Search Results (199)

Gliomas, particularly IDH-wildtype ones, are associated with poor prognosis, yet their immunological landscape remains uncertain. We analyzed RNA sequencing data from 55 glioma patients, estimating immune infiltration with CIBERSORTx and immune cell states via Ecotyper. IDH-wildtype gliomas showed significantly higher immune cell infiltration (p = 0.002), notably of regulatory T cells (Tregs) and macrophages, and a greater proportion of exhausted T cells compared to IDH-mutant gliomas. Clustering based on immune profiles revealed two groups. Cluster A, enriched for IDH-wildtype cases, exhibited heightened immune infiltration but also marked immunosuppression. Cluster B, which included both IDH-wildtype and mutant cases, showed lower levels of immune infiltration. Tumor-infiltrating lymphocyte (TIL) cultured from IDH-wildtype tumors demonstrated limited expansion following anti-PD-1, a CSF1R inhibitor, or a STAT3 inhibitor treatment, without clear cluster-specific differences. Tumor-reactive TILs were mainly observed in cluster A. These findings highlight that IDH-wildtype gliomas have an immunosuppressive and heterogeneous microenvironment, potentially limiting responses to single-agent immunotherapies. A personalized, multi-targeted approach addressing multiple immunosuppressive mechanisms may be essential to improve immunotherapy outcomes in this aggressive glioma subgroup. Full article

Background and Aim: Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, with poor prognosis despite maximal surgical resection, radiotherapy (RT), and temozolomide (TMZ) per the Stupp protocol. IDH-wild-type GBM, the predominant molecular subtype, frequently harbors EGFR amplification and is resistant to therapy, while MGMT promoter methylation predicts improved TMZ response. This study aimed to assess the prognostic impact of EGFR and MGMT status on survival and recurrence patterns in IDH-wild-type GBM. Materials and Methods: We retrospectively analyzed 218 patients with IDH-wild-type GBM treated at the Azienda Ospedaliero-Universitaria Senese (2016–2024). All patients underwent maximal safe surgical resection whenever feasible. The cohort includes patients who received gross total resection (GTR), subtotal resection (STR), or biopsy only, depending on tumor location and clinical condition, followed by intensity-modulated RT (59.4–60 Gy) with concurrent and adjuvant TMZ. EGFR amplification was assessed via FISH/NGS and immunohistochemistry; MGMT promoter methylation was determined using methylation-specific PCR. Progression-free survival (PFS), overall survival (OS), and recurrence patterns (in-field, marginal, out-field) were evaluated using Kaplan–Meier, Cox regression, and logistic regression analyses. Results: Among patients (64.7% male; mean age 61.8), 58.7% had EGFR amplification and 49.1% showed MGMT methylation. Median OS and PFS were 14 and 8 months, respectively. EGFR non-amplified/MGMT methylated tumors had the best outcomes (OS: 22.0 months, PFS: 10.5 months), while EGFR-amplified/MGMT unmethylated tumors fared worst (OS: 10.0 months, PFS: 5.0 months; p < 0.001). MGMT methylation was an independent positive prognostic factor (HR: 0.48, p < 0.001), while EGFR amplification predicted worse survival (HR: 1.57, p = 0.02) and higher marginal recurrence (OR: 2.42, p = 0.01). Conclusions: EGFR amplification and MGMT methylation significantly influence survival and recurrence dynamics in IDH-wild-type GBM. Incorporating these biomarkers into treatment planning may enable tailored therapeutic strategies, potentially improving outcomes in this challenging disease. Prospective studies are needed to validate biomolecularly guided management approaches. Full article

Objectives: To assess amide proton transfer weighted (APTw) MR imaging capabilities in differentiating high-grade glial tumors across alpha-thalassemia/mental retardation X-linked (ATRX) expression, tumor-suppressor protein p53 expression (p53), O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation, isocitrate dehydrogenase (IDH) status, and proliferation marker Ki-67 (Ki-67 index) as a preoperative diagnostic aid. Material & Methods: A total of 42 high-grade glioma WHO grade 4 (HGG) patients were evaluated prospectively (30 males and 12 females). All patients were examined using conventional MRI, including the following: T1w-MPRAGE pre- and post-contrast administration, conventional T2w and 3D FLAIR, and APTw imaging with a 3T MR scanner. Receiver operating characteristic (ROC) curves were calculated for the APTw% mean, median, and max signal for the different molecular biomarkers. A logistic regression model was constructed for combined mean and median APTw% signals for p53 expression. Results: The whole-tumor max APTw% signal could significantly differentiate MGMTp from non-MGMTp HGG, p = 0.035. A cutoff of 4.28% max APTw% signal yielded AUC (area under the curve) = 0.702, with 70.6% sensitivity and 66.7% specificity. The mean/median APTw% signals differed significantly in p53 normal versus p53-overexpressed HGG s: 1.81%/1.83% vs. 1.15%/1.18%, p = 0.002/0.006, respectively. Cutoffs of 1.25%/1.33% for the mean/median APTw% signals yielded AUCs of 0.786/0.757, sensitivities of 76.9%/76.9%, and specificities of 50%/66.2%, p = 0.002/0.006, respectively. A logistic regression model with a combined mean and median APTw% signal for p53 status yielded an AUC = 0.788 and 76.9% sensitivity and 66.2% specificity. ATRX-, IDH- wild type (wt) vs. mutation (mut), and the level of Ki-67 did not differ significantly, but trends were found: IDH-wt and low Ki-67 showed higher mean/median/max APTw% signals vs. IDH-mut and high Ki-67, respectively. ATRX-wt vs. mutation showed higher mean and median APTw% signals but lower max APTw% signal. Conclusions: APTw imaging can potentially be a useful marker for the stratification of p53 expression and MGMT status in high-grade glioma in the preoperative setting and potentially aid surgical decision-making. Full article

A histological evaluation remains the cornerstone of diagnosing highly malignant osteosarcoma, having demonstrated its efficacy and reliability over several decades. However, despite these advancements, misdiagnoses with severe consequences, including inadequate surgical procedures, continue to occur. Consequently, there is a pressing need to further enhance diagnostic security. Adjunct immunohistochemical approaches have demonstrated significant effectiveness in regard to cancer diagnostics, generally. However, their utility for identifying highly malignant osteosarcoma is limited. Molecular genetic findings have significantly improved the diagnosis of Ewing’s sarcoma by identifying specific translocations and have been used to detect specific IDH gene mutations in chondrosarcoma. Nevertheless, molecular genetic alterations in highly malignant osteosarcoma exhibit a high degree of complexity, thereby limiting their diagnostic utility. Given that only 1–2% of the human genome comprises protein-coding sequences, the growing number of non-coding regulatory RNAs, which are increasingly being elucidated, has garnered substantial attention in the field of clinical cancer diagnostics. Over the past several years, patterns of altered non-coding RNA expression have been identified that facilitate the distinction between benign and malignant tumors in various organs. In the field of bone tumors, the experience of this approach has been limited thus far. The divergent expression of microRNAs has demonstrated utility for differentiating osteosarcoma from osteoblastoma and discriminating between osteosarcoma and giant-cell tumors of bone and fibrous dysplasia. However, the application of non-coding RNA expression patterns for the differential diagnosis of osteosarcoma is still in its preliminary stages. This review provides an overview of the current status of non-coding RNAs in osteosarcoma diagnostics, in conjunction with a histological evaluation. The potential of this approach is discussed comprehensively. Full article

Acute myeloid leukemia (AML) has traditionally been linked to a poor prognosis, particularly in older patients who are ineligible for intensive chemotherapy. The advent of Venetoclax, a powerful oral BH3 mimetic targeting anti-apoptotic protein BCL2, has significantly advanced AML treatment. Its combination with the hypomethylating agent azacitidine (AZA/VEN) has become a standard treatment for this group of AML patients, demonstrating a 65% overall response rate and a median overall survival of 14.7 months, compared to 22% and 8 months with azacitidine monotherapy, respectively. However, resistance and relapses remain common, representing a significant clinical challenge. Recent studies have identified molecular alterations, such as mutations in FLT3-ITD, NRAS/KRAS, TP53, and BAX, as major drivers of resistance. Additionally, other factors, including metabolic changes, anti-apoptotic protein expression, and monocytic or erythroid/megakaryocytic differentiation status, contribute to treatment failure. Clinical trials are exploring strategies to overcome venetoclax resistance, including doublet or triplet therapies targeting IDH and FLT3 mutations; novel epigenetic approaches; menin, XPO1, and MDM2 inhibitors; along with immunotherapies like monoclonal antibodies and antibody–drug conjugates. A deeper understanding of the molecular mechanisms of resistance through single-cell analysis will be crucial for developing future therapeutic strategies. Full article

Background: Chondrosarcoma is the second most common bone tumor in adults with an average incidence of 0.1–0.3 individuals per 100,000 per year. These tumors are often resistant to chemotherapy and radiation, and surgical excision is a mainstay of current treatment. However, survival in the setting of metastatic disease is still poor, and research is needed to identify prognostic biomarkers and potential therapeutic targets. Several studies have examined the role of IDH mutations in chondrosarcoma, but the results vary widely. The goal of this analysis was to aggregate individual patient data from these studies and conduct a high-powered analysis of the impact of IDH mutations on survival outcomes in chondrosarcoma. Methods: Chondrosarcoma studies that included data on the IDH mutation status of tumors were queried, and the individual datasets reporting patient and tumor variables were extracted. The data from these studies were added to the internal dataset from the authors’ home institution. Two-sample tests for equality of proportions were used to assess the distribution of sample characteristics between groups. Univariate Kaplan–Meier (KM) curves and multivariate Cox Proportional Hazards (CPH) models were used to assess the relationship between tumor IDH mutations and five and ten-year patient overall survival (OS). Results: The final cohort included 1152 patients sourced from 21 studies and the authors’ internal dataset. IDH mutations were more common in higher grade tumors and were more likely to be found in individuals over 60 years old. Patients with IDH mutant tumors had shorter five-year OS in univariate KM analysis when analyzing all chondrosarcomas combined. However, multivariate CPH models accounting for age and tumor grade, found that the effect of IDH mutation was isolated to patients with dedifferentiated tumors only. Patients with IDH mutant dedifferentiated tumors displayed significantly shorter five-year OS (HR: 1.99, p = 0.02) relative to patients with IDH wild-type (WT) dedifferentiated tumors. The primary predictor of five-year OS in the conventional chondrosarcoma cohort was tumor grade, regardless of IDH mutation status (HR: 2.72, p < 0.005). Discussion: IDH mutations are relatively common in cartilaginous neoplasms (including benign tumors), with the literature reporting rates as high as 50% in chondrosarcomas. Prior studies have investigated the link between IDH1/2 mutation status, tumor grade and overall survival, with mixed results on the effect of IDH mutation on survival. Vuong et al. performed a meta-analysis in 2021 and found that IDH mutation was associated with older patient age, larger tumor size, higher tumor grade, and increased risk of death compared to WT tumors. Our analysis, which builds on the Vuong et al. study, indicates that IDH status itself is not independently predictive of overall survival in conventional chondrosarcoma, however, it does correlate with survival in dedifferentiated tumors. Further analysis is needed to investigate the potential correlation of IDH mutations in higher grade tumors and patients of older age. Full article

Telomere maintenance mechanisms (TMMs) play a critical role in cancer biology, particularly in lower-grade gliomas (LGGs), where telomere dynamics and pathway activity remain poorly understood. In this study, we analyzed TCGA-LGG and CGGA datasets, focusing on telomere length variations, pathway activity, and survival data across IDH subtypes. Additional validation was performed using the GEO COPD and GBM datasets, ensuring consistency in data processing and batch effect correction. Our analysis revealed significant differences in TEL pathway activation between Short- and Long-TL groups, emphasizing the central role of TERT in telomere maintenance. In contrast, ALT pathway activation displayed subtype-specific patterns, with IDH-wt tumors exhibiting the highest ALT activity, primarily driven by the RAD51 branch. Validation using CGGA data confirmed these findings, demonstrating consistent TEL and ALT pathway behaviors across datasets. Additionally, genetic subtype analysis revealed substantial telomere length variability associated with ATRX and IDH mutation status. Notably, IDHwt-ATRX WT tumors exhibited the shortest telomere length and the highest ALT pathway activity. These findings highlight distinct telomere regulatory dynamics across genetic subtypes of LGG and provide new insights into potential therapeutic strategies targeting telomere maintenance pathways. Full article

Background and Objectives: This study aims to evaluate the overall survival benefits of repeat resection in patients with recurrent glioblastoma, IDH-wildtype (rGBM), and to identify factors for long-term survival, including the role of clinical, radiological, and molecular parameters. Methods: This longitudinal matched case-control study included 60 patients with rGBM divided into two groups: one surgery (n = 30) and repeat resection (n = 30). The baseline characteristics, preoperative and postoperative volumes, and molecular markers were assessed. Survival analyses were conducted using the Log-rank test, and associated factors with long-term survival were identified in the repeat resection cohort. Results: The patients who underwent repeat resection had a significantly longer median survival of 23.9 months compared to 9.2 months in the one-surgery group (p < 0.001). Preoperative tumor volume was found to correlate with postoperative residual volume in repeat resections. The patients with no residual contrast-enhancing tumor volume (0 cm³) after repeat resection had a median survival of 19.33 months, while those with any residual volume had a median survival of 10.13 months. The patients with lower KPS (≤70) and GCS (≤13) scores at the time of the repeat resection tended to have shorter survival, underscoring the potential clinical relevance of functional status when evaluating surgical candidacy. Conclusions: Complete repeat resection may improve overall survival in patients with recurrent IDH-wildtype GBM and should be considered earlier as a therapeutic option rather than a diagnostic or salvage procedure. Early surgical intervention, before declines in the KPS and GCS or tumor volumes become unmanageable, may lead to better outcomes. Further studies with larger cohorts are needed to confirm these findings. Full article

Background/Objectives: Glioblastoma IDH-wildtype CNS WHO grade 4 and astrocytoma IDH-mutant WHO grade 4 (together, high-grade gliomas: HGGs) are the most prevalent malignant brain tumors, carrying a poor prognosis despite multimodal treatment. Surgical site infections (SSIs) represent a relative frequent postoperative complication in HGG patients. Despite multimodal treatment protocols combining surgery, radiotherapy, and temozolomide chemotherapy, HGGs remain associated with a dismal prognosis, underscoring the need to evaluate how SSIs impact disease progression and survival outcomes. This study’s aim was to investigate the influence of SSIs on the clinical course of patients with HGGs. Methods: A comprehensive review of medical records for HGG patients treated at our institution between 2010 and 2024 identified 26 patients with SSIs. These patients were compared to an age-matched control group with the same histological diagnosis and treatment regimen. This study analyzed overall survival (OS), microbiological data, and pathological parameters to assess the impact of SSIs on patient outcomes. Survival differences between the infected and non-infected groups were evaluated using Kaplan–Meier survival curves. Remarkably, three patients with exceptionally long overall survival were highlighted in this study. Results: Among the cohort of 2008 patients with HGG surgery, 26 patients developed SSIs. An age-matched control group of 26 patients was identified, none of whom experienced SSIs. Comparing the OS between the infected and uninfected groups, a statistically significant improvement in OS was observed in the infected group (p = 0.049). The median OS in the infected group was 388 days, slightly shorter than the median OS of 422 days in the control group. However, the mean OS was markedly higher in the infected group (674 days) compared to the control group (442 days). The standard deviation of OS in the infected group was notably expansive, indicating substantial variability in survival outcomes. A cluster of infected patients with SSIs near the time of diagnosis had shorter OS, while other infected cases demonstrated significantly longer survival, exceeding both median and mean OS values. In contrast, the uninfected group showed limited standard deviation values, with uniformly distributed individual OS data around the median and mean values. Expectedly, IDH mutation status significantly influenced the survival in cohort patients. However, when stratified by infection status, no association between IDH mutation and improved infection-related survival was identified. The microbiological profile of SSIs was diverse, encompassing Gram-positive and Gram-negative bacteria as well as aerobic and anaerobic organisms. Conclusions: These findings underscore the heterogeneity of infection-related outcomes and their potential impact on survival in HGG patients. According to our knowledge, our study is one of the largest retrospective studies to date investigating and confirming the significant relationship between SSIs and HGG patients’ survival. Our results confirm the Janus Face phenomenon of infections, having both negative and positive effects depending on the context. Full article

Background/Objectives: Glioblastoma ranks among the most aggressive brain tumors, with poor prognosis. Currently, there are insufficient data regarding the prognostic value of isocitrate dehydrogenase (IDH) mutation status and inflammatory markers. This study demonstrates the prognostic value of IDH mutation status and preoperative inflammatory markers in glioblastoma. Methods: This single-center retrospective study encompassed 66 glioblastoma patients who had surgical treatment in our institution from January 2020 to March 2022. The patients were categorized into two groups: IDH-mutant (n = 30) and IDH-wild-type (n = 36). We made a comparative assessment of demographic characteristics, clinical parameters, preoperative blood parameters, and survival outcome across the two groups. Statistical analyses included Kaplan–Meier survival curves, ROC analysis, and multivariate Cox regression. Results: The IDH-mutant group demonstrated a significantly lower mean age (53.93 ± 12.00) compared to the wild-type group (62.39 ± 10.12) (p = 0.003). Median overall survival was notably longer in the IDH-mutant group, at 16.0 months, versus 6.5 months in the wild-type group (p = 0.030). An elevated neutrophil/lymphocyte ratio above 3.39 (sensitivity 95.12%, specificity 52.0%) and a platelet/lymphocyte ratio exceeding 136.25 (sensitivity 80.49%, specificity 64.0%) were associated with poor prognosis. Cox regression analysis identified IDH-wild-type status (HR = 2.84, 95% CI: 1.56–5.18) and elevated NLR (HR = 1.84, 95% CI: 1.16–2.92) as independent poor prognostic factors. Conclusions: We show that IDH-wild-type glioblastomal patients have a significantly poorer overall prognosis. In this case, the metrics of preoperative neutrophil/lymphocyte ratio and platelet/lymphocyte ratio seem to be supplied with some value as biomarkers for the expansion of the disease and predicting likely outcomes. Full article

Background: Dynamic susceptibility contrast perfusion MRI (DSC-MRI) is a promising non-invasive examination to predict histological and molecular characteristics of brain gliomas. However, the diagnostic accuracy of relative cerebral blood volume (rCBV) is heterogeneously reported in the literature. This systematic review and meta-analysis aims to assess the diagnostic accuracy of mean rCBV derived from DSC-MRI in differentiating Isocitrate Dehydrogenase (IDH)-mutant from IDH-wildtype gliomas. Methods: A comprehensive literature search was conducted in PubMed, Web of Science, and EMBASE up to January 2025, following PRISMA guidelines. Eligible studies reported mean CBV values in treatment-naïve gliomas with histologically confirmed IDH status. Pooled estimates of standardized mean differences (SMDs), diagnostic odds ratios (DOR), and area under the receiver-operating characteristic curve (AUC) were computed using a random-effects model. Heterogeneity was assessed via I² statistic. Meta-regression analyses were also performed. Results: An analysis of 18 studies (n = 1733) showed that mean rCBV is significantly lower in IDH-mutant gliomas (SMD = −0.86; p < 0.0001). The pooled AUC was 0.80 (95% CI, 0.75–0.90), with moderate sensitivity and specificity. Meta-regression revealed no significant influence of DSC-MRI acquisition parameters, although a flip angle showed a trend toward significance (p = 0.055). Conclusions: Mean rCBV is a reliable imaging biomarker for IDH mutation status in gliomas, demonstrating good diagnostic performance. However, heterogeneity in acquisition parameters and post-processing methods limits generalizability of results. Future research should focus on standardizing DSC-MRI protocols. Full article

Background/Objectives: Non-invasive motor mapping with navigated transcranial magnetic stimulation (nTMS) is an established diagnostic tool to identify spatial relationships between functional and tumor areas and to characterize motor excitability. Recently, nTMS has been used to analyze the impact of different brain tumor entities on motor excitability. However, entity-specific excitability patterns are not sufficiently validated yet. Methods: We retrospectively analyzed nTMS motor mapping data of 800 motor-eloquent brain tumor patients in this observational study. The motor excitability profile consisted of four nTMS parameters (resting motor threshold (RMT), cortical motor area, amplitude and latency) measured on both hemispheres. The relationship between motor excitability parameters and tumor entity, glioma subtype and motor status were assessed using multiple regressions analyses. Regression models included patient- and tumor-specific factors. Results: Gliomas had more frequent pathologic RMT ratios (OR 1.76, 95%CI: 1.06–2.89, p = 0.030) compared to benign entities. In the subgroup of gliomas, pathologic RMT ratios were more associated with the isocitrate dehydrogenase (IDH)-wildtype status (OR 0.43, 95%CI: 0.23–0.79, p = 0.006) and less so with higher WHO grades (OR 1.61, 95%CI: 0.96–2.71, p = 0.074). This was true for both IDH-mutant astrocytomas (OR 0.43, 95%CI: 0.20–0.91, p = 0.027) and IDH-mutant oligodendrogliomas (OR 0.43, 95%CI: 0.20–0.93, p = 0.031). Motor area enlargement on the tumor hemisphere was more frequently observed in lower WHO-graded gliomas (OR 0.87, 95%CI: 0.78–0.97, p = 0.019). Interestingly, a larger cortical motor area was additionally found for oligodendrogliomas on the healthy hemisphere (OR 1.18, 95%CI: 1.01–1.39, p = 0.041). Motor deficits were related with higher RMT (OR 1.12, 95%CI: 1.05–1.21, p = 0.001), reduced amplitude (OR 0.78, 95%CI: 0.64–0.96, p = 0.019) and prolonged latency (OR 1.12, 95%CI: 1.02–1.24, p = 0.025) in the tumor hemisphere. Conclusions: Neuroplastic phenomena such as adjustment of the motor excitability level and an enlargement of the nTMS-positive motor area were more frequently observed in benign tumors and in IDH-mutated gliomas. Consequently, patients experienced motor deficits less often, suggesting a differentiated susceptibility to resection-related paresis. Future studies will analyze which stimulation paradigms are most effective in stimulating and optimizing neuroplasticity processes to improve the functional outcomes (and thus the quality of life) for patients. Full article

Background/Objectives: The purpose of this study was to evaluate the performance of diffusion kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), and diffusion microstructure imaging (DMI) in differentiating molecular subtypes of adult-type gliomas. Methods: Standardized MRI was performed and evaluated in 59 patients with adult-type glioma. DKI, NODDI, and DMI parameter values were quantitatively evaluated in ROIs in contrast-enhancing/solid tumor tissue and five concentric shells with peritumoral tissue. DKI, NODDI, and DMI parameters of (i) glioblastomas, Isocitrate dehydrogenase (IDH) wildtype; (ii) astrocytomas, IDH mutant; and (iii) oligodendrogliomas, IDH mutant were compared with analysis of variance (ANOVA). Receiver operating characteristic curve (ROC) curve analysis was conducted to discriminate firstly between IDH mutant and IDH wildtype gliomas and then between IDH mutant astrocytomas and oligodendrogliomas. Results: Significant differences between the three aforementioned subtypes were found for the apparent diffusion coefficient (ADC) and mean kurtosis (MK) and again for the orientation dispersion index (ODI) and intra-axonal volume fraction (v-intra). The diagnostic accuracy depended on the distance to the contrast-enhancing/solid tumor tissue. Some NODDI and DMI parameters significantly predicted the IDH status and significantly discriminated between astrocytomas and oligodendrogliomas; however, ADC and MK showed the best prediction in both ROC analyses (maximum AUC 0.910 (CI 0.824–0.995)). Conclusions: The evaluation of peritumoral tissue can be a valuable procedure, while NODDI and DMI appear to be promising but are currently inferior to DKI in predicting glioma subtypes categorized according to the WHO 2021 classification. Full article

Background: Cholangiocarcinoma, a malignancy originating from the bile ducts, poses significant treatment challenges due to its typically late diagnosis and limited therapeutic options. However, recent advances in molecular genetics enable more personalized treatment approaches. A notable breakthrough in this context is the identification of isocitrate dehydrogenase (IDH) mutations, particularly IDH1 and IDH2, which occur in a subset of cholangiocarcinoma patients. Those with IDH1/2 mutations may benefit from targeted therapies. For instance, Ivosidenib, an IDH1 inhibitor, has shown efficacy in clinical trials, offering a new therapeutic option for patients with IDH1-mutant cholangiocarcinoma. Developing and implementing standardized protocols for testing and reporting mutation status are crucial for consistency and accuracy in clinical practice. Both the Idylla™ IDH1-2 Mutation Assay Kit as a FastTrack method and Next-Generation Sequencing (NGS) panels play critical roles in molecular characterization of cholangiocarcinoma. Methods: Under this aspect, a set of cholangiocarcinomas was tested using the Idylla™ platform regarding the respective recommended guidelines and standards of DIN EN ISO:17020 and DIN EN ISO:15198. Results: Overall, 25 clinically diagnosed intrahepatic cholangiocarcinomas or Adeno-CUPs were analyzed. IDH1/2 mutations were identified in 68% (17/25) of cases using both methods, with high concordance between NGS and Idylla™ results. Discrepancies were observed in two samples, where Idylla™ detected no mutations, but NGS reported IDH1 and IDH2 mutations, respectively. Conclusions: Idylla^TM offers a rapid, user-friendly, and specific method for detecting IDH1/2 mutations, ideal for immediate clinical needs. NGS, while more time-consuming and costly, provides comprehensive genetic profiles valuable for personalized medicine and research. The choice between these methods should be guided by the clinical context, resource availability, and individual patient needs. For routine diagnostics, we recommend an algorithmic approach starting with the FastTrack method followed by NGS for wildtype cases. Full article

Introduction: Glioma Grade 4 (GG4) tumors, which include both IDH-mutated and IDH wild-type astrocytomas, are the most prevalent and aggressive form of primary brain tumor. Radiomics is gaining ground in neuro-oncology. The integration of this data into machine learning models has the potential to improve the accuracy of prognostic models for GG4 patients. Karnofsky Performance Status (KPS), an established preoperative prognostic factor for survival, is commonly used in these patients. In this study, we developed a nomogram to identify patients with improved functional performance as indicated by an increase in KPS after surgery by analyzing radiomic features from preoperative 3D MRI scans. Methods: Quantitative imaging features were extracted from the -3D T1 GRE sequence of 157 patients from a single center and were used to develop the machine learning (ML) model. To improve applicability and create a nomogram, multivariable logistic regression analysis was performed to build a model incorporating clinical characteristics and radiomics features. Results: We labeled 55 cases in which KPS was improved after surgery (35%, KPS-flag = 1). The resulting model was evaluated according to test series results. The best model was obtained by XGBoost using the features extracted by pyradiomics, with a Matthew coefficient score (MCC) of 0.339 (95% CI: 0.330–0.3483) in cross-validation. The out-of-sample evaluation on the test set yielded an MCC of 0.302. A nomogram evaluating the improvement of KPS post-surgery was built based on statistically significant variables from multivariate logistic regression including clinical and radiomics data (c-index = 0.760, test set). Conclusions: MRI radiomic analysis represents a powerful tool to predict postoperative functional outcomes, as evaluated by KPS. Full article