RADI-21. Feasibility of Gamma Knife Surgery for patients with 20 or more brain metastases

Background The current standard-of-care treatment for brain metastases (BM)≥20 is Whole Brain Radiotherapy (WBRT), which can cause neurocognitive decline detrimental to patients’ quality of life, especially if their functional status is good on presentation. The benefits of Gamma Knife Surgery (GKS) have been shown for BM≤10, but there is no consensus on the upper limit where GKS is no longer beneficial. We hypothesize that selected patients with ≥20 BM may benefit by replacing WBRT with GKS to preserve neurocognition without compromising intracerebral tumor control and overall survival, with additional treatments as needed. Methodology This is retrospective analysis of 31 patients with ≥20 BM who underwent single-session GKS between 2016–2021. Twenty-two patients had ECOG of 0 at the time of GKS. Median number of BM at GKS was 30 (20–79) with median total tumour volume 4cm3 (2–28 cm3). Median marginal dose was 20Gy (10-25Gy). Results Median overall survival following GKS was 14-months (95%CI 4-24months), justifying GKS in this population. 11/12 patients that died succumbed due to extracranial disease, while 1 patient, who was treated with WBRT before GKS, succumbed to intracranial tumor progression. Local tumor control achieved was achieved for 63% of patients at 2-years and distal tumor control in 24% of patients at 1.5-years without additional radiation treatment. Salvage GKS was given in seven patients and salvage WBRT in three. One local recurrence was surgically resected. Systemic treatment given to most patients probably contributed to intracranial tumor control. No patients developed significant neurocognitive deficits attributable to GKS during the follow-up period of median 7-months (Q1-Q3: 3-12months). Conclusion Most patients treated with GKS for ≥20 BM have sufficient survival time to benefit from the treatment. Local and distal recurrences can be managed with systemic treatment, salvage GKS, or WBRT, resulting in intracerebral tumor control in vast majority of cases.

Comparison of amino acid radiotracers L-[methyl-11 C]methionine and О-2-[18F]fluoroethyl-L-tyrosine for PET/CT imaging of cerebral gliomas

Introduction. The radiotracer L-[methyl-11C]methionine (Met) has long been considered the tracer of choice in CNS tumors diagnosis using positron emission tomography, combined with computed tomography (PET/CT). However, there are more and more logistic arguments for the introduction of fluorinated amino acids into diagnostics, in particular, O-2-[18F]fluoroethyl-L-tyrosine (FET), for which our institute has developed its own method of radiochemical synthesis. The aim of the study was to compare amino acid radiotracers L-[methyl-11C]methionine (Met) and O-2-[18F]fluoroethyl-L-tyrosine (FET) in the imaging of cerebral gliomasusing PET/CT. Materials and methods. PET/CT studies using Met and FET were performed in 36 patients (15 men and 21 women) aged 28 to 73 years with suspected intracerebral tumor before surgery of biopsy. Pathohistologicalstudy verified gliomas(n-31) or other tumors (n=3), inflammatory process (n=2). The analysis of results included visual comparison of images, calculation of the tumor-to-brainratio (TBR) and metabolic tumor volume for Met and PET. Results. Visual and quantitative analysis of the scans revealed that tumor uptake pattern of FET was similar to those of Met. No significant differences were found in the TBR of both radiotracers in tumors of different grades of malignancy. A strong significant correlation (r=0,9) was revealed between the TBR of Met and FET in gliomas. There were no significant differences between tumor metabolic volumes when using the same cutoff values for both radiotracers. The ROC analysis established the same diagnostic value of Met and FET in differentiating low and high grade gliomas (area under curve 0,884 and 0,881, respectively). Conclusion. Amino acid radiotracers provide comparable diagnostic information in preoperative imaging of gliomas using PET/CT, which makes it possible to recommend FET as an adequate alternative to Met for PET centers without on-site cyclotron.

Possibilities of small-size glioblastoma visualization by PET-CT with 11C-choline (experimental study)

Introduction. The minimum size of malignant brain tumors detected by positron emission and computed tomography (PET-CT) exceeds 6-7 mm. One of the ways to increase the sensitivity of PET-CT in detecting of malignant brain tumors is to increase the administered activity of the radiopharmaceutical 11C-choline.Purpose & tasks. The aim of the study was to experimentally study the possibility of obtaining a small-size glioblastoma (GB) images (up to 4 mm) by PET-CT with the 11C-choline.Materials and methods. The study was performed on 24 rats with implanted intracerebral tumor «Glioma C6» (glioblastoma). Animals underwent magnetic resonance imaging (MRI) with contrast enhancement (CE) and PET-CT with 11C-choline for 21 days after tumor transplantation.Results. It was shown that using two methods: MRI with CE and PET-CT with 11C-choline, a glioblastoma up to 4 mm can be convincingly visualized.Conclusion. The data obtained can be crucial for early detection of glioblastoma, justification of treatment tactics, evaluation of the treatment effectiveness and prediction the outcome of the disease.

Radiological characteristics study on epithelioid glioblastoma, a rare subtype of GBM

Purpose Epithelioid glioblastoma (eGBM) is rare and a newly recognized subtype of GBM. Given the short of studies focusing on radiological characteristics of these tumors, we aimed to report the radiological features of eGBM deriving from six patients. Methods Six patients with pathologically diagnosed as eGBM were enrolled in this retrospective study. CT and pre-operative MR examinations with conventional and advanced sequences, such as diffusion weighted imaging and so on were analyzed. Immunohistological staining and mutation analysis of BRAF V600E was also explored. Results Only case 6 showed a co-locating tumor which was verified to be a diffuse astrocytoma (WHO II), other cases demonstrated single intracerebral tumor. Majority of the tumors originated in cerebral cortex, two cases involved corpus callosum. Tumors demonstrated iso-, hypo- or mixed intensity on T1WI, hyper- or mixed intensity on T2WI and FLAIR, heterogeneous enhancement on post-contrasted imaging. Involvement of leptomeninge, which appeared as leptomenigeal thickening and abnormal enhancing was discovered in 4 cases. Peritumoral edema (4/6) and hemorrhage (3/6) was common, calcium was only seen in case 5. Notable restrictive diffusion and consequently decreased rADC was found in solid component in 5 cases. Most cases demonstrated increased Cho and Lac/Lip value on 1H-MRS, and promoted rCBV value on PWI. The cases with CT examination showed an ill-defined mass with mixed density. Conclusions Although there are some overlaps between typical GBM and eGBM, some radiological characteristics, such as location (often in cerebral cortex), involvement of leptomeninge and intratumoral calcium, may support the diagnosis of eGBM.

Dynamic urinary proteomic analysis in a Walker 256 intracerebral tumor model

Patients with primary and metastatic brain cancer have an extremely poor prognosis, mostly due to the late diagnosis of disease. Urine, which lacks homeostatic mechanisms, is an ideal biomarker source that accumulates early and highly sensitive changes to provides information about the early stage of disease. A rat model mimicking the local tumor growth process in the brain was established with intracerebral Walker 256 (W256) cell injection. Urine samples were collected on days 3, 5 and 8 after injection and then analyzed by LC-MS/MS. In the intracerebral W256 model, no obvious clinical manifestations changes or abnormal MRI signals were found on days 3 and 5; at these time points, nine proteins were changed significantly in the urine of all 8 tumor rats. On day 8, when tumors were detected by MRI, twenty-five differential proteins were identified, including 10 proteins that have been reported to be closely related to tumor metastasis or brain tumors. The differential urinary proteomes were compared with those from the subcutaneous W256 model and the intracerebral C6 model. Few differential proteins overlapped. Specific differential protein patterns were observed among the three models, indicating that the urinary proteome can reflect the difference when tumor cells with different growth characteristics are inoculated into the brain and when identical tumor cells are inoculated into different areas, specifically, the subcutis and the brain.

A Case of Nongerminomatous Germ Cell Tumor of the Pineal Region: Risks and Advantages of Biopsy by Endoscopic Approach

A 21-year-old male was admitted to our department with headache and drowsiness. CT scan and MRI revealed acute obstructive hydrocephalus caused by a pineal region mass. The serum and CSF levels of beta-human chorionic gonadotropin (beta-hCG) were 215 IU/L and 447 IU/L, respectively, while levels of alpha-fetoprotein (AFP) were normal. A germ cell tumor (GCT) was suspected, and the patient underwent endoscopic third ventriculostomy (ETV) with biopsy. After four days from surgery, the tumor bled with mass expansion and ETV stoma occlusion; thus, a ventriculoperitoneal shunt was positioned. After ten months, the tumor metastasized to the thorax and abdomen with progression of intracerebral tumor mass. Despite the aggressive nature of this tumor, ETV remains a valid approach for a pineal region mass, but in case of GCT, the risk of bleeding should be taken into account, during and after the surgical procedure.