bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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 &gt;3cm. Although 88.2% would refer if &gt;1 brain metastasis, only 35.3% would if &gt;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

Abstract

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

Abstract

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

Abstract

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&lt;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.