
Authors: Takada Shigeki , Makino Yasuhide , Yamamoto Etsuko , Sano Noritaka , Sawada Masahiro , Tanji Masahiro , Mineharu Yohei , Kikuchi Takayuki , Arakawa Yoshiki
Published: November 2024

BACKGROUND

Surgical resection of insular glioma remains challenging due to the complex functional involvement and the intricate vascularization of the insular lobe. We reviewed clinical outcomes of awake surgery with intraoperative MRI for insular glioma at our hospital.

METHODS

We retrospectively reviewed the records of 27 consecutive patients with insular gliomas who underwent surgical treatment between 2014 and 2024. The extent of resection (EOR), ischemic complication and Karnofsky Performance Status (KPS) at postoperative discharge were analyzed in the awake surgery (AS) group compared to the non-awake surgery (NAS) group.

RESULTS

There were basal ganglionic involvement (12 cases), Berger-Sanai zone III&IV (10 cases), and I, II, III&IV (6 cases). Surgical resection was performed in 24 cases (biopsy in 3 cases). Elective awake surgery: 18 cases (of which 5 were abandoned due to poor arousal); intraoperative MRI: 24 cases. Additional resection after intraoperative MRI review was performed in 10 cases. The followings were studied in 24 cases where surgical resection was performed. In characteristics, basal ganglionic involvement was significantly different (3 patients in AS group and 7 patients in NAS group, p=0.04). The mean EOR was 81.4% in AS group vs. 53.4% in NAS group (p=0.008). Ischemic complication rate on postoperative MRI was 15.4% (2 cases) in AS group and 9.1% (1 case) in NAS group; all of them had no permanent neurological symptoms. The deterioration of KPS at discharge was not found in both groups.

CONCLUSION

The clinical outcomes of insular glioma in awake surgery with intraoperative MRI in this study was comparable to those of the previous reports. It was indicated that awake surgery with intraoperative MRI contributes greatly to maximum safe resection for insular glioma.
SURG-13. PATHOLOGICAL EXAMINATION OF MENINGIOMA RECURRENCE AFTER ABSORBABLE ARTIFICIAL DURA MATER RECONSTRUCTION
Authors: Hirai Nozomi , Saito Norihiko , Koyahara Yuki , Hiramoto Yu , Fujita Satoshi , Nakayama Haruo , Hayashi Morito , Ito Keisuke , Iwabuchi Satoshi
Published: November 2024

INTRODUCTION

In meningioma surgery, the removal of the tumor and tumor-attached dura mater is essential. Due to its high affinity, absorbable artificial dura mater is used for the reconstruction of dural defects. In this study, we report a pathological examination of dural-like tissue in a case of meningioma that recurred at the same site after the use of absorbable artificial dura mater during initial surgery.

METHOD

We investigated two cases in which absorbable artificial dura mater was used for dural reconstruction during meningioma resection, and subsequently, a recurrent lesion was identified at the site of the dural reconstruction. We examined MRI images and surgical and pathological findings at the time of recurrence in these cases.

RESULT

All patients underwent total resection, and the pathological diagnosis was atypical meningioma. MRI images at the time of recurrence revealed multiple meningiomas along the artificial dura site. Gross findings during recurrent surgery indicated that the absorbable dura had been replaced by dura-like tissue, with the tumor also attached to the same site. Pathological findings showed bundles of fibrous tissue within the dura-like tissue, albeit with a sparser density compared to autologous dura mater. Meningioma cell invasion and angiogenesis were also observed in the dural-like tissue.

DISCUSSION

In all cases, multiple meningiomas were found along the dural-like tissue. This suggests that meningioma cells invading the dural-like tissue may have used it as a scaffold for meningioma recurrence. Future studies are necessary to determine the appropriateness of absorbable artificial dura mater for dural defect sites during malignant meningioma surgery.
SURG-17. SALVAGE SURGERY FOR LOCAL PROGRESSION AFTER RADIATION THERAPY OF BRAIN METASTASES
Authors: Arita Hideyuki , Umehara Toru , Takano Koji , Okita Yoshiko , Kinoshita Manabu
Published: November 2024

Recent advances in cancer treatments have prolonged survival after the onset of brain metastases (BM), and this trend increases the risk of local progression (LP) after radiotherapy (RT)of BM. Salvage options include surgical resection, re-irradiation and medical therapies, but there is no standard management for this clinical setting. This study aimed to evaluate the outcome of salvage surgery. We performed surgical resection for intracranial metastases in 221 cases in a single institution between Apr 2014 and Mar 2024. Of those, the data of the cases underwent initial surgery after irradiation for BM were extracted. After excluding duplicated cases and those underwent surgery within one month after irradiation, we finally analyzed 49 cases. Overall survival (OS) and local progression free survival (LPFS) were evaluated by Kaplan-Meier method. All but two cases had a history of stereotactic radiosurgery/radiotherapy for BM. Histopathological diagnosis of surgical specimens was tumor recurrence in 33 cases and radiation necrosis (RN) in 16 cases. RN cases showed longer duration between radiation and LP, when comparing with recurrent cases (median 42.3. vs. 9.3 months). OS was longer in RN cases than in tumor recurrent cases (median 68.5 vs. 26.9 months). In the recurrent cases, preoperative poor KPS (under 70), active state of extracranial lesions and RPA class were associated with shorter OS. Extent of resection, postoperative chemotherapy and local irradiation did not have significant impact on OS. Twenty cases experienced local recurrence after salvage surgery, and LPFS was 7.0 months. Any of extent of removal, postoperative chemotherapy and RT were not associated with LPFS. We reported relatively long survival after salvage surgery for local failure of BM after irradiation. Salvage surgery should be considered especially in patients with good extracranial control and performance status. High recurrence rate after salvage treatment urges the development of additional treatment approaches.
SURG-20. DEVELOPING ENDOSCOPIC RESECTION OF COLLOID CYSTS: A 25-YEAR EXPERIENCE IN 200 PATIENTS
Authors: Tosi Umberto , Haghdel Arsalan , Zappi Kyle , Uribe Rafael , Guadix Sergio , Villamater Francis , Souweidane Mark
Published: November 2024

Endoscopic resection is a legitimate treatment alternative for third ventricular colloid cysts. Increasing experience and the development of new surgical instruments and techniques have allowed this approach to reach clinical prominence. In this study, we review our 25-year experience with endoscopic resection of colloid cysts, assess factors predictive of operative success, and critically analyze our evolving clinical practice. Therefore, a prospective database was used to review all patients that had endoscopic removal of a third ventricular colloid cyst between 1995 and 2021. Demographics, imaging features, presenting symptomatology, operative approach, surgical outcomes, and complications were analyzed in 5-year intervals to determine changing patterns over time. Bivariate analyses were carried out to understand factors predisposing to outcome. Kaplan-Mayer curves were used to analyze time-to-recurrence. Over this 25-year continuum an increase in the proportion of treated patients who were asymptomatic (p < 0.001) was observed. The rate of recurrence and length of stay all decreased over time (p < 0.001) – now, with median length of stay of 1 day. The rate of complete cyst removal (CCR) increased (p < 0.001). Rate of major complications or need for postoperative CSF diversion remained low. Bivariate analyses indicated how incomplete cyst removal (ICR) was associated with recurrence. In conclusion, our 25-year experience posits endoscopic resection as an increasingly safe approach to third ventricular colloid cysts, with low recurrence rates and negligible complications. These results are attributed in-part to a continuous adaptation related to instrumentation, technique, perioperative strategy, and experience.
SURG-24. MAXIMAL SAFE RESECTION OF INSULAR GLIOMAS: AN EVALUATION OF SURGICAL AND PROGNOSTIC OUTCOMES IN 461 CASES
Authors: Al-Adli Nadeem N , Young Jacob S , Li Jing , Quintana Daniel , Dada Abraham , Menna Grazia , Gerritsen Jasper K W , Morshed Ramin A , Hervey-Jumper Shawn L , Berger Mitchel S
Published: November 2024

INTRODUCTION

Insular gliomas are challenging to resect due to nearby functional cortical/subcortical structures and delicate Sylvian/sub-insular vascularity. Motor/language mapping and surgical experience are necessary for maximal safe resection (MSR).

METHODS

Outcomes were retrospectively evaluated following MSR in the largest single-institution series to date. 461 cases, between 1997 and 2022, were classified according to the Berger-Sanai system. Contrast-enhancing (CETV) and non-contrast-enhancing (nCETV) tumor volumes were calculated manually.

RESULTS

The final cohort comprised 226 high-grade (IDH-mutant, n=82) and 226 low-grade (IDH-mutant, n=101) tumors. Median nCETV was 47.7ml (grade 2, n=226), 72.6ml (grade 3, n=136), and 46.8ml (grade 4, n=90). Median CETV was 22ml for grade 3 and 13.6ml for grade 4 tumors. Most were classified as Zone I (37%), IV (8.6%), or I+IV (15%). For high-grade tumors, median CE-EOR was 96.1% (range, 29.7-100), which was highest in Zone I (100%), and supra-maximal resection was achieved in 5 cases. For low-grade tumors, median nCE-EOR was 82.4% (range, 28.4-100), which was highest in Zone 4 (85%). Additionally, initial nCETV in low-grade tumors was not associated with nCE-EOR, even when controlling for location. New postoperative motor deficits by discharge were significantly higher in Zones II (24%), I+II (22%), and III (23%). For dominant-hemisphere tumors, language deficits were highest in Zone I+II (44%), Giant (32%), and Zone II+III (29%) tumors. At 3 months, language deficits persisted in Giant (7.1%) tumors and motor deficits persisted in Giant (6.4%) and Zone II (5.9%) tumors. Median overall survival (OS) was 114.6 (grade 2), 108.6 (grade 3), and 14.7 (grade 4) months. In primary high-grade tumors, OS was longer with CE-EOR > 97.1% (36.8 vs.14.7 months, p=.04) and nCE-EOR of > 80.8% (91.3 vs. 20.2 months, p<.001).

CONCLUSIONS

In a high-volume academic center, surgical resection of insular gliomas with cortical/subcortical mapping can achieve excellent EOR with minimal language and motor morbidity.
SURG-31. HYBRID THERAPY FOR NEWLY DIAGNOSED AND RECURRENT GLIOBLASTOMA: STAGED PROCEDURE INTEGRATING OPEN SURGICAL RESECTION WITH LASER INTERSTITIAL THERMAL THERAPY
Authors: Berke Chandler , Khalafallah Adham , Lu Victor , Gurses muhammet , Ivan Michael , Komotar Ricardo , Shah Ashish
Published: November 2024

BACKGROUND

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults with a median overall survival (OS) of 15.6 months. Despite advancements, 5-year survival rates have not significantly improved. Laser interstitial thermal therapy (LITT) has been employed to treat both newly diagnosed (nGBM) and recurrent GBM (rGBM) with demonstrable safety and efficacy. Traditionally, LITT has been limited to smaller lesions given physical and thermal constraints.

OBJECTIVE

We present two case examples of a novel, hybrid treatment approach to GBM, utilizing both surgery and laser ablation as part of a single-staged procedure.

METHODS

Two geriatric (>65 years) patients with nGBM or rGBM were treated with surgical resection followed by LITT the subsequent day. Both patients underwent preoperative magnetic resonance imaging (MRI) showing multifocal disease with a dominant component, causing mass effect in the second case, and an unresectable component.

RESULTS

The first case underwent surgical resection of a large, multicentric rGBM in the parieto-occipital region, followed by LITT of an unresectable lesion in the inferior temporal gyrus. The second patient underwent surgical resection of the dominant temporal lobe component, and LITT of the insular component. Neither patient had intraoperative or ablation complications. Both patients had stable postoperative neurological exams and were discharged on the day after ablation, with no new deficits at follow-up.

CONCLUSION

The prognosis for GBM remains dismal despite significant research and attempts at advancements in patient management. Surgical resection is a critical component of the GBM treatment paradigm. However, surgery alone is not sufficient in many patients. LITT has shown promise for improving GBM outcomes, mainly due to its minimal invasiveness, enhanced immune responses, BBB disruption, and cytoreductive potential. We demonstrate a novel, hybrid approach to GBM using hybrid surgical resection and LITT in a single-staged procedure to overcome traditional constraints of LITT.
SURG-37. ADVANCING GLIOBLASTOMA RESEARCH THROUGH RESECTION MODELS
Authors: Hurtado Thenzing Judá Silva , Yong Raymund , Tsankova Nadejda
Published: November 2024

Regardless of its cellular and molecular heterogeneity, glioblastoma (GBM) tumors share a common hallmark: an infiltrative growth pattern that poses challenges to surgical resection and leads to incomplete tumor removal. As part of the current standard-of care treatment, patients undergo surgery in addition to temozolomide and radiation therapy. In GBM research, mice are often used to replicate tumor development and test treatments, but this approach typically omits the crucial aspects of surgical intervention, and thus fails to recapitulate important aspects of human GBM disease progression at the surgical margin. Here we address this challenge by developing a technique for tumor resection in mice. First, we implant the infiltrative patient derived GBM cell line Akaluc G16302 in the frontal cortex, specifically at anteroposterior 2mm, mediolateral 0.5mm, dorsoventral 1mm starting from bregma. After 6 weeks, we anesthetize the mouse and do a craniotomy at the injection site, approximately 3-4mm in diameter. We perform a circumferential cut using a curved Fukushima scissor at the edges of the craniotomy area and scoop the tumor core, mimicking surgical resection. Mice survive the surgery and are alive up to 37 days post-resection. Histology confirms resection of tumor cells and a surgical tumor margin remaining in the xenograft animal. In our pilot study, mice undergoing resection displayed significantly increased overall survival compared to mice without surgery (log-rank p-value = 0.0448; n=6; survival range of 91-100 days for control and 97-107 days for resected mice), recapitulating survival benefit also seen in humans. This preliminary data demonstrates the feasibility of the technique and resection-associated survival benefit. Such advancements enable researchers to more accurately replicate the biology of GBM progression and treatment response observed in human patients, bringing us closer to modeling the clinical scenario in mice. Key words: Glioblastoma, resection, biopsy
SURG-39. LONG-TERM RESULTS OF INTERVENTION FOR GROWING INCIDENTAL MENINGIOMAS OR CONTINUED ACTIVE SURVEILLANCE, A PROSPECTIVE COHORT STUDY
Authors: Strømsnes Torbjørn , Lund-Johansen Morten , Behbahani Maziar , Skeie Geir Olve , Skeie Bente Sandvei
Published: November 2024

Incidental meningiomas are common findings. They represent a clinically challenging cohort, without a detailed consensus on their management. The risk of tumor progression and that of intervention must be considered. Long-term prospective data on incidental meningiomas are sparse. We aimed to evaluate the long-term effect of Gamma Knife Radiosurgery (GKRS), surgical resection and continued observation for growing incidental meningiomas. A prospective database of 62 patients (70 tumors) commenced under active surveillance was established in 2009. Radiological and clinical data was obtained until sept 2023. The results of long-term observation (group 1) and intervention with GKRS (group 2) or surgery (group 3) at progression was analyzed. Due to growth, 41 (58.6%) tumors were treated. The mean growth rate was higher prior to GKRS (2.1 cm 3 /y) and surgery (0.4 cm 3 /y) than during long-term active surveillance (0.009 cm 3 /y) (p < 0.001). The meningiomas became in mean 31.3% and 99.1% smaller after GKRS and resection, respectively. In comparison, tumors under long-term surveillance increased in mean 27.2% (p < 0.001). According to the RANO response criteria, the complete, partial, and minimal response versus stable disease rates were higher following intervention, the overall progressive disease rates were similar (Group 1; 20.7%, group 2: 11.4% and group 3: 16.7%) (p = 0.232). Treatment versus no-treatment did not affect overall survival (Group 1; 10.3 y, group 2: 11.8 y and group 3: 13.5 y (p = 0.264). No symptom development was registered in group 1. In group 2, 2.9% experienced transient (grade 2) adverse events, and in group 3, 50% suffered permanent (grade 4) adverse events according to the Common Terminology Criteria for Adverse Events (CTCEAv5). Intervention reduces tumor volume; however, the clinical significance remains uncertain and side effects are not negligible. Active surveillance is safe, saves > 40% of patients from unnecessary interventions and does not compromise future treatments. The optimal timing of intervention should be further explored.
SURG-41. OPTIMIZING PATIENT OUTCOMES IN PETROCLIVAL MENINGIOMA TREATMENT: EVALUATING SURGICAL, RADIOSURGICAL, RADIOTHERAPY AND COMBINED TREATMENT APPROACHES
Authors: Nasta Shagun , Persad Amit , Shaghaghian Elaheh , Hori Yusuke , Emrich Sara Coleman , Ustrzynski Louisa , Tayag Armine , Park David , Chang Steven
Published: November 2024

Petroclival meningiomas pose a formidable challenge due to their proximity to critical neurovascular structures, necessitating complex surgical interventions with a high risk of complications. Stereotactic radiosurgery (SRS) offers an alternative or complementary treatment option, yet the optimal treatment strategy remains undefined. We aimed to evaluate the local control rates following surgical resection, radiotherapy, and SRS for petroclival meningiomas and to assess the incidence of cranial nerve palsies associated with each treatment modality. This retrospective study reviewed medical records of patients treated for petroclival meningiomas at Stanford University between 1980-April 2024. Pre- and post-treatment radiological data were analyzed to assess local control. Cranial nerve function was evaluated pre- and post-treatment, and at last follow-up. A total of 171 patients (129 females; median age 54.65 years) diagnosed with petroclival meningioma were identified. Treatment modalities included: 31 patients underwent surgical resection alone, 27 received SRS alone, 11 received radiotherapy alone, 36 underwent combined surgical resection and SRS, 28 received combined surgical resection and radiotherapy, 9 were treated with a triad of surgical resection, SRS, and radiotherapy, and 29 were managed with serial imaging alone. The percentage change of tumor volume from diagnosis to follow-up for these groups was -55.6%, 28.9%, 73.0%, -64.9%, -12.0%, 35.3%, and -8.8%, respectively. The incidence of new cranial nerve palsies was highest (68%) in patients who underwent surgical resection. The percentage of worsening pre-existing palsies was greater in patients receiving single-modality non-surgical treatment. Surgery, radiotherapy, and SRS demonstrated promising local control rates for specific patient cohorts with petroclival meningiomas. Patients receiving combination therapies generally fared better than those receiving single-modality treatments, with surgery followed by SRS yielding the best outcome. The incidence of cranial nerve palsies was lower following SRS and radiotherapy compared to surgery. Future research should focus on refining multi-modal treatment strategies to minimize complications and improve patient quality of life.
SURG-44. TO PROCEED OR NOT TO PROCEED: THE IMPACT OF FROZEN SECTION PATHOLOGY ON INTRAOPERATIVE BRAIN BRACHYTHERAPY IMPLANTATION FOR RECURRENT GLIOBLASTOMA
Authors: Zeller Sabrina , Soldozy Sauson , Spirollari Eris , Rao Divya , Floyd John , Zhu James , Hanft Simon
Published: November 2024

BACKGROUND

Glioblastoma (GBM) is a highly aggressive malignancy that recurs in up to 90% of patients following standard-of-care therapy, including surgical resection, concurrent chemoradiotherapy, and subsequent adjuvant chemotherapy. In cases of prior radiation therapy (RT) use, one option for localized, recurrent GBM (RGBM) is STaRT (Surgically Targeted Radiation Therapy) (GammaTile, GT Medical Technologies, Tempe AZ USA), a form of brachytherapy utilizing cesium-131 seeds implanted at the time of re-resection. One of the potential concerns with STaRT implantation for RGBM is that intraoperative frozen section pathology may demonstrate only necrosis, in which case further RT may not be advisable. This concern is often cited as a deterrent to offering an intraoperative brachytherapy treatment in RGBM cases. Herein we review the frequency of intraoperative frozen section diagnosis returning radiation necrosis leading to aborted GammaTile placement.

METHODS

The GammaTile Registry, a prospectively enrolling multi-center phase 4 study (NCT04427384), was assessed for all patients receiving intraoperative brachytherapy for RGBM from 10/2020 to 3/2024. Data regarding patient demographics, procedure details, and pathology were extracted and analyzed.

RESULTS

A total of 122 RGBM patients with a median age of 59 years (range 28-86) were scheduled for STaRT. Of these, 109 (89.3%) patients had confirmed prior radiation with a median RT dose of 60.0Gy (range 16-75). Only two (1.6%) planned cases of GammaTile placement were aborted after intraoperative frozen section pathology demonstrated extensive radiation necrosis without viable tumor. The patients had received fractionated RT to 55.8Gy and 60.0Gy, respectively. While both frozen samples were predominantly necrosis, the final pathology demonstrated foci of residual glioblastoma in both cases.

CONCLUSIONS

While it is uncommon in RGBM to abort STaRT due to intraoperative pathology indicating only radiation necrosis, careful consideration should be given when aborting the procedure as in this series final pathology ultimately demonstrated viable tumor cells.
SURG-45. OUTCOMES OF PATIENTS RECEIVING SURGICAL RESECTION AND STEREOTACTIC RADIOSURGERY VS. STEREOTACTIC RADIOSURGERY ALONE FOR MOTOR CORTEX METASTASES
Authors: Juncker Ryan , Finger Guilherme , Weber Matthieu , Wu Kyle , Damante Mark , Kreatsoulas Daniel , Elder James Bradley
Published: November 2024

BACKGROUND

Local therapy for brain metastases typically involves stereotactic radiosurgery (SRS), with surgical resection considered for larger and/or symptomatic tumors. For lesions in eloquent areas, surgical management is controversial given the risks of neurologic deficits. This study compared clinical outcomes in patients with motor cortex metastases who received surgery + SRS or SRS alone.

METHODS

Patients treated for motor cortex metastases from 1/2018 – 12/2022 were identified. Demographic/preoperative variables included age, gender, race, tumor histology, adjuvant therapies, pre-treatment neurological exam, and Karnofsky Performance Scale. Treatment variables included the number of brain metastases, maximum tumor diameter, and radiation dose/number of fractions. Outcome measures included post-treatment neurological exam, seizures, and overall survival (OS).

RESULTS

351 charts were identified – 80 surgery + SRS and 271 SRS alone. 50 consecutive patients in each group were included in this analysis. Surgery + SRS patients were younger (59.0 vs. 63.9; P=0.020) with larger tumors (2.8 vs. 0.83cm; P<0.001), while the SRS only group had more brain metastases per patient (2 vs. 6; P<0.001). No differences were seen in the remaining demographic/preoperative variables. Pre-treatment, surgery + SRS patients had significantly increased frequency (45/50, 90% vs. 25/50, 50%; P<0.001) and severity (4 vs. 5; P=0.001) of motor deficits, and a higher likelihood of seizures (25/50, 50% vs. 8/50, 16%; P<0.001). Despite the surgery + SRS group being more symptomatic pre-treatment, the frequency and severity of motor deficits and seizures was similar between cohort’s post-therapy. Surgery + SRS patients also demonstrated higher rates of pre- to post-treatment improvement in motor function (29/45, 64% vs. 3/25, 12%; P<0.001) and longer OS from the date of treatment (7.5 vs 4 months; P=0.021).

CONCLUSION

Given the equivalent neurological outcomes, higher rates of functional improvement, and improved oncologic outcomes, surgery should be a consideration for patients with brain metastases in eloquent areas, particularly those with symptomatic lesions.
SURG-46. ENDOLYMPHATIC SAC TUMORS: A CASE REPORT AND REVIEW OF THE LITERATURE
Authors: Turner Scott , Carillo Jose , Anker Lars , Stelling Adam
Published: November 2024

Endolymphatic sac tumors are rare, histologically benign tumors that pose a danger of local bony destruction. Definitive treatment is complete surgical resection but the use of subsequent radiotherapy remains controversial and is typically used for residual or recurrent disease. Additionally, these tumors are associated with von-Hippel-Lindau (VHL) syndrome and are present in 10-30% of patients with this autosomal dominant disorder. We present the case of a 69 year-old woman who presented with cranial nerve 7 and 8 palsies that had started in the 1990s and was found to have a left CPA mass. She underwent pre-operative embolization followed by 2 stage craniotomy and post-operative radiotherapy. Testing for the VHL mutation was negative.
SURG-53. LONG TERM FOLLOW-UP OF RESECTION PLUS CESIUM-131 BRACHYTHERAPY FOR PREVIOUSLY IRRADIATED RECURRENT BRAIN METASTASES
Authors: Yacoub Irini , Young Robert J , Reiner Anne S , Gantini-Larsen Alexandra , Yamada Yoshiya , Pike Luke R G , Krebs Simone , Damato Antonio , Aramburu-Nunez David , Yu Kenny Kwok Hei , Brennan Cameron , Tabar Viviane , Moss Nelson S , Imber Brandon S
Published: November 2024

BACKGROUND

Recurrent brain metastases (rBM) after previous radiosurgery present a clinical dilemma, as the advantages of reirradiation need to be weighed against the potential of significant radiation toxicity. Salvage resection with Cs-131 brachytherapy offers improved dosimetry due to reduced integral dose to healthy brain compared to repeat radiosurgery. We previously reported initial results of rBM treated with resection and salvage Cs131 brachytherapy; we present an updated analysis of tumor control with extended follow-up.

METHODS

We analyzed consecutive patients with rBM previously treated with radiosurgery, who underwent salvage resection plus implantation of Cs131 seeds (GammaTile, GT Medical Technologies). The prescribed brachytherapy dose was 60 Gy at 5mm from the cavity. Median follow-up was calculated using reverse Kaplan-Meier. Local recurrence was defined by new nodular contrast enhancement with hyperperfusion within 5mm of the resection cavity. Marginal recurrence was defined as >5mm but not beyond 1cm from the cavity. Local control and overall survival (OS) from brachytherapy were analyzed using Kaplan-Meier.

RESULTS

Twenty-five patients underwent Cs131 implantation in 30 tumor cavities. The median presurgical rBM maximal diameter was 2.95 cm (range 1.1-6.3). The most common histology was lung adenocarcinoma (n=8, 27%) followed by breast (n=7, 23%) and renal cell (n=3, 10%). Radiographic gross- or near-total resection was achieved in 80% of lesions. The median number of Cs131 seeds implanted was 17, (range 6-30), (median strength 3.5 U/seed). With median follow-up of 37 months (95%CI:29-45), twelve and 24-month OS was 55% and 41%, respectively. Four tumors recurred (3 in-field, one marginal) for a 1- and 2-year local control rate of 87% and 81%, respectively. Data for adverse radiation effects is under analysis and will be presented.

CONCLUSIONS

With over 3 years of follow-up, intraoperative brachytherapy with collagen-embedded Cs131 implants was associated with durable local control for this challenging clinical scenario. A randomized Phase II trial of Cs131 vs. standard of care for rBM (NCT04690348) is actively accruing.