Introduction:Mucoepidermoid carcinoma (MEC) of the breast is an exceptionally rare salivary gland-type malignancy with uncertain prognostic behaviour. This study compared the clinicopathologic characteristics, treatment patterns, and survival outcomes of MEC and invasive ductal carcinoma not otherwise specified (IDC-NOS) using Surveillance, Epidemiology, and End Results (SEER) data. Material and methods:A retrospective cohort analysis of SEER data (1975-2022) identified cases with MEC (n = 42) and IDC-NOS (n = 50,881). Demographic, clinicopathologic, and treatment variables were compared using χ2 and one-way analysis of variance tests. Overall survival (OS) and disease-specific survival (DSS) were analysed with Kaplan-Meier and Cox proportional hazards models. Results:Mucoepidermoid carcinoma cases were older (≥ 70 years: 91.0% vs. 31.1%; p < 0.001) and predominantly White. Compared with IDC-NOS, MEC exhibited lower HER2 positivity (0.0% vs. 31.4%), oestrogen receptor/progesterone receptor expression (31.0% and 0.0% vs. 60.1% and 52.3%), and distant metastasis (0.0% vs. 20.1%) (all p < 0.001). Mucoepidermoid carcinoma cases were less likely to undergo surgery (85.7%) or receive systemic therapy (40.5%, p < 0.05). Only five deaths (OS) and three (DSS) occurred among MEC cases. Kaplan-Meier curves showed similar early survival, but MEC survival plateaued after 120 months, whereas IDC-NOS declined steadily. Multivariable Cox analysis revealed higher all-cause mortality for IDC-NOS (adjusted hazard ratios [HR] = 3.80, 95% CI: 1.18-12.22), with no significant difference in cancer-specific mortality (HR = 2.32, 95% CI: 0.71-7.58). Conclusions:Mucoepidermoid carcinoma exhibits distinct clinicopathologic features, limited metastatic potential, and favourable long-term survival despite frequent triple negativity. Its indolent course supports conservative management for low-grade cases, warranting further molecular and prognostic studies.
Introduction:Fibroblast growth factor receptor (FGFR) signalling is implicated in breast cancer (BC) progression, but little is known about FGFR status as the disease develops. We evaluated FGFR1-4 expression changes in primary tumours (PT) and matched lymph node metastases (LNM) in the context of BC phenotype and circulating tumour cell (CTC) burden. Material and methods:Fibroblast growth factor receptor 1-4, oestrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2) and Ki-67 were assessed immunohistochemically in paired PT and LNM. Circulating tumour cells were quantified by imaging flow cytometry in 67 BC patients and correlated with BC phenotype and FGFR status. Results:Switch of the BC subtype between PT and LNM was observed in 3/23 cases (13.0%). In contrast, discordance in FGFR expression occurred in 11/22 (50.0%), 5/22 (22.7%), 12/22 (54.5%), and 5/21 (23.8%) cases for FGFR1, FGFR2, FGFR3, and FGFR4, respectively; in most discordant cases, the difference reflected increased expression in LNM. Circulating tumour cells were detected in 22/67 patients (32.8%), with a median burden of 5.7 CTCs per 1 million peripheral blood mononuclear cells (interquartile ranges: 3.0-17.8). Circulating tumour cell presence was not associated with lymph node (LN) status (p = 0.806). Circulating tumour cell presence was more frequent in cases with FGFR1 discordance than in FGFR1-concordant tumours (63.6% vs. 9.1%; p = 0.024). Circulating tumour cell burden correlated inversely with FGFR1 level in LNM (Spearman's ρ = -0.49, p = 0.021). A shift in the FGFR1 status was noted exclusively in HER2-negative tumours. Conclusions:The observed association between CTCs and FGFR1 status conversion, but not LN involvement in the context of disease progression, may reflect a previously unrecognised biological feature of FGFR1- positive cells, most likely restricted to HER2-negative breast cancer.
Introduction:Although computed tomography (CT)-based assessment of body composition has demonstrated that the prognostic value in oncological patients of traditional single-slice manual segmentation is limited by variability and time constraints. This study aims to evaluate the prognostic significance of artificial intelligence (AI)-driven, fully automated volumetric body composition analysis in patients with colorectal liver metastases (CRLM). Material and methods:Clinical and imaging data were collected from 177 patients with CRLM (105 males and 72 females) with a mean age of 59.72 ±12.19 years. Contrast- enhanced CT scans performed within six weeks of partial hepatectomy were processed using a custom AI-driven segmentation pipeline. Segmentation accuracy was assessed using the Dice coefficient. A Cox proportional- hazards model was employed to analyse the relationship between body composition parameters and overall survival. Results:The segmentation model achieved a median Dice coefficient above 0.99. The final survival model identified nine significant predictors of overall survival, including muscle segment volume percentage, mean Hounsfield units (HU) of the muscle segment, maximum tumour size (cm), sex, presence of multiple metastases (≥ 2), extrahepatic disease, prior chemotherapy before liver resection, non-alcoholic steatohepatitis, and histopathological treatment response > 50%. A higher muscle volume percentage was associated with improved survival (HR = 0.69, p < 0.05), while increased mean HU in muscle segment related to a higher hazard of death (HR = 1.36, p < 0.05). Conclusions:Automated skeletal muscle measurements revealed significant associations with survival, emphasising their role in outcome prediction and underscoring the need for further validation in larger, multi-institutional cohorts.
Introduction:Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis and limited therapeutic options. Fangchinoline, a bisbenzylisoquinoline alkaloid, has demonstrated anticancer activity; however, its molecular mechanism in TNBC remains unclear. This study aimed to investigate the anticancer effects of fangchinoline and explore its potential molecular mechanisms in TNBC. Material and methods:An integrated in vitro and in silico approach was employed. Molecular docking and molecular dynamics simulations were conducted to evaluate the interaction of fangchinoline with TGF-β1 and mTOR proteins. Cytotoxicity was assessed in murine 4T1 TNBC-cells.Flow cytometry was used to analyse cell cycle distribution, apoptosis, and protein expression related to the PI3K/Akt/mTOR pathway and p53. Results:Fangchinoline demonstrated strong binding affinity toward TGF-β1 and exhibited selective cytotoxicity against 4T1 cells (IC50 = 25.95 µM). Treatment induced apoptosis and mild G2/M phase arrest. In addition, changes in the expression of PI3K, Akt, mTOR, and p53 proteins were observed. These findings suggest that fangchinoline may suppress cell proliferation and promote apoptosis, possibly through modulation of the PI3K/Akt/mTOR signalling pathway; however, this interpretation is based on protein expression data without phosphorylation analysis or functional validation. Conclusions:Fangchinoline exhibits potential anticancer activity against TNBC-cells by inducing apoptosis and affecting key survival-related pathways. Further studies are required to confirm its molecular mechanisms and therapeutic potential.
Appendiceal mucinous neoplasms are rare tumours whose terminology, staging and management remain difficult to align with conventional colorectal cancer paradigms. Low-grade appendiceal mucinous neoplasm (LAMN) is well established, whereas high-grade appendiceal mucinous neoplasm (HAMN) remains less clearly defined in clinical practice. This review summarises current evidence on the classification, pathological distinction, clinical behaviour, prognosis and management of LAMN and HAMN. Both entities share a non-infiltrative growth pattern, but HAMN is distinguished by high-grade cytologic atypia and a greater association with high-grade peritoneal disease once dissemination occurs. In appendix-confined, non- perforated disease, HAMN seems to behave more like LAMN than invasive adenocarcinoma, so high-grade cytology alone should not be taken as an indication for routine right hemicolectomy. When perforation, extra-appendiceal mucin or peritoneal involvement is present, management should be escalated to specialist multidisciplinary assessment, with surveillance and consideration of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy tailored to disease extent. Management should therefore integrate histology with disease extent, perforation status, peritoneal cellularity and dissemination pattern rather than rely on the cytologic grade alone.
Extravasation of cytostatic drugs is a rare but potentially devastating complication of chemotherapy in children, leading to severe pain, tissue necrosis, functional impairment, and cosmetic deformities. Despite its importance, management protocols remain inconsistent. This paper presents structured instructions to support rapid recognition, intervention, and prevention of cytostatic extravasation in paediatric patients, aiming to reduce morbidity and optimise outcomes. The guidance was developed from published recommendations, systematic reviews, and institutional experience, and it provides a stepwise algorithm for immediate management: stopping infusion, retaining intravenous access for aspiration, marking and documenting the affected site, and performing clinical assessment. Specific measures include aspiration techniques for peripheral and central lines, administration of antidotes such as dexrazoxane, dimethyl sulfoxide, or hyaluronidase, and application of cold or warm compresses depending on the cytostatic agent. Preventive strategies emphasise correct vessel selection, careful cannula monitoring, and strict adherence to administration procedures. For advanced necrosis or refractory injury, surgical approaches - such as early wash-out, liposuction, excision with negative- pressure wound therapy, skin grafting, and complex reconstructions - are outlined. The proposed framework integrates available evidence and expert consensus into a practical and user-friendly protocol. Its implementation may facilitate early detection, minimise the risk of severe complications, and promote standardised paediatric oncology care. In conclusion, cytostatic extravasation in children requires prompt, structured, interdisciplinary management. Early use of specific antidotes and supportive measures can prevent irreversible damage, while preventive strategies and vigilant monitoring remain crucial. Surgical interventions should be reserved for severe, non-responsive cases.
Introduction:This study aims to evaluate the association of baseline serum vascular endothelial growth factor A (VEGF-A) and lactate dehydrogenase (LDH) levels with subsequent response to sequential neoadjuvant chemotherapy followed by radiotherapy in patients with locally advanced-stage nasopharyngeal carcinoma (LA-NPC). Material and methods:A prospective nested case-control study using consecutive sampling with an outcome-based quota cap was conducted involving patients with World Health Organisation type 3 NPC, stage III-IVA. Patients were treated with three cycles of taxane-cisplatin-based neoadjuvant chemotherapy followed sequentially by definitive intensity-modulated radiotherapy. Serum VEGF-A and total LDH levels were measured prior to therapy using enzyme-linked immunosorbent assay. Treatment response was assessed using Response Evaluation Criteria in Solid Tumours 1.1 criteria at a fixed time point of 8 weeks after the completion of all planned treatment, and categorised as positive (complete or partial response) or negative (stable or progressive disease). Statistical analyses including bivariate testing, receiver operating characteristic analysis, and multivariate logistic regression. Results:A total of 58 patients were analysed. In univariate binary logistic regression assessments, high exploratory baseline serum VEGF-A (≥ 128.525 ng/l; p = 0.011) and LDH (≥ 66.485 U/l; p = 0.009) levels were significantly associated with subsequent negative treatment response. In a pre-specified multivariable model adjusted for age and VEGF-A, an elevated baseline total LDH level remained a significant independent predictor of treatment non-responsiveness (adjusted OR = 4.68; 95% CI: 1.46-15.00; p = 0.009), whereas VEGF-A lost statistical significance (p = 0.257). Conclusions:Elevated baseline serum VEGF-A and LDH protein levels are associated with non-responsiveness to sequential neoadjuvant chemotherapy and radiotherapy in LA-NPC. Pre-treatment total LDH acts as a significant, independent exploratory indicator of treatment non-responsiveness.
Introduction:The clinical value of the 5-fluorouracil (5-FU) bolus in modern multidrug regimens for metastatic colorectal cancer (mCRC) is uncertain, with concerns about added haematologic toxicity. This study assessed the impact of omitting the 5-FU bolus on survival and toxicity in patients receiving mFOLFOX6-based chemotherapy. Material and methods:In this retrospective multicentre cohort, 267 mCRC patients treated between June 2020 and June 2024 at Menoufia University Hospitals and the National Cancer Institute, Cairo University, received either bolus-free nbFOLFOX (n = 141) or standard mFOLFOX6 (n = 126), with or without bevacizumab or anti-epidermal growth factor receptor therapy. Progression-free survival (PFS) and overall survival were analysed using Kaplan-Meier and Cox models. Results:Bolus omission produced a statistically significant but clinically small PFS improvement (mean 10.029 vs. 9.319 months; hazard ratio [HR] 1.532, 95% CI: 1.194-1.967; p = 0.001). Overall survival was similar between groups (mean 21.7 vs. 20.7 months; median 20.667 vs. 20.633 months; HR 1.242, 95% CI: 0.966-1.597; p = 0.089). Multivariate analysis identified bolus inclusion as an independent predictor of inferior PFS (HR 1.433, p = 0.006). High-grade neutropenia was significantly reduced with nbFOLFOX (14.9% vs. 25.4%, p = 0.019). Conclusions:Omitting the 5-FU bolus does not compromise survival and reduces haematologic toxicity, supporting individualised treatment decisions, particularly in settings of drug shortages or high toxicity risk.
This article is aimed to report our initial experience with the bispecific T-cell engager teclistamab administered with concomitant radiotherapy, including reirradiation, in two patients with widespread multiple myeloma, including hepatic and meningeal relapse, respectively. This is a retrospective patient record assessment at a single institution. Both patients had previously received several lines of systemic therapy and radiotherapy to multiple target volumes, resulting in a considerable cumulative bone marrow dose when completing their recent courses in 2025. The Patient 1 started current radiotherapy with already compromised blood cell counts, while the Patient 2 had preserved values, except for lymphocytes. Both patients rapidly developed grade 4 haematological toxicity (white blood cells and platelets) but recovered within few weeks. Radiotherapy did not cause other acute toxicity greater than grade 2. Given the serious haematological toxicity observed in our patients, hospitalization and close monitoring by a dedicated team of experienced haematologists may become necessary in complex settings like those described here. Their expertise might also be required to manage cytokine release syndrome and potentially life-threatening neutropenic infections.
Introduction: Oropharyngeal carcinoma (OPC) represents one of the most rapidly increasing head and neck cancers worldwide, with prognosis strongly influenced by human papillomavirus (HPV) infection. Given the clinical significance, there is a strong demand to evaluate novel biomarkers to monitor treatment outcomes. Therefore, we conducted a study to assess the prognostic value of citrulline, a well-established marker of enterocyte injury, in patients undergoing OPC treatment. Material and methods: We reanalysed a cohort of patients with OPC recruited across three tertiary oncology centres in Poland. All patients were treated with intensity-modulated radiotherapy, with concurrent chemotherapy. Serum citrulline levels were measured prior to treatment using a dedicated ELISA kit. The associations between pre-treatment citrulline levels, clinical characteristics, and patient survival outcomes were evaluated. Results: A total of 64 patients treated with chemoradiotherapy (CRT) were included. The baseline citrulline level showed no significant association with clinical characteristics. In univariable Cox regression, tumour size, along with induction chemotherapy, were significantly associated with poorer overall survival (OS) and progression-free survival (PFS). In contrast, the baseline citrulline level was not predictive in univariate analysis. In the subgroup analysis of patients with positive HPV status, both the larger tumour size and higher citrulline level were significantly associated with poorer OS and PFS. Conclusions: Baseline citrulline demonstrated prognostic value for OS and PFS in HPV-positive patients treated with CRT. These findings suggest a potential role for citrulline as a biomarker of treatment-related vulnerability in OPC and warrant further validation in larger, independent cohorts.
Introduction: The aim of this study was to assess the inflammatory status of patients with pancreatic cancer (PC) prior to the initiation of the first course of chemotherapy and to ascertain the most precise systemic inflammation index for predicting overall survival (OS). Material and methods: A single-centre retrospective analysis involving 310 patients with PC was conducted. Blood samples were collected from patients during chemotherapy qualification, either on the first day of chemotherapy or the day before the first chemotherapy dose. The following inflammatory indices were calculated: systemic immune-inflammation index, systemic inflammation response index, and inflammatory benchmark index (IBI). Statistical analyses were performed utilizing appropriate tests (e.g., the log-rank test). Results: All parameters were significant predictors of mortality; however, their area under the curve indicated only a moderate ability to differentiate mortality risk. Among the indices analysed, IBI was the sole metric that predicted OS in adjuvant (p < 0.05) and palliative (p < 0.001) cohorts, alongside disease-free survival (p < 0.04) and progression-free survival (p < 0.009). In the multivariate analysis, only IBI was proven to be statistically associated with OS (p < 0.043). Furthermore, IBI well stratified the tumour stage. Conclusions: All analysed indices related to inflammation and immune response may function as prognostic markers; however, additional studies are required to determine their precise cut-off value. In our investigation, IBI exhibited a distinctive protective effect, culminating in a 65% reduction in mortality, thereby underscoring the importance of C-reactive protein in patient stratification.
Metronomic cyclophosphamide is occasionally used as maintenance therapy for patients with metastatic triple-negative breast cancer (TNBC), although there is limited long-term safety data. In this case study, we present the patient with metastatic TNBC who achieved a durable complete response and subsequently received metronomic cyclophosphamide for seven years. Progressive cytopenias prompted an investigation, which revealed myelodysplastic syndrome with monosomy 7 once reversible causes had been addressed, including vitamin deficiencies, Helicobacter pylori infection and previous hepatitis C exposure. Following discontinuation of cyclophosphamide, gradual haematological recovery was observed, and the patient remains without radiological evidence of progression. This case highlights the potential for late haematological toxicity associated with prolonged exposure to low doses of alkylating agents, emphasises the need for periodic reassessment of maintenance therapy in long-term responders, and shows that persistent cytopenias require evaluation of alternative causes rather than being solely attributed to chemotherapy.
Introduction:Fangchinoline, a bisbenzylisoquinoline alkaloid derived from Stephaniae tetrandrine, is known for its antioxidant and anticancer potential. This study aimed to explore fangchinoline's anticancer targets in silico and evaluate its effects on human epidermal growth receptor-2 (HER-2) overexpressing MCF-7 breast cancer cells. Material and methods:Potential molecular targets were identified using GeneCards and DisGeNET, with intersecting genes analysed via DAVID and Cytoscape. Molecular docking and 50-nanosecond molecular dynamics simulations were conducted against ERBB2, IGF1R, and ADRB2 proteins. Cytotoxicity was evaluated through 3-(4,5-dimethylthiazole-2-yl)-2,5- diphenyl tetrazolium bromide assay, while flow cytometry assessed cell cycle distribution, apoptosis, expression of PI3K, Akt, mTOR, p53, HER-2, and reactive oxygen species (ROS) levels. Results:A total of 256 overlapping genes were identified, and ERBB2 emerged as the most promising target with a binding affinity of -8.57 kcal/mol. Fangchinoline exhibited cytotoxicity against MCF-7/HER-2 cells with an IC50 of 9.67 ±0.14 µM. Fangchinoline induced G2-M arrest and significantly increased apoptosis. Flow cytometry revealed downregulation of PI3K (-42.1%), Akt (-38.6%), and mTOR (-45.3%), with a corresponding upregulation of p53 (+59.8%) compared to controls. Reactive oxygen species production was elevated by +48.5% after treatment. Conclusions:Fangchinoline exhibits promising anticancer activity by targeting ERBB2 and modulating critical oncogenic and apoptotic pathways. Its ability to upregulate p53 and ROS while suppressing PI3K/Akt/mTOR signalling suggests its strong potential as a HER-2-targeted therapeutic agent.
Extranodal marginal zone lymphoma (EMZL), which has an indolent course, rarely occurs in arytenoid cartilage. Diagnosis of the condition in such an infrequent location is challenging and demands the use of various methods, such as magnetic resonance imaging and histopathological examination of the tissue sections acquired during microlaryngoscopy. We present an infrequent case of a 61-year-old patient who was diagnosed with EMZL of arytenoid cartilage after a four-year period of surveillance and examinations. Chemoimmunotherapy was implemented in this case as a successful method of treatment, as it included bendamustine and rituximab. The disease was in remission after the treatment.
Introduction: Radiodensity of subcutaneous adipose tissue (SAT), measurable on routine computed tomography (CT), may reflect metabolic status and cachexia, both of which influence cancer outcomes. However, its prognostic role in metastatic non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI) remains unclear. This study aimed to evaluate the prognostic value of SAT radiodensity in this patient population. Material and methods: The retrospective analysis included 92 patients with stage IV NSCLC receiving ICI. Subcutaneous adipose tissue radiodensity (Hounsfield units) was measured from pre-treatment CT at the L3 level and categorized into quartiles. Kaplan-Meier analysis, log-rank test, and Cox proportional hazards models were used. Nonlinear associations were assessed using restricted cubic splines. Cox models were? adjusted for demographic, clinical, and treatment factors. A p-value < 0.05 was considered statistically significant. Results: Median overall survival for Q1, Q2, Q3, and Q4 was 13.4, 26.3, 18.4, and 14.2 months, respectively (log-rank p = 0.0226). Compared with Q1, Q2 showed a significantly reduced mortality risk across all models (fully adjusted hazard ratios = 0.32, 95% CI: 0.15-0.64, p = 0.002). Q3 and Q4 were not significantly different from Q1. Restricted cubic spline analysis revealed a mild U-shaped relationship (p for nonlinearity = 0.0094), with intermediate SAT density linked to best outcomes. Programmed death ligand 1 expression significantly modified the SAT-survival association (p for interaction < 0.0001). Conclusions: Moderate SAT radiodensity was associated with improved survival in metastatic NSCLC patients on ICI, potentially reflecting an optimal metabolic-immune balance. Subcutaneous adipose tissue density, easily obtained from routine imaging, warrants further prospective validation as a scalable prognostic biomarker.
Introduction: Abnormal cellular me-tabolism is one of the characteristics of tumour cells. However, the differ-ences in the global metabolomics between normal and tumour tissues remain unclear. In this study, we have proposed a diagnostic and prognos-tic model for colorectal cancer (CRC) based on metabolomics and genomics. Material and methods: Metabolomics data of CRC patients was obtained from the MetaboLights repository, and identified the characteristic metabo-lites of CRC cells through orthogonal partial least squares discriminant anal-ysis (OPLS-DA). Then we performed differential analysis of these metabo-lites between normal and tumour tis-sues. Subsequent enrichment analysis was used to analyse the signalling pathways related to the differential metabolites. Finally, we combined me-tabolomics and genomics to construct a prognostic model, and detected the expression of key metabolites and genes in CRC cell lines by using ELISA and western blot. Results: Based on the variable import-ant in projection values of OPLS-DA, we identified 318 characteristic me-tabolites. By conducting differential analysis of these metabolites, we iden-tified 30 downregulated and 42 upreg-ulated metabolites in colorectal cancer. The combined analysis of enrichment pathways revealed that 5 pathways were enriched in both metabolomics and transcriptomics. Conclusions: We established a prog-nostic model through univariate Cox and least absolute shrinkage and se-lection operator regression, and then verified the excellent application value of the model for patient prognosis through receiver operating characteris-tic curves and survival analysis. Finally, ELISA and western blot experiments showed that compared with normal colorectal epithelial cells, the levels of estradiol and formimidoyltrans-ferase cyclodeaminase proteins were increased, while the levels of methi-onine and SLC5A1 proteins were de-creased in CRC cells.
Introduction: Brain metastases from solid tumours are the most common intracranial neoplasms and significantly impact patients' quality of life and overall survival (OS). Despite advances in oncological therapies, these patients have often been excluded from clinical trials, limiting our understanding of the efficacy of new treatments, such as immunotherapy, in this population. Investigating the tumour microenvironment (TME) of brain metastases is challenging, particularly in determining whether immunotherapy is effective for these lesions. The aim of this study is to investigate the host's immune response to primary tumours and concomitant brain metastases in the central nervous system from various malignancies. Material and methods: A retrospective study was conducted to examine tumour-infiltrating lymphocytes (TIL) and the expression of programmed cell death 1 and programmed death ligand 1 (PD-L1) in tissue samples from 72 patients with predominant solid tumours and synchronous or metachronous brain metastases. Correlations with different parameters were analysed to evaluate the prognosis of these patients. Results: All metastatic tumour samples exhibited decreased intraepithelial CD3 and CD8 levels compared to primary tumours, with variable FOXP3 levels and no consistent difference in PD-L 1 levels in tumour cells. Programmed death ligand 1 expression in immune cells was generally lower in metastatic lesions compared to primary tumours. The median OS from diagnosis (OS1) was 19.1 months (95% CI: 13.6-35.1), and the median OS from the diagnosis of brain metastases (OS2) was 11.35 months. Conclusions: The brain TME demonstrates varying levels of TIL and immune checkpoint expression, highlighting the need for further research to develop effective therapies for intracranial metastases.
Introduction:The study was aimed to analyse the impact of the tumour type and other patient- and disease-related baseline parameters in a consecutive cohort managed with best supportive care (BSC) in northern Norway. Material and methods:This is a retrospective analysis of 149 patients managed with BSC without any systemic cancer-directed therapy or local brain-directed measures (2007-2024). Eleven patients were originally supposed to start active treatment and 12 had received prior prophylactic whole-brain irradiation (WBRT). Uni- and multivariate analyses of prognostic factors for survival were performed. Results:Median survival after radiological diagnosis was 1.3 months (95% CI: 1.08-1.52) for all 149 patients combined. The 3- and 6-month survival rates were 20% and 1%, respectively. Neither prior WBRT nor upfront intention to treat were associated with survival. Steroid responders survived significantly longer than non-responders. The multivariate Cox model suggested that survival mainly depends on Karnofsky performance status (< 70 vs. ≥ 70), extracranial metastases (present/absent), and primary tumour type (better in renal cell cancer/malignant melanoma vs. all others combined), p ≤ 0.01 for all three predictors of survival. Conclusions:All prognostic strata in our study had median survival times < 2.5 months, indicating an inevitable poor outcome, despite presence of statistically significant differences, e.g. for the primary tumour type. The clinical impact of prognostic scores would thus be very limited. Median survival was similar in historical studies of BSC. Best supportive care is a reasonable choice in patients with brain metastases and very short life expectancy, as also evident from prospective research.
Introduction:Glioblastoma (GBM) is the most aggressive primary brain tumour in adults. Systemic immunometabolic alterations are increasingly implicated in its pathogenesis, yet sex- and age-specific patterns remain unclear, especially in Uzbekistan. To characterize circulating cytokine and biochemical profiles in newly diagnosed GBM patients and assess sex- and age-related differences. Material and methods:This cross-sectional study included 26 GBM patients (18 females, 8 males) and 26 matched healthy controls. Serum interleukin (IL)-10, IL-1β, IL-6, tumor necrosis factor-α, and IFN-γ were measured by enzyme-linked immunosorbent assay, and biochemical parameters (alkaline phosphatase, alanine aminotransferase - ALT, aspartate aminotransferase - AST, bilirubin, calcium, magnesium, iron, creatinine, uric acid, lactate dehydrogenase - LDH, phosphorus) were analysed by automated assays. Data were evaluated using ANOVA, t-tests, correlations, and principal component analysis (p < 0.05). Results:No sex-based differences were observed (p > 0.05). Older patients had higher uric acid (p = 0.029) and borderline elevated IL-10 (p = 0.048) levels. Pro-inflammatory cytokines correlated with metabolic markers (ALT, AST, uric acid, LDH) and bilirubin correlated with iron/LDH. Conclusions:Glioblastoma-related immunometabolic profiles are influenced mainly by tumour-intrinsic factors rather than sex, while age contributes to metabolic shifts. These findings provide novel regional data and support cytokine-biochemical profiling for biomarker development.
Grey zone lymphoma (GZL) is a rare and aggressive B-cell lymphoma, exhibiting features of both diffuse large B-cell lymphoma and classical Hodgkin's lymphoma (cHL). Due to its rarity, especially in paediatric patients, no standardized treatment protocols exist. The disease presents diagnostic challenges and limited treatment options. Recent studies suggest that immune checkpoint inhibitors, such as pembrolizumab, may offer a promising treatment for refractory cases. A 15.5-year-old male initially presented with huge mediastinal tumour, fluid in the pleural cavity, enlargement of supraclavicular lymph nodes, left subclavian and diaphragmatic nodes and lung infiltration. Initial histopathological examination suggested cHL, but after progression on the first-line therapy (EuroNet-PHL-C2 protocol), biopsy confirmed mediastinal GZL. Despite further chemotherapy (COP, R-COPADM, R-CYM, R-CYVE, R-ICE), the disease continued to progress. Pembrolizumab was introduced after further progression. Following eight months of the treatment, positron emission tomography scans showed a complete metabolic response. The patient underwent autologous stem cell transplantation and continued pembrolizumab for 27 months, maintaining stable small residual tumour with a complete metabolic response. This case highlights the diagnostic challenges and treatment difficulties in paediatric GZL. Pembrolizumab, a programmed death 1 inhibitor, demonstrated efficacy in a heavily pretreated patient with refractory disease. Although pembrolizumab is widely used in adults, this successful application in paediatric GZL suggests its potential as a therapeutic option for this rare lymphoma subtype also in children and adolescents. Pembrolizumab occurred to be effective in refractory paediatric GZL, supporting the need for further studies to assess its safety and efficacy in larger cohorts.
