bluuebunny/crossref_metadata_2025 huggingface dataset:
P19.12.A QUANTIFICATION OF DIVERSE IMMUNE CELL SUBSETS IN PRIMARY MENINGIOMAS
Authors: Giuliani Canizales N , Lotsch C , Warta R , Jassowicz L , von Deimling A , Sahm F , Unterberg A , Herold-Mende C
Published: October 2024

BACKGROUND

Meningiomas (MGM) often exhibit clinically aggressive progression, although being primarily benign. Immunotherapy could be an alternative treatment, but knowledge regarding meningioma immunobiology remains limited. This study delved into less explored subtypes, such as B cells, NK cells, and granulocytes, to analyze their associations with disease progression and cell-cell relations.

MATERIAL AND METHODS

A cohort comprising 100 primary MGM cases was used, including all WHO grades (°1, °2, and °3), and DNA methylation classes (MCs; benign, intermediate, and malignant). To quantify infiltration of T cells, B cells, NK cells, neutrophils, and eosinophils, tumor tissue cryo-sections were obtained from the institutional biobank. Immunofluorescence stainings were performed on tumor cryo-sections and digitized as high-resolution multiple image alignments for semi-automated cell counting. The infiltration rates were then correlated with clinical data, including clinical grading, age, sex, progression-free survival (PFS) and overall survival.

RESULTS

Each subtype´s median cell infiltration varied, with T cells (0.64%) having the highest, followed by neutrophils (0.079%), B cells (0.003%), NK cells (0.006%), and eosinophils (0.0018%). B cell infiltration correlated with increasing T cells, as did eosinophils with neutrophils. WHO°1 cases exhibited higher NK cell and eosinophil infiltration compared to other WHO grades. High NK cell infiltration was characteristic of the benign MC. Neutrophils and NK cells infiltrated more in the younger sub-population (<61yo). Overall, patients with higher PFS tended to have higher infiltration of T cells, NK cells, and eosinophils, but lower B cells and neutrophils. Aggregates of T cells and B cells were found in 10% of cases, which also showed high infiltration rates of all cell types and higher PFS.

CONCLUSION

This study provides infiltration rates of rarer immune cell subtypes and their variation with clinical grading, age, and sex, as well as their relevance for MGM progression.
P20.01.B A MONO-INSTITUTIONAL RETROSPECTIVE ANALYSIS OF MENINGEAL SOLITARY FIBROUS TUMOR/ HEMANGIOPERICYTOMA: CLASSIFICATION AND GRADING SCHEMES CORRELATION WITH OUTCOME
Authors: Redaelli V , Patanè M , Pinzi V , Del Bene M , Gaviani P , Botturi A , Simonetti G , Calatozzolo C , Silvani A , Pollo B , Marucci G
Published: October 2024

BACKGROUND

The aim of the present study was to enrol a large mono-institutional cohort of patients affected by meningeal solitary fibrous tumor (SFT)/hemangiopericytoma (HPC), collecting all available clinical features and information about treatments and outcomes, in order to: - classify this population according to the 2021 WHO CNS Classification and comparing that with the previous 2016 WHO Classification; - better characterize and analyse the prognostic significance of clinical and pathological variables; - identify patients with high risk of recurrence and metastases, to improve the management of these neoplasms, with benefits also for health service

MATERIAL AND METHODS

This retrospective study included 77 patients with histopathologically proven SFT/HPC. Reclassification according to the 2021 and 2016 WHO guidelines was done. Progression-free survival (PFS) and Overall Survival (OS) were evaluated for all patients.

RESULTS

The median follow-up period was 105 months. The median PFS and OS were 106 and 154 months, respectively. Correlating OS of patients to WHO grading we observed that all Grade 1 patients according to the 2016 WHO Classification are all still alive, while only 57% of patients with Grade 1 according to the 2021 WHO Classification are alive. At the same time, only 18% of patients with Grade 1 according to the 2016 WHO Classification relapsed, while 50% of patients with Grade 1 according to the 2021 WHO Classification relapsed. These differences resulted statistically significant (p<0.05). Regarding Grades 2 and 3 cases, the differences between the WHO Classifications did not reach the level of significance.

CONCLUSION

In conclusion, the 2016 WHO Classification of SFT/HPC demonstrated a greater ability to discriminate aggressive from more indolent cases, in comparison to the 2021 WHO Classification.
P20.07.A CLINICAL OUTCOMES OF LOW-GRADE INTRACRANIAL GANGLIOGLIOMA IN ADULT POPULATION
Authors: Kulkarni J , Hutton D , Syed K , Cearns M D , Mills S J , Jenkinson M D
Published: October 2024

BACKGROUND

Gangliogliomas are rare, primary tumors of the central nervous system that occur more commonly in the paediatric and young adult demographic. While they are generally low-grade and have a favorable prognosis, tumor recurrence and progression to malignancy may occur. The aim of this study was to investigate risk factors for recurrence and the outcomes of intracranial ganglioglioma in the adult population.

MATERIAL AND METHODS

Thirteen adult patients with WHO grade 1 and 2 ganglioglioma were identified retrospectively from patient database at a tertiary neurosurgical center between 2010 and 2022. Patient characteristics, MRI features, tumor location, clinical and seizure outcomes were obtained. Surgical treatment strategies were categorized into subtotal (STR) or gross total resection (GTR).

RESULTS

Median patient age was of 29.0 years with 84.6% (n=11) temporal lobe tumors and the most common presentation (69.2%) being seizures. STR and GTR were achieved in five and nine patients, respectively. Adjuvant radiotherapy was not administered to any patient. Only one patient with STR had a recurrence at 65 months during the median follow up period of 6.5 years. Two patients had persisting seizures at last outpatient follow-up. There were no deaths.

CONCLUSION

Adult intracranial gangliogliomas WHO grade 1 or 2 have an extremely favorable prognosis with a recurrence rate of less than 10%. In cases where GTR is achieved, long term MRI surveillance is not required. Patients can be safely discharged after annual MRI for 3 years post surgical treatment. In patients where STR is achieved, annual MRI surveillance is required although the recurrence and progression rates remain low.
P20.20.B SINGLE-CENTER EXPERIENCE IN THE MANAGEMENT OF ADULT MEDULLOBLASTOMAS: A RETROSPECTIVE ANALYSIS
Authors: Kamer S , Karaman E , Acar M , Anacak Y
Published: October 2024

BACKGROUND

Medulloblastoma is a type of brain tumor that is less common in adults than in children. The standard treatment involves surgically removing as much of it as possible, followed by radiation therapy and chemotherapy. However, because this type of tumor is rare in adults, there is limited information available about its clinical characteristics and prognostic factors. This study aims to investigate the clinical features and treatment outcomes of adult patients who received postoperative radiotherapy for medulloblastoma at a single tertiary center.

MATERIAL AND METHODS

Patients aged 18 or above with a pathologic confirmation of medulloblastoma diagnosis who received postoperative craniospinal irradiation (CSI) at our institution between 2000-2021, was included in the study. Radiotherapy was administered with 3D conformal technique initially to whole cranium and spinal axis to 36Gy, followed by 18Gy boost to posterior fossa or tumor bed with 1.8Gy per fraction. Clinical characteristics, prognostic factors and survival outcomes were obtained from follow-up visits and electronic health records.

RESULTS

31 cases (median age:28 (19-44)) were analyzed, of which 54.8% were male. The pathologic diagnoses comprised of 51.6% for desmoplastic/nodular histology, 41.6% classical histology and 6.4% anaplastic histology. 25 cases were at non-metastatic stage according to Chang Classification. Total tumor resection (residual disease <1.5cm2) was achieved in 83.9% cases. Twenty-one cases (67.7%) were categorized as standard risk, while ten were classified as high-risk group. Median treatment time was 47 days (38-71) and time between surgery and radiotherapy was 44 days (14-110). Median follow-up time was 91 months. Overall, 70.4% of patients were alive and no evidence of disease while 8 of patients were deceased. Six deaths were due to disease progression, one to traumatic intracranial hemorrhage, and the cause of death for one patient could not be obtained. 5 and 10-year overall survival was found to be 89.4% and 71.9%, respectively. Sex, histopathologic subtype, risk group were not found to be statistically significant prognostic factors, whereas a prolonged duration between surgery and radiotherapy (> 6 weeks) correlated adversely with prognosis (p: 0.025). Relapse-free survival was estimated to be 71.8% and 68.2% for 5- and 10-years, respectively. Nine recurrences occurred, all being in primary site with two also recurred in spinal axis. Seven cases received surgery, five received chemotherapy and five cases received radiotherapy as a salvage treatment. Five of nine patients were deceased due to disease progression after salvage treatment.

CONCLUSION

Adult patients with medulloblastoma have a better prognosis compared to pediatric patients. Craniospinal irradiation is a crucial part of local treatment. Extended follow-up is needed to monitor for recurrence and toxicity.
P22.06.A DOES ADDING INFORMATION ON PATIENT GOALS VIA AN APP IMPROVE SHARED DECISION-MAKING IN NEUROSURGICAL CONSULTATIONS WITH BRAIN TUMOR PATIENTS?
Authors: Bras I J , Rutten G J , Sitskoorn M M , Hoogendoorn A P , Gehring K
Published: October 2024

BACKGROUND

In shared decision-making (SDM), the patient serves as the expert on their own life, while the health care professional (HCP) provides medical expertise. Recent models of SDM propose incorporating patient “goals” into the decision-making process (i.e. what patients find important activities or roles in everyday life), to better align treatment with patient preferences and everyday life priorities. This study aims to evaluate the effect of an intervention for tracking patient goals and symptoms (the Goings-On app). We will assess the number and nature of goals that brain tumor patients enter into the app, their experiences with using the app and the degree of SDM. We hypothesize that the use of the Going-on app leads to more goal-oriented discussions and will improve SDM.

MATERIAL AND METHODS

Data was collected for an observational and an intervention cohort of non-treated patients with a newly diagnosed presumed glioma or meningioma. The Goings-On app allows patients to enter their own goals (including personal photos), and symptoms, and log them daily. This information is made available to the neurosurgeon in the electronic patient file for use during the consultation. Consultations were audio-recorded and evaluated using the OPTION-MCC. This observer-based coding scheme is used to rate SDM behaviors of the HCP, patient and informal caregiver regarding: (1) goal talk: eliciting and identifying patient goals, (2) option talk: alternate options and information about options, (3) team talk: support deliberation/forming a partnership, (4) decision talk: eliciting preferences and integrating preferences and (5) evaluation talk. Following the consultation, questionnaires concerning Goings-On app usage were administered.

RESULTS

Patients in the intervention cohort (n=49) entered on average 4.7 ± 1.8 [range 1-9] goals into the Goings-On app, with the majority of goals belonging to the categories: Social/Role/Relationship (32%), Leisure/Pleasure (26%) and Everyday/Practical (22%). Of the patients who completed the questionnaires (n=44), 61% reported that their goals were discussed during the consultation, with 84% of them finding the experience pleasant and 85% considering it meaningful. Rating of SDM behaviors for the observational cohort (n=66) and the intervention cohort and analysis of between-group differences, from the audio-recordings is ongoing. Results will be expected end of July 2024.

CONCLUSION

In this study, patients reported various goals via the Goings-On app that were discussed in over half of the neurosurgical consultations, with predominantly positive patient experiences. Further investigations will show whether eliciting and depicting patient goals improves SDM for brain tumor patients during neurosurgical consultations.
P22.07.A END-OF-LIFE CHALLENGES IN NEURO-ONCOLOGICAL PATIENT CARE: A YOUNGNOA SURVEY
Authors: Lazaridis L , Pepper N , Agkatsev S , Bodensohn R , Berg R , Seliger C , Hau P , Platten M , Combs S , Mildenberger I , Müther M , Kebir S
Published: October 2024

BACKGROUND

Despite advanced treatments, malignant brain tumors inevitably relapse, almost always causing significant functional and neurological impairments in patients. Thus, palliative care is crucial in managing individuals with malignant brain tumors. It is essential for neuro-oncologists to be well-prepared and supported to openly communicate about and meet the palliative needs of these patients. With this survey, we sought to evaluate palliative care practices in Germany and their impact on the treatment of neuro-oncological patients.

MATERIAL AND METHODS

We conducted an anonymous, interdisciplinary survey targeting palliative care practices among neuro-oncologists in Germany, all members of the Neuro-oncology Working Group “Neuroonkologische Arbeitsgemeinschaft” (NOA) of the German Cancer Society (Deutsche Krebsgesellschaft, DKG). The questionnaire, designed in close coordination with board-certified palliative care specialists, was distributed to 450 physicians. It collected personal information and assessed respondents’ knowledge of and access to palliative care structures. The survey was conducted online from March 31 to April 30, 2023.

RESULTS

Ninety-two physicians (39 female, 52 male, 1 unspecified) participated and completed the survey (response rate: 20%). Of these, 81 (88%) reported feeling comfortable with end-of-life conversations, while 11 (12%) did not. No significant differences were observed between the two subgroups regarding their level of medical education (p=0.7140), workplace (p=0.4966), sex (p=0.9999), medical specialty (p=0.5478), or region of practice (p=0.9999). However, those comfortable with end-of-life discussions had significantly more palliative care training either during specialty training (p=0.0475) or through active participation in palliative care courses (p=0.0254). Further detailed analysis is in progress.

CONCLUSION

The survey indicates that while the majority of participants are comfortable with end-of-life discussions, a clear correlation exists between their comfort level and the extent of palliative care training received. This highlights the critical need for enhanced and targeted palliative care education within neuro-oncology training programs to better prepare physicians for the complex communication and care challenges in neuro-oncological palliation. Further analysis will continue to explore additional educational and systemic factors that could increase the quality of palliative care in neuro-oncology.
P23.01.A ANCIENT SCHWANNOMA MASKING DIAGNOSIS OF SECONDARY NORMAL PRESSURE HYDROCEPHALUS IN A 65-YEAR-OLD MALE PRESENTING WITH GAIT INSTABILITY: A SYSTEMATIC REVIEW AND ILLUSTRATIVE CASE
Authors: Torio J R , Rabe Y , Meceda E , Fandialan E
Published: October 2024

BACKGROUND

NPH can present as primary or secondary. Recent studies indicated that most symptoms can emerge early, while some showed delayed onset. These differences in patterns underscores the complexity of NPH relationship with its underlying causes and highlights the need for further research to elucidate the temporal dynamics of its development, aiding in early detection and appropriate management strategies.

MATERIAL AND METHODS

We report a case of a 65-year-old male diagnosed of sNPH, initially treated for a confounding left cerebellopontine angle schwannoma. A systematic search was conducted using MeSH keywords “Secondary Normal Pressure Hydrocephalus”, “Intracranial Tumors” and “Normal Pressure Hydrocephalus” on February 2024, across multiple databases. A total of 504 records were identified, wherein 110 articles were excluded and only four studies satisfied the inclusion criteria.

RESULTS

A total of 1312 cases were identified and diagnosis of NPH made through clinical history, PE and imaging studies. Of the etiologies identified in 2 studies, SAH accounted for 46.5%, post-traumatic 29%, and malignant pathology for 6.2% only. VPS insertion was the preferred treatment in all of the studies. In the study of Daou, 84.2% of patients with sNPH from SAH improved after shunt insertion, while 83% of patients with post-traumatic sNPH and 86.4% of patient with tumors, which is similar to the other studies.

CONCLUSION

Prompt identification of sNPH is crucial because its outcomes differ from iNPH. A comprehensive evaluation to determine the etiology of sNPH is indispensable in guiding appropriate management strategies to ensure optimal outcomes for affected individuals.
P23.02.A BPPV IS A SIGNIFICANT CAUSE OF DIZZINESS IN VESTIBULAR SCHWANNOMA TREATED WITH STEREOTACTIC RADIOSURGERY
Authors: Jethwa J , Williams L , Davenport S , Adonis A
Published: October 2024

BACKGROUND

Vestibular schwannoma (VS), a vestibulocochlear nerve tumour, causes disequilibrium (sensory disorientation) and imbalance. The Royal Marsden Hospital (RMH) treats VS with stereotactic radiosurgery (SRS). Those with vestibular symptoms are referred for vestibular rehabilitation, where co-existing Benign Paroxysmal Positional Vertigo (BPPV) has been found on numerous occasions. BPPV causes vertigo on head movements due to dislodged crystals in the vestibular apparatus. UK incidence is 0.04%, with causative factors being head injury, increased age, and inner-ear inflammation such as infection. Cardinal signs are history of vertigo on head movements, and vertigo and nystagmus on Dix-Hallpike testing. BPPV is treated by the Eply manoeuvre. No evidence exists of significant post-SRS BPPV in VS, but does in nasopharyngeal cancer receiving similar SRS to VS.

PURPOSE

To investigate incidence of post-SRS BPPV in VS.

METHODS

A case-note audit of VS referred for rehabilitation from 2017-2022, identifying subjective BPPV symptoms, vertigo and nystagmus on Dix-Hallpike testing, and BPPV treatment outcome.

RESULTS

24.6% (n=16) of VS patients referred to physiotherapy with dizziness had co-existing BPPV post-SRS. This was significant (p= < 0.001) compared to UK incidence. Diagnosis was confirmed by resolution of vertigo following treatment in all cases. However, disequilibrium associated with VS remained in all. In 68.7%, nystagmus was significantly absent (p=0.002) on BPPV testing compared to post-SRS nasopharyngeal cancer population. There was no significant difference in age between those with and without BPPV. The time from SRS to BPPV was 2-43 weeks (mean=12).

DISCUSSION

This is the first study finding significant incidence of BPPV in VS post-SRS. Remaining disequilibrium following successful BPPV treatment confirmed dual causes of dizziness. The causative factor is likely inflammation caused by SRS as there was no age difference, no head injury or inner-ear infection, and all cases occurred post-SRS. As BPPV occurred over a wide time following SRS, degradation of crystals may be attributable to acute inflammation and/or delayed inflammation from radiation necrosis. Lack of nystagmus in BPPV with VS may cause misdiagnosis, affecting clinical management. A theory for absent nystagmus is: nystagmus is a result of vestibular imbalance. However, VS causes slowly progressing vestibular imbalance allowing the central nervous system time to compensate, resulting in lack of nystagmus.

CONCLUSION

BPPV should be considered a side-effect of SRS in VS. Nystagmus should not be a diagnostic essential to avoid misdiagnosis and ensure correct management. More robust research is necessary to substantiate findings.
P26.13.A TUMOR TREATING FIELDS (TTFIELDS) AT A FREQUENCY OF 100 KHZ AND 170 KHZ OPEN THE BLOOD-BRAIN BARRIER (BBB) IN A 3D IN VITRO BBB-MODEL
Authors: Lysinger A S , Salvador E , Vormwald L , Ernestus R , Löhr M , Hagemann C
Published: October 2024

BACKGROUND

The highly restrictive properties of the blood-brain barrier (BBB) pose a critical hurdle in combatting brain cancer. Tumor Treating Fields (TTFields) are a non-invasive treatment modality comprised of alternating electric fields of intermediate frequency (100-500 kHz) and low intensity (1-3 V/cm) that are CE-approved for WHO grade 4 glioma, and FDA-approved for the treatment of glioblastoma. At 100 kHz, TTFields loosen the BBB by reversibly delocalizing various tight junction and associated proteins in vascular brain endothelial cells, allowing drug delivery to peripheral regions of the brain. We investigated the effects of TTFields at 100 kHz and 170 kHz on a 3D human cell-based BBB in vitro model with the goal of improving on the outcomes already demonstrated at 100 kHz.

MATERIAL AND METHODS

The in vitro BBB model combines human brain microvascular endothelial cells (HBMVEC) grown on glass coverslips and immortalized pericytes in transwell inserts, or vice versa, two crucial cell types responsible for BBB integrity. Cells were treated with TTFields at either 100 kHz or 170 kHz for 72 h, whereas untreated cells served as controls. Change in BBB permeability was assessed by fluorescein permeation assays with dextran molecular weights of 4 kDa, 40 kDa and 70 kDa immediately before and after 72 h of TTFields administration. Effects on a molecular level were investigated by immunofluorescence staining of junctional proteins ZO-1, PECAM-1 and Claudin-5 in HBMVEC after 72 h of treatment with either frequency and their expression was monitored by Western-blotting.

RESULTS

Permeability assay of various fluorescein molecules demonstrated consistent increase in HBMVEC permeability among all treated groups compared to untreated cells for molecular weights of 4 kDa and 40 kDa with a significant increase from 100 kHz to 170 kHz, as well as significant increase in permeability for 70 kDa after treatment at 170 kHz. Staining of junctional proteins ZO-1, PECAM-1 and Claudin-5 revealed delocalization from the cell membrane to the cytoplasm in all treated samples, while Western-blot proved that their expression did not change in relation to untreated controls.

CONCLUSION

TTFields with a frequency of 170 kHz showed consistent or improved effects on BBB permeabilization over 100 kHz by rearranging tight junction proteins in HBMVEC in vitro, without impairing tight junction protein expression.
P27.05.B DECODING GLIOBLASTOMA SURVIVAL: UNRAVELING THE PROGNOSTIC POTENTIAL OF OLFACTORY FUNCTION IN A PROSPECTIVE OBSERVATIONAL STUDY
Authors: Oster C , Matyar A , Hummel T , Hattingen E , Schmidt T , Jokisch M , Jokisch D , Ahmadipour Y , Sure U , Stuschke M , Tertel T , Giebel B , Kleinschnitz C , Scheffler B , Deuschl C , Kebir S , Glas M
Published: October 2024

BACKGROUND

Olfactory impairment is a common neurologic deficit among glioblastoma patients. We have previously shown that glioblastoma patients with reduced smell sensitivity had lower overall survival rates compared to those with normal olfactory function. A notable limitation in that study was the unequal distribution of prognostic factors between the two groups, and the absence of continuous olfactory assessments during treatment to investigate if therapy-associated neurotoxicity could be a contributing factor to diminished olfactory acuity. In this trial olfactory function will be evaluated in glioblastoma patients as a prognostic marker with regard to overall survival, neurocognition and quality of life.

METHODS

This prospective, multicenter study is set to recruit 64 glioblastoma patients alongside 64 healthy controls. Stratification of participants is based on prognostically relevant variables such as resection status, MGMT promoter methylation status, radiographic involvement of olfactory brain areas, olfactory function, age, and Karnofsky performance status scale. We utilize Sniffin´ Sticks to evaluate olfactory function through identification and threshold tests, and this assessment is carried out longitudinally throughout the therapy starting from tumor diagnosis. Infiltration of the olfactory nerves or olfactory brain are scrutinized using a high-resolution coronal T2-weighted sequence which is added to a dedicated brain tumor protocol. MRI images are independently reviewed by two board-certified radiologists from distinct institutions, who are blinded to the patients’ olfactory function status. Furthermore, quality of life data, neuropsychological testing, and psychosomatic screening are performed at specific intervals throughout the study. Also, we examine next-generation sequencing results to investigate potential genetic associations with hyposmia in glioblastoma patients.

RESULTS

The first participant was enrolled in May 2023. Currently, 16 patients and three controls are already enrolled (April 2024). Plans are underway to open a second study site in 2024, with the aim to complete recruitment by December 2025. Follow-up assessments will continue until December 2027. We anticipate that the final results of the study will be available in 2028.

CONCLUSIONS

In the process, this study is the first prospective study which investigates the olfactory function systematically as prognostic factor in glioblastoma patients.
P27.07.A EFFICACY AND SAFETY OF STUPP REGIMEN WITH OR WITHOUT ANLOTINIB FOR NEWLY DIAGNOSED GLIOBLASTOMA: A MULTICENTER, DOUBLE-BLIND, RANDOMIZED PHASE II TRIAL
Authors: Chen Y , Liu G , Sun P , Li M , Yang X , Pan L , Wang L , Hua Y , Zhao M , Liu Y , Ran J , Cai H , Lu X , Jiang H , Li X , Zheng W , Liu Z , Lin S , Deng M , Yang Q , Guo C , Li J , Chen Z
Published: October 2024

BACKGROUND

The STUPP regimen, which consists of postoperative radiotherapy with concurrent temozolomide (TMZ) followed by up to six cycles of adjuvant TMZ chemotherapy, is the established standard treatment for newly diagnosed glioblastoma (GBM). However, its effectiveness is limited. Anlotinib, a multi-kinase inhibitor targeting tumor angiogenesis and cell proliferation, has demonstrated promising results in preclinical GBM models and phase I clinical trials. In order to assess the efficacy and safety of combining the STUPP regimen with anlotinib, we conducted a phase II trial aimed at evaluating their combined effects. (NCT 04959500).

MATERIAL AND METHODS

This study is a multicenter, double-blind, randomized, placebo-controlled trial with an expected 150 patients randomly assigned 1:1 ratio to receive TMZ-based radiochemotherapy with anlotinib or placebo. Eligibility criteria include histologically confirmed GBM, ECOG performance score ≤2, age ≥18 years, and lack of significant comorbidity. The primary endpoint is median progression-free survival (PFS), while secondary endpoints include 1-year overall survival rate, PFS at 6 months, overall response rate, duration of response, disease control rate, quality of life, and toxicity.

RESULTS

From July 2021 to April 28th, 2024, 153 patients were enrolled. The results in this abstract were all obtained without exposing the blind state. The median PFS was 10.22 months (95% CI, 9.43-11.93) in the overall patient population, while the predicted mPFS of placebo group was 7 months according to the results of STUPP and AVAGlio trials. The median OS was 18.69 months (95% CI, 15.90-26.71). The 1-year overall survival rate is 75.71% (95% CI, 64.82%-79.11%), and the 2-year overall survival rate is 42.04% (95% CI, 33.14%-50.67%). 26.8% of patients experienced at least one grade 3 or higher treatment-related adverse events (TRAEs). 11.1% of patients experienced serious treatment-related adverse events. The most frequent grade 3 or higher TRAEs were lymphocytopenia, thrombocytopenia, leukopenia, decreased neutrophil count.

CONCLUSION

The current research findings, conducted under the condition of data blinding, suggest that the combination of anlotinib with the STUPP regimen demonstrates promising therapeutic efficacy and favorable tolerability in the treatment of patients. These results indicate the potential of this treatment modality as a viable option in clinical practice.
P27.22.B SEMISITTING POSITION VS. STANDARD SUPINE POSITION IN REDUCING INTRACEREBRAL BLEEDINGS DURING STEREOTACTIC BRAIN BIOPSY
Authors: Bonosi L , Carone G , Porto E , Barbotti A , Galbiati T , Del Bene M , Di Meco F
Published: October 2024

BACKGROUND

Stereotactic brain biopsy (SBB) represents a minimally invasive procedure to acquire tissue samples for histological diagnosis. Despite SBB’s many benefits, there is a chance of hemorrhagic complications. The incidence of hemorrhagic complications following SBB is not well established, but studies suggest that it may be higher than previously thought. In semi-sitting position (30° elevation of the head), the intracranial pressure is lower than in supine position due to decreased venous congestion. In our hypothesis, intraoperative bleeding may be reduced by exploiting semi-sitting position, potentially leading to decreased surgical morbidity.

MATERIAL AND METHODS

We conducted a retrospective monocentric 2-arms cohort study at our institution (Istituto “C. Besta” in Milan, Italy). We reviewed all patients who underwent stereotactic brain biopsy from the 1st of March 2023 to the 1st of April 2024. The primary endpoint is to demonstrate the improved safety of the semi-sitting position, as assessed by the absence of intracranial bleeding on postoperative CT scans compared to standard supine position.

RESULTS

Our analysis covered 78 patients, with 39 undergoing biopsy in the semi-sitting position and the remaining 39 in supine positions. Out of those in the semi-sitting position, 5 exhibited a hemorrhagic spot along the catheter’s edge or within the lesion as revealed by CT scans. This contrasts with the 14 instances found among patients not in the semi-sitting position, indicating a statistically significant difference (p-value: 0.028). However, no other significant correlations were observed in CT findings, such as bleeding, when compared to age (p-value: 0.352), biopsy site (p-value: 0.355), number of samples (p-value: 0.141), or histology (p-value: 0.251).

CONCLUSION

This study can potentially shed light on an innovative approach for patient positioning in stereotactic brain biopsy. The observed decrease in intraoperative bleeding may decrease procedure-related risks and surgical morbidity. As a result, patient safety and outcomes can be improved.
P27.24.A SYSTEMIC AND LOCAL THERAPIES BEFORE AND AFTER DIAGNOSIS OF LEPTOMENINGEAL DISEASE IN PATIENTS WITH BRAIN METASTASES: AN EXPLORATIVE, SINGLE-CENTER RETROSPECTIVE COHORT STUDY
Authors: Wasilewski D , Eitner C , Murad S , Shaked Z , Steinle J , Sargut A , Wetzel-Yalelis A , Roethe A , Jelgersma C , Mertens R , Truckenmüller P , Früh A , Rösler J , Wessels L , Kroneberg D , Kowski A , Radbruch H , Ehret F , Kaul D , Frost N , Onken J , Keller U , Sehouli J , Vajkoczy P , Keilholz U , Misch M
Published: October 2024

BACKGROUND

Leptomeningeal metastasis (LMD), the dissemination of cancer cells into leptomeninges and/or cerebrospinal fluid, is believed to increase in incidence due to improved survival of oncological patients. Real-world data on therapies before and after diagnosis of LMD in brain metastasis patients are still limited. We aimed to characterize local and systemic therapies before and after diagnosis of LMD in these patients.

MATERIAL AND METHODS

We included 120 patients (treated from 2012 to 2023) with underlying solid malignancy, presence of brain metastasis together with leptomeningeal spread, either confirmed by MRI, cerebrospinal fluid sampling, or both modalities. Data on demographics, radiological, and therapy-related characteristics were collected. Kaplan-Meier estimates and Cox model regression analysis were performed to identify factors associated with survival.

RESULTS

Breast cancer (35.8%), NSCLC (20.8%), melanomas (16.7%), and gastric cancer (5.7%) were among the most common entities. In 56% of cases, the diagnosis was made by MRI, in 5% by cerebrospinal fluid puncture (LP) alone, and in 39% by both MRI and LP. The median overall survival (OS) of the cohort was 2.77 months [95% CI: 2.27 - 4.20]. Patients who received systemic after diagnosis of LMD, either chemotherapy (n=26), targeted therapies (n=21) or checkpoint inhibitors (n=9) showed increase survival as compared to respective control patients. The only independent prognostic factors at diagnosis of LMD were presence of lung cancer (HR: 2.36 [95% CI: 1.28 - 4.4], p=0.006) and melanoma (HR: 2.30 [95% CI: 1.27 - 4.2], p=0.006). Local or systemic treatment modalities before LMD diagnosis were not associated with survival.

CONCLUSION

This study provides insights into the complex treatment modalities for LMD patients, both in terms of prior therapies and therapies after diagnosis of LMD. These results underscore the need for large prospective multi-center registries and interventional studies to further improve interdisciplinary and personalized therapy for these patients.
P27.30.B VALIDATING THE NEUROLOGIC ASSESSMENT IN NEURO-ONCOLOGY SCALE FOR VIRTUAL VISITS: A PILOT STUDY
Authors: Roberto K , Granovskaya I , Chan A , Theriault A , Mitchell S , Perry J , Nayak L , Lim-Fat M
Published: October 2024

BACKGROUND

The Neurological Assessment in Neuro-Oncology (NANO) scale is a tool used to objectively assess nine clinically relevant domains of neurological function in patients with brain tumors to complement radiographic assessment and other clinician and patient-reported outcomes. Virtual visits for brain tumor patients are feasible and can improve clinical trial access for patients. The use of NANO in virtual care has not been validated, and we aim to determine whether a virtual NANO (vNANO) assessment is a feasible and reproducible alternative to in-person NANO for patients with glioblastoma.

METHODS

The study is a single-centre prospective study designed to evaluate and validate a modified NANO assessment for virtual visits. Instructions for the vNANO assessment were formulated and verified by 4 different neurologists including 3 neuro-oncologists and 1 expert in virtual neurological care. As part of the study design, a virtual visit is scheduled within one week of the routine standard of care in-person clinic visit and is done over Zoom for Healthcare. vNANO is performed independently using the vNANO scorecard by two providers sequentially and separately to assess inter-observer variability. Both evaluators are blinded to the MRI results to limit bias. An in-person visit is scheduled within one week of vNANO, and a NANO is performed by the same first provider to assess intra-observer variability. The duration of the virtual and in-person assessments are captured. Patients and clinicians are asked to complete a telehealth satisfaction survey at the end of the in-person visit. The primary endpoints are to demonstrate that 1) an adapted vNANO assessment is feasible and 2) to determine inter- and intra-observer concordance between in-person and vNANO. The secondary endpoint is to assess patient and clinician satisfaction with virtual versus in-person visits.

RESULTS

Sixty patients with glioblastoma will be enrolled in the study and accrual is ongoing at the time of submission (> 18 years old, English-speaking, KPS > 60). Preliminary results indicate that vNANO is time efficient and feasible with all patients completing the vNANO assessments without significant logistical or technological difficulties to date.

CONCLUSION

Our study will compare in-person and virtual NANO assessments in glioblastoma patients. If validated, vNANO may be adopted for virtual visits in the context of clinical trials for glioblastoma patients. The study is funded by the Academic Health Science Centre Alternative Funding Plan Innovation Fund.
Valuing nature as urban health infrastructure: a pathway to a nature positive city
Authors: Kernaghan Sam , Sturgeon Amanda
Published: October 2024

‘Nature-positive’ is the term used to describe a city where nature—species and ecosystems—are being restored and regenerated rather than declining. Despite the provision of nature being elevated as a priority across Sydney (especially open space, trees and canopy cover), and despite new national Nature Positive legal reforms, there is not adequate investment in living infrastructure—trees, plants, parks and waterbodies—nor the measurement strategies to focus that investment where it is most needed. This lack of investment means we miss out on five key benefits of having more nature in urban areas: reduced heat and improved air quality; better climate resilience through mitigation of flooding, storms and sea level rise; increased mental health and happiness; enhanced biodiversity and reinforcing connected city systems as waterways and green spaces deliver carbon capture, water filtration and stormwater capture benefits. The solutions are in our hands—individually and collectively. There are many place-based opportunities for growing Sydney’s living infrastructure, from our own backyards and balconies, to parklands and pocket parks; from our streets, laneways and leftover spaces to infrastructure corridors, railways, rivers and waterways; from schools and hospitals, to the rooftops and facades of existing and new buildings across the city and the opportunity to protect and restore nature in greenfield development areas. To change how we value natural infrastructure across our city we need to: (i) enable community education and Indigenous knowledge by stepping up education and awareness programmes for communities, including establishing a Centre for Urban and Indigenous Ecology; (ii) set metropolitan and local targets for living infrastructure—not just trees—and monitor and evaluate progress towards those targets; (iii) manage living infrastructure as an asset, at all levels of government, and embed living infrastructure outcomes in public sector procurement systems; and (iv) drive structural investment in living infrastructure by introducing a green factor tool to incentivize new development; establishing a living infrastructure fund; and adopting a framework for valuing living infrastructure in major projects.
Advanced three-dimensional anatomical mapping of saphenous and inferior medial genicular nerve branching: enhancing precision in knee joint denervation
Authors: Yu Paula J , Loh Eldon , Agur Anne M R , Tran John
Published: October 2024

Background

Radiofrequency ablation is a common non-opioid treatment to manage chronic knee pain. The inferior medial genicular nerve is conventionally targeted. It has been suggested that the infrapatellar branch (saphenous nerve) should also be targeted. There is controversy regarding the contribution of the infrapatellar branch to the innervation of the knee joint capsule.

Objective

(1) Identify the frequency of the branching pattern(s) of the infrapatellar branch in three-dimensional (3D); (2) Assess spatial relationships of branches of infrapatellar branch to the inferior medial genicular nerve; (3) Determine if capturing infrapatellar branch could result in additional benefit to the existing protocol.

Design

Anatomical study.

Methods

The infrapatellar branch and inferior medial genicular nerve were serially dissected, digitized, and modelled in 3D in 7 specimens (mean age 91.3 ± 6.5; 2F/5M) and their relationship documented. The spatial relationship of the nerves was used to assess the anatomical efficacy of including the infrapatellar branch in the protocol.

Results

The infrapatellar branch is most frequently a cutaneous nerve. This nerve was variable and found to be unbranched or have 2-3 branches and in all specimens was located superficial to the branches of inferior medial genicular nerve. When the infrapatellar branch (1) coursed more distally, the strip lesion would not capture the infrapatellar branch but would capture inferior medial genicular nerve consistently; (2) overlapped with the inferior medial genicular nerve, the strip lesion would capture both nerves.

Conclusions

Proposed protocol targeting the infrapatellar branch is likely to capture the inferior medial genicular consistently regardless of the anatomical variation of the infrapatellar branch.
Using survey experiment pretesting to support future pandemic response
Authors: Tappin Ben M , Hewitt Luke B
Published: October 2024

The world could witness another pandemic on the scale of COVID-19 in the future, prompting calls for research into how social and behavioral science can better contribute to pandemic response, especially regarding public engagement and communication. Here, we conduct a cost-effectiveness analysis of a familiar tool from social and behavioral science that could potentially increase the impact of public communication: survey experiments. Specifically, we analyze whether a public health campaign that pays for a survey experiment to pretest and choose between different messages for its public outreach has greater impact in expectation than an otherwise-identical campaign that does not. The main results of our analysis are 3-fold. First, we show that the benefit of such pretesting depends heavily on the values of several key parameters. Second, via simulations and an evidence review, we find that a campaign that allocates some of its budget to pretesting could plausibly increase its expected impact; that is, we estimate that pretesting is cost-effective. Third, we find pretesting has potentially powerful returns to scale; for well-resourced campaigns, we estimate pretesting is robustly cost-effective, a finding that emphasizes the benefit of public health campaigns sharing resources and findings. Our results suggest survey experiment pretesting could cost-effectively increase the impact of public health campaigns in a pandemic, have implications for practice, and establish a research agenda to advance knowledge in this space.
Deep-learning CT imaging algorithm to detect usual interstitial pneumonia pattern in patients with systemic sclerosis-associated interstitial lung disease: association with disease progression and survival
Authors: Stock Carmel J W , Nan Yang , Fang Yingying , Kokosi Maria , Kouranos Vasilios , George Peter M , Chua Felix , Jenkins Gisli R , Devaraj Anand , Desai Sujal R , Denton Christopher P , Wells Athol U , Walsh Simon L F , Renzoni Elisabetta A
Published: October 2024

Objectives

Interstitial lung disease (ILD) is the most common cause of death in patients with systemic sclerosis (SSc), although disease behaviour is highly heterogeneous. While a usual interstitial pneumonia (UIP) pattern is associated with worse survival in other ILDs, its significance in SSc-ILD is unclear. We sought to assess the prognostic utility of a deep-learning high resolution CT (HRCT) algorithm of UIP probability in SSc-ILD.

Methods

Patients with SSc-ILD were included if HRCT images, concomitant lung function tests and follow-up data were available. We used the Systematic Objective Fibrotic Imaging analysis Algorithm (SOFIA), a convolution neural network algorithm that provides probabilities of a UIP pattern on HRCT images. These were converted into the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED)-based UIP probability categories. Decline in lung function was assessed by mixed-effect model analysis and relationship with survival by Cox proportional hazards analysis.

Results

Five hundred and twenty-two patients were included in the study; 19.5% were classified as UIP not in the differential, 53.5% as low probability of UIP, 25.7% as intermediate probability of UIP, and 1.3% as high probability of UIP. A higher likelihood of UIP probability expressed as PIOPED categories was associated with worse baseline forced vital capacity (FVC), as well as with decline in FVC (P = 0.008), and worse 15-year survival (P = 0.001), both independently of age, gender, ethnicity, smoking history and baseline FVC or Goh et al. staging system.

Conclusion

A higher probability of a SOFIA-determined UIP pattern is associated with more advanced ILD, disease progression and worse survival, suggesting that it may be a useful prognostic marker in SSc-ILD.
The crosstalk between primary MSCs and cancer cells in 2D and 3D cultures: potential therapeutic strategies and impact on drug resistance
Authors: Rehman Ayesha , Panda Sameer Kumar , Torsiello Martina , Marigliano Martina , Tufano Camilla Carmela , Nigam Aditya , Parveen Zahida , Papaccio Gianpaolo , La Noce Marcella
Published: October 2024

The tumor microenvironment (TME) significantly influences cancer progression, and mesenchymal stem cells (MSCs) play a crucial role in interacting with tumor cells via paracrine signaling, affecting behaviors such as proliferation, migration, and epithelial-mesenchymal transition. While conventional 2D culture models have provided valuable insights, they cannot fully replicate the complexity and diversity of the TME. Therefore, developing 3D culture systems that better mimic in vivo conditions is essential. This review delves into the heterogeneous nature of the TME, spotlighting MSC-tumor cellular signaling and advancements in 3D culture technologies. Utilizing MSCs in cancer therapy presents opportunities to enhance treatment effectiveness and overcome resistance mechanisms. Understanding MSC interactions within the TME and leveraging 3D culture models can advance novel cancer therapies and improve clinical outcomes. Additionally, this review underscores the therapeutic potential of engineered MSCs, emphasizing their role in targeted anti-cancer treatments.
TARDBP drives T‐cell acute lymphoblastic leukemia progression by binding MDM2 mRNA, involving β‐catenin pathway
Authors: Mai Yumiao , Jing Zhaohe , Sun Pan , Wang Yingjie , Dong Pengpeng , Liu Jian
Published: October 2024

T‐cell acute lymphoblastic leukemia (T‐ALL) is a dangerous hematological malignancy. The trans‐activation response DNA binding protein (TARDBP), an RNA/DNA binding protein, is involved in the growth and metastasis of multiple cancers. However, TARDBP has not been reported in T‐ALL. It was found that TARDBP was highly expressed in pediatric T‐ALL samples by microarray GSE26713 (log2 fold change >1, p < .05). Herein, TARDBP was silenced and overexpressed by lentivirus transduction in T‐ALL cell lines, including Jurkat and Molt4 cells. In vitro, silencing TARDBP inhibited T‐ALL cell proliferation and cycle progression and accelerated cell apoptosis, while overexpressing TARDBP induced the opposite effects. In addition, we investigated whether the β‐catenin pathway could be activated by TARDBP in T‐ALL cells. Moreover, XAV‐939, a β‐catenin inhibitor, was capable of suppressing the malignant phenotypes in TARDBP‐overexpressed T‐ALL cells. In vivo, TARDBP‐silenced or TARDBP‐overexpressed T‐ALL cells were injected into mice. We found that TARDBP promoted T‐ALL cell growth in the spleens and bone marrows of mice. On the basis of GSE26713, there was a significant correlation between TARDBP and mouse double minute 2 (MDM2). The RIP‐PCR assay demonstrated that TARDBP bound MDM2 mRNA in T‐ALL cells. The rescue experiments further revealed the roles of the TARDBP/MDM2 axis in T‐ALL cell phenotypes, which was also reflected by mRNA‐seq. In aggregate, we explored a promising biomarker, TARDBP, for T‐ALL treatment. The underlying mechanisms might involve the interaction with MDM2 mRNA and the regulation of the β‐catenin pathway.