bluuebunny/crossref_metadata_2025_split huggingface dataset:
P11.44.A THE ROLE OF RADIOTHERAPY IN MALIGNANT PERIPHERAL NERVE SHEATH TUMORS: A MULTICENTER COHORT STUDY
Authors: Jansma C Y M N , Coert J H , Grünhagen D J , Verhoef C , Martin E , Taal W 
Published: September 2023

Abstract

BACKGROUND
Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are rare and aggressive malignant soft-tissue sarcomas (STS), of which 40% are associated with neurofibromatosis type 1 (NF1). Current treatment in localized disease mainly revolves around surgical excision, yet MPNSTs harbor a high probability of local recurrence (LR). Radiotherapy (RT) is increasingly being used, as it improves local control in STS, yet does not impact survival. Nevertheless, its use is controversial in some cases as major wound complications can be much higher and NF1 patients harbor a potential higher risk for secondary malignancies as MPNST commonly arise within plexiform neurofibromas. This study evaluates the use of RT in these rare tumors and tries to understand its impact in local control, especially in the NF1 setting.

MATERIAL AND METHODS
Surgically treated primary MPNSTs between 1988 to 2019 in the MONACO multicenter cohort were included. Demographic and treatment differences, especially the use of RT, between NF1 and non-NF1 were analyzed. Univariate and multivariable logistic regression analyses were used to identify factors independently associated with the use of radiotherapy. Multivariate Cox regression analyses were performed to identify factors associated with LR in NF1 patients.

RESULTS
A total of 528 patients (31.8% NF1) were included, of which 149 (28.2%) developed a LR. RT was administered in 53.2% of patients (55.6% in NF1). Of these, 26.7% received neoadjuvant RT, and 71.2% adjuvant RT. The use of both treatment modalities was similar between patients with and without NF1. Multivariable regression showed that microscopically positive margins and high-grade tumors were independent factors for the use of RT. The rate of RT use in NF1 did not alter after correcting for tumor-, patient- and surgical factors. RT did not impact overall survival in sporadic and NF1 associated MPNST. In NF1 patients, microscopically positive margins (R1) (HR 3.2; 95% CI, 1.41-7.62), tumor size &gt;5cm (HR 2.2; 95% CI, 1.14-4.3), and a high grade (HR 3.13; 95% CI, 1.23-7.98) were independent risk factors for the development of a LR. Correcting for tumor-, patient- and surgical factors, use of RT was not associated lower rates of LR, in contrast to the sporadic population.

CONCLUSION
Radiotherapy is commonly used in MPNST treatment regardless of its origin in NF1. While it may impact LR rate in sporadic patients, this is less clear in NF1 patients. Further studies are needed to evaluate its role and indications in NF1 associated MPNST.
P11.45.B LOCAL RECURRENCE IN MALIGNANT PERIPHERAL NERVE SHEATH TUMORS: A MULTICENTER COHORT STUDY
Authors: Jansma C Y M N , Acem I , Coert J H , Taal W , Grünhagen D J , Verhoef C , Martin E 
Published: September 2023

Abstract

BACKGROUND
Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are rare and aggressive malignant soft-tissue sarcomas (STS) and compromise 5-10% of STS. About 40% of MPNST cases are associated with neurofibromatosis type 1 (NF1). High-grade MPNSTs have a high probability rate of a local recurrence (LR). Risk factors vary in current literature due to its rarity, as does the optimal treatment for LRs. Factors include the role of radiotherapy, surgical margins and NF1. This study investigated both gaps in knowledge.

MATERIAL AND METHODS
Surgically treated primary MPNSTs between 1988 to 2019 in the MONACO multicenter cohort were included. Multivariate Cox regression analyses were performed to identify factors associated with LR and overall survival (OS) after a LR diagnosis. Treatment of LR was evaluated.

RESULTS
A total of 507 patients were included in this analysis, of which 142 developed a first LR. A high-grade (HR 3.40; 95% CI, 1.32-8.70) , microscopically positive margins (R1) (HR 3.6; 95% CI, 2.16-6.00), and tumor size (HR 2.14; 95% CI, 1.04-4.42) were independent risk factors for the development of a LR. Radiotherapy (HR 0.43; 95% CI, 0.23-0.79), on the other hand, reduced the risk. Patients with a LR had significantly worse OS. Most LRs (50.7%) were treated surgically without additional therapy. Only a small amount of patients (11.3%) received additional radiotherapy.

CONCLUSION
This analysis provides important insights into clinicopathologic, and treatment factors associated with a LR and outcomes in MPNST patients. NF1 is not associated with an increased risk of developing a LR1 whereas other clinical factors are.
P11.51.B STATUS EPILEPTICUS IN WHO GRADE 2 AND 3 DIFFUSE GLIOMA - PREVALENCE AND PREDICTORS
Authors: Venugopal H , Berendsen S , van Kessel E , Seute T , Leijten F S S , Robe P A , Snijders T J 
Published: September 2023

Abstract

BACKGROUND
Status Epilepticus (SE) is a potentially life-threatening and highly debilitating manifestation of diffuse glioma. Glioma-associated SE has yet been poorly studied; consequently, evidence-based recommendations for clinical management are scarce. Prevalence and predictors of SE might vary across the biomolecular heterogeneity of glioma. We aimed to determine the prevalence of SE in grade 2 and 3 diffuse glioma throughout the disease trajectory, and identify associated baseline determinants (BD) and short-term determinants (STD).

MATERIAL AND METHODS
We conducted a single-center retrospective cohort-study in a consecutive cohort of patients with WHO grade 2 and 3 glioma, diagnosed between 2010 and 2017. Candidate determinant variables included demographic, clinical and tumor-related variables at first surgery (BD) and epilepsy-associated variables immediately preceding the first SE after diagnosis (STD). Occurrence of BD and STD was correlated to (a) all occurrences of SE and (b) SE with in-hospital treatment separately. A within-patient comparison of STD-frequency between a 30-day hazard period and control period, defined relative to the index-SE, was executed. Univariable and multivariable logistic regression analyses were performed for both BD and STD.

RESULTS
SE occurred in one third of the total cohort (n=63/197). Nearly 14% had an in-hospital treated SE. We identified several baseline clinical and tumor-related correlates of SE in the univariable analyses, including central, parietal and occipital tumor localization, tumor grade, extent of resection and acute symptomatic seizure occurrence after first surgery. In the multivariable model for all SE, parietal tumor localization and acute symptomatic seizure occurrence after first surgery were associated with an increased risk of SE, whereas baseline Karnofsky Performance Score (KPS) and cognitive disorders were associated with a decreased risk; for in hospital-treated SE, the model was too underpowered for valid analyses. None of the STD were significant predictors of (in-hospital) SE.

CONCLUSION
One third of patients with grade 2 and 3 diffuse glioma developed a SE at any timepoint after diagnosis. Baseline parietal tumor localization, postsurgical acute symptomatic seizure occurrence, KPS and cognitive status were identified as independent determinants of SE. These explorative findings, if validated, could guide personalized risk stratification, patient counselling and therapeutic decision-making in the clinic.
P11.52.A LONG-TERM SURVIVORS OF GLIOBLASTOMA: A SINGLE-CENTRE RETROSPECTIVE STUDY
Authors: Fortuna A , Luz P , Cordeiro M 
Published: September 2023

Abstract

BACKGROUND
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, yet, despite advancements in understanding its biology, it remains an incurable disease with a high mortality rate. Less than 5% of patients survive beyond 5 years, making identification of factors associated with long-term survival critical in improving outcomes for patients with glioblastoma.

MATERIAL AND METHODS
In this retrospective study, we conducted a descriptive analysis of patients who were diagnosed with glioblastoma and survived for 19 months or longer after their initial diagnosis. We included patients discussed on the multidisciplinary tumour board from September 2020 to June 2022.

RESULTS
We evaluated 43 patients, 9 of these had a survival rate of more than 19 months, with a median survival of 25.53 months. The date of diagnosis ranged from May 2017 to August 2021. The majority were male (n=7). The median age at diagnosis was 58 years (minimum 35, maximum 73). Most had good performance status (PS): 4 had ECOG 0 and 4 had ECOG 1. Concerning tumor characteristics, most presented in the parietal lobe (n=7) and 6 were IDH wild type. Other genetic alterations were not evaluated. Four patients underwent macroscopic total resection, 3 underwent partial resection, 1 partial resection and subsequent total excision and 1 biopsy. All patients completed the STUPP protocol, with half of the patients on corticoids during the protocol. Of the 9 patients, 7 relapsed. After relapse, 2 patients underwent bevacizumab, 2 patients underwent total resection one with adjuvant STUPP protocol and one with adjuvant lomustine, 1 patient had radiotherapy and bevacizumab, 1 patient had bevacizumab and lomustine and 1 patient had temozolamide in monotherapy. Out of these, 6 patients had disease progression and only 4 received a second line of treatment. All 4 patients progressed and received treatment. Of these, 3 progressed and only 1 patient received therapy. At the end of follow-up, early April 2023, 4 patients were still alive.

CONCLUSION
With all these data profiles of long-term survivors of GBM and the pooled evidence from the literature, this extremely favorable prognostic group is still difficult to define. However, clinical and tumour characteristics of long-term survivors may differ from those of shorter-term survivors. In our series, long-term survivors were found to be IDH wild-type in the majority, young male, with good PS at the time of diagnosis and had GBM located in the parietal lobe. Larger series of patients and longer follow-up periods are needed to draw more robust conclusions about prognostic and predictive factors.
P11.57.B OVER ONE YEAR OF SURVIVAL DIFFERENCE BETWEEN DISTINCT COHORTS OF GLIOBLASTOMA PATIENTS
Authors: Poon M T C , Woo P Y M , El Helali A , Brennan P M 
Published: September 2023

Abstract

BACKGROUND
Understanding the differences in outcomes based on study and patient characteristics can inform better research designs and improve the interpretation of translational glioblastoma studies.

MATERIAL AND METHODS
This study compared the clinical features and median overall survival (mOS) of 2,203 patients from two genomic cohorts (The Cancer Genome Atlas [TCGA] and the Chinese Glioma Genome Atlas [CGGA]) and two consecutive regional cohorts (Hong Kong [HK] and Southeast [SE] Scotland) with histologically confirmed glioblastoma.

RESULTS
A total of 2,203 patients with newly diagnosed glioblastoma were identified, including 414 from SE Scotland, 1,033 from HK, 510 from TCGA, and 246 from CGGA. In patients who have available treatment data and received standard chemoradiotherapy, the mOS was 35.2 months (95%CI 27.1-50.2) in SE Scotland, 22.2 (95%CI 19.0-25.5) in HK, and 14.1 months (95%CI 11.8-17.9) in TCGA. Using data from 1,023 patients from SE Scotland (N=414) and HK (N=609) where sufficient data was available, the multivariable Cox regression model did not demonstrate survival differences among patients treated in HK compared to those treated in SE Scotland (hazard ratio 0.93; 95%CI 0.80-1.08; p=0.30).

CONCLUSION
Survival differences between distinct cohorts of glioblastoma patients warrant further investigations into associated determinants to assess reproducibility and generalizability of research.
P11.61.B TUMOR ASSOCIATED EPILEPSY AND RESTRICTION OF DRIVING PRIVILEGES IN THE FIRST YEAR AFTER BRAIN TUMOR SURGERY
Authors: Dimov D D , Lazarov S , Simon M 
Published: September 2023

Abstract

BACKGROUND
In most countries, the risk of postoperative seizures prompts regulations restricting driving privileges at least temporarily following brain tumor operations. The present study investigated the frequency of epileptic seizures and driving habits in the first year after brain tumor operations in a prospective and a retrospective patient cohort.

MATERIAL AND METHODS
The authors studied overall 523 patients undergoing surgery for a brain tumor at the authors’ institution (prospective cohort, 09/2021-09/2022: N=313 and retrospective cohort, 01/2020-12/2020: N=210). Clinical data were obtained by reviewing patient charts and through (telephone) interviews.

RESULTS
The cohort included 160 (30.6%) meningiomas, 135 (25.6%) glioblastomas, 111 (21.2%) metastases and 56 (10.7%) other gliomas. 135/523 (25.8%) presented with seizure(s). At 3 months (excluding early post operative seizures) overall 57 (10.9%; prospective vs. retrospective cohort: 13.2 vs. 8.1%) patients reported seizure(s). The seizure incidence at 1 year was 18.4% (prospective vs. retrospective cohort: 18.7 vs. 18.2%). 22/173 (12.7%) patients reported de-novo seizures at 1 year. Significant predictors of seizures at 1 year included preoperative seizures (p&lt;0.001), an adverse preoperative and postoperative KPI (p=0.038 and p=0.001) as well as postoperative NANO (p&lt;0.001) score and histology (e.g. meningiomas: 7.5%, metastases: 22.0%, glioblastomas: 38.5%, other gliomas: 18.8%; p&lt;0.001). 219/318 (69.9%) assessable patients were not driving in 3 months. Reasons included no driver’s license (6.3%), death (7.9%), neurological deficits (38.4%), epilepsy (9.0%), and personal choice (12.9%). 91.3% of glioblastoma patients did not drive in 3 months (cf. metastases: 77.8%, other gliomas. 72.4%, meningiomas: 43.8%; p&lt;0.001).

CONCLUSION
We documented a high incidence of postoperative seizures and potential risk factors in patients following brain tumor surgery. Our figures support postoperative restriction of driving privileges even in seizure-naive patients (12.7% de-novo seizures at 1 year). Of note, epilepsy was the reason for not driving after surgery for a brain tumor only in 9.0%.
P11.68.A INTRA-ARTERIAL ADMINISTRATION OF [68GA]GA-PSMA-11 IN MALIGNANT PRIMARY AND SECONDARY BRAIN TUMOURS; A NOVEL APPROACH THAT SIGNIFICANTLY INCREASES TUMOUR UPTAKE AND POTENTIAL OF/FOR THERANOSTIC STRATEGIES
Authors: Pruis I J , van Doormaal P , Balvers R K , van den Bent M J , Harteveld A A , de Jong L C , Konijnenberg M , Segbers M , van Dis V , van den Bosch T P , Verburg F A , Smits M , Veldhuijzen van Zanten S E M 
Published: September 2023

Abstract

BACKGROUND
Primary and secondary brain tumours carry a dismal prognosis and require new treatment strategies. First studies into novel radionuclide therapies have thus far yielded little success, potentially because of limitary uptake in tumour upon intravenous (IV) administration. The aim of the present study was to show that intra-arterial (IA) administration of radiopharmaceuticals will lead to much higher uptake and, consequently, to higher delivered dose to the tumour, which convincingly outweighs the systemic non-target uptake.

MATERIAL AND METHODS
Ten patients with malignant brain tumours (n=5 high-grade glioma (HGG), n=5 brain metastasis (BM)) twice received 1.5 MBq/kg [68Ga]Ga-PSMA-11 followed by PET-MRI at 90, 165 and 240 minutes post-administration, first upon IV and subsequently upon selective IA administration, with a median interval time of 5 days. Standardised uptake values (SUVs) were calculated for tumour, and non-target sites (contralateral healthy brain, salivary glands and liver) using volumes of interest (VOIs). Tumour-to-liver (T/L), tumour-to-salivary gland (T/SG) uptake-ratios and simulated achievable tumour doses with either [177Lu]Lu- or [225Ac]Ac-PSMA were calculated for each patient. Paired T-test and Wilcoxon signed rank-test were performed to compare outcomes.

RESULTS
All patients showed significantly higher uptake in tumour following IA administration compared to IV administration, with a median SUVmax of 142.8 (range: 31.3-336.8) versus 10.5 (range: 5.1-17.1, P=0.005). Healthy brain showed no significant uptake, independent of the route of administration (SUVmean range: &lt;0.1-0.1). Uptake at non-target sites was comparable following IA and IV administration, resulting in more favourable T/SG-ratios of 8.4 (median, range: 1.8-18.9) for IA versus 1.8 (0.9-7.0) for IV; P=0.005 and T/L-ratios of 26.5 (7.4-68.7) for IA versus 1.8 (0.9-7.0) for IV; P=0.005. Simulations showed a maximum delivered dose to the tumours for a single treatment cycle to be 68 Gy (median, range: 5-282) for [177Lu]Lu- and 78 Gy (5-174) for [225Ac]Ac-PSMA when administered intra-arterially, versus 10 Gy (1-37) and 18 Gy (1-49), when administered intra-venously.

CONCLUSION
Selective IA administration of radiopharmaceuticals in malignant brain tumours leads to a significant and therapeutically relevant increase in target to non-target uptake ratios. This observation opens new avenues for the development of theranostic strategies for patients with HGG and BM whom we, to date, have no curative treatment to offer.
P11.77.B PREDICTING SURVIVAL IN GLIOBLASTOMA PATIENTS WHO DON’T UNDERGO NEUROSURGERY
Authors: de Haan Y , de Roover M , Duijnkerke D , Colmer N , Smits M , Dirven C M F , Vincent A J P E 
Published: September 2023

Abstract

BACKGROUND
Patients with glioblastoma have poor overall survival (OS), even with surgical treatment and adjuvant therapy. However, up to a quarter of patients with presumed glioblastoma does not receive any form of treatment and not much is known in the literature about this population. Their OS is estimated to be around 1.2 months. Generally, patients with presumed glioblastoma that don’t receive any form of treatment do so either because of their poor physical condition or because of their own preference. Receiving a terminal diagnosis comes with psychological and existential distress and providing a more personalized prognosis of survival may be beneficial in acceptance and end-of-life decision-making. We aimed to evaluate overall survival in a large cohort and analyze which clinical and radiological factors predict overall survival in this population.

METHODS
Patients in this retrospective cohort were included in a tertiary hospital in the Netherlands. Patients were eligible if they were aged above 18 years old and didn’t receive any treatment for their presumed glioblastoma. We used a log-rank test to analyze the differences in the survival between the groups are not fit enough for surgery and the group that prefers to not undergo any treatment. We performed Cox regression to analyze the predictive value of clinical and radiological factors on survival.

RESULTS
Between January 1st, 2010 and 31st December 2022 212 patients were included. The median OS of the entire cohort was 2.68 months. In the group with poor physical condition as reason for not undergoing surgery, the median OS was 1.92 months versus an OS of 2.73 months in the group that didn’t want to undergo treatment (p=0.0174). In univariate Cox regression analysis, location in the right hemisphere, not receiving any treatment because of poor physical condition, tumor crossing the midline, Karnofsky Performance Scale lower than 70, a multifocal lesion in the contralateral hemisphere and NIHSS of 5 or higher had a statistically significant increased Hazard Ratio for OS.Additional analysis of the statistical significance in a multivariable model is still ongoing.

CONCLUSION
This large retrospective cohort of patients with presumed glioblastoma that don’t receive any treatment provides more robust information about expected median overall survival and gives physicians better tools in conversations about end-of life care based on factors that influence survival.
P11.80.A DOUBLE BLIND RANDOMISED TRIAL WITH ADD-ON OF VALGANCICLOVIR OR PLACEBO TO STANDARD THERAPY OF NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Stragliotto G , Pantalone M , Brandas P , Sagerup-Bjorland L , Söderberg-Naucler C 
Published: September 2023

Abstract

BACKGROUND
The origin of glioblastoma is not known. Our earlier and other groups research have shown the presence of cytomegalovirus in glioblastoma, but not in adjacent tumor-free tissue. Furthermore there is a significant correlation between the amount of virus proteins in the tumor and prognosis, patients with low tumoral load have longer survival compared to patient with hogh tumoral viral load. In a retrospective study with 100 newly diagnosed patients with glioblastoma we showed tha the addition of valganciclovir yielded a median survival of 25 months as compared to 13 months for contemporary controls from the same institution. In the case of maximal surgical resection, the median survival reached 29 months. We therefore aimed to run a randomised doule blind study in newly diagnosed glioblastoma.

MATERIAL AND METHODS
The study started in September 2019, and has the goal to recruit 220 patients, 110 in the valganciclovir group and 110 in the placebo. A macroscopic surgery (at least 90% resection of contrast enhancing tumor on post op MRI), followed by radiation and chemotherapy with temozolomide. Patients receive the study drug, 900mg twice daily during the first 6 weeks, followed by maintenance 450mg twice daily for 2 years. There is no cross-over. The use of Optune is allowed. There is a stratification for MGMT methylation status. Only IDH1 wt tumors can be included, and the randomization has to take place within 10 weeks from surgery. The primary outcome is overall survival, secondary endpoints are the proportion surviving at 2 years and quality of life. 20 patients who fullfilled inclusions criteria have not been randomised.

RESULTS
since September 2019, 120 patients have been included at Karolinska Hospital in Stockholm. The oncology clinics in Oslo and Stavanger started including patients in September 2022, and have so far included 20 patients. At Karolinska there are 47 MGMT methylated and 73 unmethylated. Nineteen deceased patients and 45 deceased respectively. The median survival is 22 and 14 months respectively. Forteen patients with MGMT methyl completed the study (24 months and 6 months follow-up) versus 8 in the unmethylated. The survival of 20 patients not randomised was 18 months. Five patients showed reversibel hematological side effects grade 3-4, always with the initial high dose and concomittant to radiochemotherapy. No patient stopped the study due to side effects.

CONCLUSION
the is an ongoing trial, that has recruited about 35 patients per year at the main center, even during the 2 years of pandemics. about half of newly diagnosed patients are eligible for this study, and more than 80% of eligible patients are randomized which is remarkable for this category of patients. There may be a trend as a group for positive survival results, but we need to wait the final results, which may be available in 2-3 years. The study wil recruit until December 2024.