bluuebunny/crossref_metadata_2025_split huggingface dataset:
P11.10.B USEFULNESS OF PHOTODYNAMIC THERAPY (PDT) WITH TALAPORFIN SODIUM FOR GLIOBLASTOMA
Authors: Sasayama T , Tanaka K , Nagashima H , Fujita Y , Yamanishi S 
Published: September 2023

Abstract

BACKGROUND
Photodynamic therapy (PDT) with talaporfin sodium uses the toxicity of singlet oxygen generated by a reaction between a photosensitizer in tumor cells and light with a specific wavelength. PDT was introduced in our hospital in April 2017. We retrospectively analyzed the glioblastoma (GBM) patients treated with PDT and compared with the patients who did not receive PDT.

MATERIAL AND METHODS
From April 2015 to March 2023, total 145 patients with GBM were treated in our hospital. Among them, 90 patients with GBM were performed PDT. Patients of recurrence, IDH mutant, biopsy and no chemo/radiotherapy were excluded. After the tumor had been resected as extensively as possible, the region of probable tumor invasion in the resection cavity were irradiated superficially with a 664-nm diode laser for 180 sec (27 J/cm2) at a power density of 150 mW/cm. The patients’ characteristics, adverse event, changes of the MR image, recurrence pattern, outcome of the patients were analyzed. In addition, survival time of the patients between the PDT group and the non-PDT group was compared.

RESULTS
A total of 80 GBM patients were analyzed. Forty-four patients received PDT. Gross total resection (GTR), Subtotal resection(STR), and partial resection were performed in 56, 16, and 8 patients, respectively. In the PDT group, 4 patients had adverse event; cyst formation, venous infarction, brain swelling, and delirium. In most of the patients, linear high signals of 5-7 mm on DWI were detected at the surface of the resected cavity and matched the PDT-irradiated area from 1 day after PDT. All hyperintense signal on DWI disappeared in about 30 days without any neurological deterioration. Sixty-seven patients had recurrence (PDT group; 33 cases, non-PDT group; 34 cases). Recurrence pattern of distant/dissemination were significantly increased in the PDT group compared with the non-PDT group. The PDT group tended to have longer survival in both OS (p=0.08) and PFS(p=0.07) than the non-PDT group. In multivariate analysis for OS, age and MGMT promotor methylation were significant prognostic factors, but not PDT.

CONCLUSION
PDT was safety and useful for GBM. However, the PDT group had significantly more distant/disseminated recurrences than the non-PDT group. We need to analyze more cases to clarify efficacy and recurrence patterns.
P11.12.B SEIZURES IN PATIENTS WITH BRAIN METASTASES FROM BREAST CANCER: RESULTS FROM A RETROSPECTIVE SINGLE-CENTRE STUDY
Authors: Bruno F , Pellerino A , Borgognone M , Palmiero R , Bertero L , Marchesani E M , Garbossa D , Soffietti R , Rudà R 
Published: September 2023

Abstract

BACKGROUND
Seizures may be a symptom of brain metastases (BrMs) from breast cancer. Gross-total resection (GTR) is known to correlate with a better seizure control, while the impact of radiotherapy (RT) and chemotherapy (CT) still remains uncertain. In this study, we aimed to explore which clinical and molecular factors might affect seizure control in a cohort of patients with BrMs from breast cancer. Patients and

METHODS
We retrospectively included patients ≥18 with surgically resected BrMs from primary breast cancer treated in our Institution from 1991 to 2022.

RESULTS
We included 79 patients in the analysis. Thirty-three (41.7%) had a history of seizures. Seizures prevailed in patients &lt; 50 vs ≥ 50 (59.0% vs 32.0%, p=0.021), and they were not associated with BrMs location, number, or morphology (cystic vs non-cystic; bleeding vs non-bleeding). Patients with low (score 0-1) vs high (score 2-3) STAT3 expression in the peritumoural reactive astrocytes (RAs) had a slightly higher incidence of seizures (50.0% vs 35.0%, p=0.337). Seizure incidence did not differ between HER2+, HR+/HER2- and TNBC patients. Seizures tended to be more common after non-GTR as compared with GTR (21.0% vs 11.0%, p=0.293). RT and CT did not affect seizure control.

CONCLUSION
Younger age was associated with a higher risk of seizures, whereas different molecular subgroups (HER2+, HR+/HER2-, TNBC) or STAT3 expression in the RAs were not. To our knowledge, this is the first real-life study investigating the correlation between seizures and clinical and molecular factors in patients with BrM from breast cancer.
P11.13.A FREQUENCY AND SURVIVAL OUTCOMES OF MOLECULAR GLIOBLASTOMA IN IDH-WILD HISTOLOGICALLY LOWER-GRADE GLIOMAS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Nakasu S , Deguchi S , Nakasu Y 
Published: September 2023

Abstract

BACKGROUND
The WHO 2021 classification defines IDH wild-type (IDHw) histologically lower-grade glioma (hLGG) as molecular glioblastoma (mGBM) if TERT promotor mutation (pTERTm), EGFR amplification or chromosome 7 gain and 10 loss aberrations are indicated. However, majority of studies reported that patients with mGBM were likely to undergo biopsy rather than resection and less likely to receive adjuvant radiochemotherapy. Thus, while most studies have suggested the prognostic correspondence between hGBM and mGBM, the equivalence has not been sufficiently demonstrated. Furthermore, molecular marker frequency in IDHw hLGGs differ extensively between studies (pTERTm rates = 15% to &gt;70%). It is unclear if such differences are caused by methodological or other factors, however, differences may affect tumor classification and prognostication.

MATERIAL AND METHODS
We systematically reviewed articles of IDHw hLGGs studies in PubMed, Ovid MEDLINE, Cochrane library and Scopus, andmeta-analyzed mGBM prevalence and overall survival (OS) according to the PRISMA statement.

RESULTS
We selected 49 studies (N = 3748) for the analyses. mGBM rates in IDHw hLGG were significantly lower in Asian regions (43.7%, 95% confidence interval [CI: 35.8-52.0]) when compared with non-Asian regions (65.0%, [CI: 52.9-75.4]) (P = 0.005). IDHw hLGGs without pTERTm rarely expressed other molecular markers in Asian studies when compared with non-Asian studies. We compared OS rates of IDHw hLGG tumors between Asian and non-Asian studies using individual patients’ data. The median OS rate in Asian mGBM tumors (21.1 months [CI: 16.1-24.7]) was similar to in non-Asian tumors (20.8 months [CI: 17.9-22.7]) (P = 0.45). Patients with mGBM had significantly longer OS times when compared with histological GBM (hGBM) (pooled hazard ratio (pHR) in univariate analyses 0.824, [CI: 0.694-0.98], P = 0.028, I2 = 46%)). Moderate heterogeneity improved in the pooled HR in multivariate analyses, which showed a significantly better OS in mGBM (HR 0.61 [CI: 0.50-0.74], I2 = 0%) (P &lt; 0.0001). In patients with mGBM, histological grade was a significant prognostic factor (P = 0.018), as was age (P = 0.001) and surgical extent (P = 0.018).

CONCLUSION
Patients with mGBM have better OS when compared with patients with hGBM, especially when grade II histology is indicated. We identified differences between Asian and non-Asian regions in terms of molecular marker frequency pattern for mGBM in IDHw hLGG. However, OS rates in patients with mGBM were concordant between Asian and non-Asian cohorts.
P11.15.A IMPACT OF PERIOPERATIVE DEXAMETHASONE IN THE CONTEXT OF NEUROSURGICAL BRAIN METASTASIS RESECTION
Authors: Wasilewski D , Bukatz J , Peukert R , Shaked Z , Poeser P , Karbe A , Trelinska-Finger A , Jelgersma C , Frueh A , Raspe M , Radbruch H , Capper D , Schlaak M , Thuss-Patience P , Bischoff P , Horst D , Krentzke M , Xu R , Ehret F , Kaul D , Misch M , Bullinger L , Frost N , Vajkoczy P , Onken J 
Published: September 2023

Abstract

BACKGROUND
Patients with brain metastases that undergo brain metastasis resection regularly receive perioperative dexamethasone. We sought to evaluate whether perioperative dexamethasone in brain metastases is linked to survival.

MATERIAL AND METHODS
Retrospective data on perioperative dexamethasone dosage in resected brain metastasis patients at three hospital sites of the Charité from 2010-2022 were collected. Cut-off values for cumulative perioperative dexamethasone dose as a continuous predictor variable for survival were determined using maximally selected rank statistics. Patients were dichotomized based on determined cut-offs of cumulative dexamethasone (pre-operative: &lt; 40 mg vs ≥ 40 mg; post-operative: &lt; 180 mg vs ≥ 180 mg) and pre- and postoperative: &lt; 281 mg vs ≥ 281 mg). Medical records included baseline demographic, radiological, histopathological and treatment-related characteristics. Based on cut-off values for dexamethasone downstream statistical analyses included Kaplan-Meier, Cox proportional hazards regression for overall survival with adjustment for potential confounders including age, gender, Karnofsky performance index and presence of extracranial metastasis via propensity score matching.

RESULTS
539 patients were included. Median follow-up time was 58,97 months. After adjusting for age, gender, Karnofsky performance index and presence of extracranial metastasis patients with higher cumulative perioperative dexamethasone (≥281 mg) showed shorter survival (HR: 1.47 (1.20-1.80, p&lt;0.001) as compared to patients with lower cumulative doses (&lt;281 mg). This effect remained significant after correction for patients that died within 3 months after resection and for patients with KPS below 50% and, independently from this approach performing propensity score matched-based analysis of the total cohort of patients, respectively.

CONCLUSION
Cumulative perioperative dexamethasone is associated with decreased survival in the context of brain metastasis resection. Strict dosage, down taper or methods reducing corticosteroid dependency should be regularly evaluated in clinical practice in patients with brain metastases
P11.17.A TEMOZOLOMIDE ONLY FOR GBM MGMT PROMOTER METHYLATEDELDERLY PATIENTS IN REAL CLINICAL SET
Authors: Falah E , Furman O , Haisraely O , Atar is N , Jan E , Zach L , Taliansky A 
Published: September 2023

Abstract

BACKGROUND
The course of glioblastoma (GBM) is worse in elderly and low KPS patients. The NORDIC and NOA08 clinical trials proved the non-inferiority of temozolomide (TMZ) treatment to radiotherapy alone for GBM MGMT promoter methylated (MGMT MET) elderly patients. TMZ alone is thus recommended in guidelines as first line of treatment for this group of patients. The data of real life efficacy of this treatment are sparse.

MATERIAL AND METHODS
We retrospectively evaluated the data of GBM MGMT MET patients, older than 65y that were treated in the Neuro-oncology unit at Sheba MC during 2012-2022. The treatment was adjuvant TMZ 200mg/m2/day 5 days q28 days. We compared treatment outcomes in our patients to the results of the NORDIC and NOA08 RCTs.

RESULTS
36 patients were included in our analysis with stereotactic biopsy for diagnosis in 47% of them: 34 patients had GBM, 1 had WHO grade 3 Astrocytoma and in 1 patient the diagnosis was made by imaging (non diagnostic biopsy). Of this group, 25 were males and 11 females. The mean age was 76y (64-90) and 96% had KPS ≤ 60. Only one patient had IDH 1 mutation and in 9 cases IDH status was unknown. The interval from diagnosis to treatment was 2-19 weeks (median 6 weeks). The number of TMZ cycles was 1-12 (mean of 4 cycles after the exclusion of 11 patients who received less than 3 cycles). Median PFS/OS was 3 /7.5 months and 5/11 months respectively for the whole group and for patients that received ≥3 cycles. The 12/18/24 months survival rate was 33%/13%/8% respectively. 21 patients received second line treatment: 13 radiotherapy, 1 TMZ re-challenge and 7 Bevacizumab. Eight patients received a third line of treatment: 2 radiotherapy, 4 Bevacizumab, 1 Procarbazine and 1 TMZ. Grade 3-4 hematological toxicity was documented in 20% of the patients, with infections in 12.5% and bleeding in 4%. Fatigue was reported in 17% of the patients.

CONCLUSION
While our patients were older and with lower KPS than the patients in the RCTs the efficacy of TMZ only treatment was comparable with the clinical trials results with mOS of 11/11.9/8.3 month in Sheba/NOA08/Nordic patients, PFS of 5/8.4/NA in Sheba/NOA08/Nordic patients respectively. The main toxicity reported in all 3 data sets was hematological 20%/38%/12% in Sheba/NOA08/Nordic patients. We can conclude that TMZ only for GBM MGMT MET elderly patients in real clinical set is a valuable and safe first line treatment. &lt;!--EndFragment--&gt;
P11.20.B ASSOCIATION OF HAND-FOOT SKIN REACTIONS WITH SURVIVAL IN RECURRENT GLIOBLASTOMA PATIENTS TREATED WITH REGORAFENIB
Authors: Werner J , Hau P , Kowalski T , Treiber H , Roth P , Wollring M M , Stetter I , Tscherpel C , Rosen E K , Ceccon G S , Chapuy C I , Schlegel U , Weller M , Fink G R , Galldiks N 
Published: September 2023

Abstract

BACKGROUND
The phase 2 REGOMA trial suggested a survival benefit of the multikinase inhibitor regorafenib for the treatment of patients with glioblastoma at first recurrence. Hand-foot skin reactions (HFSR) following multikinase inhibitor therapy have been reported as a predictor for prolonged survival in patients with solid tumors. Data on the predictive value of HFSR in patients with recurrent glioblastoma undergoing regorafenib therapy remain scarce.

MATERIAL AND METHODS
Fifty-seven patients (age range, 35-77 years) with recurrent IDH-wildtype glioblastomas were retrospectively identified from five centers in Germany and Switzerland. Regorafenib was administered at 160 mg/d for the first three weeks of each 4-week cycle, with individual dose adjustments according to toxicity. Patients were stratified into two groups based on the occurrence of HFSR following regorafenib. Group differences were investigated using the Mann-Whitney rank-sum test and Fisher's exact test. Kaplan-Meier analysis was used for univariate analyses, and the Cox proportional hazards regression model for multivariate analyses.

RESULTS
Patients received a median of two regorafenib cycles (range, 1-14 cycles). Median follow-up after recurrence was 7.0 months (range, 0.6-35.9 months). The median number of previous treatment lines was 2 (range, 1-6 lines). At the time of data analysis, 47 patients (82%) had died. HFSR were observed in 14 of 57 patients (25%) and was associated with a significantly longer OS (10.6 vs. 6.0 months; P=0.040). No significant group differences (HFSR compared to no HFSR) were observed regarding age, the extent of resection, MGMT promoter methylation, Karnofsky performance status, or number of completed regorafenib cycles (all P&gt;0.05). Cox proportional hazards regression analysis confirmed that HFSR were associated with longer OS (P=0.039; HR, 0.438), independent of age, Karnofsky performance status, and the number of previous treatment lines (all P&gt;0.05).

CONCLUSION
Our results suggest that the occurrence of HFSR following regorafenib is associated with longer OS in recurrent glioblastoma patients.
P11.25.A TUMOR TREATING FIELDS (TTFIELDS) REAL-WORLD EXPERIENCE IN NEWLY DIAGNOSED GLIOBLASTOMA: A SYSTEMATIC LITERATURE REVIEW AND META-ANALYSIS OF OVERALL SURVIVAL
Authors: Ballo M T , Conlon P , Lavy-Shahaf G , Kinzel A , Vymazal J , Rulseh A M 
Published: September 2023

Abstract

BACKGROUND
Tumor Treating Fields (TTFields) are electric fields that disrupt processes critical for cancer cell viability and tumor progression by a multi-modal mechanism of action. TTFields therapy is FDA-approved for newly diagnosed glioblastoma (ndGBM) based on results from the randomized, phase 3 EF-14 study (NCT00916409). We assessed the overall survival (OS) benefit of adding TTFields therapy to standard of care (SOC) for patients with ndGBM treated in clinical practice, as well as the relationship between OS and device usage rate.

MATERIAL AND METHODS
A systematic literature review (PubMed, Embase, and Cochrane Library) identified single-cohort and comparative clinical studies that assessed survival in patients with ndGBM who received TTFields therapy. Inter-study heterogeneity was quantified using the Higgins I2 statistic and Cochran Q test. A distribution-free random-effects method was used to pool survival curves.

RESULTS
Nine studies were identified that evaluated survival with TTFields therapy in ndGBM. Of these, the 7 studies (1430 patients) that compared TTFields therapy with SOC to SOC alone were included in a pooled analysis for OS. The pooled data showed significantly longer OS with TTFields therapy/SOC vs SOC alone (hazard ratio [HR]: 0.63; 95% CI, 0.53-0.75; P&lt;0.001). A sensitivity analysis indicated that the effect was robust and independent of any individual study. In post-approval studies, pooled median OS was 22.2 months (95% CI, 17.3-42.6) for TTFields therapy/SOC and 17.3 months (95% CI, 13.6-22.0) for SOC alone. Gross total resection was generally more prevalent in the real-world setting, irrespective of TTFields use. Among studies evaluating device usage, an average usage rate of ≥75% was associated with prolonged OS vs &lt;75% usage (pooled HR: 0.60; 95% CI, 0.48-0.73; P&lt;0.001).

CONCLUSION
Pooled analysis of comparative TTFields therapy studies suggests a significant survival benefit with TTFields added to SOC for patients with ndGBM, and that a recommended 75% usage rate may be clinically meaningful in the real-world setting.
P11.27.A RADIOTHERAPY-INDUCED CHANGES IN THE BRAIN: A LONGITUDINAL STUDY IN PATIENTS WITH LOW-GRADE GLIOMAS
Authors: Wickborn K , van der Weide H L , Kramer M C A , de Vries E F J , Borra R J H , Spikman J M , Buunk A M , van der Weijden C W J , van der Hoorn A 
Published: September 2023

Abstract

BACKGROUND
Low-grade gliomas (LGG) are brain tumors with a comparably moderate malignancy grade and slow progression. Most patients are young to middle-aged adults with a relatively good prognosis given the advancement of multimodal treatment

METHODS
. Radiotherapy (RT) is an integral component of this treatment. During RT, protons or photons are used to eradicate the tumor while minimizing the damage to surrounding areas. However, healthy brain tissue is inevitably exposed to radiation, which can have adverse effects with a severe impact on the cognition and quality of life of survivors. With the improved survival of patients, understanding RT-induced changes and their consequences becomes more and more important. Here, we investigate the volumetric changes in LGG patients 2.5 years after treatment to gain insights into the neuronal long-term effects of RT.

MATERIAL AND METHODS
To quantify the volumetric changes in the brain of LGG patients over time, LGG patients (N= 17) were scanned before and 2.5 years after proton RT. For both time points, volume parameters per brain structure were extracted using T1w MRI scans and cNeuro® software. The volumes of the structures in the tumor-contralateral hemispheres before RT were compared with the measures 2.5 years after RT using paired samples t-tests or nonparametric alternatives.

RESULTS
Analysis of the total grey matter of the contralateral hemisphere indicated a statistically significant volumetric reduction in our cohort 2.5 years after RT. An analysis targeting volumetric changes in the contralateral hippocampus also indicated a statistically significant decrease. In the following steps, additional structures will be analyzed.

CONCLUSION
Preliminary results suggest a potential RT-induced decrease in the tumor-contralateral grey matter and hippocampal volume 2.5 years after treatment. Volumetric changes will be compared with the received radiation dose per structure using radiation dose distribution maps.
P11.33.B A PATIENT WITH GLIOBLASTOMA AND EXTENSIVE EXTRANEURAL METASTASES - DOES MOLECULAR BIOLOGY PLAY A CRUCIAL ROLE?
Authors: Moen Taule E , Brekke J , Miletic H , Sætran H , Maric S , HogenEsch I , Mahesparan R 
Published: September 2023

Abstract

BACKGROUND
Extraneural metastases of glioblastoma (GBM) are rare, reported incidence in literature is 0.4% to 2%. There is a lack in epidemiological data, and what little exists is outdated. The most commonly reported sites of metastases are bone, lymph node and lung. There is an insufficient understanding of the biological mechanism of metastasis, nevertheless, surgical intervention and peritoneal seeding through a ventriculoperitoneal shunt have been postulated as rational routes for the tumor cells. However, reports show metastasizing GBM in patients where neither of these procedures have been performed and therefore biological aspects should be elucidated. Previously, some few genomic studies have shown high mutational burden and that some mutations are only detected in the metastases, indicating clonal evolution. Commonly TP53, TERT, PTEN and CDKN2A/B have been revealed as shared mutations.

MATERIAL AND METHODS
A 55-year-old man presented with approximately 2 months of progressive headache and behavioral changes. Brain MRI revealed a left temporal lesion suspicious of GBM and no extracranial metastasis was detected. The patient underwent near total surgical resection and completed Stupp protocol. Nine months later, he was admitted to the local hospital with reduced general condition, tachypneic and lower back pain, but subsequent CT of thorax and abdomen revealed multiple pathological lesions in mediastinum, bones, lung, soft tissue, and mesentery. MRI confirmed the findings and a large soft tissue lesion at the level of the 6th thoracic vertebrae, was biopsied and showed metastasis from GBM. There was also local progression of the primary tumor in the brain. Treatment strategy was changed to a combination of lomustine, vincristine and bevacizumab. It was collected blood samples from the patient in respect of circulating tumor cells. A molecular characterization of the tumor samples was performed.

RESULTS
The primary tumor was MGMT promotor methylated, IDH-1/-2 wildtype, had no TERT promotor mutation, TP53 wildtype and ATRX was intact. The biopsy of the paravertebral lesion showed infiltration of a low differentiated, highly cellular tumor. Immunohistochemically the tumor cells were positive for GFAP, OLIG2 and S100. The molecular features revealed no mutation in BRAF or NTRK. Interestingly, PD-L1 was extremely upregulated, may indicating a potential benefit of immune-checkpoint inhibitors for extraneural metastases. A literature survey is done to find out any risk factors for metastasis.

CONCLUSION
We report a rare case of GBM with extensive extraneural metastases. This underlines the importance of comparing molecular biology, localization, and other patient and tumoral factors in order to identify any specific risk factor for metastasis. In turn, helping to stratify the follow up of this subgroup in the future.