Bainolsson3077
Median time to local progression was 22.9 months in the FSRT group compared to 14.5 months in the SRS group (p = 0.022). Overall radionecrosis rate at 12 months was 3.4% for FSRT and 14.8% for SRS (p = 0.010). Radionecrosis °IV requiring resection with histologic proof of radiation necrosis also was significantly reduced in the FSRT group (FSRT 0.0% vs. SRS 3.9%, p = 0.041). Selleckchem Guanidine In multivariate analysis, FSRT was associated with reduced risk of progression (HR 0.47, p = 0.015) and reduced risk of radionecrosis (HR 0.18, p = 0.045). Conclusions This volumetric study provides initial evidence that the improvements in therapeutic ratio expected for FSRT in larger brain metastases, might equally extend into the domain of smaller metastases, traditionally less considered for fractionated treatment. FSRT might constitute an important tool to further increase local control and reduce radionecrosis risk in stereotactic radiotherapy for brain metastases, that should be assessed in randomized intervention trials.
Tumor-infiltrating immune cells might add a predictive value for the prognostic stratification of patients with pancreatic ductal adenocarcinoma (PDAC) and chemotherapy response. We aimed to develop a prognostic model based on the tumor-infiltrating immune cell signature to improve the prediction of survival and chemotherapy benefits of patients with PDAC.
The abundance of tumor-infiltrating immune cells for 661 patients with PDAC from four different cohorts with survival data was collected in the training cohorts. Cox regression analysis and meta-analysis of immune cells were conducted to generate the tumor immune cell score (TICS) for prognostic stratification. Other two independent cohorts including 188 patients were then used to validate the model. Those patients who underwent chemotherapy were used to further analyze the value of TICS for predicting the chemotherapy response. Furthermore, the difference in the somatic mutations and immune-related molecules between the TICS subgroups was analyzed.
6 out of 28 immune cells were found to be significantly associated with PDAC prognosis in the training cohorts (all
< 0.05). The developed TICS could significantly predict the PDAC survival and chemotherapy benefit both in the training and the external validation cohorts (log-rank test,
< 0.05). Significant differences were found in different TICS subgroups in terms of the immune characteristics, checkpoint genes, and tumor mutational burden. Functional and pathway analyses further proved that the TICS was significantly related to the tumor immunity response in patients with PDAC.
TICS might be used to predict PDAC patients with a better survival and greater chemotherapy benefit.
TICS might be used to predict PDAC patients with a better survival and greater chemotherapy benefit.
Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor monotherapy has been approved as second-line or later therapy in advanced non-small-cell lung cancer (NSCLC). The study aimed to compare the clinical outcomes of PD-1 inhibitor plus chemotherapy with PD-1/PD-L1 inhibitor monotherapy as second-line or later therapy in advanced NSCLC.
The clinical data of patients with advanced NSCLC who received PD-1/PD-L1 inhibitors as second-line or later line therapy was retrospectively collected. Patients were assigned to one of the two groups according to the therapeutic modality used PD-1/PD-L1 inhibitor monotherapy group or PD-1 inhibitor plus chemotherapy combination therapy group. Disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated between the two groups. The prognostic effect of the derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) on the outcomes was also evaluated.
From April 2017 to October 2019, a total of 84 paent between the monotherapy group and the combination therapy group (19.2 vs. 18.9%,
= 1.000). One patient in the PD-1 inhibitor plus chemotherapy group died of immune-related pneumonitis.
The clinical outcomes of PD-1 inhibitor plus chemotherapy as second-line or later therapy were similar to those of PD-1/PD-L1 inhibitor alone in advanced NSCLC.
The clinical outcomes of PD-1 inhibitor plus chemotherapy as second-line or later therapy were similar to those of PD-1/PD-L1 inhibitor alone in advanced NSCLC.Background Neuroendocrine tumors (NETs) are rare, but their worldwide incidence is gradually increasing. NETs are generally heterogeneous; however, in rare cases, they have been shown to change their phenotype (i.e., nonfunctional to functional or one functional phenotype to the addition of another functional phenotype). Here, we present two cases of liver metastatic NETs with phenotype transformation at the advanced stage that led to life-threatening events. Case presentation A 73-year-old woman had a small intestinal nonfunctional NET with liver metastasis. After uncontrollable liver metastasis at the advanced stage, she developed duodenal perforation with hypergastremia. The patient was treated with octreotide and proton pump inhibitors and underwent endoscopic closure for duodenal perforation, but her general condition gradually deteriorated, and she died 2 weeks after duodenal perforation. Another patient, a 50-year-old man, had a functional NET (gastrinoma) with liver metastasis and duodenal ulcer. After uncontrollable liver metastasis at the advanced stage, he developed hypoglycemia. Although octoreotide and diazoxide were administrated for hyperalimentation, his hypoglycemia was uncontrollable, and he died after 4 months owing to general deterioration. Conclusion The present cases show that advanced NETs with treatment-uncontrollable liver metastasis can transform their phenotype, specifically from a nonfunctional NET into a functional NET, and from one functional NET into the addition of another functional NET. These experiences suggest that the presence of treatment-resistant liver metastasis might be a hallmark of the potential to gain novel functions.The prognosis of hepatocellular carcinoma (HCC) is closely associated with the occurrence of distant metastases, which is likely due to circulating tumor cells (CTCs). However, the low number of CTCs is the main obstacle limiting research of the mechanism of CTC metastasis. Here, We evaluated the role of ubiquitin-specific protease 1 (USP1) in promoting CTC survival during blood-borne metastases. We observed that USP1 was frequently upregulated in CTCs and correlated with metastasis and a reduced overall survival rate of patients. Additionally, genetic knockout of USP1 the survival rate of CTCs. Further analyses showed that USP1 mediates oncogenic activity by deubiquitinating and stabilizing transducin β-like 1 X-linked receptor 1 (TBLR1), which plays essential roles in regulating Wnt signaling. These results demonstrated that USP1 may act as an essential factor in promoting the survival of CTCs and suggest that inhibition of USP1 is a potential strategy for HCC treatment.
