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Background: Immunotherapy has revolutionized the treatment of advanced lung cancer. Nevertheless, it remains unclear whether adding stereotactic body radiotherapy (SBRT) to immunotherapy (IT) further improves responses and survival outcomes. Therefore, in this pooled analysis, we comprehensively compared IT plus SBRT with IT alone in patients with advanced lung cancer., Methods: Online databases, including PubMed, Web of Science, Embase, and Cochrane CENTRAL, were systematically searched on April 24, 2022. Eligible studies were randomized clinical trials comparing IT plus SBRT to IT. The primary outcomes were the objective response rate (ORR) and disease control rate (DCR). Progression-free survival (PFS) and overall survival (OS) were explored as secondary outcomes., Results: Overall, three phase 2 randomized clinical trials with a total of 146 previously treated lung cancer patients were enrolled. The median PFS and OS were 3.8 months and 9.5 months for IT plus SBRT versus 2.4 months and 6.1 months for IT. Comparing IT plus SBRT with IT alone, pooled risk ratios for ORR and DCR were 1.95 (95% confidence interval 1.07-3.53, p  = 0.03) and 1.28 (0.94-1.73, p  = 0.12). While pooled hazard ratios were 0.77 (0.25-2.42, p  = 0.66) for PFS and 0.71 (0.16-3.21, p  = 0.65) for OS, respectively. No publication bias was found across the trials., Conclusion: Compared to IT alone, the addition of SBRT improved the best response but failed to prolong the survival outcomes in treating advanced lung cancer patients. Future studies are necessary to explore new modalities of the combination of IT and SBRT., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Bi-Cheng Wang et al.)

Background: Ubiquitin-like with PHD and ring-finger domain 1 (UHRF1) has been defined as an oncogene in tumor cells. However, the role of UHRF1 in mediating metastasis in thyroid cancer remains unexplored. In this study, we aimed to investigate the metastatic function and the potential mechanisms of UHRF1 in thyroid cancer., Methods: Transwell assays were used to detect the metastatic capability of thyroid cancer. Dual-luciferase reporter assays were applied to examine the activation of transcription factors. Coimmunoprecipitation assays and immunofluorescence staining assays were used to elucidate the potential mechanisms of UHRF1 in promoting the metastasis of thyroid cancer., Results: In this study, we found that overexpression of UHRF1 promoted the metastasis of papillary thyroid cancer cells, and suppression of UHRF1 decreased the metastasis of anaplastic thyroid cancer cells. Regarding the signaling pathway in regulating metastasis, UHRF1 directly combined and activated the transcription factor c-Jun/AP-1 in the nucleus, subsequently increasing the transcription of IL-6 and MIF., Conclusion: Our results suggest that UHRF1 could induce the metastasis of thyroid cancer, and the potential signaling pathway might be that UHRF1 activates c-Jun/AP-1 to increase the expression of IL-6 and MIF. These findings provide a novel mechanism of UHRF1 and illustrate that UHRF1/AP-1 complex could be a potential therapeutic target for patients with thyroid cancer., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Bo-Hua Kuang et al.)

Background: The prognosis of patients with extensive-stage small cell lung cancer (SCLC) is poor. Adding an immune checkpoint inhibitor (ICI) to chemotherapy may exert a synergistic effect and improve survival outcomes. However, for treatment-naive extensive-stage SCLC patients, the efficacy of immunotherapy in combination with cytotoxic chemotherapy remains controversial., Objective: To evaluate the benefits and risks of the combination of immunotherapy and chemotherapy and to assess the comparative effectiveness of different first-line treatment strategies for extensive-stage SCLC., Methods: PubMed, Web of Science, EMBASE, and Cochrane Library were searched for randomized clinical trials studying different immunotherapeutics for patients with previously untreated extensive-stage SCLC up to Feb 16, 2020. The primary outcomes were overall survival (OS) and progression-free survival (PFS), and the secondary outcomes were objective response rate (ORR), disease control rate (DCR), and adverse events., Results: We identified 141 published records, and 4 studies (comprising 2202 patients) were included in the analysis. Immunotherapy (including ipilimumab, atezolizumab, and durvalumab) plus chemotherapy was associated with better OS (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.75-0.93; risk ratio (RR) 0.90, 95% CI 0.81-1.00) and PFS (HR: 0.81, 95% CI 0.74-0.88; RR 0.96, 95% CI 0.93-0.99) than placebo plus chemotherapy. The addition of immunotherapy to chemotherapy showed similar improvement in ORR, DCR, and adverse events versus placebo plus chemotherapy. On the surface under the cumulative ranking (SUCRA) analysis, the anti-PD-L1 agent, atezolizumab, had the highest likelihood of achieving improved OS (93.4%) and PFS (95.0%)., Conclusion: In the first-line setting, combining immunotherapy with chemotherapy is better than standard chemotherapy in terms of OS and PFS. Across the eligible studies, PD-L1 inhibitors might be preferred. Further explorations of more ICIs in the first-line treatment for extensive-stage SCLC patients should be needed., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Bi-Cheng Wang et al.)