bluuebunny/crossref_metadata_2025 huggingface dataset:
P10.16.A FULLY AUTOMATED APPROACH TO PREDICT THE VISUAL OUTCOME AFTER PITUITARY ADENOMA SURGERY BASED ON PREOPERATIVE MRI USING DEEP LEARNING
Authors: Zhang Y
Published: October 2024

BACKGROUND

Accurate prediction of the postoperative visual recovery is important to clinical decision-making for pituitary adenoma patients, while still remains a challenge in clinical practice. The purpose of the present study is to predict the visual outcome after pituitary adenoma surgery based on preoperative MRI using a fully automated approach with convolutional neural network (CNN).

MATERIAL AND METHODS

A total number of 205 qualified pituitary adenoma patients were retrospectively enrolled and subdivided into the recovery cohort (n = 132) and the non-recovery cohort (n = 73), according to results of the visual testing at least six months after endoscopic endonasal transsphenoidal surgery. Based on preoperative T2-weighted images, a fully automated model was built by connecting two CNN models for optic chiasm segmentation and visual outcome prediction, respectively. The optic chiasm automatically segmented by the state-of-the-art nnU-Net architecture were utilized for establishment of the predictive model for visual outcome based on ResNet18. The proposed model was first trained in the development set (n = 163) and then applied in the independent test set (n = 42). Moreover, the test set was further divided into three subsets according to different MR scanners to evaluated the generalizability of our model.

RESULTS

The CNN model for optic chiasm segmentation achieved an average dice similarity coefficient of 0.831. The predictive model showed feasible performances in predicting the postoperative visual outcome, achieving an accuracy of 0.833 in the test set, with area under the receiver operating characteristic curve of 0.857, sensitivity of 0.815 and specificity of 0.867. Moreover, our model also demonstrated good generalizability, with accuracy of 0.813-0.875 across different MR scanners.

CONCLUSION

The proposed fully automated model represented the potential to be an accurate and generalizable approach for the prediction of the postoperative visual recovery of pituitary adenoma patients.
P10.23.B PREDICTING LOCAL CONTROL OF BRAIN METASTASES AFTER STEREOTACTIC RADIOSURGERY: A FUSION OF CLINICAL, RADIOMICS AND DEEP LEARNING FEATURES
Authors: Kanakarajan H , De Baene W , Sitskoorn M , Hanssens P
Published: October 2024

BACKGROUND

Timely identification of local failure after Stereotactic Radiosurgery (SRS) offers the opportunity for appropriate treatment modifications that may result in improved treatment outcomes, patient survival, and quality of life. Previous studies showed that the addition of either radiomics or deep learning features to clinical features increased the accuracy of the models in predicting local control (LC) of brain metastases after SRS. To date, however, no study combined both radiomics and deep learning features together with clinical features to develop machine learning algorithms to predict LC of brain metastases. In this study, we examined whether a model trained with a combination of all these features could predict LC better than models trained with only a subset of these features.

MATERIAL AND METHODS

Pre-treatment brain MRIs and clinical data were collected retrospectively for 129 patients at the Gamma Knife Center of Elisabeth-TweeSteden Hospital (ETZ), Tilburg, The Netherlands. The patients were split into 103 patients for training and 26 patients for testing. The segment-based radiomics features were extracted using the radiomics feature extractor of the python radiomics package. The deep learning features were extracted using a fine-tuned 3D ResNet model and then combined with the clinical and radiomics features. A Random Forest classifier was trained with the training data set and then tested with the test data set. The performance was compared across 4 different models trained with clinical features only, clinical and radiomics features, clinical and deep learning features, and clinical, radiomics and deep learning features.

RESULTS

The prediction model with only clinical variables demonstrated an area under the receiver operating characteristic curve (AUC) of 0.82 and an accuracy of 75.6%. The prediction model with the combination of clinical and radiomics features demonstrated an AUC of 0.880 and an accuracy of 83.3% whereas the prediction model with the combination of clinical and deep learning features demonstrated an AUC of 0.863 and an accuracy of 78.3%. The best prediction performance was associated with the model that combined the clinical, radiomics and deep learning features with an AUC of 0.886 and 87% accuracy.

CONCLUSION

Machine learning models built on radiomics features and deep learning features combined with patient characteristics show potential to predict LC after SRS with high accuracy. The promising findings from this study demonstrate the potential for early prediction of SRS outcome for brain metastasis prior to treatment initiation and might offer the opportunity for appropriate treatment modifications that may result in improved treatment outcomes, patient survival, and quality of life.
P11.01.A ACROMEGALY’S EFFECT ON COGNITIVE FUNCTIONS IN PATIENTS WITH PITUITARY ADENOMA
Authors: Bala A , Olejnik A , Dziedzic T , Kunert P
Published: October 2024

BACKGROUND

Acromegaly is a condition caused by pituitary adenomas, which results in increased growth hormone (GH) secretion. For a long time, the main concern in acromegalic patients was on the physical symptoms and problems, which frequently overshadowed the possible neuropsychological outcomes. As a result, the impact of GH overproduction on cognitive functioning is still unclear. The study aimed to evaluate the association between acromegaly and cognitive performance among individuals with pituitary tumors.

MATERIAL AND METHODS

The study included 24 patients with pituitary tumors secreting GH (age: 42.9±11.7; years of education: 12.8±3.6) and a control group of 24 demographically matched healthy participants. The study excluded participants who had a history of neurological or psychiatric illnesses, substantial visual field abnormalities, or were taking chronic medication for another illness. Subjects were tested with a comprehensive battery of neuropsychological tests, assessing memory (California Verbal Learning Test - CVLT, Rey-Osterrieth Complex Figure (ROCF) - recall, Digit Span from WAIS-R), attention (Color Trails Test, Visual Elevator from TEA), verbal fluency (semantic and phonemic), naming (Boston Naming Test), visuospatial functions (Rey-Osterrieth Complex Figure - copy, Block Design from WAIS-R), and executive functions (Tower of London - ToL, Stroop Test). To avoid the influence of medication intake, patients with adenoma underwent cognitive evaluations at the start of their medical therapy.

RESULTS

The study found significant differences in functioning between patients and healthy individuals, specifically in verbal (delayed recall in CVLT: p < 0.01) and visual (ROCF: p < 0.01) memory, attention (Visual Elevator from TEA: p < 0.05), executive functions (ToL extra moves: p < 0.05), and working memory (Digit Span backwards: p < 0.05). There were no significant differences in naming, verbal fluency, or visuospatial skills. Larger tumors were correlated with greater deficiencies of attention (Visual Elevator from TEA: r = -0.6, p < 0.05) and verbal memory (delayed recall in CVLT: r = -0.4, p < 0.05). However, there were no associations between test outcomes and GH levels.

CONCLUSION

Overproduction of GH can have an impact on cognitive processes such as memory, attention, and executive functioning. Hence, the neuropsychological evaluation should be considered the gold standard in the diagnostic process of this group of patients.
P11.07.B RELIABILITY OF POSTOPERATIVE NEUROPSYCHOLOGICAL SCREENING IN PATIENTS WITH PRIMARY BRAIN TUMORS BY VIDEO CONSULTATION AND IN-PERSON
Authors: van Buijtene W , Butterbrod E , Rutten G , Gehring K
Published: October 2024

BACKGROUND

Since COVID-19 there has been an increase in consultations with patients in neuro-oncological practice via video teleconferencing (VTC). While VTC can increase access to care, the degree to which cognitive screening can be reliably conducted via VTC in brain tumor patients is unclear. The aim of this study is to investigate reliability of a predominantly computerized cognitive screening conducted via VTC (Teams) vs in-person in a Dutch hospital.

MATERIAL AND METHODS

Glioma and meningioma patients underwent an in-person neuropsychological screening as part of standard care before surgery. Between May 2020 and October 2022, patients underwent their 3-month follow-up as part of their standard care via VTC due to COVID. Before May 2020, patients underwent this follow-up in-person. The screening consisted of a computerized battery (CNS vital signs) and paper and pencil tasks (Fluency, Digit span forward and backward). We compared the stability of raw scores over time of patients undergoing VTC vs. in-person administration with intraclass correlation coefficients (ICCs, continuous scores) and absolute agreement (non-continuous scores). We also statistically compared percentages of patients showing reliable change between groups (α=0.05).

RESULTS

Compared to the in-person group (n=112), the VTC (n=112) group was younger (51±14 vs 58±14 years), contained more male patients (56% vs 34%) and more patients with higher education (49% vs 29%). The groups did not differ on other sociodemographic, tumor or treatment characteristics. The majority of test measures for both the VTC (13 out of 15) and in-person group (10 out of 15) had acceptable to excellent ICC values (range 0.50-0.91 vs 0.61-0.87). ICCs of reaction time scores on simpler tests, the Stroop test part 1 (0.45 vs 0.47), and a Continuous Performance test (0.37 vs 0.46), and of a Visual Recognition test (0.33 vs 0.44) were low for both groups. ICCs of a Verbal Recognition test (0.44 vs 0.65) and Digit Span test backward (0.44 vs 0.65) were low only for the VTC group. The degree of agreement on non-continuous measures was similar for both groups, except for Continuous Performance test accuracy. Significantly more patients in the VTC group showed reliable improvement on the Continuous Performance test (15% vs 11%).

CONCLUSION

Neuropsychological screening via video consultation is a promising method, as it can provide opportunities for more patients to receive care from home. Reliability was comparable for VTC and in-person administration for most measures. Performances over time assessed via VTC appeared less stable for Digit span backward, a paper and pencil test, and for Verbal Recognition accuracy, a computerized test. Future research into patient characteristics of the VTC group, and consequences for performances, is warranted.
P12.14.A PROFILING THE PERIPHERAL IMMUNE RESPONSE FOLLOWING NEUROSURGICAL RESECTION OF GLIOBLASTOMA
Authors: Patterson A B , Zeitlberger A M , Bozinov O , Ludewig B , Pikor N B , Neidert M C
Published: October 2024

BACKGROUND

To enhance the efficacy of immunotherapy against glioblastoma, we aim to develop a strategy for the ex-vivo expansion of tumor antigen-specific T cells, followed by an adaptive T cell transfer directly into the tumor cavity. This pilot project, investigating the peripheral immune response, will address the potential release of tumor antigens into the periphery during surgery by examining if there is an increase in the number of antigen-specific T cells following the resection.

MATERIAL AND METHODS

Patients are enrolled in the study before surgery and peripheral blood mononuclear cells (PBMCs) are isolated from venous blood collected as a baseline time point. A tissue lysate is created from bulk tumor tissue during surgery as the source of antigens for later cell stimulation experiments. A single cell suspension made from tumor tissue will provide two populations of cells: “normal” and “tumor-enriched” to validate the use of lysate-derived antigens. Patients are requested to return to the clinic 2, 4, and 12 weeks after surgery where PBMCs are isolated and viably frozen until all time points are collected. The tumor lysate, cells, and PBMCs are co-incubated and the expression profiles of PBMCs are examined via flow cytometry using a high-dimensional 30 marker panel. FACS-sorted antigen-specific T cells will further be profiled via single cell 5’ sequencing (10x Chromium V3) and functionally tested using autologous patient-derived organoid killing assays.

RESULTS

Preliminary data using longitudinal blood sampling shows that autologous lysate elicits activation of CD8+ T cells in patient PBMCs, especially 2 weeks after surgery, according to several classical T cell activation markers. Co-incubation conditions have been examined to determine the kinetics of CD137 expression, with 12 hours of incubation revealing the highest expression of CD137 over 48 hours. Concentrations of tumor lysate have also been compared between 100ng/mL and 3µg/mL. Interestingly, lower protein concentrations have shown higher activation of T cells. Lysate protein concentrations, cell ratios, and co-incubation times are tested in patient samples to ensure that the highest expression of CD137+ T cells is captured and analyzed.

CONCLUSION

The completion of this study will determine the best clinical time point for T cell collection of patient PBMCs for antigen-specific T cell expansion and subsequent administration of the immunotherapy directly into the tumor cavity.
P13.03.B CLINICAL APPLICATION OF HYPER ARC TECHNOLOGY FOR BRAIN METASTASES: INSIGHTS FROM A SINGLE INSTITUTION EXPERIENCE
Authors: Skoblar Vidmar M , Smrdel U
Published: October 2024

BACKGROUND

Hyper Arc is an innovative software introduced at the Institute of Oncology Ljubljana in June 2020. It enables high-precision treatment of multiple brain lesions with a single isocenter and with the potential to address an unlimited number of targets. This software is particularly useful in the local treatment of brain metastases, which are increasingly common causes of morbidity and mortality in patients with malignant diseases. Based on the latest research and guidelines, stereotactic radiosurgery is considered the primary choice to improve survival and may be the best treatment choice for multiple brain metastases.

MATERIAL AND METHODS

From June 2020 to December 2023, a total of 525 stereotactic radiosurgeries for brain metastases were performed. We analyzed all irradiated patients.

RESULTS

The most common metastases treated were from lung cancer (45.7%), followed by breast cancer (17.7%), malignant melanoma (16.6%), kidney (13.5%), digestive tract (3.8%), testes (1.1%), thyroid (1%) and ovaries (0.6%). The number of procedures increased over the years, with 24 in 2020, 121 in 2021, 172 in 2022, and 203 in 2023. 68.4% of patients are still alive. The highest number of irradiated metastases was 19, completed in just 20 minutes. Before the introduction of this technique, only 5 to 6 metastases could be treated due to the need for individual isocenters for each lesion. With the new technology, the same amount of time is required whether treating one or multiple metastases.

CONCLUSION

The treatment of brain metastases has become an increasingly complex field that requires multidisciplinary decisions regarding local and systemic treatment strategies as well as follow-up care. In the past two decades, the role of radiotherapy evolved from being solely palliative to offering ablative local treatments that can potentially improve survival rates. Hyper Arc is an innovative software for implementing stereotactic radiosurgery allowing monoisocentric irradiation of multiple lesions in a short time. This has led to an increase in the number of stereotactic radiosurgery performed at the Institute of Oncology Ljubljana.
P14.10.B DIGITAL AND AI TECHNOLOGY APPIED IN NEUROSURGERY PROMOTES THE FORMATION OF A NEW PARADIGM OF PREOPERATIVE PLANNING, VIRTUAL SURGERY & INTRAOPERATIVE GUIDANCE FOR BRAIN TUMORS
Authors: Yang X , Zhang P , Guo J , Shi W , Chen T , Chen T
Published: October 2024

BACKGROUND: I

n this study, we aims to establish a new paradigm of preoperative planning, virtual surgery, and intraoperative guidance for brain tumor surgery, based on a new preoperative planning and intraoperative guidance system for brain tumors.

MATERIAL AND METHODS

(1) Complete multimodal cranial imaging, functional mapping, and fiber tracing before surgery. Reconstruct the overall structure of the brain, including the cortical sulcus and gyrus, cortical vein, functional area adjacent to the brain tumors, and their connectivity fiber; (2) Analyze the topological pathways surrounding brain lesions and complete preoperative planning; (3) Applying virtual reality and augmented reality technology to surgical decision-making, preoperative training, and virtual surgery to enhance the realism of preoperative planning and the effectiveness of surgical training; (4) Introducing augmented reality technology in surgical positioning and scalp flap planning; (5) Based on the automatic partitioning and topological structure of the cortex, determine cortical approach to the tumor; (6) Real time fusion of surgical navigation and ultrasound imaging to guide the resection of deep tumors.

RESULTS

(1) Through virtual reality and augmented reality technology, preoperative topological structure analysis of tumors can be achieved, which can predict neural function remodeling and facilitate the maximum removal of brain parenchymal tumors; (2) Virtual reality technology and augmented reality technology, through visualization and three-dimensional presentation, promote young doctors to understand the relationship between the brain structure at the lesion site and the overall brain structure, as well as the relationship between the lesion and brain function and surrounding blood vessels. They are a new way of surgical training; (3) The guidance of digital technology can achieve optimal positioning and skin flap design, avoiding the mismatch between the skin flap designed solely based on the surgeon's experience and the surgical approach in a visual way, which can cause difficulties in surgical resection; (4) The automated partitioning technology and topological structure display of the cerebral cortex help to enhance understanding of cortical partitioning and indication of cortical pathways during surgery, which can replace electrophysiological techniques in judging the central sulcus; (5) The fusion technology of neuronavigation and intraoperative ultrasound can compensate for the non real-time nature of navigation and the limitation of ultrasound only indicating lesion sound and shadow, achieving real-time and good structural guidance during surgery.

CONCLUSION

We believe that the development of digital and intelligent technology will continue to help us establish a developing strategy for precision neurosurgery in the new era.
P14.13.B IN VIVO EFFICACY OF TUMOR TREATING FIELDS (TTFIELDS) FOR GLIOBLASTOMA USING NOVEL MOUSE HEAD ARRAYS
Authors: Zbidat S , Blatt R , Sellevoll M , Gabay M , Schlachet I , Cahal S , Davidi S , Tzchori I , Haber A , Giladi M , Palti Y
Published: October 2024

BACKGROUND

Tumor Treating Fields (TTFields) therapy is CE marked for the treatment of grade 4 glioma. TTFields therapy is based on continuous, non-invasive delivery of electric fields by two array pairs placed on the patient’s scalp. Preclinical animal studies of glioblastoma (GBM) - the most common type of grade 4 glioma - are mainly performed in mouse models. However, arrays for application of TTFields to the mouse head are lacking therefore limiting the possibility of conducting in vivo studies for GBM treatment. The small dimensions and specific geometries of the mouse head make the development of such arrays challenging.

MATERIAL AND METHODS

We tested various array layouts to identify one that will be suited to the specific structure of the mouse head and will minimally restrict head movement. We investigated adhesive tapes to allow good skin adherence but at the same time easy array removal. We performed field measurements using a floating scope to validate that the intensity was sufficient within the region to which the tumor was to be inoculated. Finally, we conducted an efficacy study with the new arrays, using GL-261 GBM cells intracranially injected into C57BL/6 mice. Eleven days following tumor inoculation we commenced treatment with sham-heat (control) or TTFields, continuously for 12 days. We measured tumor volume by magnetic resonance imaging (MRI) before and after treatment, and calculated tumor volume fold change. We also recorded electric currents and treatment usage throughout the study.

RESULTS

To overcome the limitations imposed by the small head size, we developed a layout with two arrays situated on the head and opposing arrays located on the torso of the mouse. In addition, the arrays for the head were divided into two smaller disks. We identified a thin and transparent adhesive tape (facilitating correct array positioning) with good tackiness and easy removal (without leaving residual adhesive on the skin). Field intensity was found to be higher in the posterior side of the mouse head, at a location more directly underneath the arrays, and overall the arrays met the minimum treatment requirements: current ≥ 50 mA, usage ≥ 75%, field intensity ≥ 1 V/cm RMS. Efficacy was detected for treatment of GBM, with 31% lower tumor growth at treatment end in TTFields-treated versus the control group.

CONCLUSION

Our newly developed arrays are flexible and strongly adhering to enable efficient electric field delivery. The new arrays allowed TTFields delivery to mice heads at sufficient intensities and showed efficacy for treating GBM in mice. The new arrays will facilitate continued preclinical studies to broaden the understanding of the effects of TTFields on GBM for further advancing this research field.
P17.03.A CASE REPORT: CLEAR CELL CARCINOMA KIDNEY CANCER WITH BRAIN METASTASIS TREATED WITH KETOGENIC METABOLIC THERAPY
Authors: Zapata M , Acevedo A
Published: October 2024

BACKGROUND

Kidney cell carcinoma corresponds to the 14th cause of incidence in cancer in the world. Mortality is about 12.8 ASR in USA and 3.8 in Colombia. Metastatic disease corresponds to 14% of the patients, having worse prognosis compared to those patients with local or locally advanced disease. We want to share our experience of a patient with brain metastatic disease in clear cell carcinoma of the kidney, treated with TKI, IO and ketogenic metabolic therapy (KMT) with outstanding results. Case summary: 65-year-old female, first diagnosed in 2011 with a clear cell carcinoma stage III, due to pT3aNxM0 at diagnosis, managed with radical nephrectomy. After this patient was 3 years free of disease, she developed in 2014 a meta-chronic papillary thyroid carcinoma stage III, due to T1N1M0, managed with total thyroidectomy plus nodal dissection, and adjuvant iodine therapy with 100 mci. In 2019 the patient presented a pulmonary new lesion, with confirmation of clear cell carcinoma, and was treated with pazopanib due to poor tolerance to sunitinib. In September 2022 the patient presented four lesions in both cerebral hemispheres, mainly involving the right frontal lobe as well as the mesial region of both temporal lobes. Neurosurgery performed a biopsy, confirming clear cell carcinoma. The patient received IMRT holoencephalic over 5 daily sessions. We started treatment with nivolumab in September 2022. After receiving 5 cycles of IO, the patient consulted due to new onset of convulsion, documenting edema of the main lesion, and neurologic worsening. After evaluating the case, we started anticonvulsive treatment and a short period of steroid, with recovery of her function. We used this treatment for around 10 days, and continued immunotherapy and anti-convulsant therapy. In January 2023, we started KMT, at a relation 3:1, measuring ketones and neurologic status constantly. After confirmation of ketones in urine or blood, we started adjustment of therapy to improve compliance. In July 2023, the patient didn’t require assistance to medical appointments, was capable of being free of anticonvulsive therapy, and her cognitive functions were all preserved. In January 2024, the patient remained with partial response, and dietary supplementation (ketovie) was stopped.

CONCLUSION

This case supports the use of KMT in clear cell renal carcinoma scenarios, in which it can be associated with a synergistic effect to ITK and/or immunotherapy, as well as radiotherapy modalities, improving progression-free survival and functional improvement without increasing toxicity.
P17.09.A EVALUATION OF SARCOPENIA AS A PROGNOSTIC FACTOR FOR SURVIVAL AFTER STEREOTACTIC RADIOTHERAPY AND RADIOSURGERY
Authors: Cvek J , Palička M , Reguli Š , Knybel L , Lipina R
Published: October 2024

BACKGROUND

Brain metastases (BM) occur in 20-40% of patients with primary extracerebral malignancies. Even with the development of increasingly effective systemic anticancer treatments, they represent a frequent challenge in oncology, and radiosurgery is becoming an increasingly preferred option for patients with this diagnosis. Sarcopenia is a condition in which there is a progressive loss of muscle mass, and one possible way of measuring this may be to evaluate the muscles in the skull region, specifically the musculus temporalis. The aim of this study is to analyze the clinical results and prognostic factors.

MATERIAL AND METHODS

In the period from August 2010 to 2020, 376 patients (200 men, 176 women) with brain metastases from solid tumors were treated with the CyberKnife device at the associated neuro-oncology center of the Ostrava University Hospital. Precise registration of á 1 mm CT and MR images (T1 with i.v. contrast agent) was used to define the target volume. A 0.2-1 mm margin was used to define the PTV. Dose calculation was performed using sequential optimization, and online image management was based on repeated planar imaging of the skull base along with comparison of reconstructed navigational CT projections. In addition to clinical data, musculus temporalis thickness measurements were retrospectively performed with bilateral averaging.

RESULTS

On the basis of the retrospective evaluation, 207 patients (55%) had solitary lesions and 169 (45%) had multiple lesions. The median age was 64 years (range 57-71).The prescribed total dose was 1x20-22 Gy per 50-70% isodose for solitary lesions up to 2 cm, and 3x9 Gy per 55%-65% isodose for larger lesions or multiple lesions. Generalization of non-small cell lung cancer was in 114 patients (30%), melanoma in 49 patients (13%), colorectal cancer and conventional renal cell carcinoma in 46 patients (12%), breast cancer in 43 patients (11%) and other solid tumors in 78 patients (21%). The median thickness of the musculus temporalis was 8.4 mm (7.2-9.8); when compared with the median thickness of the muscle of the general population adjusted for age, 53% of patients in our cohort showed evidence of sarcopenia. The median overall survival was 6 months and 5-year survival were 9%. In unifactorial analysis, renal cell carcinoma metastases showed the best prognosis, but in multifactorial analysis the difference was not statistically significant. Sarcopenia was a statistically significant factor for mortality at 6 months for the male subpopulation only, 69% vs. 48% (p=.005), the difference at 12 months was no longer significant, 84% vs. 74% (p=.083), and at 24 months the mortality was similar, 91% vs. 87% (p=.323).

CONCLUSION

Measurement of sarcopenia by musculus temporalis thickness appears to be a rapid and promising parameter that can be used to prognosticate patients.
P17.11.B INTERIM ANALYSIS OF A PHASE II TRIAL OF INTRAOPERATIVE RADIOTHERAPY (IORT) WITH INTRABEAM AFTER SURGICAL RESECTION OF BRAIN METASTASES (BM) (NCT05084092)
Authors: Macià i Garau M , Plans Ahicart G , Lucas Calduch A , García Expósito N , Rosselló Gómez A , Fernández Coello A , Vidal Sarró N , Majós Torró C , Pons Escoda A , Ventura Bujalance M , Martín Vaello R , Saldaña Gutiérrez P
Published: October 2024

BACKGROUND

The addition of external radiotherapy (RT) improves local control after surgical resection of brain metastases (BM). IORT involves delivering of a single, high dose of radiation directly to the tumor bed during surgery offering several advantages: precise targeting of tumor bed, potentially reduction of radiation-related complications and rapid start of systemic treatment if indicated.

MATERIAL AND METHODS

We have analysed the results of the first 20 patients included in a Phase II trial. Inclusion criteria: KPS ≥ 70%, complete resection judged by Neurosurgeon, peroperative histological confirmation of BM, no dural attachment, adequate distance to organs at risk and informed consent. Previous RT was allowed. After en bloc resection, administration of a fixed dose of 15,40 Gy prescribed at 2 mm depth with INTRABEAM (X-ray 50 Kv) using the appropriated sized applicator was planned. Primary endpoint was local (cavity) progression free survival.

RESULTS

from June 2020 to March 2024 we have included 39 patients. 12 patients were excluded for various reasons. This communication reports the first 20 analysable patients. Median age was 58,8 years (40-78). 12 males (60%) and 8 females (40%). Lung cancer was the most frequent primary tumour (55%), followed by breast (15%) and melanoma (15%). Median DS-GPA was 2,9 (1-4). Median KPS was 87,4 (60-100). All patients except one were oligometastatic. Surgery was complete in 100% of cases. All patients received the prescribed dose with a median surface dose of 22,34 Gy (20,06-24,2) with a median applicator size of 23,25 mm (15-45) in a median time of 16,25 minutes (7,40-39,29). One patient suffered thrombocytopenia and cerebral bleeding. Another patient presented an asymptomatic distal jugular and lateral sinus thrombosis discovered in the postoperative MRI. Median hospitalization time was 5,6 days. After a minimum and median follow-up of 12 and 29,4 months, 4 patients died prematurely. Regional (brain) progression of the remaining 16 patients was 43,8% including 1 nodular leptomeningeal disease 6 month after surgery. Many patients received new local treatments with RT; 2 patients were treated with salvage WBRT. Local (cavity) control at 1 and 2 years was 93,8% and 92,9% with only one local relapse at 8 months after surgery that was treated with salvage SRS. We noted only one symptomatic radiation necrosis in a patient previously locally treated by FSRT.

CONCLUSION

IORT appears as a feasible, safe and highly effective option to ensure local control after surgery of BM with minimal risk of complications.
P17.16.B POTENTIAL BARRIERS TO STEREOTACTIC RADIOSURGERY (SRS) REFERRAL AT THE BEATSON, WEST OF SCOTLAND CANCER CENTRE (BWOSCC): AN ONCOLOGY REGISTRAR’S POINT OF VIEW
Authors: Walker S , Nowicki S , James A , Williamson A
Published: October 2024

BACKGROUND

At BWOSCC, we are constantly striving to optimise our SRS service. To better understand potential barriers to SRS referral, we surveyed our registrars to assess their understanding of suitability criteria for SRS and the current service at BWOSCC. Registrars were targeted as, with their frequent rotation through different tumour sites, or whilst on-call, they are often the first point of contact for patients in the West of Scotland with newly diagnosed brain metastases.

MATERIAL AND METHODS

28 oncology registrars currently working at BWOSCC were invited to complete a survey using an online survey tool (Google form™). The survey was developed by a SABR clinical research fellow, two neuro-oncology consultants and a consultant Neuro-oncology radiographer. The survey compromised 21 items: 15 close-ended questions; 3 multiple choice questions; 2 demographic questions and 1 open-ended question.

RESULTS

17/28 registrars responded. 70.6% were aware there is an SRS service at BWOSCC; only 1 knew where to find the electronic referral form. 41.2% would consider referring a patient with brain metastasis >3cm. Although 88.2% would refer if >1 brain metastasis, only 35.3% would if >3 brain metastases present. 70.6% would not refer if systemic disease was uncontrolled. 82.4% would refer if previous neurosurgery had been performed. Only 41.2% felt previous whole brain radiotherapy (WBRT) was not a barrier to referral. 82.4% were comfortable to refer if previous PB (partial brain) RT was delivered; 76.5% if previous SRS. 94.1% said if prognosis was ≤3 months they would not refer. 100% would refer if PS 0 or 1; 82.4% if PS2; 94.1% would not refer if PS3. 88.2% stated CT and MRI are optimal pre-treatment imaging. 11.8% stated the duration of planning and treatment appointments would discourage them from referring; 17.6% said the mask and set-up position would, and 11.8% declared the geographical location of the patient would. 88.2 % feel they don’t receive enough teaching on SRS; most would prefer SRS teaching in specialty trainee year 4.

CONCLUSION

Survey results demonstrated a positive awareness of the SRS service, but responses suggest a lack of understanding about suitability criteria for SRS. Improved education of SRS is required at registrar-level to help better inform clinicians practicing at BWOSCC. Moving forward, we will: update the SRS referral form, highlighting where it can be accessed; survey the consultants; provide registrar SRS teaching; discuss SRS education with the training programme director and re-survey.
P17.24.A STEREOTACTIC RADIOSURGERY FOR INTRACRANIAL METASTASES IN OLDER PEOPLE: RIGHT FOR ALL?
Authors: Main S , Rajkumar L , Bhusal S , Chia K , Al-Salihi O , Brazil L , Swampillai A , Hassan S , Akhtar Y , Mazumder A , MacDonald M , Manik V
Published: October 2024

BACKGROUND

Stereotactic radiosurgery(SRS) is an established treatment for local control of intracranial (IC) metastatic disease. Clinical trials under-represent older people. Older patients may have complex additional co-morbid conditions. This study addresses SRS for brain metastases in older patients.

MATERIAL AND METHODS

Retrospective observational study of ≥75 years receiving SRS for IC metastatic disease November 2017-November 2023(N=96). Patients were treated at a single tertiary centre in the UK with Linac-based SRS. Patients treated more than once in the study period were included in survival analysis from incident treatment. Rockwood frailty scores (RFS) were assigned retrospectively. Adverse events assessed by hospital admissions or additional steroid requirements related to SRS and within six months of treatment. Data collected from electronic patient records. Survival analysis conducted with Kaplan Meier methodology and Cox proportional hazard modelling using the R language.

RESULTS

Median age was 78(75-93) & 241 metastases were treated. Lung cancer (55.2%) was the most common primary tumour followed by melanoma (27.1%) and most were treated for a single lesion (65.6%) (range 1-18). For 81.8% of patients, this was the first episode of treatment for IC disease; 4 had received craniotomy and adjuvant SRS as part of an initial treatment strategy. Over half (55.2%) of patients received further systemic therapy for their primary. Median total planning treatment volume 2.18cc (0.1-17.3cc). Post SRS, 38.2% of patients were admitted to hospital and 36.4% required additional steroids. There is a correlation of tumour volume with both admission and need for additional steroids (0.38, p≤0.001; 0.38, p≤0.001).Median overall survival (mOS) is 13.1months (mo) (95%CI:8.7-24.8mo). On univariate analysis, first or subsequent brain treatment (p=0.026), number of previous lines of systemic therapy (P=0.0036), subsequent systemic therapy (p≤0.001), RFS (p≤0.001), total PTV volume (p=0.013); and tumour type (p≤0.001) all predict survival. The number of lesions treated and radiological disease control at the point of referral were not statistically significant. Variables identified as statistically significant in univariate models were included in Cox proportional hazard model: RFS (Hazard ratio (HR) 1.91, p=0.04); subsequent systemic therapy (HR: 0.50, p=0.020) and first or subsequent brain treatment (HR: 0.25, p=0.026) were independent predictors of survival.

CONCLUSION

SRS remains an effective treatment in those ≥ 75. A major factor in predicting survival is patient frailty and their ability to receive subsequent systemic therapy. Hospital admission were seen in a third of patients and correlates with the tumour volume which signifies the importance of careful patient selection.
P17.25.B TARGETING AURKA-MEDIATED NOTCH SIGNALLING IN HER2+ BREAST CANCER BRAIN METASTASIS WITH ALISERTIB
Authors: Powell A , Preković S , Cocchiglia S , Jagušt P , Hill A D , Zwart W , Young L , Varešlija D
Published: October 2024

BACKGROUND

Breast cancer brain metastasis (BCBM), occurring in 10-38% of patients, notably affects those with HER2-positive and triple-negative subtypes, representing a significant clinical challenge. The molecular subtype of the originating tumor significantly impacts the likelihood and progression of BCBM, with HER2 positive and triple-negative breast cancer (TNBC) carrying the bigger risk. Critically, brain metastases manifest distinct genomic and phenotypic characteristics compared to their primary tumours. The lack of comprehensive understanding of these factors contributes to the scarcity of effective treatments for BCBM.

MATERIAL AND METHODS

This study leveraged the distinct genomic and phenotypic characteristics of BCBM through RNA sequencing (N=63) and DNA whole exome sequencing (N=39) of patient-matched primary and brain metastatic samples, identifying AURKA as a clinically actionable target. High-throughput drug screen was carried out in five BCBM cell lines using AURKA pathway inhibitors. Investigation of AURKA in a BCBM context was carried out in both in vitro and ex vivo assays utilizing both AURKA-specific inhibitor, Alisertib, and siRNA-mediated knockdown of AURKA.

RESULTS

Amplifications in AURKA were identified in this BCBM patient cohort and high AURKA mRNA expression was associated with poor overall survival and survival post brain metastasis. Genetic and pharmacological inhibition of AURKA, using both siRNA and Alisertib, exhibited significant anti-tumor effects in various BCBM models, including cell lines, mammospheres, patient-derived organoids, and brain organotypic cultures, with pronounced efficacy in HER2-positive BCBM models. Furthermore, AURKA was found to modulate Notch signaling in HER2+ve BCBM, implicated in promoting therapeutic resistance and stemness, with the co-activator MAML1 essential for this process. AURKAhigh/MAML1high tumours were associated with poorer survival outcomes.

CONCLUSION

These results suggest AURKA as a critical vulnerability in BCBM, offering new avenues for treatment strategies targeting both its kinase-dependent and -independent functions to potentially improve patient outcomes.
P18.12.B CLINICAL, MOLECULAR, AND TRANSCRIPTOMIC FEATURES ASSOCIATED WITH SEIZURES AT ONSET IN PATIENTS WITH GLIOBLASTOMA
Authors: Rossi J , Picca A , Carpentier C , Dridi Aloulou A , Mathon B , Bielle F , Donati B , Froio E , Serra S , Ciarrocchi A , Pisanello A , Valzania F , Hoang-Xuan K , Sanson M
Published: October 2024

BACKGROUND

Seizures occur in up to 60% of patients with glioblastoma (GBM), revealing the tumor in 25-30% of cases. The understanding of the tumor biology associated with epilepsy as the presenting symptom remains limited. Moreover, despite growing preclinical evidence of a link between epileptogenesis and tumorigenesis, the prognostic role of seizures at onset remains debated, partly due to study heterogeneity.

MATERIAL AND METHODS

We leveraged a homogeneous cohort of WHO 2021 GBM patients from our Institution with available clinical, molecular, and transcriptomic data. We retrospectively queried clinical records to identify the presence and characteristic of seizures at disease onset.

RESULTS

in our cohort of 231 GBM patients, 36% presented with seizures: of them, 47% were focal, 11% focal with impaired awareness, and 42% generalized. We did not observe significant differences in terms of age, sex, type of surgery, and tumor localization between the two groups. Patients presenting with seizures had a higher Karnofsky Performance Status score (median KPS: 90 vs. 80, p<0.01) and tended to have a less frequently mutated TERT promoter (86% vs. 94%, p=0.07). Seizures at onset were not associated with overall survival neither in univariate (HR 1.10, C.I. 0.83 - 1.46, p=0.50) nor in multivariate Cox regression analysis (HR 1.16, C.I. 0.86 - 1.57, p= 0.33). Differences in terms of gene expression will be assessed on 3’ RNA sequencing data.

CONCLUSION

Despite the presence of seizures at diagnosis was associated with higher performance status and a distinct molecular profile, it does not predict survival.
P18.29.A METHYLATION PATTERN OF ANDROGEN RECEPTOR REGULATORS IN ADULT-TYPE DIFFUSE GLIOMAS
Authors: Gatto L , Asioli S , Morandi L , Di Nunno V , Tosoni A , Bartolini S , Griva L , Melotti S , Foschini M , Franceschi E
Published: October 2024

BACKGROUND

Androgen receptor (AR) is a ligand-mediated transcription factor that belongs to the superfamily of steroid receptors. AR is overexpressed in several solid tumors and is a potential therapeutic target. The AR gene is located on X chromosome at Xq11-12. In addition to AR, a group of genes involved in the regulation of AR function and expression are located on X chromosome: FLNA, UXT genes and the MAGE family genes, (MAGEA1, MAGEA2, MAGEA3, MAGEA9, MAGEA11, MAGEC1, MAGEC2). Our study aims to characterize AR in adult-type diffuse gliomas, evaluating the AR status and the methylation pattern of AR regulatory genes.

MATERIAL AND METHODS

In this retrospective analysis we included patients diagnosed with adult-type diffuse gliomas grade 2 or 3 or 4 according to WHO 2021 classification, treated at our institution. Immunohistochemistry (IHC) and gene methylation analysis were performed to evaluate AR expression and its regulatory status.

RESULTS

We included samples from 50 patients (M:F=26:24). Immunohistochemical AR positivity was predominant in males (p= 0.04) and in patients with glioblastoma IDH-wild type compared to lower grade adult-type diffuse gliomas (p= 0.04). AR positivity was more frequent in astrocytomas IDH-mutant compared to oligodendrogliomas IDH-mutant and 1p19q codeleted (p= 0.02). Moreover, AR expression was more frequent in MGMT unmethylated gliomas compared to MGMT methylated tumors (p=0.02). AR was found hypomethylated in cases with immunohistochemical positivity AR (Kruskal Wallis<0.05). UXT, MAGEA1and MAGEA1-11 were hypermethylated in AR positive gliomas (Kruskal Wallis<0.05). AR hypomethylation was deeper in GB (Kruskal Wallis<0.05).

CONCLUSION

AR overexpression seems to be predominant in male patients with high-grade unmethylated adult-type diffuse gliomas. The AR gene promoter is hypomethylated in AR positive adult-type diffuse gliomas. Methylation pattern of AR regulatory genes located on X chromosome regulate AR expression. These data suggest that AR signaling may be promising for potential treatment using antiandrogen therapies.
P18.38.A ROLE OF CARBOHYDRATE-BINDING PROTEINS IN CONTROLLING GLIOBLASTOMA STEM CELL FATE AND TUMORIGENESIS
Authors: Sliusar M , Chaillot L , Burban A , Sharanek A , Bikfalvi A
Published: October 2024

BACKGROUND

Carbohydrate-binding proteins, galectins (GAL, LGALS), is a family of proteins that specifically bind β-galactoside sugars. Some members of the GAL family have been shown to be associated with tumor development, including glioblastoma (GB). However, their precise role is poorly investigated.

MATERIAL AND METHODS

Publicly available data sets were analyzed with SUMO software. scRNA-seq data analysis was conducted with the R toolkit Seurat and SingleR package. For in vitro experiments, patient-derived glioblastoma stem cells (GSCs) BTSC73 and BTSC12 were used as cellular models. Differentiation was induced by culturing GSCs on laminin-coated plates in media supplemented with 10% FBS. Hypoxia-response was studied at 1% O2. For depletion experiments siRNA silencing was used as well as CRISPR-Cas9. Proliferation was assessed by EDU staining. Cell death was assessed using Annexin/PI double staining assay.

RESULTS

We first conducted an in silico analysis for LGALS1, -3, -8, and -9 expression in GB. We found that specific combinations of these Galectins are associated with a poor prognosis. In GB patients. When scRNASeq data were analyzed, Galactins are distributed heterogeneously in different cell types in the tumor. For example, Gal3 is expressed in tumor cells, macrophages, and T-cells. We then conducted in vitro experiments to assess the role of Gal3 and Gal9. Depletion of LGALS3 in BTSC73 led to a decrease in cell number related to an effect on proliferation but not apoptosis. In addition, LGALS3 depletion in GSCs reduced stemness markers such as Sox2 and Nestin. We also investigated LGALS3 and LGALS9 expression during differentiation and found their expression increased which was also the case under hypoxia.

CONCLUSION

This indicates that Gals and especially Gal3 and Gal9 are involved in GB development including, proliferation stemness and differentiation.
P18.41.A SINGLE CENTRE EXPERIENCE OF BENEFIT OF CHEMOTHERAPY WITH 40GY/15# RADIOTHERAPY IN PATIENTS WITH GLIOBLASTOMA MULTIFORME (GBM)
Authors: Streatfield K , Davies A , Glendenning J , Forner S L
Published: October 2024

BACKGROUND

GBM patients are associated with a poor prognosis. Hypofractionated radiotherapy (RT) - 40Gy/15# - is standard in the older population (>70), lower performance status and in extensive disease. This regimen provides a median overall survival (mOS) of 8 months and progression free survival (PFS) of 3.9 months (1). The addition of Temozolomide increases outcomes (mOS 9.3 months, PFS 5.3 months). Methylated MGMT status further improves mOS to 13.5 months (2). This review analyses outcomes of patients treated with this regimen at the Kent Oncology Centre (KOC).

MATERIAL AND METHODS

A retrospective review of GBM patients at the regional KOC treated with the 40Gy/15# regimen between 2018 and 2022. Demographics, histology, treatment and survival data were gathered through electronic records. Statistical information was gathered using Python and the Lifelines survival analysis library.

RESULTS

Data was collected for 82 GBM patients with a 33-80 age range. Of the cohort, 39 patients (48%) were female and 43 were male (52%). Type of surgery was divided into biopsy (46%) and debulking (50%), with the remaining not applicable. Within the cohort, 27 patients received temozolomide with RT, with an average of 5 adjuvant cycles received; the remaining receiving RT alone (55). 28 patients were MGMT methylated, 48 unmethylated, with the remaining unknown. mOS for the total population was 8 months. In MGMT methylated patients, OS increased to 13 months. In the sub group of unmethylated patients OS increased to 10 months with the addition of temozolomide, compared to 7 months for radiotherapy alone. PFS was measured as the time between the date of action sheet and date of first progression. For the whole cohort this was 4 months, however this increased to 5 months for the methylated cohort. The addition of temozolomide for unmethylated patients showed no improvement for PFS.

CONCLUSION

Local results support previously published trial data, validating the use of chemotherapy for GBM patients, regardless of MGMT status, with additional overall survival benefit. However, unmethylated patients saw no additional PFS benefit from temozolomide.