Testicular cancer is the most common form of cancer in young men of reproductive age and its incidence is increasing globally. With the currently successful treatment and 95% survival rate, there is a need for deeper understanding of testicular cancer-related infertility. Most patients with testicular cancer experience semen abnormalities prior to cancer therapy. However, the exact mechanism of the effect of testicular cancer on sperm anomalies is not known. Mitochondria are organelles that play a crucial role in both tumorigenesis and spermatogenesis and their malfunction may be an important factor resulting in sperm abnormalities in testicular cancer patients. Within the scope of this review, we will discuss current knowledge of testicular cancer-related alterations in the ATP production pathway, a possible pathophysiological switch from oxidative phosphorylation (OXPHOS) to glycolysis, as well as the role of oxidative stress promoting sperm dysfunction. In this regard, the review provides a summary of the impact of testicular cancer on sperm quality as a possible consequence of impaired mitochondrial function including the energy metabolic pathways that are known to be altered in the sperm of testicular cancer patients.
BACKGROUND: Systemic treatment with immune combinations is the gold standard for metastatic renal cell carcinoma (mRCC) worldwide. The systemic immune-inflammation index (SII) is a prognostic marker for several types of malignant neoplasms, including mRCC, in the era of tyrosine kinase inhibitor (TKI) treatment. Data regarding the prognostic value of the SII in patients with mRCC treated with immunotherapy are scarce and controversial. METHODS: We retrospectively collected the data of patients with mRCC from 56 centers in 18 countries. SII (Platelet × Neutrophil/Lymphocyte count) was calculated prior to the first systemic treatment and cut-off was defined by a survival receiver operating characteristic (ROC) analysis. The primary objective of our retrospective study was to assess the outcomes of patients treated with first-line immunotherapy. RESULTS: Data from 1034 mRCC patients was collected and included in this analysis. The SII cut-off value was 1265. After a follow-up of 26.7 months, and the overall survival (OS) and progression-free survival (PFS) were 39.8 and 15.7 months, respectively. According to SII (low vs. high), patients with low-SII had longer OS (55.7 vs. 22.2 months, P < .001), better PFS (20.8 vs. 8.5 months, P < .001), and higher overall response rate (52 vs. 37%, P = .033). CONCLUSION: A high SII is associated with poor oncological outcomes in patients with mRCC. SII could be an easily accessible prognostic indicator for use in clinical practice.
- MeSH
- analýza přežití MeSH
- karcinom z renálních buněk * patologie MeSH
- lidé MeSH
- nádory ledvin * patologie MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- zánět patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Renal c carcinoma (RCC) is one of the most common urinary cancers worldwide, with a predicted increase in incidence in the coming years. Immunotherapy, as a single agent, in doublets, or in combination with anti-vascular endothelial growth factor receptor tyrosine kinase inhibitors (TKIs), has rapidly become a cornerstone of the RCC therapeutic scenario, but no head-to-head comparisons have been made. In this setting, real-world evidence emerges as a cornerstone to guide clinical decisions. OBJECTIVE: The objective of this retrospective study was to assess the outcome of patients treated with first-line immune combinations or immune oncology (IO)-TKIs for advanced RCC. DESIGN, SETTING, AND PARTICIPANTS: Data from 930 patients, 654 intermediate risk and 276 poor risk, were collected retrospectively from 58 centers in 20 countries. Special data such as sarcomatoid differentiation, body mass index, prior nephrectomy, and metastatic localization, in addition to biochemical data such as hemoglobin, platelets, calcium, lactate dehydrogenase, neutrophils, and radiological response by investigator's criteria, were collected. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. The median follow-up was calculated by the inverse Kaplan-Meier method. RESULTS AND LIMITATIONS: The median follow-up time was 18.7 mo. In the 654 intermediate-risk patients, the median OS and PFS were significantly longer in patients with the intermediate than in those with the poor International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria (38.9 vs 17.3 mo, 95% confidence interval [CI] p < 0.001, and 17.3 vs 11.6 mo, 95% CI p < 0.001, respectively). In the intermediate-risk subgroup, the OS was 55.7 mo (95% CI 31.4-55.7) and 40.2 mo (95% CI 29.6-51.6) in patients treated with IO + TKI and IO + IO combinations, respectively (p = 0.047). PFS was 30.7 mo (95% CI 16.5-55.7) and 13.2 mo (95% CI 29.6-51.6) in intermediate-risk patients treated with IO + TKI and IO + IO combinations, respectively (p < 0.001). In the poor-risk subgroup, the median OS and PFS did not show a statistically significant difference between IO + IO and IO + TKI. Our study presents several limitations, mainly due to its retrospective nature. CONCLUSIONS: Our results showed differences between the IO + TKI and IO + IO combinations in intermediate-risk patients. A clear association with longer PFS and OS in favor of patients who received the IO + TKI combinations compared with the IO-IO combination was observed. Instead, in the poor-risk group, we observed no significant difference in PFS or OS between patients who received different combinations. PATIENT SUMMARY: Renal cancer is one of the most frequent genitourinary tumors. Treatment is currently based on immunotherapy combinations or immunotherapy with tyrosine kinase inhibitors, but there are no comparisons between these.In this study, we have analyzed the clinical course of 930 patients from 58 centers in 20 countries around the world. We aimed to analyze the differences between the two main treatment strategies, combination of two immunotherapies versus immunotherapy + antiangiogenic therapy, and found in real-life data that intermediate-risk patients (approximately 60% of patients with metastatic renal cancer) seem to benefit more from the combination of immunotherapy + antiangiogenic therapy than from double immunotherapy. No such differences were found in poor-risk patients. This may have important implications in daily practice decision-making for these patients.
177Lu-PSMA-617 představuje cílenou radioligandovou terapii, která nabízí novou naději pacientům s pokročilým karcinomem prostaty. Tato inovativní léčba, schválená Evropskou lékovou agenturou (EMA) v prosinci 2022, se zaměřuje na cílenou iradiaci buněk karcinomu prostaty s minimálním poškozením okolních zdravých tkání. Představuje významný pokrok ve zlepšení přežití a kvality života pacientů s metastatickým kastračně rezistentním karcinomem prostaty (mCRPC) po progresi na léčbě cílené na androgenový receptor a chemoterapii.
177Lu-PSMA-617 represents a targeted radioligand therapy that offers new hope for patients with advanced prostate cancer. Approved by the European Medicines Agency (EMA) in December 2022, this innovative therapy targets targeted irradiation of prostate cancer cells with minimal damage to surrounding healthy tissues. It represents a significant advance in improving survival and quality of life for patients with metastatic castration- -resistant prostate cancer (mCRPC) after progression on androgen receptor-targeted therapy and chemotherapy.
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
PURPOSE: The CD47 molecule, often referred to as the "do not eat me" signal, is frequently overexpressed in tumor cells. This signaling pathway limits phagocytosis by macrophages. Our objective was to determine CD47 abundance in various soft tissue sarcomas (STS) to investigate whether it could serve as a potential evasion mechanism for tumor cells. Additionally, we aimed to assess the prognostic value of CD47 expression by examining its association with different clinicopathological factors. This study aimed to elucidate the significance of CD47 in the context of emerging anti-tumor targeting approaches. METHODS: In this retrospective study, formalin-fixed paraffine-embedded (FFPE) tumor tissues of 55 treatment-naïve patients were evaluated by immunohistochemistry for the abundance of CD47 molecule on tumor cells. The categorization of CD47 positivity was as follows: 0 (no staining of tumor cells), 1 + (less than 1/3 of tumor area positive), 2 + (between 1/3 and 2/3 of tumor area positive), and 3 + (more than 2/3 of tumor area positive for CD47). Next, we compared CD47 abundance between different tumor grades (G1-3). We used Kaplan-Meier survival curves with log-rank test to analyze the differences in survival between patients with different CD47 expression. Moreover, we performed Cox proportional hazards regression model to evaluate the clinical significance of CD47. RESULTS: CD47 is widely prevalent across distinct STS subtypes. More than 80% of high grade undifferentiated pleiomorphic sarcoma (UPS), 70% of myxofibrosarcoma (MFS) and more than 60% of liposarcoma (LPS) samples displayed a pattern of moderate-to-diffuse positivity. This phenomenon remains consistent regardless of the tumor grade. However, there was a tendency for higher CD47 expression levels in the G3 group compared to the combined G1 + G2 groups when all LPS, MFS, and UPS were analyzed together. No significant associations were observed between CD47 abundance, death, and metastatic status. Additionally, high CD47 expression was associated with a statistically significant increase in progression-free survival in the studied cohort of patients. CONCLUSION: This study highlights the potential of the CD47 molecule as a promising immunotherapeutic target in STS, particularly given its elevated expression levels in diverse sarcoma types. Our data showed a notable trend linking CD47 expression to tumor grade, while also suggesting an interesting correlation between enhanced abundance of CD47 expression and a reduced hazard risk of disease progression. Although these findings shed light on different roles of CD47 in STS, further research is crucial to assess its potential in clinical settings.
- MeSH
- antigeny CD47 metabolismus MeSH
- dospělí MeSH
- lidé MeSH
- lipopolysacharidy MeSH
- makrofágy patologie MeSH
- nádory měkkých tkání * patologie MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- sarkom * terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Východiska: Kabozantinib je inhibitor tyrozinkinázy (tyrosin kinase inhibitor – TKI) proti receptoru pro vaskulární růstový faktor (VEGFR), podobně i MET a AXL. V klinické studii METEOR prokázal u pacientů s metastatickým renálním karcinomem (mRCC) účinnost ve srovnání s everolimem po předchozí léčbě TKI. Cíl: Stanovení účinnosti a tolerance kabozantinibu ve druhé nebo vyšší linii léčby mRCC po předchozí léčbě inhibitory tyrozinkinázy. Pacienti a metody: Celkem bylo hodnoceno 45 pacientů s mRCC léčených ve dvou onkologických centrech (Krajská nemocnice Liberec, Fakultní nemocnice Motol) v klinické praxi. Stanovili jsme přežití bez známek progrese (progression-free survival – PFS) a celkové přežití (overall survival – OS) pomocí Kaplan-Meierovy analýzy a vliv faktorů na léčebné výsledky pomocí regresní analýzy. Statistické zhodnocení bylo provedeno na hladině významnosti α = 0,05. Výsledky: Medián sledování byl 24 měsíců. Medián PFS činil 8,7 měsíce (95% CI 6,7–19,5), medián OS činil 21,6 měsíce (95% CI 13,2–nedosaženo). Parciální remise byla pozorována u 42,5 %, stabilizace onemocnění u 37,8 % pacientů. Primární progrese byla zjištěna u 20 % nemocných. V regresní analýze jsme prokázali prognostický příznivý vliv na prodloužení PFS u pacientů ve vyšším věku a s delším trváním první linie terapie. Regresní analýza dále prokázala příznivý vliv na prodloužení OS u pacientů v lepším celkovém stavu, při delším trvání léčby první linie a u pacientů, u kterých byla po selhání kabozantinibu indikována imunoterapie. Toxicita stupně 3–4 byla pozorována u 37,8 % pacientů, dominoval průjem. Závěr: Naše společná analýza potvrdila účinnost a toleranci kabozantinibu v léčbě druhé a vyšší linie mRCC.
Background: Cabozantinib is a tyrosine kinase inhibitor (TKI) that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL. In METEOR study, cabozantinib demonstrated efficacy when compared with everolimus in pacients with metastatic renal cell cancer (mRCC) after previous TKI therapy. Purpose: The determination of efficacy and tolerance of cabozantinib in the second or higher lines of the therapy of mRCC after previous treatment with tyrosinkinase inhibitors. Patients and methods: A total of 45 patients with mRCC were treated in two oncology centers (Regional Hospital Liberec and University Hospital Motol, Prague) in clinical practice. We determined progression free survival (PFS) and overall survival (OS) according to Kaplan-Meier analysis. We performed a multivariate analysis of the risk factors for treatment outcomes (PFS, OS) by Cox regression analysis. All statistics were evaluated at the significance level of α = 0.05. Results: A median of follow-up was 24 months. Median PFS was 8.7 months (95% CI 6.7–19.5), median OS was 21.6 months (95% CI 13.2–not achieved). Parcial remission was described in 42.5% patients, stabilization in 37.8% patients. Progression as the best response was demonstrated in 20% of patients. Regression analysis demonstrated a statistically significant favorable prognostic effect on PFS in patients at older age and patients with longer first-line therapy. The regression analysis demonstrated a statistically significant favorable prognostic effect on OS in patients with Eastern Cooperative Oncology Group (ECOG) performance status 0, patients with longer-first line therapy and patients treated with immunotherapy in the next lines. Grade 3–4 toxicity was described in 37.8% patients. The most common type of toxicity was hypertension. Conclusion: Our analysis demonstrated the efficacy and good tolerance of cabozantinib in with mRCC treated by cabozantinib in second-line therapy.
