Intratreatment Tumor Volume Change During Definitive Chemoradiotherapy is Predictive for Treatment Outcome of Patients with Esophageal Carcinoma

Background: This study aimed to assess the predictive value of tumor volume changes of esophagus evaluated by serial computed tomography (CT) scans before, during, and after radical chemoradiotherapy (CRT) for treatment outcomes in patients with esophageal cancer (EC). Methods: Fifty-three patients with histologically confirmed EC were included for analysis. Gross tumor volume of esophagus (GTVe) was manually contoured on the CT images before treatment, at a twentieth fraction of radiotherapy, at completion of CRT and three months after treatment. GTVe reduction ratio (RR) was calculated to reveal changes of tumor volume by time. The Kaplan–Meier method was used to estimate survival and for univariate analysis. The Cox regression model was performed for multivariate analysis. Results: Predominant reduction of GTVe was observed during the first 20 fractions of radiotherapy. Age, pretreatment GTVe, GTVe three months after treatment and GTVe RR at twentieth fraction of radiotherapy were all significantly associated with overall survival (OS) in a univariate analysis. Gender was correlated with locoregional recurrence-free survival (LRRFS) in univariate analysis. Multivariate analysis showed that GTVe ≤20 cc, GTVe RR at twentieth fraction of radiotherapy ≥35% were positive predictive factors of OS and pretreatment GTVe ≤20 cc was prognostic for a favorable LRRFS. Conclusion: Pretreatment tumor volume and intratreatment volume reduction ratio are reliable prognostic factors for esophageal cancer treated with definitive CRT

Effectiveness and safety of pelareorep plus chemotherapy versus chemotherapy alone for advanced solid tumors: a meta-analysis

Background: Pelareorep is an oncolytic virus that causes oncolytic effects in many solid tumors, and it has shown therapeutic benefits. However, few studies have compared pelareorep combined with chemotherapy to traditional chemotherapy alone in advanced solid tumors. Consequently, we intended to evaluate the effectiveness and safety of pelareorep plus chemotherapy in this paper.Methods: We searched four databases including PubMed, Embase, Cochrane Library and Web of Science comprehensively for studies comparing pelareorep combined with chemotherapy to chemotherapy alone in the treatment of advanced solid tumors. The outcomes measures were 1-year overall survival (OS), 2-year OS, 4-month progression-free survival (PFS), 1-year PFS, objective response rate (ORR), any-grade adverse events (any-grade AEs), and severe AEs (grade ≥ 3).Results: There were five studies involving 492 patients included in the study. Combination therapy did not significantly improve clinical outcomes in terms of 1-year OS [RR = 1.02, 95%CI = (0.82–1.25)], 2-year OS [RR = 1.00, 95%CI = (0.67–1.49)], 4-month PFS [RR = 1.00, 95%CI = (0.67–1.49)], 1-year PFS [RR = 0.79, 95%CI = (0.44–1.42)], and ORR [OR = 0.79, 95%CI = (0.49–1.27)] compared to chemotherapy alone, and the subgroup analysis of 2-year OS, 1-year PFS, and ORR based on countries and tumor sites showed similar results. In all grades, the incidence of AEs was greater with combination therapy, including fever [RR = 3.10, 95%CI = (1.48–6.52)], nausea [RR = 1.19, 95%CI = (1.02–1.38)], diarrhea [RR = 1.87, 95%CI = (1.39–2.52)], chills [RR = 4.14, 95%CI = (2.30–7.43)], headache [RR = 1.46, 95%CI = (1.02–2.09)], vomiting [RR = 1.38, 95%CI = (1.06–1.80)] and flu-like symptoms [RR = 4.18, 95%CI = (2.19–7.98)]. However, severe adverse events did not differ significantly between the two arms.Conclusion: Pelareorep addition to traditional chemotherapy did not lead to significant improvements in OS, PFS, or ORR in advanced solid tumor patients, but it did partially increase AEs in all grades, with no discernible differences in serious AEs. Therefore, the combination treatment is not recommended in patients with advanced solid tumors.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=400841, identifier CRD4202340084

A study of multinucleated giant cells in esophageal cancer

Objectives: To evaluate the occurrence, abundance, distribution, nature and clinical significance of multi-nucleated giant cell (MGC) in esophageal cancer. Materials and methods: MGCs were examined with conventional pathology, immunohistochemistry and immunofluorescence in 107 esophageal cancer tissues. The findings were correlated to pathological diagnosis and clinical behavior of the cancers. Results: MGCs were identified in 31.7% (34/107) of the cases. MGCs were positive for CD11c, CD11b, CD32, CD16, HLA-DR and MMP9, and negative for CD163, CD206 and CD64 giving a molecular profile of proinflammatory M1 but not immunosuppressive M2. MGCs were significantly related to decreased lymph node metastasis (p = 0.011), low pTNM stage (p = 0.044), favorable survival (p = 0.04), squamous cell cancer type rather than other histopathological subtypes (p = 0.020) and associated to better differentiation (p = 0.063). Conclusions: MGCs belong to M1 macrophage and perform phagocytosis and scavenging of cancer cells that would benefit patients' survival and could serve as a prognostic marker

Table1_Effectiveness and safety of pelareorep plus chemotherapy versus chemotherapy alone for advanced solid tumors: a meta-analysis.docx

Background: Pelareorep is an oncolytic virus that causes oncolytic effects in many solid tumors, and it has shown therapeutic benefits. However, few studies have compared pelareorep combined with chemotherapy to traditional chemotherapy alone in advanced solid tumors. Consequently, we intended to evaluate the effectiveness and safety of pelareorep plus chemotherapy in this paper.Methods: We searched four databases including PubMed, Embase, Cochrane Library and Web of Science comprehensively for studies comparing pelareorep combined with chemotherapy to chemotherapy alone in the treatment of advanced solid tumors. The outcomes measures were 1-year overall survival (OS), 2-year OS, 4-month progression-free survival (PFS), 1-year PFS, objective response rate (ORR), any-grade adverse events (any-grade AEs), and severe AEs (grade ≥ 3).Results: There were five studies involving 492 patients included in the study. Combination therapy did not significantly improve clinical outcomes in terms of 1-year OS [RR = 1.02, 95%CI = (0.82–1.25)], 2-year OS [RR = 1.00, 95%CI = (0.67–1.49)], 4-month PFS [RR = 1.00, 95%CI = (0.67–1.49)], 1-year PFS [RR = 0.79, 95%CI = (0.44–1.42)], and ORR [OR = 0.79, 95%CI = (0.49–1.27)] compared to chemotherapy alone, and the subgroup analysis of 2-year OS, 1-year PFS, and ORR based on countries and tumor sites showed similar results. In all grades, the incidence of AEs was greater with combination therapy, including fever [RR = 3.10, 95%CI = (1.48–6.52)], nausea [RR = 1.19, 95%CI = (1.02–1.38)], diarrhea [RR = 1.87, 95%CI = (1.39–2.52)], chills [RR = 4.14, 95%CI = (2.30–7.43)], headache [RR = 1.46, 95%CI = (1.02–2.09)], vomiting [RR = 1.38, 95%CI = (1.06–1.80)] and flu-like symptoms [RR = 4.18, 95%CI = (2.19–7.98)]. However, severe adverse events did not differ significantly between the two arms.Conclusion: Pelareorep addition to traditional chemotherapy did not lead to significant improvements in OS, PFS, or ORR in advanced solid tumor patients, but it did partially increase AEs in all grades, with no discernible differences in serious AEs. Therefore, the combination treatment is not recommended in patients with advanced solid tumors.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=400841, identifier CRD42023400841</p

A tumor suppressor protein encoded by circKEAP1 inhibits osteosarcoma cell stemness and metastasis by promoting vimentin proteasome degradation and activating anti-tumor immunity

Abstract Background Osteosarcoma (OS) is one of most commonly diagnosed bone cancer. Circular RNAs (circRNAs) are a class of highly stable non-coding RNA, the majority of which have not been characterized functionally. The underlying function and molecular mechanisms of circRNAs in OS have not been fully demonstrated. Method Microarray analysis was performed to identify circRNAs that are differentially-expressed between OS and corresponding normal tissues. The biological function of circKEAP1 was confirmed in vitro and in vivo. Mass spectrometry and western blot assays were used to identify the circKEAP1-encoded protein KEAP1-259aa. The molecular mechanism of circKEAP1 was investigated by RNA sequencing and RNA immunoprecipitation analyses. Results Here, we identified a tumor suppressor circKEAP1, originating from the back-splicing of exon2 of the KEAP1 gene. Clinically, circKEAP1 is downregulated in OS tumors and associated with better survival in cancer patients. N6-methyladenosine (m6A) at a specific adenosine leads to low expression of circKEAP1. Further analysis revealed that circKEAP1 contained a 777 nt long ORF and encoded a truncated protein KEAP1-259aa that reduces cell proliferation, invasion and tumorsphere formation of OS cells. Mechanistically, KEAP1-259aa bound to vimentin in the cytoplasm to promote vimentin proteasome degradation by interacting with the E3 ligase ARIH1. Moreover, circKEAP1 interacted with RIG-I to activate anti-tumor immunity via the IFN-γ pathway. Conclusion Taken together, our findings characterize a tumor suppressor circKEAP1 as a key tumor suppressor regulating of OS cell stemness, proliferation and migration, providing potential therapeutic targets for treatment of OS