bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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 &gt;10% had ~10 times risk of locomarginal progression compared to Ki-67 ≤10% (p&lt;0.001). In tumors with Ki-67 &gt;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

Abstract

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 &gt;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

Abstract

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

Abstract

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

Abstract

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

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 &lt; 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

Abstract
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 &lt; 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

Abstract

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

Abstract

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

Abstract
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

Abstract
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 &lt; 0.001) was observed. The rate of recurrence and length of stay all decreased over time (p &lt; 0.001) – now, with median length of stay of 1 day. The rate of complete cyst removal (CCR) increased (p &lt; 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.