Search

Most of the currently used cancer immunotherapies inhibit the programmed cell death protein 1 (PD1)–programmed cell death 1 ligand 1 (PDL1) axis of T‐cells. However, dendritic cells (DCs) controlled by natural killer (NK) cells via the FMS‐related tyrosine kinase 3 (FLT3) axis are necessary for activation of T‐cells. The aim of the study was to evaluate FLT3 as a prognostic factor and determine its role in immune infiltration (with emphasis on NK cells and DCs). Using The Cancer Genome Atlas (TCGA) database, we performed bioinformatic analysis of the gene expression datasets of 501 lung squamous cell carcinoma (LUSC) and 515 lung adenocarcinoma (LUAD) patient who had corresponding clinical data [analysis was performed in R (version 4.2.0)]. Disease‐free survival (DFS) differed between the FLT3‐low and FLT3‐high expression groups, respectively, in LUSC (61.0 vs 71.3 months P = 0.075) and LUAD (32.7 vs 47.5 months P = 0.045). A tumor microenvironment (TME) with high immune infiltration and rich in T‐cell exhaustion markers was observed in the FLT3‐high group. We showed overexpression of NK cell and DC gene signatures in the FLT3‐high expression group as well as overexpression of key effector genes of the cyclic GMP‐AMP synthase (cGAS)–stimulator of interferon genes protein (STING) pathway, which is crucial in response to radiotherapy. High expression of FLT3 in the TME was associated with immune cell infiltration (especially of NK cells and DCs), increased expression of T‐cell exhaustion markers and expression of effector genes of the cGAS‐STING pathway, which may consequently increase susceptibility to immunotherapy and radiotherapy. High FLT3 expression correlated with prolonged DFS in the LUSC and LUAD cohorts. [ABSTRACT FROM AUTHOR]

Background and Objectives: More than 430,000 new cases of renal cell carcinoma (RCC) were reported in 2020. Clear cell RCC, which occurs in 80% of cases, is often associated with mutations in the VHL gene, leading to dysregulation of hypoxia-induced transcription factors pathways and carcinogenesis. The purpose of this study is to examine the adverse events (AEs) of cabozantinib treatment and the relationship between individual patient factors and the frequency of their occurrence in detail. Materials and Methods: Seventy-one patients with metastatic RCC were treated with second or further lines of cabozantinib at the Department of Genitourinary Oncology, Maria Sklodowska-Curie National Research Institute of Oncology. Comprehensive data, including demographics, clinicopathological factors, and AEs, were collected from January 2017 to June 2021. This study evaluated the impact of various patient-related factors on the rate of adverse events and treatment tolerance using a Cox proportional hazards model. Results: Cabozantinib-induced AEs were significantly associated with body mass index (BMI), body surface area (BSA), IMDC prognostic score, and treatment line. Notably, patients receiving cabozantinib post-tyrosine kinase inhibitors reported fewer AEs. Dose reduction was unrelated to adverse event frequency, but patients requiring dose reduction were characterized with lower body mass and BSA but not BMI. Conclusions: The factors described make it possible to predict the incidence of AEs, which allows for faster detection and easier management, especially in the high-risk group. AEs should be reported in detail in real-world studies, as their occurrence has a significant impact on prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Geriatric patients with metastatic renal cell carcinoma (mRCC) are underrepresented in clinical trials. Evaluation of the efficacy of the treatment and assignation of individuals to proper prognostic groups is an absolute necessity to guarantee them the best possible care. Material and methods: A total of 138 geriatric patients with mRCC treated with first-line tyrosine kinase inhibitors (TKIs) at the Maria Skłodowska-Curie National Research Institute of Oncology were retrospectively analyzed to determine whether the body mass index (BMI) and pan-immune-inflammation value (PIV) are prognostic values for overall survival (OS) and progression-free survival (PFS) in this type of cancer. For this purpose, Cox's proportional hazard model was used. Results: The median duration of follow-up for surviving patients was 46.6 (95% CI: 17.4-75.8) months. The median OS and PFS were respectively 33.8 months (95% CI: 23.8-47.8) and 19.1 months (95% CI: 15.0-23.3). BMI (p = 0.034) and PIV (p < 0.001) were statistically significantly associated with OS, and PIV (p = 0.001) was statistically significantly associated with PFS. The risk of death for patients from the high-PIV group (cut-off point: 548) was 3.4 times higher than for those with lower PIV values. The corresponding risk of progression for patients from the high-PIV group was 2.2 times higher. The G8 geriatric screening tool was not identified as a prognostic factor. Conclusions: Lower PIV and obesity are associated with longer OS in geriatric mRCC patients treated with TKIs in the first line. These factors may be considered while making treatment decisions if further studies show the same results. [ABSTRACT FROM AUTHOR]

Introduction: Urothelial carcinoma is the most common type of urinary tract malignancy. Current treatment options, including platinum-based chemotherapy or immunotherapy, present significant challenges, ranging from limited efficacy to severe toxicities. Recent developments in antibody-drug conjugates (ADC), such as enfortumab vedotin (EV), promise to significantly improve overall survival. The study aims to evaluate the efficacy and tolerability of EV. In addition, we highlight the observed benefits of next-line treatment after progression. Material and methods: This retrospective study involved 16 patients with advanced urothelial cancer treated with EV at the Department of Genitourinary Oncology, Maria Skłodowska-Curie National Research Institute of Oncology between November 2022 and November 2023. The study evaluated patients' medical history, response to EV treatment, and side effects. Notably, the study included patients who had already exhausted standard treatment options and who were treated with EV through a rescue access procedure. Results: Partial response was observed in 4 out of 9 (44%) patients with available imaging. Common terminology criteria for adverse events (AE) grade 3 and 4 were observed in 3 out of 16 patients, which subsequently required dose reduction. Conclusions: Enfortumab vedotin demonstrates effectiveness in real-world settings in treating advanced urothelial cancer. Proper management of AE in experienced centres may further prolong survival. Personalized treatment and the development of new ADC represent the future for improved patient outcomes. [ABSTRACT FROM AUTHOR]

Background: To assess and compare mid-term outcomes and the quality of life (QoL) in patients with multivessel coronary artery disease (MVD) and moderate ischemic mitral regurgitation (IMR), treated with either coronary artery bypass grafting (CABG; group I) or CABG + mitral annuloplasty (CABG+MA; group II) in 12-months follow-up after surgery. Methods: We prospectively analyzed 74 patients (50.7% female, 66 [67-72] years) with at least moderate IMR, 3-24 weeks after myocardial infarction (MI). The effective regurgitation orifice (ERO) was used for a quantitative IMR assessment. To evaluate QoL we used a Short Form-36 (SF-36) questionnaire. Results: Patients in group II spent more time in the hospital, expired more infection complications and received more often in-hospital complications requiring use amines and intra-aortic balloon pump as compared to those in group I. Analysis of SF-36 showed that all patients treated surgically notable improved their QoL during 12 months of follow-up. Conclusion: We observed a significant improvement in QoL among patients with MVD in 12 months follow-up after surgery irrespective of treatment type. [ABSTRACT FROM AUTHOR]

Background: Today no established biomarkers are available for the early diagnosis of takotsubo syndrome and its differentiation from ST-segment elevation myocardial infarction. We hypothesized that copeptin and copeptin/NT-proBNP ratio may serve a routine marker combination for non-invasive differentiation. Methods: The study compared the serum concentrations of copeptin, troponin I (TnI) and NT-proBNP in 19 consecutive women diagnosed with takotsubo syndrome according to the Mayo Clinic criteria and 10 consecutive women diagnosed with ST-segment elevation myocardial infarction. Results: Copeptin concentrations were significantly lower in patients with takotsubo syndrome than in patients with ST-segment elevation myocardial infarction. The diagnostic accuracy to distinguish takotsubo syndrome from ST-segment elevation myocardial infarction is highest for copeptin/NTproBNP ratio, copeptin/TnI at admission ratio and copeptin alone (AUC 0.8713, 0.8538, 0.8480, respectively). Conclusions: The serum copeptin to NTproBNP ratio could be an additional tool in the non-invasive differentiation between takotsubo syndrome and ST-segment elevation myocardial infarction. However, further researches are needed. [ABSTRACT FROM AUTHOR]

Background: Echocardiography is the first exam to establish the myocardial function in patients with takotsubo syndrome (TTS). However, ECG-Gated Myocardial Single-Photon Emission Tomography (G-SPECT) also allows to calculate left ventricular ejection fraction (LVEF) and can be useful in early stadium of TTS. Aim: To compare LVEF obtained from 99mTc-MIBI G-SPECT and echocardiography in patients with TTS. Material and Methods: Study population: 20 patients in medium age 77 (62-89) with TTS were included. In all patients 99mTc-MIBI G-SPECT and echocardiography was performed on the same day. Results: LVEF measured by G-SPECT and echocardiography ranged from 34 to 83% and 38 to 69%, respectively. The LVEF values for ECHO were significantly lower than for SPECT. The correlation between the LVEF was r = 0.76. The calculated correlation coefficient (r) for linear regression analysis was 0.64. The following equation shows the approximate interdependence of both LVEF calculations: LVEF GSPECT = 10.35 + 0.93 * LVEF Echo. Conclusions: G-SPECT tends to overerestimate LVEF compared to echocardiography so these imaging techniques should not be used interchangeably. Calculated equation should be used for comparison of LVEF. [ABSTRACT FROM AUTHOR]

Mixed epithelial and stromal tumor (MEST) is a rare neoplasm of the kidney, affecting mostly women at menopausal age. While few cases of malignant transformation have been described in the literature, MEST is usually considered a benign tumor with minimal risk of local recurrence or distance metastases. The current study presents a case of a 18-year old male patient with a cystic tumor of the left kidney incidentally diagnosed on magnetic resonance imaging of the heart performed for other reasons. The patient underwent a partial nephrectomy, with perioperative course being uneventful. The pathology report revealed MEST of the kidney. No local recurrence nor disease progression have been observed in the patient during the one-year follow-up period. The present case report is evidence that may help in developing guidelines on the management of patients with benign renal masses. [ABSTRACT FROM AUTHOR]

Introduction: Geriatric patients with metastatic renal cell carcinoma (mRCC) are underrepresented in clinical trials. Evaluation of the efficacy of the treatment and assignation of individuals to proper prognostic groups is an absolute necessity to guarantee them the best possible care., Material and Methods: A total of 138 geriatric patients with mRCC treated with first-line tyrosine kinase inhibitors (TKIs) at the Maria Skłodowska-Curie National Research Institute of Oncology were retrospectively analyzed to determine whether the body mass index (BMI) and pan-immune-inflammation value (PIV) are prognostic values for overall survival (OS) and progression-free survival (PFS) in this type of cancer. For this purpose, Cox's proportional hazard model was used., Results: The median duration of follow-up for surviving patients was 46.6 (95% CI: 17.4-75.8) months. The median OS and PFS were respectively 33.8 months (95% CI: 23.8-47.8) and 19.1 months (95% CI: 15.0-23.3). BMI ( p = 0.034) and PIV ( p < 0.001) were statistically significantly associated with OS, and PIV ( p = 0.001) was statistically significantly associated with PFS. The risk of death for patients from the high-PIV group (cut-off point: 548) was 3.4 times higher than for those with lower PIV values. The corresponding risk of progression for patients from the high-PIV group was 2.2 times higher. The G8 geriatric screening tool was not identified as a prognostic factor., Conclusions: Lower PIV and obesity are associated with longer OS in geriatric mRCC patients treated with TKIs in the first line. These factors may be considered while making treatment decisions if further studies show the same results., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Termedia.)

Introduction: Cabozantinib is an oral inhibitor of MET, AXL, and vascular endothelial growth factor receptors. It has an immunomodulatory effect and may influence the tumor's microenvironment and make mutated cells more sensitive to immune-mediated killing. These properties have made cabozantinib an effective drug for first-line or subsequent-line treatment after progression of metastatic renal cell carcinoma (mRCC), even after immunotherapy., Material and Methods: Seventy-one patients with mRCC were treated with second or further lines of cabozantinib at the Department of Genitourinary Oncology, Maria Sklodowska-Curie National Research Institute of Oncology. This study retrospectively evaluated the effectiveness of cabozantinib in subsequent lines of treatment. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints. The best overall response (BOR) to cabozantinib was the secondary endpoint. For this purpose, Cox's proportional hazard model was used., Results: The median PFS was 11 months (5; 23) and the median OS was 16 months (10; 42) and differed significantly in the second and further lines of treatment. Progression in the second and further lines was observed in 28 (93%) and 27 (66%) patients, respectively (p = 0.006). Partial response as the BOR was observed in one patient (3%) in the second line and 13 patients (32%) in the further lines (p = 0.012)., Conclusions: Cabozantinib has antitumor effects in the second and further lines of treatment. In this study we observed high efficiency of cabozantinib in further lines of treatment., Competing Interests: Honoraria: Angelini, Astellas, Astra Zeneca, Bayer, Bristol Myers Squibb, IPSEN, Janssen, Merck MSD, Novartis, Pfizer, Research Funding: Novartis. All unrelated to the present paper.The authors declare no conflict of interest., (Copyright © 2023 Termedia.)

Introduction: Urothelial carcinoma is the most common type of urinary tract malignancy. Current treatment options, including platinum-based chemotherapy or immunotherapy, present significant challenges, ranging from limited efficacy to severe toxicities. Recent developments in antibody-drug conjugates (ADC), such as enfortumab vedotin (EV), promise to significantly improve overall survival. The study aims to evaluate the efficacy and tolerability of EV. In addition, we highlight the observed benefits of next-line treatment after progression., Material and Methods: This retrospective study involved 16 patients with advanced urothelial cancer treated with EV at the Department of Genitourinary Oncology, Maria Skłodowska- Curie National Research Institute of Oncology between November 2022 and November 2023. The study evaluated patients' medical history, response to EV treatment, and side effects. Notably, the study included patients who had already exhausted standard treatment options and who were treated with EV through a rescue access procedure., Results: Partial response was observed in 4 out of 9 (44%) patients with available imaging. Common terminology criteria for adverse events (AE) grade 3 and 4 were observed in 3 out of 16 patients, which subsequently required dose reduction., Conclusions: Enfortumab vedotin demonstrates effectiveness in real-world settings in treating advanced urothelial cancer. Proper management of AE in experienced centres may further prolong survival. Personalized treatment and the development of new ADC represent the future for improved patient outcomes., Competing Interests: BSK Honoraria: Angelini, Astellas, Astra Zeneca, Bayer, Bristol Myers Squibb, IPSEN, Janssen, Merck MSD, Novartis, Pfizer. All unrelated to the present paper. JK Honoraria: Angelini, Astellas, Astra Zeneca, Bayer, Bristol Myers Squibb, IPSEN, Janssen, Merck MSD, Novartis, Pfizer, Research Funding: Novartis.The authors declare no conflict of interest., (Copyright © 2023 Termedia.)

About 40% of clear cell renal cell carcinoma (ccRCC) cases carry the pbrm1 mutation inactivating BAF180 subunit of the SWI/SNF chromatin remodeling complex (CRC). Here we show that the majority of transcriptomic changes appear at the stage I of ccRCC development. By contrast, the stage II ccRCC exhibits hyperactivation of DNA replication demonstrated by the overexpression of several genes, e.g., RRM1 and RRM2 genes encoding subunits of ribonucleotide reductase (RNR) complex. We found that the degree of RRM1 and RRM2 upregulation in ccRCC patients depends on pbrm1 mutation. We show that the BAF180 protein product of the PBRM1 gene directly binds to RRM1 and RRM2 loci . The BAF180 binding regions are targeted by regulatory proteins previously reported as SWI/SNF CRC interacting partners. BAF180 binding to RRMs loci correlates with enrichment of H3K27me3 in case of RRM1 and H3K14Ac on RRM2 , indicating the existence of differential regulatory mechanism controlling expression of these genes. We found that the strong overexpression of RRM2 in ccRCC patient samples correlates with T cell infiltration. Surprisingly, the majority of tumor infiltrating lymphocytes (TILs) consisted of CD4 + T cells. Furthermore, we show that exhausted CD4 + T cells induced the expression of the RRM2 gene in the primary ccRCC cell line. Collectively, our results provide the link between PBRM1 loss, RRM2 expression and T cell infiltration, which may lead to the establishment of new treatment of this disease., Competing Interests: None., (AJCR Copyright © 2021.)

Background: Echocardiography is the first exam to establish the myocardial function in patients with takotsubo syndrome (TTS). However, ECG-Gated Myocardial Single-Photon Emission Tomography (G-SPECT) also allows to calculate left ventricular ejection fraction (LVEF) and can be useful in early stadium of TTS., Aim: To compare LVEF obtained from 99mTc-MIBI G-SPECT and echocardiography in patients with TTS., Material and Methods: Study population:20 patients in medium age 77(62-89) with TTS were included. In all patients 99mTc-MIBI G-SPECT and echocardiography was performed on the same day., Results: LVEF measured by G-SPECT and echocardiography ranged from 34 to 83% and 38 to 69%, respectively. The LVEF values for ECHO were significantly lower than for SPECT. The correlation between the LVEF was r = 0.76. The calculated correlation coefficient (r) for linear regression analysis was 0.64. The following equation shows the approximate interdependence of both LVEF calculations: LVEF GSPECT = 10.35 + 0.93 * LVEF Echo., Conclusions: G-SPECT tends to overerestimate LVEF compared to echocardiography so these imaging techniques should not be used interchangeably. Calculated equation should be used for comparison of LVEF.