Ondrej Kalita

Background: Segmentation enables extraction of quantitative imaging features to enhance glioma diagnosis by volumetric measurements and treatment response assessment. This narrative review evaluates open-source software for glioma segmentation and alignment with Response Assessment in Neuro-Oncology (RANO 2.0) volumetric criteria. Approach: In this narrative review, we evaluated thirteen open-source tools selected for multimodal MRI sequence support (T1W, T1CE, T2W, FLAIR), performance on public datasets (BraTS Challenge), and applicability to RANO 2.0 volumetry. Assessment included Dice scores, workflow efficiency, advantages, limitations, and clinical translation potential. Results: Tools achieved Dice scores 0.73–0.92 for tumor subregions. Despite high analytical validation, clinical utility is limited: 85% of treatment response studies have bias risk in patient selection per QUADAS-2 appraisal. Critically, as of November 2024, no automated tools have been formally validated specifically against RANO 2.0 criteria, despite their 2023 emphasis on volumetric standardization. Conclusion: Open-source segmentation tools show promise for standardizing glioma volumetry with emerging tools (GlioMODA, AutoRANO) explicitly targeting RANO 2.0-compatible volumetric assessment. Hybrid approaches combining open-source innovation with commercial clinical integration could optimize clinical translation.

The best results in glioblastoma (GBM) are obtained through aggressive treatment comprising maximally radical but safe resection followed by chemoradiotherapy. However, certain patients will undergo only stereotactic biopsy. This paper aims to evaluate life expectancy in GBM patients who underwent only stereotactic biopsy, including the effect of subsequent oncological treatment. Patients with confirmed GBM histology who had undergone stereotactic biopsy between June 2006 and December 2016 were retrospectively selected. Each patient had received a CT scan, followed by an MRI scan with a contrast agent. None of the patients were amenable to microsurgical resection. Of the 60 patients, 41 (69%) received no subsequent oncological treatment, while 14 (23%) underwent isolated radiotherapy. Mean survival time of all patients was 2.8 months. Those who received no additional treatment had an average survival time of 2.3 months; patients who received any type of oncological treatment was 3.7 months. Of these, those receiving radiotherapy alone had a mean survival of 3.1 months. Patients who received oncological treatment with the Stupp protocol had a survival time of 6.6 months. Diagnostic and surgical advances related to GBM treatment mean that radical resections can be performed even in eloquent brain areas. However, patients not indicated for resection will experience a major reduction in life expectancy. Patients who underwent stereotactic biopsy and received some form of oncological treatment experienced slightly increased overall survival relative to patients with a natural disease course. Patients with favorable clinical factors reacted better to treatment.

Glioblastoma inevitably recurs, but no standard regimen has been established for treating this recurrent disease. Several reports claim that reoperative surgery can improve survival, but the effects of reoperation timing on survival have rarely been investigated. We, therefore, evaluated the relationship between reoperation timing and survival in recurrent GBM. A consecutive cohort of unselected patients (real-world data) from three neuro-oncology cancer centers was analyzed (a total of 109 patients). All patients underwent initial maximal safe resection followed by treatment according to the Stupp protocol. Those meeting the following criteria during progression were indicated for reoperation and were further analyzed in this study: (1) The tumor volume increased by >20–30% or a tumor was rediscovered after radiological disappearance; (2) The patient’s clinical status was satisfactory (KS ≥ 70% and PS WHO ≤ gr. 2); (3) The tumor was localized without multifocality; (4) The minimum expected tumor volume reduction was above 80%. A univariate Cox regression analysis of postsurgical survival (PSS) revealed a statistically significant effect of reoperation on PSS from a threshold of 16 months after the first surgery. Cox regression models that stratified the Karnofsky score with age adjustment confirmed a statistically significant improvement in PSS for time-to-progression (TTP) thresholds of 22 and 24 months. The patient groups exhibiting the first recurrence at 22 and 24 months had better survival rates than those exhibiting earlier recurrences. For the 22-month group, the HR was 0.5 with a 95% CI of (0.27, 0.96) and a p-value of 0.036. For the 24-month group, the HR was 0.5 with a 95% CI of (0.25, 0.96) and a p-value of 0.039. Patients with the longest survival were also the best candidates for repeated surgery. Later recurrence of glioblastoma was associated with higher survival rates after reoperation.

Stroke-like syndrome is defined as a rare, delayed complication of brain oncotherapy. Cases with more favorable brain cancer diagnoses and longer life expectancy have been previously reported, but here we present, for the first time, three long-term survivors of glioblastoma with stroke-like syndromes. Three young or middle-aged patients underwent tumor resection and chemoradiotherapy. They received regular clinical and imaging follow-up with stable neurological status and no signs of tumor recurrence. They exhibited varied signs and symptoms (motor and sensory deficits, aphasia, memory and cognitive disorders, seizures, and headache) accompanied by imaging abnormalities. Stroke-like syndromes developed within 2-5 days and resolved in 2-6 weeks. Diffusion-weighted MRI and T2 brain perfusion abnormalities were demonstrated in all patients. In addition, there was focal T1 MRI contrast enhancement due to blood-brain barrier disruption. In addition to tumor recurrence, classic stroke, encephalitis, metabolic and mitochondrial disorders, and post-seizure swelling should be excluded. The imaging indicated intensive MRI scanning and symptomatic medication (steroids supplemented by antiepileptics, vasoactive agents, etc.) for judicious management. With respect to the course, an invasive procedure was still considered an option. All stroke-like syndromes are diagnoses of exclusion. To avoid misinterpretation of imaging findings as glioblastoma recurrence and avert recall oncotherapy or redundant interventions, better understanding of delayed complications of brain tumor therapy is crucial.

Patients below 55 years were genetically studied because the prevalence of isocitrate dehydrogenase 1 (IDH1) decreases in older patients and on grounds of cost-effectiveness, as suggested by the World Health Organization (WHO) in 2016. The aim of our study was to use novel massively parallel sequencing (MPS) approaches to examine rare variants of IDH1/2 in Czech diffuse astrocytic and oligodendroglial tumors (gliomas) patients below 55 years of age who had been immunohistochemically (IHC) diagnosed as IDH1 R132H negative. The IHC IDH1 status (wild type or mutant) of 275 tissue samples was analyzed using antibodies against the IDH1 R132H protein. Sixty-three samples of 55 years old patients with IHC IDH1 WT status were genotyped using two different MPS technologies to detect rare IDH1 and IDH2 variants. The tiered IHC (60 positive) and molecular (10 positive) approach thus revealed that 70 of the 275 samples (25%) bore IDH1/IDH2 mutations. The combined molecular and IHC approach thus revealed that 70 of the 275 samples (25%) considered in the study bore IDH1/IDH2 mutations. IHC detection of the IDH1 R132H variant should be routinely complemented with MPS to detect rare IDH1/2 variants in glioma patients below 55 years of age with negative IHC result of IDH R132H variant.

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This prospective population-based study on a group of 132 resected IDH-wildtype (IDH-wt) glioblastoma (GBM) patients assesses the prognostic and predictive value of selected genetic biomarkers and clinical factors for GBM as well as the dependence of these values on the applied therapeutic modalities. The patients were treated in our hospital between June 2006 and June 2015. Clinical data and tumor samples were analyzed to determine the frequencies of TP53, MDM2, EGFR, RB1, BCR, and CCND1 gene aberrations and the duplication/deletion statuses of the 9p21.3, 1p36.3, 19q13.32, and 10p11.1 chromosome regions. Cut-off values distinguishing low (LCN) and high (HCN) copy number status for each marker were defined. Additionally, MGMT promoter methylation and IDH1/2 mutation status were investigated retrospectively. Young age, female gender, Karnofsky scores (KS) above 80, chemoradiotherapy, TP53 HCN, and CCND1 HCN were identified as positive prognostic factors, and smoking was identified as a negative prognostic factor. Cox proportional regression models of the chemoradiotherapy patient group revealed TP53 HCN and CCND1 HCN to be positive prognostic factors for both progression-free survival and overall survival. These results confirmed the influence of key clinical factors (age, KS, adjuvant oncotherapy, and smoking) on survival in GBM IDH-wt patients and demonstrated the prognostic and/or predictive importance of CCND1, MDM2, and 22q12.2 aberrations.

Východiska: Primární intrakraniální sarkomy představují vzácná onemocnění. S ohledem na chybějící randomizované studie vycházíme v léčebném algoritmu obvykle z extrapolace dat z extrakraniálních variant těchto sarkomů nebo pouze z publikovaných kazuistik, ovšem s vědomím specifik radioterapie v oblasti mozkové tkáně a omezeného průniku cytostatik přes...

Glioblastoma (GBM) is the most common primary brain tumour in adults with nearly 100% mortality. Despite aggressive therapy, overall survival of GBM patients remains poor due to intrinsic or acquired resistance to maximal treatment modality based on combination of radiation and chemotherapy. The biological background behind GBM progression after first line therapy is mostly unknown and thus, there are only limited targeted therapeutic options for the second line treatment. The main goal of this study was to elucidate genetic landscape in paired samples of primary versus recurrent GBM and to validate prognostic and predictive value of the most significant differences in independent cohort of GBMs. The cohort consists of 43 paired samples obtained during 1st surgery followed by radiochemotherapy (at least 54 Gy plus 3 cycles of temozolomide) and during the second palliative surgery. The analysis comprises genome copy number variations (24/43 samples) and fluorescent in situ hybridization determined gene and chromosomal region statuses for EGFR, p53, RB1, MDM2, CDKN2A and 1p, 19q, 10p. Methylation-specific PCR was used for analysis of MGMT promoter methylation and competitive amplification of differentially melting amplicons PCR for IDH1/2 mutations detection. The validation of the most relevant alterations was performed on independent cohort of non-paired 104 tumors. Statistically the most significant differences of GBM progression induced by combination of chemo and/or radiotherapy were: EGFR amplification, CDKN2A loss, MDM2 gain, PDGFRA gain and GSTT1 loss in primary tumors and GSTM1 gain in recurrent tumors. Univariate analysis of overall survival for significant copy number alterations proofs significantly worse prognosis for patients harboring GSTT1 deletion in primary tumor. The analysis revealed trend of better prognosis in patients with CDKN2A deletion and GSTM1 amplification in recurrent tumors. Significantly worse prognosis had GBM patients harboring GSTT1 gene aberrations and was also confirmed in independent validation cohort of unpaired GBMs in multivariate analysis adjusted for age and Karnofsky score. Full data with statistical analysis will be presented in the poster. The molecular genetic background of paired samples of primary and recurrent form of GBM revealed association with glutathione S-transferases genes. The significance of GSTT1 gene aberration was validated in independent group of GBM and thus supports the theory of in involvement of redox enzymes in GBM chemoradiation response and tumor progression. The financial support of grants TACR TE02000058, IGA_LF_2018_005 is gratefully acknowledged. Authors thank the collaborating neurosurgical centers from Ostrava (CGB laboratory), Brno (CEITEC) and Prague (Faculty Hospital Královské Vinohrady).