AbstractObjectives: The treatment approaches for patients with locally advanced hypopharyngeal squamous cell carcinoma (LA-HSCC) still lack standardized guideline. Therefore, this study aims to clarify the most beneficial non-surgical treatment options for patients with HSCC. Methods: A total of 136 patients with stage III/IV LA-HSCC were enrolled. The treatment groups included concurrent chemoradiotherapy (CCRT)(n=42), induction chemotherapy+CCRT (Indu+CCRT)(n=33), and induction chemotherapy+radiotherapy (Indu+RT)(n=61). We performed a retrospective analysis to evaluate the survival of patients and examine the occurrence of acute adverse effects (AEs) using SPSS software. Results: The overall survival (OS) rates were 37.9%, 34.4%, and 15.7% in CCRT, Indu+CCRT, and Indu+RT groups (P=0.043), while the 5-year PFS rates were 35.6%, 42.3%, and 19.2% respectively (P=0.045). Subgroup analysis (age≥61) showed that OS have no difference between CCRT and Indu+CCRT groups, but higher than Indu+RT group. Subgroup analysis of PFS revealed that Indu+CCRT group had better outcomes for patients with N2-3 stage or stage IV (P=0.011, P=0.025). About 97.0% patients in Indu+CCRT group occurred adverse events (AEs) and 48.5% occurred stage III-IV AEs, which were both highest among 3 groups. Conclusion: The data indicate that there is no significant difference in survival benefits between CCRT and Indu+CCRT for LA-HSCC patients, but both higher than Indu+RT. However, CCRT was recommend to older patients (≥61 years), and Indu+CCRT was recommend to patients with stage IV disease or advanced N stage.
This review mainly summarises the progress in the preparation methods of organic compound/g-C 3 N 4 . Various materials such as different types of organic compound/g-C 3 N 4 composites and their related energy and environmental applications are discussed.
e14043 Background: Hypoxia inducible factor-1α (HIF-1α) up-regulates the expression of programmed death ligand-1 (PD-L1) in some extracranial malignancies. However, whether it also increases PD-L1 expression in intracranial tumor is still unknown. Here we explored the relationship between HIF-1α and PD-L1 expression in glioma, and investigated their clinical significance. Methods: Tumor tissues from 120 patients with glioma, were analyzed for PD-L1 and HIF-1α expression using immunohistochemistry. And results were verified in vitro, using U251, U343 glioma cell lines. Gene expression were evaluated by quantitative PCR; protein levels were analyzed by Western blot; ChIP-qPCR (chromatin immunoprecipitation coupled with quantitative PCR) analysis showed the relationship between HIF-1α and PD-L1. Glioma in situ model were used to explore whether HIF-1α inhibitor (PX-478) can enhance anti-PD-L1 therapy responses. Tumor volume was measured twice weekly. Immune data were further analyzed by FACS DIVA 7.0 or Flow Jo 7.6.5 software. Results: In glioma patients, HIF-1α and PD-L1 were markedly overexpressed in high grade glioma (HGG) tissues and were both associated with poorer overall survival(OS) (PD-L1( < 5% vs. ≥ 5%): 3, 5, 10-year OS: 78.1%, 50.5%, 27.2% vs. 45.4%, 11.8%, 0%, P = 0.0026; HIF-1α( < 1% vs. ≥ 1%): 3, 5, 10-year OS:74.2%, 66.8%, 53.4% vs. 61.6%, 21.0%, 0%, P = 0.001). And the expression of PD-L1 was significantly positively correlated with the expression of HIF-1α in glioma patients ( r = 0.412, P < 0.001). In glioma cell lines, PD-L1 expression was significantly induced under hypoxia condition, but the enhanced PD-L1 expression was abrogated by either HIF-1α knock-down or HIF-1α inhibitor treatment. Furthermore, ChIP-qPCR analysis showed the direct binding of HIF-1α to PD-L1 proximal promoter, providing evidence that HIF-1α up-regulate PD-L1 expression in glioma cells. In glioma murine model, combination treatment with HIF-1α inhibitor and anti-PD-L1 antibody caused a more pronounced suppressive effect on tumor growth compared to mice treated with either single agent. Immunologically, the combination treatment improved both dendritic cell (DC) and CD8 + T cell activation. Conclusions: Multiple findings demonstrated that positive relationship between HIF-1α and PD-L1 existed in glioma cells under hypoxia condition. These observations also provide invaluable information that hypoxia contributes to a key phase of glioma cells evading adaptive immunity, thereby promoting malignant progression and poorer clinical outcomes. Given these, it would be a potential strategy to target HIF-1α in combination with the blockage of PD-1/PD-L1 pathway for anti-cancer in the future.
Background: It has been proven that the levels of soluble programmed death-ligand 1 (sPD-L1) are associated with prognosis in extracranial malignancies. However, the expression of sPD-L1 in glioma patients receiving radiotherapy (RT) remains unclear. The purpose of this study was to evaluate the concentration of sPD-L1 in the plasma of glioma patients before and after RT and to explore its relationship with clinical outcomes. Methods: Between October 2017 and September 2018, glioma patients treated with RT (30 ± 10 Gy, 2 Gy/f) were enrolled, and blood samples were collected before and after RT. We quantified the sPD-L1 levels by enzyme-linked immunosorbent assay (ELISA). The isocitrate dehydrogenase-1 (IDH-1) promoter status and Ki-67 expression of tumors were evaluated by immunohistochemistry. Glioma murine model were used to address whether circulating sPD-L1 molecules are directly targeted by an anti-PD-L1 antibody. The associations between sPD-L1 and clinical features were assessed with Pearson's or Spearman's correlation analysis. The progression-free survival (PFS) and overall survival (OS) were determined by the Kaplan-Meier method. Results: Sixty glioma patients were included, with a median age of 52 years. The proportions of grade I, II, III, and IV gliomas were 6.7%, 23.3%, 28.4% and 41.6%, respectively. The baseline sPD-L1 levels were significantly associated with tumor grade, IDH-1 mutation status and Ki-67 expression. Using 14.35 pg/mL as the cutoff, significantly worse PFS and OS were both observed in patients with higher baseline levels of sPD-L1 (P = 0.027 and 0.008, respectively). RT significantly increased the mean level of sPD-L1 (P < 0.001). Further analysis showed that the level of sPD-L1 in IDH-1 mutation patients was higher than that in wild-type patients. Furthermore, an analysis of glioma murine model indicated that anti-PD-L1 antibody combine with RT can be a potentially powerful cancer therapy. Conclusion: This study reported that sPD-L1 might be a potential biomarker to predict the outcome in glioma patients receiving RT. The elevated level of sPD-L1 after RT suggested that the strategy of a combination of immune checkpoint inhibitors and RT might be promising for glioma patients, especially for those with IDH-1 mutations.
Previous studies have shown that the 5-year survival rates of patients with nasopharyngeal carcinoma (NPC) were still not ideal despite great improvement in NPC treatments. To achieve individualized treatment of NPC, we have been looking for novel models to predict the prognosis of patients with NPC. The objective of this study was to use a novel deep learning network structural model to predict the prognosis of patients with NPC and to compare it with the traditional PET-CT model combining metabolic parameters and clinical factors.A total of 173 patients were admitted to 2 institutions between July 2014 and April 2020 for the retrospective study; each received a PET-CT scan before treatment. The least absolute shrinkage and selection operator (LASSO) was employed to select some features, including SUVpeak-P, T3, age, stage II, MTV-P, N1, stage III and pathological type, which were associated with overall survival (OS) of patients. We constructed 2 survival prediction models: an improved optimized adaptive multimodal task (a 3D Coordinate Attention Convolutional Autoencoder and an uncertainty-based jointly Optimizing Cox Model, CACA-UOCM for short) and a clinical model. The predictive power of these models was assessed using the Harrell Consistency Index (C index). Overall survival of patients with NPC was compared by Kaplan-Meier and Log-rank tests.The results showed that CACA-UOCM model could estimate OS (C index, 0.779 for training, 0.774 for validation, and 0.819 for testing) and divide patients into low and high mortality risk groups, which were significantly associated with OS (P < .001). However, the C-index of the model based only on clinical variables was only 0.42.The deep learning network model based on 18F-FDG PET/CT can serve as a reliable and powerful predictive tool for NPC and provide therapeutic strategies for individual treatment.
Rationale: The pathogenesis and progression of lung cancer is a complicated process in which many genes take part. But molecular gene testing is typically only performed in advanced-stage non-squamous non-small-cell lung cancer (NSCLC). The value of tyrosine kinase inhibitors (TKI) administration is not widely recognized with respect to early-stage NSCLC. Patient concerns: Here, we present a case of a man, heavy smoker who initially presented with stage IA lung adenocarcinoma (LADC). Three years after a lung lobectomy, he was diagnosed with advanced lung squamous cell carcinoma (SCC), according to laboratory, imaging, and pathological examinations. Diagnoses The case initially had an early-stage LADC with an L858R epidermal growth factor receptor (EGFR) mutation. A subsequent advanced SCC bearing EGFR L858R/T790M mutations occurred 3 years after surgery. Interventions: The comprehensive therapy we utilized, including surgical resection for the early-stage lesion and GP chemotherapy and local radiotherapy as the first line therapy along with gefitinib maintenance treatment for the advanced metachronous second primary tumors (MST). Outcomes: The synthetical therapy, have resulted in our patient with remaining alive and progression free for 4.5 years. Lessons: This case suggests that changes in molecular pathology should be monitored closely throughout cancer progression to guide personalized therapy and improve prognosis. We further review administration of TKI to early-stage NSCLC and to the metachronous second primary tumors (MST) in survivors.
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