bluuebunny/crossref_metadata_2025_split huggingface dataset:
P13.01.A 11C-METHIONIN PET FOR RADIOTHERAPY TREATMENT PLANNING IN PATIENTS WITH RAPID EARLY PROGRESSION AFTER GLIOBLASTOMA SURGERY: PROSPECTIVE PHASE II TRIAL
Authors: Kazda T , Lakomy R , Hynkova L , Pospisil P , Vasina J , Belanova R , Prochazka T , Rehak Z , Adam J , Sana J , Burkon P , Slavik M , Selingerova I , Jancalek R , Fadrus P , Kalita O , Polachova K , Stepankova T , Lojova M , Slampa P 
Published: October 2024

Abstract

BACKGROUND
Radiotherapy (RT) is a standard treatment for nearly all glioblastoma patients following initial surgery. Few retrospective studies indicate negative prognostic instances of progression during the planning magnetic resonance (MR) (up to 1 week before initiating RT), termed Rapid Early Progression (REP). The optimal RT management for REP patients remains uncertain. The objective of this prospective phase II trial (NCT05608395) is to assess impact of 11C-Methionine PET used for RT planning in REP glioblastoma patients. It is one of the first prospective clinical interventional trials focused on this specific cohort of patients.

MATERIAL AND METHODS
We enrolled glioblastoma, IDHwt, or Astrocytoma, IDHmt, WHO grade IV patients, who developed REP characterized by 1) increase in postoperative residuum by ≥ 25%, 2) appearance of new contras enhancing lesion, 3) unequivocal progression of the unresected satelite. Patients received treatment based on the Stupp or Perry protocol. Treatment response was evaluated using RANO criteria. RT target volumes were delineated as follows: Gross tumor volume included tumor cavity, enhancing lesion and 11C-MET PET (1.3 tumor-to-background ratio). The clinical target volume was GTV plus a modified 2cm margin reflecting surrounding organs at risk. Volumetric analyses of different radiotherapy target volume were performed using EclipseTM software including patterns of failure.

RESULTS
During 12/2020 - 12/2023, total of 31 patients were enrolled (16 treated via abbreviated RT course); median age 60 years, ECOG 0-1 in 28 patients, median follow up 20 months. No effect of 11C-MET PET - based radiotherapy treatment planning of GBM patients with REP was observed on PFS (median 3.4 months comparing to 4.9 in historical control cohort) and OS (12.3 months comparing to 15.7 months). Median MET volume was 7.3cm3 (43% of MRI volume), MET avidity was presented in 7 patients et least 1cm beyond MRI volume. Central recurrence was presented in 87% patients.

CONCLUSION
The optimal treatment of patients with REP is unknown and needs to be studied in more details including dose escalation studies with reduced target margins potentialy directed also by aminoacid PET examination. Adjustment of target radiotherapy volumes using 11C-MET PET did not lead to improved PFS or OS. Supported by NU20-03-00148.
P13.10.A NORADRENERGIC AGONISTS AS NEW TREATMENT OPPORTUNITY AGAINST RADIATION-INDUCED COGNITIVE DECLINE
Authors: De Bie I , Berden L , Peeters B , Vanhove C , Boterberg T , Tabury K , Primac I , Raedt R , Benotmane R 
Published: October 2024

Abstract

BACKGROUND
Pediatric patients undergoing cranial irradiation are at risk of developing neurocognitive impairments. Mechanistically, radiation-induced injury to the hippocampi could play an important role in this debilitating condition, by inducing loss of neural stem/progenitor cells (NSCs/NPCs) and neuroinflammation, eventually leading to hippocampal atrophy. Noradrenergic (NA) agonists can potentially mitigate this radiation-induced cognitive decline by reducing cell death and inflammation. Therefore, we hypothesize that pharmacological boosting of NA will attenuate radiation-induced impairments in neurogenesis and decrease neuroinflammation, resulting in decreased memory dysfunction.

MATERIAL AND METHODS
Mice were irradiated with a single fraction of 10 Gy at P22. Reboxetine and Atipamezole were administered as 7 daily intraperitoneal injections, starting immediately after radiation. Sham therapy was administered in an identical manner by injecting equivalent volumes of sterile 0.9% NaCl. At 6 hours, 1 week, and 1 month post-radiation, radiation-induced NSCs/NPCs death, deficits in neurogenesis, and inflammation were investigated with histology. Additionally, at 1 month post-irradiation, hippocampal atrophy and memory deficits were investigated by ex-vivo MRI and a behavioral test battery, respectively.

RESULTS
We report that Reboxetine and Atipamezole significantly mitigate radiation-induced toxicity in the hippocampi. At 6 hours post-irradiation, NA agonists reduce radiation-induced apoptosis and microglial inflammation compared to sham treatment. A substantial reduction in the number of NSCs/NPCs and immature neurons within the hippocampal dentate gyrus was observed at both 1 week and 1 month post-irradiation. This deleterious effect of irradiation on neurogenesis was significantly attenuated by Reboxetine and Atipamezole, at both timepoints. Considerable hippocampal volume loss was observed after radiotherapy, which was prevented by both drugs. Finally, behavioral testing revealed that treatment with Reboxetine after radiotherapy successfully mitigated radiation-induced deficits in working and reference memory.

CONCLUSION
The present findings document the marked benefits of NA treatment against radiation-induced hippocampal NSCs/NPCs death, impaired hippocampal neurogenesis, neuroinflammation, and hippocampal atrophy. Additionally, we demonstrate that Reboxetine is able to mitigate radiation-induced memory dysfunction, which highlights the potential of NA treatment for resolving long-standing complications faced by pediatric brain tumor survivors. This project is supported by BOF (Bijzonder Onderzoeksfonds) - Ghent University (I. De Bie is a PhD fellow, grant number 01D07923).
P14.03.B A PROSPECTIVE MULTI-CENTERED, ASSESSOR BLINDED INTERIM STUDY FOR BRAIN TUMOR DIAGNOSIS BY USING CONFOCAL FLUORESCENCE ENDOMICROSCOPY (CCELL - EX VIVO)
Authors: Kang S , Byun Y , Hong D , Won J , Kang H , Kim J , Lee S , Kim M , Kim Y , Park K , Kong D , Park C 
Published: October 2024

Abstract

BACKGROUND
To address an intraoperative brain tumor diagnosis by frozen section(FS) which is time-consuming and traumatic, confocal laser endomicroscopy (CLE) has actively been explored as a promising alternative tool. In this study, we aimed to demonstrate that novel CLE image evaluation by a neuropathologist is as effective as frozen section diagnosis for histopathological assessment during brain tumor surgery.

MATERIAL AND METHODS
Utilizing a novel confocal endomicroscopy (cCeLL) wherein tissues were pretreated with indocyanine green, a prospective multicenter, assessor-blinded interim analysis was conducted at three tertiary medical institutions in the Republic of Korea. Patients newly diagnosed with brain tumors between May 2023 and April 2024 were included. Each tissue sample was divided into three smaller pieces for permanent section analysis, frozen section analysis and cCeLL-Ex vivo imaging. A designated neuropathologist interpreted all cCeLL-Ex vivo images. Statistic evaluation was performed by comparing both frozen section analysis and cCeLL-Ex vivo with permanent H&E diagnosis. The total time from sample preparation to diagnosis was also calculated.

RESULTS
A total of 274 samples were acquired from 242 patients. The predominant tumor types were meningioma (32.1%), glioma (24.8%) and pituitary adenoma (9.49%). The majority of tissue samples (86.9%) were obtained from the tumor core. Non-diagnostic tissues constituted 4.38% in frozen section and 6.57% in cCeLL-Ex vivo imaging. The diagnostic accuracy of cCeLL-Ex vivo was on par with frozen section analysis, with 96.1% and 96.9%, respectively. Both methods demonstrated comparable diagnostic sensitivity (FS vs cCeLL-Ex vivo: 99.2% vs 98.3%) and specificity(FS vs cCeLL-Ex vivo: 76.0% vs 77.8%). There were no statistically significant differences in diagnostic accuracy between frozen section (FS) and cCeLL imaging for each tumor type. The average number of cCeLL images required for neuropathologic assessment was 15.84, varing based on the tumor type, with a range of 5.05 to 27.8. The mean duration from sample preparation to diagnosis was 8 minutes and 40 seconds in cCeLL-Ex vivo and 24 minutes and 35 seconds in frozen section (p-value &lt; 0.001).

CONCLUSION
cCeLL-Ex vivo has shown promising tool as an alternative intraoperative brain tumor diagnosis compared to frozen section analysis. Future studies are anticipated to further validate its clinical utility and provide additional evidence supporting the potential of cCeLL imaging in clinical practice.
P14.14.A INTRA-ARTERIAL CHEMOTHERAPY TREATMENT FOR RELAPSING GLIOBLASTOMA: RESULTS FROM A FIVE-YEAR SERIES
Authors: Roy L , Roy M , Gahide G , Latulippe J , Fortin D 
Published: October 2024

Abstract

BACKGROUND
Glioblastoma (GBM) is the most common and aggressive type of primary brain tumour in adults. The GBM malignant phenotype depicts anarchic invasion of the brain parenchyma as well as radio-/chemoresistant properties. The complete surgical resection is unachievable and responses to standard therapy are invariably transient. In addition to the malignant GBM phenotype, the blood-brain barrier (BBB) is one of the prominent features that limits the efficacy of chemotherapy. Indeed, this facet of the brain’s blood vessels significantly blocks the passage of numerous therapeutic molecules from the blood stream to the brain. Tumour progression often occurs during or after standard first-line therapy which includes radiotherapy with concomitant and adjuvant temozolomide. The median overall survival (OS) is 14.6 months, but recurrence occurs on average only seven months after the initial diagnosis. At relapse, there is no consensus on the standard of care and the median OS ranges between three and nine months. At our institution, we use intra-arterial infusion to treat relapsing GBMs. This delivery strategy bypasses the first pass and significantly increases the local peak plasma concentration and area under the curve. This leads to a 3 to 5 fold increase of the chemotherapy concentration in the glioma-infiltrated brain parenchyma. Over the last 15 years, we have treated more than 722 patients for a total of 3600 intra-arterial chemotherapy (IAC) procedures.

MATERIAL AND METHODS
In this revision of the 2018-2023 series, we treated 59 relapsing GBM patients. Every IAC procedure was completed every four to six weeks. We reviewed the medical files to follow treatment evolution, tumour response and for grades 3 and 4 toxicity.

RESULTS
During this five-year period, a total of 406 arteriographic procedures were completed. The following chemotherapeutic agents were used: carboplatin, melphalan, methotrexate, Caelyx, carboplatin + melphalan, carboplatin + methotrexate, carboplatin + etoposide phosphate or melphalan + methotrexate. The median OS from diagnosis and relapse were 24 and 9 months respectively. A total of 28 patients suffered one or more grade 3 hematological toxicity events (17% of IAC cycles). Likewise, 24 grade 4 hematological toxicity events occurred in 16 patients (6% of IAC procedure).

CONCLUSION
In comparison with published clinical trials results, the data from our series suggest that IAC is a promising strategy for the treatment of relapsing GBM. We will gather more data and perform uni- and multivariate analyses. Moreover, we will soon begin a randomized clinical trial to test the combination of carboplatin + etoposide phosphate and carboplatin + Caelyx in the treatment of relapsing GBM. Furthermore, we are currently conducting preclinical experiment using topotecan, cytarabin and paclitaxel to determine their effectiveness in the IAC setting.
P14.16.A IS A LINAC WITH A 5MM MLC WIDTH REALLY A BARRIER TO IMPLEMENTING A HIGH-QUALITY COMPLEX SRS SERVICE?
Authors: Dean C , Bowles S , MacDougall N , Cook J , Rozati H , Lewis R 
Published: October 2024

Abstract

BACKGROUND
Stereotactic Radiosurgery (SRS) for patients with intracranial disease is increasing, especially for smaller and more numerous metastases. In England, Varian HyperArc using a Truebeam linac is nationally commissioned via benchmarking.
HyperArc contains SRS-specific optimisation and non-coplanar VMAT delivery and is an attractive option due to its cost effectiveness compared with competing specialised platforms such as Elekta GammaKnife and Accuray CyberKnife.
Depsite these benefits, the treatment of small targets or those with highly complex shapes is dominated by specialised platforms with a largely stated reason being perceived concern over delivered dosimetric certainty. This work assesses achievable dosimetric accuracy for complex SRS using Varian HyperArc suing a standard 120-leaf 5mm width MLC.

MATERIAL AND METHODS
Four patients with small and/or complex PTVs previously treated with CyberKnife at our institution were identified:26 metastases 24Gy/1f (PTV min. volume 0.01cc);5 metastases 24 Gy/1f (PTV min. volume 0.11cc);Pituitary adenoma 25Gy/1f (PTV width min. 5 mm near optics);Acoustic neuroma 21 Gy/3f (PTV width min. 3 mm near cochlea).
Patients were re-planned with HyperArc using 4 arcs at 6FFF, emulating the prescription dose spillage (PDS) & modified gradient index (mGI) achieved in the CyberKnife plans. Plans were produced in Eclipse v17.1, calculated using the AAA algorithm (v 17.1.0.1) on a 1mm calculation grid. The plan was then transferred to a CT scan of an in-house water equivalent phantom containing radiochromic EBT3 film in clinically meaningful coronal and sagittal dose planes and re-calculated.
All plans were delivered under image guidance and the 2D film dosimetry was compared with the calculated dose from Eclipse using a global 5%/1mm (TH 20%) gamma test using well-established absolute dose film methodology in Sun Nuclear SNC Patient (v 8.2).

RESULTS
In all cases, HyperArc had very similar plan quality to CyberKnife, with maximum dose gradients between 20-23% of prescription dose per mm beyond the PTV (up to 5.8Gy/mm). Up to 1mm geometric offset was permitted to allow for imaging localization & film registration uncertainty in the analysis. Mean gamma pass rates were 93.3% pre-alignment and 98.5% post-alignment.

CONCLUSION
The very high gamma pass rates achieved in this novel work illustrate excellent delivered dose accuracy for high-quality SRS plans.
The use of a radiochromic film dosimetry allows for the demonstration of such accuracy using a standard Truebeam linac without the use of a high-definition MLC even for the smallest and most complex SRS targets.
This work enables us to re-think previously held beliefs around perceived dosimetric limitations of multi-arc VMAT with a 5 mm MLC width for the delivery of high-quality SRS. Removing this barrier could start to bridge the existing gap in worldwide SRS service provision for patients.
P14.17.B MINI-CRANIOTOMY FOR RESECTION OF INTRA-AXIAL TUMOURS: EVALUATION OF TECHNIQUE USING PROPENSITY-SCORE MATCHING
Authors: Waqar M , Dainton A , Abdelaal A , Nambiar R , Maye H , Karabatsou K , D'Urso P 
Published: October 2024

Abstract

BACKGROUND
Minimally-invasive neurosurgical techniques are increasingly utilised in neurosurgery and there is growing evidence to support their use in intra-axial tumour resection. In this case control study, we compare outcomes between patients undergoing mini-craniotomy and larger sized craniotomies for intra-axial tumours using propensity-score matching.

MATERIAL AND METHODS
Review of prospective institutional database (N = 465) of adult patients undergoing intra-axial tumour resection from 2014-2021. Propensity-score matching was used to create matched groups of patients who had a mini- (≤3 cm), intermediate-sized (3-5cm) and standard (&gt;5cm) craniotomies. Outcomes included extend of resection, length of postoperative stay and 6-month complications.

RESULTS
138 patients were included distributed equally between mini- (46), intermediate-sized (46) and standard (46) craniotomy groups. The primary comparison was between the mini- and standard craniotomy groups. There was no significant difference in baseline characteristics between these groups except craniotomy size (2.8 cm vs. 6.1 cm, p&lt;0.001). Importantly, the maximum tumour diameter was similar between the groups (p=0.116). A significantly greater proportion of patients in the mini-craniotomy group had a gross-total or near total resection (80% v 52%; p=0.014). Patients in the mini-craniotomy group had a shorter mean length of post-operative hospital stay at 5 days compared to 7 days (p=0.001). There was no statistical difference in the rate of 6-month complications between the two groups (p = 0.197). A secondary analysis compared the mini- and intermediate-sized craniotomy groups. The mini-craniotomy group had a shorter mean length of postoperative stay (p=0.002) and greater proportion of gross-total/near total resections (p=0.008).

CONCLUSION
Mini-craniotomy was associated with superior extent of resection and a lower length of postoperative stay. It demonstrated non-inferiority for post-operative complications. This report adds to the growing literature demonstrating the safety, feasibility and efficacy of mini-craniotomy in neuro-oncological surgery.
P14.22.B THE ROLE OF AMINO ACID PET IN RADIOTHERAPY TARGET VOLUME DELINEATION FOR ADULT-TYPE DIFFUSE GLIOMAS: A SYSTEMATIC LITERATURE REVIEW
Authors: Horsley P , Bailey D L , Schembri G , Hsiao E , Drummond J , Back M F 
Published: October 2024

Abstract

BACKGROUND
Amino acid positron-emission tomography (AA-PET) is an emerging tool to complement magnetic resonance imaging (MRI) in glioma management. This purpose of this review was to summarise the existing literature examining use of early post-operative AA-PET for radiotherapy target volume delineation.

MATERIAL AND METHODS
A systematic search of the MEDLINE and EMBASE databases was conducted using search terms related to PET, amino acid tracers, radiotherapy and gliomas. Eligible studies included those with 20 or more patients that examined post-operative AA-PET prior to adjuvant radiotherapy and reported outcomes related to radiotherapy target volumes, relationship of PET-defined volumes to patterns of failure and/or outcomes of PET-guided radiotherapy.

RESULTS
The search yielded 534 unique studies for abstract and title screening, 71 of which proceeded to full-text review and 20 met eligibility criteria for inclusion. In all studies, the diagnosis for either all or the majority of included patients was glioblastoma. Eight studies compared PET- to MRI-derived target volumes with the consistent finding that the volumes were complementary. Seven studies related PET-derived volumes to the location of subsequent failure and consistently found AA-PET to be a strong predictor of failure location. Three studies reported outcomes of AA-PET-guided radiotherapy at standard doses. Survival outcomes were similar to trials in which radiotherapy volumes were generated based on MRI alone. Four studies reported outcomes following AA-PET-guided dose-escalated radiotherapy using a variety of regimens with mixed results with respect to patterns of failure and survival. We hypothesise that substantial differences in biologically effective dose (BED) and target volume delineation strategies between studies may have influenced the observed differences in outcomes.

CONCLUSION
Post-operative AA-PET is a promising complementary tool to MRI for radiotherapy target volume delineation, with potential benefits requiring further validation including margin reduction, reduced geographical miss and facilitation of dose-escalation. Prospective dose-escalation trials using the combination of MRI and AA-PET for target volume delineation seem warranted with close attention to BED of the chosen radiation schedule. Focused research in the setting of grade 2-3 and IDH-mutant gliomas is lacking.
P14.24.A USE OF OMMAYA RESERVOIR FOR INTRATHECAL CHEMOTHERAPY AND DISEASE MONITORING IN ROUTINE CLINICAL PRACTICE: ASSESSMENT OF SAFETY AND EFFICACY
Authors: Harahsheh E , Shah S , Butterfield R , Ariete C , Lyons M , Krishna C , Fortin-Ensign S , Zimmerman R , Bendok B R , Mrugala M M 
Published: October 2024

Abstract

BACKGROUND
Leptomeningeal disease (LMD) carries poor prognosis with an average survival of 3-6 months after diagnosis. Ommaya reservoirs (OR) are an accessible alternative to serial lumbar punctures for delivery of intrathecal chemotherapy (IC) and disease monitoring but are not widely used. Intraventricular administration of chemotherapy may be associated with superior efficacy and improved patient comfort. The purpose of this study was to assess safety and efficacy of IC and disease monitoring via OR in routine clinical practice.

MATERIAL AND METHODS
Patients who received at least one administration of IC via OR for LMD between 2017 and 2022 were included. Demographics, treatment type, complications and outcomes were recorded.

RESULTS
We identified 22 patients (17 females, 5 males) with mean age 50.9 ± 14.8 years. The primary tumors were: breast (12), leukemia (3), ovarian carcinoma (3), CNS lymphoma (1), urothelial carcinoma (1), spinal melanocytoma (1), and high-grade glioma (1). A total of 208 OR injections were performed [median was 9 OR injections per patient, interquartile range (IQR) (5, 13)]. Five patients (23%) experienced mild adverse events of grade 2 or lower by Common Terminology Criteria for Adverse Events. Overall risk of adverse event from injection was 3.4% (7/208). Eight patients (36.3%) converted into negative CSF cytology (median 1 month following first injection), and 18 patients (82%) had clinical or radiological progression of their LMD (median 2 months following first injection). Eleven patients (50%) died of their LMD during follow-up. Median OS and PFS from the first injection were 5.3 months [95% CI 4.8-NE (not estimable)] and 4.3 months [95% CI 1.8-16.0], respectively.

CONCLUSION
Use of OR in routine clinical practice is a safe and feasible option and should be strongly considered for treatment and frequent disease monitoring of patients with LMD, especially in the era of circulating tumor cells analysis. The median OS in our cohort is comparable to prior published series.