bluuebunny/crossref_metadata_2025_split huggingface dataset:
P13.04.A CRANIOPHARYNGIOMA TREATMENT: PROTONS VS. PHOTONS - A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Silva Y P , Sharma E , Łajczak P , Jabbar R , Majeed M W , Ahmed A R , Petry I N S , Chawla D , Chatterjee A , Fagundes W 
Published: October 2024

Abstract

BACKGROUND
Craniopharyngiomas are complex tumors that can present significant challenges for neurosurgeons, sometimes necessitating a range of treatment modalities, including radiotherapy.

MATERIAL AND METHODS
Through a systematic review and meta-analysis, this study evaluates the effectiveness and safety of proton beam therapy compared to traditional photon therapy for craniopharyngioma treatment. We searched major databases (Pubmed, Cochrane, and Scopus) for studies comparing proton and photon therapy for craniopharyngioma. Studies published up until April 2024 were included. We assessed event-free survival and endocrine dysfunction. The risk of bias in each study was evaluated. Pooled estimates of odds ratios using random-effects models were calculated for each outcome for patients undergoing proton versus photon therapies.

RESULTS
This systematic review analyzed data from three non-randomized studies, encompassing 375 patients who received subtotal resection followed by radiation therapy for residual tumors. Patients were divided into two groups: photon therapy (n=147, 39.2%) and proton therapy (n=228, 60.8%). With a median follow-up of 5.0 to 6.4 years, the meta-analysis revealed no significant difference in event-free survival (log OR=-0.28, 95%CI=-1.49-0.93, p=0.65) or endocrine dysfunction (log OR=0.12, 95%CI=-0.36-0.60, p=0.62) between the proton and photon therapy groups. Heterogeneity among studies was low to moderate (I²=50.59% for event-free survival, I²=0.00% for endocrine dysfunction).

CONCLUSION
This review suggests proton therapy offers comparable event-free survival and endocrine dysfunction to photon therapy for craniopharyngioma, which is especially relevant considering the substantial cost differential between these treatment options. However, further research with a greater sample size is warranted to confirm this survival outcome and explore long-term toxicity differences.
P13.08.A INTRAOPERATIVE OR POSTOPERATIVE STEREOTACTIC RADIOTHERAPY FOR BRAIN METASTASES: TIME TO SYSTEMIC TREATMENT ONSET AND OTHER PATIENT-RELEVANT OUTCOMES
Authors: Dejonckheere C , Layer J , Hamed M , Schneider M , Vatter H , Herrlinger U , Grimmer M , Kugel F , Garbe S , Giordano F , Sarria G R 
Published: October 2024

Abstract

BACKGROUND
Intraoperative radiotherapy (IORT) has become a viable treatment option for resectable brain metastases (BMs). As data on local control and radiation necrosis rates are maturing, we focus on meaningful secondary endpoints such as time to next treatment (TTNT), duration of postoperative corticosteroid treatment, and in-hospital time.

MATERIAL AND METHODS
Patients prospectively recruited within an IORT study registry between November 2020 and June 2023 were compared with consecutive patients receiving adjuvant stereotactic radiotherapy (SRT) of the resection cavity within the same time frame. TTNT was defined as the number of days between BM resection and start of the next extracranial oncological therapy (systemic treatment, surgery, or radiotherapy) for each of the groups.

RESULTS
Of 95 BM patients screened, IORT was feasible in 84 cases (88%) and ultimately performed in 64 (67%). The control collective consisted of 53 SRT patients. There were no relevant differences in clinical baseline features. Mean TTNT (range) was 36 (9 - 94) days for IORT patients versus 52 (11 - 126) days for SRT patients (p = 0.01). Mean duration of postoperative corticosteroid treatment was similar (8 days; p = 0.83), as was mean postoperative in-hospital time (11 versus 12 days; p = 0.97). Mean total in-hospital time for BM treatment (in- and out-patient days) was 11 days for IORT versus 19 days for SRT patients (p &lt; 0.001).

CONCLUSION
IORT for BMs results in faster completion of interdisciplinary treatment when compared to adjuvant SRT, without increasing corticosteroid intake or prolonging in-hospital times. A randomised phase III trial will determine the clinical effects of shorter TTNT.
P13.12.B POST-PROGRESSION SURVIVAL FOLLOWING FOCAL RE-IRRADIATION WITH 20 GY IN 5 FRACTIONS IN PROGRESSIVE CNS WHO GRADE 3 ASTROCYTOMA AND GLIOBLASTOMA - A MONOCENTRIC RETROSPECTIVE ANALYSIS
Authors: Hoffmann E , Linnenschmidt M , Behling F , Renovanz M , Bombach P , Bender B , Schittenhelm J , Bodensohn R , Tabatabai G , Eckert F , Paulsen F , Niyazi K 
Published: October 2024

Abstract

BACKGROUND
Despite multimodal treatment (resection, radiation therapy, alkylating chemotherapy and/or tumor-treating fields), the treatment of progressive CNS WHO Grade 3 astrocytoma and glioblastoma remains challenging. Re-irradiation (Re-RT) might be considered in the course of the disease. Optimal fractionation/dose prescription schedules are still under investigation, underlining a gap in clinical data in this regard. Here, we retrospectively analyzed post-progression survival (PPS) and progression-free survival (PFS) in a single center cohort.

MATERIAL AND METHODS
Patients receiving Re-RT with 20 Gy in 5 fractions (4 Gy per fraction; corresponding to 35 Gy in an equivalent dose normalized to 2 Gy (EQD2)) upon progression of recurrent astrocytoma glioblastoma or grade 3 astrocytoma (12/2020-12/2022) were included. Planning target volume for Re-RT was gross tumor volume = (T1 with contrast) + 5 mm. Clinical endpoints included PPS, PFS since start of Re-RT, therapy in case of further progression, bevacizumab therapy, MGMT promotor methylation (MGMT meth), and IDH status.

RESULTS
To date, 40 patients were analyzed (27 male); median age 62.25 a, range 31-83 a; 34 GBM IDHwt, 6 other), 15 of who showed MGMT meth (24 w/o MGMT meth, 1 not determined). Primary therapy was 60 Gy with concomitant temozolomide (TMZ), TMZ + lomustine, or study medication in 30, 54.0 Gy + adjuvant TMZ in 3, and 40.05 Gy + TMZ in 7 patients. Patients received heterogenous systemic therapies and 0-3 treatment lines prior to Re-RT (median 1 prior treatment modality). Re-RT was considered in localized non-resectable progression. Median time between first line therapy and first progression was 10.8 months and between first line therapy and Re-RT 16.7 months, respectively. Seven patients received an integrated boost of up to 30 Gy. Median PFS was 2.6 months (range &lt;1-10.4 months); with 7,6 months PPS (range &lt;1 - 22.4 months). 19 patients (47.5%) received bevacizumab during further course of the disease. Following Re-RT, 16 patients (40%) received further tumor-directed therapy.

CONCLUSION
This is a heterogenous single-center cohort. PFS after Re-RT was 2.6 months, and PPS was 7.6 months, respectively, published data reporting 6-12 months PPS after re-irradiation (EQD2 ranging between 48-60 Gy) despite a comparatively low and conservative cumulative dose of 20 Gy (35 Gy EQD2). Treatment time was only 5 days. Thus, re-irradiation with 4 Gy x 5 could be an option in a palliative setting and could be included in interdisciplinary treatment discussions for progressive CNS WHO grade 3 astrocytoma and glioblastoma.
P13.15.A SULFASALAZINE AS RADIOSENSITIZER IN COMBINATION WITH STEREOTACTIC RADIOSURGERY FOR RECURRENT GLIOBLASTOMA - A PHASE 1 DOSE-ESCALATION
Authors: Skeie B , Bragstad S M , Sarowar S , Goplen D K P , Heggdal J I , Enger P 
Published: October 2024

Abstract

BACKGROUND
Glioblastoma (GBM) is an aggressive, radioresistant type of cancer with a dismal prognosis. Preclinically, Sulfasalazine (SAS) has shown radiosensitizing properties by blocking intratumoral production of glutathione (GSH). We conducted a phase 1 clinical trial to investigate safety and therapeutic potential of SAS in combination with Gamma Knife Radiosurgery (GKRS) for recurrent GBM (rGBM).

MATERIAL AND METHODS
Patients were pretreated with SAS 3 days prior to GKRS to deplete the tumor of GSH utilizing a 3 + 3 dose escalation design (1.5, 3.0, 4.5 or 6.0 g SAS/day. Endpoints were safety, quality of life (FACT-Br), changes in GSH-levels (GSH-MR spectroscopy), metabolism (11-C-MET-PET) and best radiographic response (RANO criteria). Freedom from local tumor progression (FFTP), progression-free survival (PFS) and overall survival (OS) were compared to contemporary controls.

RESULTS
Twelve patients were included. No dose limiting toxicity was observed. FACT-Br remained stable for 6 months (p= 0.056). SAS led to significant but variable reduction in intratumoral GSH levels. Six (67%) of 9 patients with PET at follow-up had reduced signal indicative of effect. Complete control was achieved for 3 (27.2%), partial response for 6 (54.5 %), stable disease for 1 (9.1 %) and immediate tumor progression in 1 (9.1 %) of the treated lesions. Median FFTP and PFS were 12.1 (95% CI 1.2 - 7.1) and 4.1 months (95% CI 1.2 - 7.1) compared to 1.6 (95% CI 1.4 - 1.8) and 1.6 (0.9 - 2.3) for controls, p &lt; 0.001 and p = 0.006, respectively. OS was longer for patients responding with compete vs. partial/stable response or progressing disease, 26.0 vs. 10.0 and 7.0 months, respectively, p = 0.017.

CONCLUSION
SAS combined with GKRS was well tolerated with preliminary evidence of anti-tumor response.
P13.16.B TARGETING RBM19 TO ENHANCE RADIOTHERAPY IN GLIOBLASTOMA
Authors: Gong Z , Li D , Cao K , Liu T , Wan Z , Wang H , Gao F , Xu T , Yang Y , Chen Y 
Published: October 2024

Abstract

BACKGROUND
Glioblastoma (GBM) treatment faces challenges due to radioresistance. This study focuses on RNA binding motif protein 19 (RBM19), a protein implicated in crucial cellular functions yet underexplored in enhancing radiosensitivity. Our research aims to elucidate the potential of RBM19 in improving radiotherapy outcomes for glioblastoma patients.

MATERIAL AND METHODS
RBM19 expression in GBM patients and normal brain tissue was analyzed using GEO datasets. The expression of RBM19 and its correlation with patient survival were assessed using clinical and follow-up data from TCGA. In vitro, we manipulated RBM19 expression in U87 and U251 glioblastoma cell lines. The radiosensitivity of cancer cells was determined through colony formation assay, apoptosis, and CCK-8 assay. The comet assay and γH2AX assay were used at different time points to detect the kinetics of DNA damage and repair. Western blot assay was applied to explore the functions of RBM19 on DNA damage response after ionizing radiation, further highlighting its role in DNA damage repair pathway. Co-immunoprecipitation was conducted to study the interaction between RBM19 and CHK1 protein. Xenografts were performed to investigate the in vivo effects of RBM19 on tumor growth.

RESULTS
Differential gene analysis identified RBM19 as consistently upregulated in GBM across multiple GEO datasets. TCGA data analysis revealed a negative correlation between RBM19 expression and overall and disease-free survival in post-radiotherapy GBM patients. In vitro, alterations in RBM19 expression influenced glioblastoma cell viability post-irradiation, knockdown reduced viability and enhanced radiosensitivity, while overexpression had the opposite effect. Comet assays demonstrated that RBM19 modification affects the extent of DNA damage post-irradiation, with knockdown exacerbating DNA damage. Immunofluorescence for γ-H2AX foci confirmed increased DNA damage in RBM19-knockdown cells. Furthermore, RBM19 knockdown significantly increased apoptosis post-irradiation. Western blot analysis showed that RBM19 influences key proteins in the DNA damage repair pathway, potentially affecting therapeutic resistance in glioblastoma cells. Co-immunoprecipitation found interactions between RBM19 and Checkpoint kinase 1 (CHK1) and ataxia telangiectasia and Rad3-related (ATR), again shedding light on its role in DNA damage repair pathways. In vivo experiments demonstrated that RBM19 knockdown extended survival and reduced tumor volume in irradiated glioblastoma-bearing mice. More DNA damage was observed in RBM19 knockdown xenografts.

CONCLUSION
RBM19 may serve as a new molecular target for radiosensitization in glioblastoma. This study provides a new direction for research and a potential therapeutic approach for the radiosensitization of clinical glioblastoma treatments.
P14.04.A A PROSPECTIVE STUDY OF TUMOR-TREATING FIELDS COMBINED WITH SYSTEMIC THERAPY IN RECURRENT GLIOBLASTOMA
Authors: Guo C , Yang Q , He Z , Duan H , Lu J , Ke C , Xie H , Chen Z , Liu R , Zhang X , Mou Y 
Published: October 2024

Abstract

BACKGROUND
Tumor-treating Fields (TTFields) monotherapy was approved for recurrent glioblastoma. However, TTFields combined with systemic therapy has not been well studied in China. This study aims to explore the efficacy and safety of such combination therapy for recurrent GBM.

MATERIAL AND METHODS
This study is a prospective, single-arm, open-label clinical trial (NCT04689087) planning to enroll 40 recurrent supratentorial GBM patients and use TTFields combined with physician chose systemic therapy. Kaplan-Meier survival curve was used to estimate PFS, OS and survival rate. The primary endpoint was 6-months OS rate (OS6). Secondary endpoints were PFS, PFS6 and safety. OS and PFS were computed from the day of initiating TTFields.

RESULTS
Fourty recurrent supratentorial GBM patients was enrolled from July 2020 to May 2023. The average age was 51 and median KPS score was 80. Sixty-eight percent (27/40) of them underwent total resection surgery and 5% (2/40) only experienced biopsy as their newly diagnosed GBM surgery. Eighty-eight percent (35/40) of patients started TTFields when they were first diagnosed as recurrence, while 12.5% (5/40) patients started TTFields at their second-time recurrence or latter. Median time from diagnosis of recurrence to initiating TTFields was 27 days. Median duration time of TTFields was 8.7 months and average compliance of TTFields was 87% (20.9 hours/day). As for molecular biomarkers, 50% (20/40) patients were MGMT protein positive and 32.5% (13/40) were TERT mutant. Chemotherapy was included in the systemic therapy in 80% (32/40) patients, antiangiogenic therapy in 60% (24/40) patients, BRAF inhibitor therapy in one patient and immune checkpoint inhibitor therapy in one patient. At data cut-off date of March 20, 2024, the median follow-up period was 20.8 months. The primary endpoint OS6 was 87.2%, the median OS was 20.2 months (95%CI 11.9-NR). Median PFS was 8.5months (95%CI 6.2-NR). PFS6 was 67.5% while the historical reference of physician’s best choice of active chemotherapy from EF-11 study showed a PFS6 of 15%. Scalp adverse events were the most common AE. Seventy-eight (31/40) of patients experienced grade 1 or 2 scalp adverse events which can be relieved by topical corticosteroids.

CONCLUSION
TTFields combined with systemic therapy showed favorable efficacy and safety in Chinese recurrent GBM patients.
P14.18.A POSTERIOR CRANIAL FOSSA RECONSTRUCTION TECHNIQUE TO REDUCE POSTOPERATIVE PSEUDOMENINGOCELE IN PEDIATRIC PATIENTS OF POSTERIOR FOSSA TUMOR SURGERY WITH SUBOCCIPITAL MIDLINE APPROACH
Authors: Tang M , Chen Y 
Published: October 2024

Abstract

BACKGROUND
Pediatric patients undergoing tumor resection through a suboccipital midline approach carry a high risk of pseudomeningocele and cerebrospinal fluid (CSF) leakage. We describe our experience of eliminating the dead space introduced by the original surgical incision compared to traditional methods to reduce this risk.

MATERIAL AND METHODS
The data of children who underwent tumor resection with a suboccipital midline approach were retrospectively analyzed. The patients were divided into a traditional group and an improved group according to whether the new technique proposed in this study was used. Complications such as pseudomeningocele, meningitis, and hydrocephalus during hospitalization and follow-up were retrospectively analyzed. Univariate and multivariate logistic regression analyses were used to explore the relationship between the use of new technology and postoperative complications. All patients were followed up regularly for 2 weeks, 1 month, and 3 months after surgery.

RESULTS
Our retrospective study identified 111 eligible pediatric patients who underwent tumor resection with a suboccipital midline approach and showed that postoperative complications were lower in the improved group than in the traditional group (39.1% vs 55.4%). This difference is particularly marked in the case of PMC (10.9% vs 27.7%, OR 0.26, p = 0.027). The use of new technology was a protective factor for postoperative PMC, while the use of new technology did not significantly lower the occurrence rate of meningitis and postoperative hydrocephalus. The pathological type of tumor may be related to the occurrence of postoperative PMC, but there was no significant statistical difference (p=0.083).

CONCLUSION
Compared with traditional surgery, eliminating the dead space caused by the primary surgical incision is a simple and feasible technique, which can reduce the incidence of pseudomeningocele.
P16.07.A STUDYING NEUROBLASTOMA TUMOR MICROENVIRONMENT THROUGH A NOVEL PRE-CLINICAL MODEL
Authors: Buxbaum C , Deo A , Manobla B , Levin S , Ash S , Shaked Y 
Published: October 2024

Abstract

BACKGROUND
Neuroblastoma is a pediatric cancer that develops from neural crest cells. It has a dramatically variable course, ranging from very aggressive disease to benign differentiation and even spontaneous regression. In neuroblastoma, a crucial prognostic marker is the distinct cutoff at 18 months of age. Thus, children older than 18 months have a significantly worse prognosis than younger children. This age cutoff was studied thoroughly, but no explanatory mechanism has been found. All current pre-clinical research encompasses models in adult subjects while the development of tumors is greatly impacted by its microenvironment, which varies between young and adult individuals, thus creating disparate biological conditions. Therefore, the development of age-relevant neuroblastoma models is of great interest, especially when age is a major prognostic factor.

MATERIAL AND METHODS
C57BL/6 mice aged 12-days (young) and 8-weeks (adults) were used to reflect the different age groups, where 12-day-old mice correspond to children younger than 18-month. Mice were orthotopically implanted into the adrenal gland with 0.5 million 9464D-luciferase tagged murine neuroblastoma cells. Tumor growth assessment was performed once a week using micro-ultrasound to estimate tumor volume. At the endpoint, tumors were harvested and prepared for histopathological and immune characterization using flow and mass cytometry.

RESULTS
Tumors exhibited divergent growth patterns when comparing young and adult mice. In the initial week following implantation, tumors in young mice showed inhibited growth in contrast to those in adult mice (0.65mm3 vs. 5.44mm3 p=0.005). Following this initial phase, tumors in young mice started to grow rapidly, eventually leading to an equal final tumor load in both groups. The tumor characteristics were notably different between the groups. For example, the tumor immune cell infiltration exhibited a significantly increased number of B cells (3.598 vs. 10.01 p=0.01), CD4 cells (31.2 vs. 41.24 p=0.32) in young mice. Conversely, adults exhibited a higher number of G-MDS’c (32.2 vs. 13.856 p=0.005).

CONCLUSION
Our study reveals a delayed development of neuroblastoma in young mice during the early post-implantation phase. This observation mimics the natural biological behavior of this disease and potentially emulates the spontaneous regression seen in children under 18 months-old. In our investigation of the tumor microenvironment, we analyzed immune cell populations, revealing notable differences between the age groups. Further and updated findings are forthcoming. This study proposes a new approach for neuroblastoma research and potentially for all preclinical studies of pediatric cancer.
P16.12.A PROPERLY TIMED AND EFFECTIVE HYDROCEPHALUS INTERVENTION ENHANCES EFFICACY IN PINEAL TUMOR MANAGEMENT
Authors: Nyalali A M , Li F , Zhang K , Leonard A 
Published: October 2024

Abstract

BACKGROUND
Pineal region tumors continue to pose challenges in their management because of their histological heterogeneity, complex anatomical location, age of presentation, and presentation with obstructive hydrocephalus. Hydrocephalus creates a paradox of management whereby both medical and surgical approaches, their timing, and outcomes are interdependent with that of hydrocephalus. We aimed to determine the more effective intervention approaches for the interdependent management of pineal tumors and the associated hydrocephalus.

MATERIAL AND METHODS
We conducted a retrospective cohort study involving 154 patients diagnosed with pineal region tumors between January 2015 and January 2021 with a minimum follow-up of one year.

RESULTS
About seventy percent (111) of patients with pineal tumors had obstructive hydrocephalus that accounted mostly for the presenting clinical symptoms (76.9 %, p=0.0001). 102 patients were intervened for hydrocephalus with about half (54) also undergoing tumor resection meanwhile the other half received chemotherapy and or radiotherapy as definitive treatments for pineal tumors. Hydrocephalus intervention was performed as primary intervention by external ventricular drainage (15), endoscopic third ventriculostomy (32), ventriculoperitoneal shunt (34), and direct tumor resection (21). Tumor resection as a secondary intervention was performed in 33 patients. Within one year, 14% of patients treated for hydrocephalus had persistent or recurrent hydrocephalus which largely occurred in patients who also had tumor removal (p=0.0001). There was a significant difference among hydrocephalus intervention approaches regarding mean surgical interventions under general anesthesia (p=0.006) and hydrocephalus-related invasive procedures such as subdural lumber puncture and drainage (p=0.016). Among the 154 patients with pineal tumors, 122 (79.2%) required intervention whereby 60 patients (49.2%) underwent tumor resection with or without adjuvant chemoradiotherapy while 62 received definitive chemotherapy and or radiotherapy. Interestingly, the extent of tumor resection was negatively affected by the interval between hydrocephalus intervention and tumor resection (p=0.009).

CONCLUSION
Ventriculoperitoneal shunting, endoscopic third ventriculostomy, and direct tumor resection remain the mainstay intervention options for pineal tumor-associated hydrocephalus. Although direct tumor removal has dual therapeutic potential by resolving hydrocephalus and tumor removal, the procedure itself increases the risk of hydrocephalus persistence or recurrence thus calling for diligently effective planning for hydrocephalus intervention parallel to the medical or surgical alternatives.