bluuebunny/crossref_metadata_2025_split huggingface dataset:
RADT-17. SINGLE INSTITUTION REVIEW OF OUTCOMES FOLLOWING STEREOTACTIC RADIOSURGERY FOR SIX TO EIGHTEEN BRAIN METASTASES: INTRACRANIAL FAILURE RATES AND NEED FOR FURTHER CRANIAL RADIOTHERAPY
Authors: Lynch Sophie , Chia Kazumi , Manik Vishal , Brazil Lucy , Forner Samantha , Venkatasai Jeyaanth , Hassan Sheila , Akhtar Yasmin , Blythe Kirsty , Al-Salihi Omar 
Published: November 2023

Abstract

BACKGROUND
A single centre retrospective review of outcomes following linear accelerator - based stereotactic radiosurgery (SRS) for patients with 6 to 18 brain metastases was conducted.

METHODS
Patients receiving SRS to multiple metastatic sites were identified from our institutional database and subsequently stratified into those with 6-9 metastases (group 1) and 10 or more metastases (group 2).

RESULTS
45 patients were evaluated in total with a mean number of metastases of 7 for group 1 and 14 for group 2. Mean total GTV volumes for each SRS treatment were 1.92cc (group 1) and 2.70cc (group 2). Median overall survival was 8 months for group 1 (0 -51 months) and 7 months (3-36 months) for group 2 . Following SRS, median time to intracranial progression was 3 months for both groups, occurring in 59% and 64% of group 1 and group 2 patients respectively. Following relapse, more patients in group 2 received whole brain/posterior fossa radiotherapy rather than SRS when compared with those in group 1 (80% vs 40%). The majority of patients surviving more than 1 year following SRS for ≥6 brain metastases had a targetable mutation (defined as any of ALK/EGFR/ROS1/BRAF mutation, ER+, HER 2+, PDL1 expression ≥ 1) in their primary tumour; 75% of group 1 and 100% of group 2.

CONCLUSIONS
Although this study represents small patient numbers, we show that long term survival can be achieved for some patients following SRS for more than 5 brain metastases. However, many patients with more than 10 brain metastases develop intracranial relapse shortly after SRS and require whole brain/posterior fossa radiotherapy, indicating these patients are less likely to benefit from SRS. The presence of a targetable mutation in the primary tumour may indicate a better outcome following SRS for more than 5 brain metastases and warrants further investigation.
RADT-22. STEREOTACTIC RADIOSURGERY FOR VESTIBULAR SCHWANNOMA WITH RADIOGRAPHIC BRAINSTEM COMPRESSION
Authors: Shah Anjay , De Leo Alexandra , Li Jonathan , Bova Frank , Friedman William , Amdur Robert 
Published: November 2023

Abstract

BACKGROUND
The safety of single treatment stereotactic radiosurgery (SRS) for vestibular schwannoma (VS) with radiographic evidence of brainstem compression- but without motor deficit- is controversial. Data on linac-based SRS in this setting are scarce. We address this deficit in the literature with a report of outcome of an unselected series of patients with VS with radiographic brainstem compression treated with linac SRS our institution.

METHODS
We included patients with unilateral VS of any size with radiographic brainstem compression at the time of SRS. All patients were without serious brainstem neurologic deficits at the time of SRS. The SRS prescription dose was 12.5 Gy in a single fraction using 6MV photon beams produced by a linear accelerator and delivered with a multiple arc technique. Inclusion in this study required at least 1 year of radiographic follow-up with magnetic resonance imaging (MRI). The primary endpoint was freedom from serious brainstem toxicity (CTCAEv5 grade &gt;3); secondary endpoint was freedom from tumor enlargement considered to represent tumor progression, or any type of enlargement requiring surgical intervention. We also assessed serious cranial nerve complications, excluding hearing loss, defined as CTCAEv5 grade 3 toxicity.

RESULTS
Among 139 patients, the median MRI follow-up time was 5 years and the median tumor size was 2.5 cm greatest axial dimension and 5cc in volume. The median brainstem D0.03cc = 12.6 Gy, and the median brainstem V10Gy = 0.4cc. At 5 years, the actuarial freedom from serious brainstem toxicity was 100% (zero cases), and freedom from tumor enlargement, either requiring surgery or due to progression, was 90%. The rate of grade 3 facial nerve damage in patients without tumor enlargement was 0.9% (1/113).

CONCLUSION
Linac-based SRS as delivered in our series for VS with radiographic brainstem compression is safe and effective.
RADT-31. OPTIMAL TIMING OF CHEMORADIATION AFTER RESECTION OR BIOPSY OF GLIOBLASTOMAS: A NATIONWIDE POPULATION-BASED STUDY
Authors: Roh Tae Hoon , Lee Yeonhu , Kim Se-Hyuk 
Published: November 2023

Abstract

BACKGROUND
The optimal time interval of concomitant chemoradiotherapy (CCRT) after surgery for newly diagnosed glioblastoma (GBM) patients remains controversial. This study was aimed to assess whether the interval between surgery and CCRT leads to a survival difference.

METHODS
Using the Korean National Health Insurance Research Database, 3,586 patients diagnosed with GBM in South Korea from 2008 to 2021 were retrospectively reviewed. The eligibility criteria were GBM-diagnosed patients who underwent surgical resection or biopsy and received CCRT (with temozolomide (TMZ)) within 6 weeks thereafter. Patients were divided into two groups based on interval between surgery and CCRT initiation: early radiotherapy (RT) within 21 days and late RT &gt; 21 days. Patients were separately examined by the type of surgery – biopsy alone or resective surgery. Overall survival (OS) was estimated using the Kaplan-Meier method and log-rank tests. Univariable and Multivariable Cox regression analyses were performed to assess the impact of the covariables on OS.

RESULTS
The median OS for early RT group was 20.47 months compared to 17.94 months of late RT group (Log rank P value of 0.0002). Early RT was associated with prolonged OS in multivariable analysis adjusting age, sex, length of stay in hospital after surgery, and the procedure type of biopsy or tumor resection. On the contrary, subgroup analysis showed that patients who received early RT after biopsy showed higher OS than the patients who received late RT (15.93 months vs. 11.83 months).

CONCLUSION
Patients who received CCRT after 21 days of operation showed better OS than those with earlier CCRT initiation. In contrast, in the group patients who received biopsy alone showed better outcomes when started RT within 21 days. This result suggests that optimal timing of initiation of CCRT after surgery for glioblastoma may be different according to the remnant tumors.
RADT-37. INTERIM RESULTS OF ACCELERATOR-BASED BORON NEUTRON CAPTURE THERAPY, RANDOMIZED CONTROLLED TRIAL FOR RECURRENT AND REFRACTORY HIGH-GRADE MENINGIOMAS
Authors: Miyatake Shin-Ichi , Wanibuchi Masahiko , Kawabata Shinji , Furuse Motomasa , Nonoguchi Naosuke , Nihei Keiji , Fu Naonori , Ono Koji 
Published: November 2023

Abstract

BACKGROUND
High-grade meningiomas (HGMs) recurred after X-ray treatment showed 5.2 months as median progression free survival (mPFS) and only 24.6 months as median overall survival (mOS) from the literatures. Recently, we showed much more excellent OS and PFS using reactor-based boron neutron capture therapy (BNCT) (Neuro-Oncology 24:90-98, 2022). Based on these data, we started “A phase II investigator-lead RCT using accelerator-based BNCT system for refractory recurrent high-grade meningioma”, with the aid of Japanese governmental financial support.

METHODS
We prepared 2 study arms, BNCT test treatment arm (12 subjects) and control best supportive care arm (6 subjects) in RCT fashion. PFS judged by third party committee was set-up as primary endpoint and PFS judged by investigators themselves and OS of BNCT arm were set-up as secondary endpoints. To diminish ethical problems of this RCT, rescue BNCT is permitted for control group patients, if they showed progress disease during the observation period. Macdonald criteria was adopted for assessment. The first patient-in was August 2019 and the last patient-in was August 2021. Interim results of this trial: Three and two grade 3 subjects were included in BNCT and control arm, respectively. Others were grade 2 subjects. As of April 20, 2023, mPFS judged by investigators showed 90 weeks and 8 weeks for BNCT and control arm, respectively (P = 0.0004). OS-2 year rates of BNCT and control arms are 91.7% and 25%, respectively (p = 0.01)

CONCLUSION
Primary endpoint, mPFS judged by third party committee is still being closed and unknown, so far, until the end of the trial (August 2024). With regard to secondary endpoints, there are marked differences in both arms in mPFS judged by investigators. Also, OS in BNCT arm is extremely excellent in comparison with EORTC RCT of “trabectedine” and PD-1 blockade reports, just recently appeared.
RADT-49. A SYSTEMATIC REVIEW AND META-ANALYSIS OF HIPPOCAMPAL AVOIDANCE IN WHOLE BRAIN RADIOTHERAPY AND PROPHYLACTIC CRANIAL IRRADIATION
Authors: Leskinen Sandra , Shah Harshal , Yaffe Beril , Schneider Shonna , Ben-Shalom Netanel , Boockvar John , D'Amico Randy , Wernicke A Gabriella 
Published: November 2023

Abstract
PURPOSE: Hippocampal-avoidance radiotherapy has been under investigation as a technique to improve neurocognitive function in patients undergoing whole brain radiotherapy (WBRT) for intracerebral tumor treatment and control. To understand the effectiveness of hippocampal-avoidance radiotherapy compared to conventional radiotherapy, we systematically reviewed hippocampal-avoidance WBRT (HAWBRT) and hippocampal-avoidance prophylactic cranial irradiation (HAPCI). METHODS: We searched the PubMed database for studies involving hippocampal-avoidance radiation therapy, adhering to PRISMA guidelines. Included studies were analyzed for median overall survival, progression-free survival, hippocampal relapse rates, and neurocognitive function testing. RESULTS: Our initial search identified 3709 results, of which 22 studies were ultimately included and a total of 1749 patients analyzed. Seven of the included studies were randomized controlled trials, five were prospective cohort studies, and ten were retrospective cohort studies. Brain metastases were the most commonly treated tumor. There were 19 studies (86.4%) that evaluated HAWBRT and/or HAPCI in patients with brain metastases. Rates of hippocampal relapse were low (overall effect size = 0.04; 95% confidence interval [0.03, 0.05]) and there was no significant difference in risk of relapse between HAWBRT and conventional WBRT (n=5 studies; risk difference = 0.01; 95% confidence interval [-0.02, 0.03]; p = 0.63). Among the thirteen studies that assessed changes in neurocognitive function, significant differences were identified in overall cognitive function and memory/verbal learning 3-24 months post-RT. Significant differences in processing speed and executive function were reported by some studies at 4 and 6 months. No studies reported differences in verbal fluency, visual learning, concentration, and psychomotor speed at any timepoint. CONCLUSION: Analyzed studies in HA-WBRT/HA-PCI showed low hippocampal relapse or metastasis rates. Significant differences in neurocognitive testing were most prominent in overall cognitive function, memory, and verbal learning. Studies were often hampered by loss to follow-up. Further studies into the effectiveness of HA-WBRT are warranted.
CTIM-06. A PHASE 2 STUDY OF A NOVEL IMMUNOTHERAPY SL-701 IN ADULTS WITH RECURRENT GLIOBLASTOMA: EXPLORING THE PROGNOSTIC VALUE OF TREATMENT-INDUCED CD8+CD57+ T-CELLS AS A MARKER FOR SURVIVAL
Authors: Peereboom David , Lindsay Ross , Badruddoja Michael , Nabors L Burt , Kumthekar Priya , Lieberman Frank , Schiff David , Sherman Jonathan , Butowski Nicholas , Dunbar Erin , Fink Karen , Iwamoto Fabio , Moertel Christopher , Schulder Michael , Walbert Tobias , Chattopadhyay Pratip , Habboubi Nassir , Grzegorzewski Krzysztof , Brooks Christopher , Reardon David 
Published: November 2023

Abstract
Recurrent glioblastoma (GBM) remains a challenging disease with limited therapeutic options and poor prognosis. SL-701 is a novel immunotherapy composed of synthetic peptides designed to elicit an anti-tumor immune response against the overexpressed GBM antigens IL-13Rα2, ephrinA2, and survivin. In this study, we present updated findings from a phase 2 clinical trial (NCT02078648) evaluating SL-701+poly-ICLC+bevacizumab, where the 12-month overall survival (OS) was 50%. Using high-parameter flow cytometry, we compared the quality of the treatment induced T-cell response in patients with an OS &lt; 12m (n = 15) versus OS &gt;12m (n = 12). Among the patients assessed, 89% exhibited heterogeneous T-cell responses against SL-701, with no discernible correlation between the response to a specific peptide and survival. Consequently, we focused on identifying other characteristics of the pan-SL701-specific T-cell response with an association to survival. Assessing all time points collected, patients with an OS &gt;12m generated a significantly higher frequency of SL-701-specific CD8 T-cells (79% increase, P &lt; 0.005) and a lower frequency of CD4+ T-cells (36% decrease, P &lt; 0.05) compared to patients with a lower OS. Moreover, the ratio of CD8:CD4 T-cells was 2-fold higher in patients with an OS &gt;12m indicating a CD8-enriched response, whereas patients with an OS &lt; 12m had a lower ratio of CD8:CD4 associated with CD4 enriched responses. Notably, patients with an OS &gt;12m, expressed CD57 (identifying highly cytotoxic, differentiated memory T-cells) on 40% of their T-cells compared to 18% in patients with an OS &lt; 12m (P &lt; 0.05). Furthermore, the ratio of SL-701 specific CD57:CD107A expressing cells trended 20% lower in patients with an OS &gt;12m, indicative of a replicating, cytotoxic T-cell response that is not terminally differentiated. These qualitative differences in the immune response, detectable as early as week 8 post treatment, may serve as biomarkers for monitoring and predicting survival. Deep sequencing of SL-701-specific T-cells is planned.
CTIM-14. PHASE 1 SAFETY LEAD-IN AND RANDOMIZED OPEN-LABEL PERIOPERATIVE STUDY OF VORASIDENIB COMBINED WITH PEMBROLIZUMAB IN RECURRENT OR PROGRESSIVE ENHANCING IDH1-MUTANT ASTROCYTOMAS: SAFETY LEAD-IN RESULTS
Authors: Wen Patrick , Peters Katherine , de la Fuente Macarena , Mellinghoff Ingo , Arrillaga-Romany Isabel , Kumthekar Priya , Clarke Jennifer , Puduvalli Vinay , de Groot John , Zhang Xiangmin , Chisamore Michael , Abshire Michelle , Mahboub Paria , Hassan Islam , Knipstein Jeffrey , Cloughesy Timothy 
Published: November 2023

Abstract
Isocitrate dehydrogenase 1 mutations (mIDH1) occur in ~80% of grade 2/3 gliomas. Vorasidenib (VOR), an oral, brain-penetrant, dual inhibitor of mIDH1/2 enzymes, is an investigational treatment for mIDH gliomas. A neoadjuvant perioperative study in grade 2/3 mIDH gliomas suggested VOR renders the tumor immune microenvironment amenable to immune checkpoint blockade. This study (NCT05484622) evaluates safety/tolerability of VOR plus pembrolizumab to determine the recommended combination dose (RCD) (safety lead-in phase), and CD3+ T-cell infiltration in tumors following preoperative treatment (perioperative phase). Seven patients with recurrent or progressive enhancing grade 2/3 astrocytoma with an IDH1-R132H mutation were dosed in the safety lead-in phase: median age 39 (range, 34–60) years, 3 (43%) female, 6 (86%) grade 3 at screening. Patients received VOR 40 mg orally once daily (QD) plus pembrolizumab 200 mg intravenously once every 3 weeks (Q3W). As of April 29, 2023, patients received a median of 2 (range, 2–5) cycles with six (86%) ongoing; one (14%) discontinued due to disease progression. No dose-limiting toxicities (DLTs), adverse events (AEs) leading to study drug discontinuation, or AEs of special interest (AESI, elevated liver transaminases) were reported during the DLT evaluation period. Six (86%) patients experienced a treatment-related AE, none of which were grade ≥ 3. One (14%) patient experienced a serious, related AE of dysphasia (leading to VOR and pembrolizumab interruption) that subsequently resolved; both drugs were resumed. After the data cut-off, one patient (14%) experienced a grade 2 AESI. Based on safety review committee evaluation, VOR 40 mg QD + pembrolizumab 200 mg Q3W was confirmed as the RCD for the recently initiated perioperative phase. In this phase, ~60 patients will be randomized 1:1:1 to the RCD, VOR 40 mg QD alone, or no treatment prior to surgery. All patients can receive the RCD post-surgery. Funding: Servier and Merck & Co., Inc.
CTIM-17. ADDITIONAL RESULTS FROM A PHASE 1B STUDY OF IGV-001 IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Perez-Olle Raul , Pennock Gregory , Scott Charles , Hooper D Craig , Judy Kevin , Andrews David 
Published: November 2023

Abstract
Imvax has developed the Goldspire™ platform to create IGV-001, an autologous biologic-device combination product for the treatment of newly diagnosed glioblastoma (ndGBM). IGV-001 consists of autologous GBM tumor cells and an antisense oligonucleotide against IGF-1R mRNA (IMV-001), irradiated and administered via biodiffusion chambers implanted in the abdomen. Together, these components stimulate immunogenic cell death and antigen release. IGV-001 was well tolerated and multiple efficacy signals were observed in a Phase 1b study in patients with ndGBM (Andrews et al., 2021), including significant improvements in progression-free survival (PFS), radiographic evidence of tumor response, and changes in immune response biomarkers. A Phase 2b randomized, multicenter, double-blind, placebo-controlled study has been initiated to assess the safety and efficacy of IGV-001 in patients with ndGBM (NCT04485949). Here we report additional data from the Phase 1b study. We identified two different outcome groups in the ITT population with 14 (42.4%) patients with good outcome (OS ≥ 22.0 months) and 19 (57.6%) with poor outcome (OS &lt; 22.0 months). We also observed a significant correlation between PFS and OS in the ITT population. Five of 33 patients (15.2%) had an OS of at least 60 months. The safety of the biodiffusion chamber implantation and explantation procedures is further supported by data from four patients that were reimplanted upon progression in the Phase 1b study. The neutrophil:lymphocyte (N:L) ratio emerged as a potential marker of good response that will be explored further in the ongoing Phase 2b study. Overall, these data support the ongoing Phase 2b randomized study designed to assess the efficacy and safety of IGV-001 in patients with ndGBM.
CTIM-19. ONCOLYTIC DNX-2401 VIROTHERAPY PLUS PEMBROLIZUMAB IN RECURRENT GLIOBLASTOMA: A PHASE 1/2 TRIAL
Authors: Nassiri Farshad , Patil Vikas , Yefet Leeor , Singh Olivia , Liu Jeff , Dang Rachel , Yamaguchi Takafumi , Daras Mariza , Cloughesy Timothy , Colman Howard , Kumthekar Priya , Chen Clark , Aiken Robert , Groves Morris , Ong Shirley , Ramakrishna Rohan , Vogelbaum Michael A , Khagi Simon , Kaley Thomas , Melear Jason , Peereboom David , Rodriguez Analiz , Yankelevich Maxim , Nair Suresh , Puduvalli Vinay , Aldape Kenneth , Gao Andrew , Lopez-Janeiro Alvaro , de Andrea Carlos , Alonso Marta , Boutros Paul , Robbins Joan , Mason Warren , Sonaben Adam , Stupp Roger , Fueyo-Margareto Juan , Gomez-Manzano Candelaria , Lang Frederick , Zadeh Gelareh 
Published: November 2023

Abstract
Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab in recurrent glioblastoma, first in a dose-escalation and then in a dose-expansion phase, in 49 patients. The primary endpoints were overall safety and objective response rate. The primary safety endpoint was met, whereas the primary efficacy endpoint was not met. There were no dose-limiting toxicities, and full dose combined treatment was well tolerated. The objective response rate was 10.4% (90% confidence interval (CI) 4.2–20.7%), which was not statistically greater than the prespecified control rate of 5%. The secondary endpoint of overall survival at 12months was 52.7% (95% CI 40.1–69.2%), which was statistically greater than the prespecified control rate of 20%. Median overall survival was 12.5months (10.7–13.5months). Objective responses led to longer survival (hazard ratio 0.20, 95% CI 0.05–0.87). A total of 56.2% (95% CI 41.1–70.5%) of patients had a clinical benefit defined as stable disease or better. Three patients completed treatment with durable responses and remain alive at 45, 48 and 60months. Exploratory mutational, gene-expression and immunophenotypic analyses revealed that the balance between immune cell infiltration and expression of checkpoint inhibitors may potentially inform on response to treatment and mechanisms of resistance. Overall, the combination of intratumoral DNX-2401 followed by pembrolizumab was safe with notable survival benefit in select patients (ClinicalTrials.gov registration: NCT02798406).
CTIM-22. PHASE I STUDY RESULTS OF THE ANTIBODY-CYTOKINE FUSION PROTEIN L19TNF IN COMBINATION WITH LOMUSTINE FOR PATIENTS WITH RECURRENT GLIOBLASTOMA REVEAL PROMISING SAFETY AND DURABLE TUMOR RESPONSES
Authors: Weiss Tobias , Puca Emanuele , Covelli Alfredo , Gramatzki Dorothee , Roth Patrick , Neri Dario , Hemmerle Teresa , Weller Michael 
Published: November 2023

Abstract
Treatment options for recurrent glioblastoma are limited and there is a need for novel effective therapies. Recently, we showed synergistic preclinical anti-tumor activity of the immunocytokine L19TNF in combination with lomustine in orthotopic immunocompetent glioma mouse models. L19TNF is an antibody-cytokine fusion protein, comprising the pro-inflammatory cytokine tumor necrosis factor (TNF) fused to the antibody L19 that binds to a tumor-specific epitope of the extracellular matrix protein fibronectin. This allows a targeted delivery of therapeutically relevant doses of TNF to the tumor site through intravenous administration while sparing healthy tissues. Here, we present results of the completed phase I part of a phase I/II open label, multicenter, randomized study to investigate L19TNF in combination with lomustine for patients with recurrent glioblastoma (NCT04573192). Fifteen patients were enrolled from February 2021 – January 2023 and treated at three different dose levels of L19TNF in combination with lomustine. Overall, the treatment was well tolerated. The most common adverse events were asymptomatic increase of liver function tests and a decrease of white blood cells and platelets. Serial MRI assessments revealed near-complete responses in 3 patients (20%) and stable disease in 8 (53%) patients. The median progression-free survival was 4.2 months, progression-free survival rate at 6 months was 46% (7/15 patients), and median overall survival has not been reached after a median follow-up of 11 months. Serial blood assessments demonstrated a treatment-associated increase in C-reactive protein, a peripheral marker for inflammation, which correlated with progression-free survival. A patient, who showed a near-complete response that lasted 12 months relapsed at a different location. Subsequent re-challenge with L19TNF and lomustine again led to a partial response. These encouraging results justify further investigations within the phase II part of the clinical trial that is recruiting patients in four countries.