High-dose versus conventional-dose irradiation in cisplatin-based definitive concurrent chemoradiotherapy for esophageal cancer: a systematic review and pooled analysis

<div><p>We investigate whether high-dose (HD, ≥60 Gy) radiotherapy in definitive concurrent chemoradiotherapy (CCRT) based on cisplatin could yield benefits compared to conventional-dose (CD) CCRT. PubMed, Embase and Google Scholar were searched and data were pooled and analyzed for response rate, survival, failure patterns and toxicity. Results showed advantages in response rate, 5-year overall survival rate, local regional recurrence and distant failure rate compared to the CD arm with no difference in Grade ≥3 acute and late esophagitis, other toxicities were rare with moderate tolerance, subgroup analysis of squamous cell carcinoma also showed advantages for HD arm. We concluded that ≥60 Gy CCRT improved clinical outcomes compared to the CD arm, especially for esophageal squamous cell carcinoma. Our findings may provide a basis for future trials.</p></div

Image_1_Long-Term Survival Outcomes and Comparison of Different Treatment Modalities for Stage I-III Cervical Esophageal Carcinoma.TIF

Purpose: To investigate the survival outcomes, prognostic factors and treatment modalities of stage I-III cervical esophageal carcinoma (CEC) patients using data from the Surveillance, Epidemiology, and End Results (SEER) database from the period 2004–2016.Methods: Patients with a histopathologic diagnosis of CEC were included. The primary endpoint was overall survival (OS). Univariate and multivariate analyses of OS were performed using Cox proportional hazards models, and OS was compared using the Kaplan-Meier method and log-rank test.Results: A total of 347 patients in the SEER database were enrolled. The median OS was 14.0 months, with a 5-year OS rate of 20.9%. The parameters that were found to significantly correlate with OS in the multivariate analysis were age at diagnosis [P Conclusions: The survival of patients with CEC remains poor. Surgery, RT and CT were all strongly correlated with OS. We recommend a triple therapy regimen for select CEC patients based on the findings of the current study, although this recommendation should be further confirmed by prospective studies with large sample sizes.</p

Table_2_Long-Term Survival Outcomes and Comparison of Different Treatment Modalities for Stage I-III Cervical Esophageal Carcinoma.docx

Purpose: To investigate the survival outcomes, prognostic factors and treatment modalities of stage I-III cervical esophageal carcinoma (CEC) patients using data from the Surveillance, Epidemiology, and End Results (SEER) database from the period 2004–2016.Methods: Patients with a histopathologic diagnosis of CEC were included. The primary endpoint was overall survival (OS). Univariate and multivariate analyses of OS were performed using Cox proportional hazards models, and OS was compared using the Kaplan-Meier method and log-rank test.Results: A total of 347 patients in the SEER database were enrolled. The median OS was 14.0 months, with a 5-year OS rate of 20.9%. The parameters that were found to significantly correlate with OS in the multivariate analysis were age at diagnosis [P Conclusions: The survival of patients with CEC remains poor. Surgery, RT and CT were all strongly correlated with OS. We recommend a triple therapy regimen for select CEC patients based on the findings of the current study, although this recommendation should be further confirmed by prospective studies with large sample sizes.</p

Table_3_Long-Term Survival Outcomes and Comparison of Different Treatment Modalities for Stage I-III Cervical Esophageal Carcinoma.docx

Purpose: To investigate the survival outcomes, prognostic factors and treatment modalities of stage I-III cervical esophageal carcinoma (CEC) patients using data from the Surveillance, Epidemiology, and End Results (SEER) database from the period 2004–2016.Methods: Patients with a histopathologic diagnosis of CEC were included. The primary endpoint was overall survival (OS). Univariate and multivariate analyses of OS were performed using Cox proportional hazards models, and OS was compared using the Kaplan-Meier method and log-rank test.Results: A total of 347 patients in the SEER database were enrolled. The median OS was 14.0 months, with a 5-year OS rate of 20.9%. The parameters that were found to significantly correlate with OS in the multivariate analysis were age at diagnosis [P Conclusions: The survival of patients with CEC remains poor. Surgery, RT and CT were all strongly correlated with OS. We recommend a triple therapy regimen for select CEC patients based on the findings of the current study, although this recommendation should be further confirmed by prospective studies with large sample sizes.</p

Table_1_Long-Term Survival Outcomes and Comparison of Different Treatment Modalities for Stage I-III Cervical Esophageal Carcinoma.docx

Purpose: To investigate the survival outcomes, prognostic factors and treatment modalities of stage I-III cervical esophageal carcinoma (CEC) patients using data from the Surveillance, Epidemiology, and End Results (SEER) database from the period 2004–2016.Methods: Patients with a histopathologic diagnosis of CEC were included. The primary endpoint was overall survival (OS). Univariate and multivariate analyses of OS were performed using Cox proportional hazards models, and OS was compared using the Kaplan-Meier method and log-rank test.Results: A total of 347 patients in the SEER database were enrolled. The median OS was 14.0 months, with a 5-year OS rate of 20.9%. The parameters that were found to significantly correlate with OS in the multivariate analysis were age at diagnosis [P Conclusions: The survival of patients with CEC remains poor. Surgery, RT and CT were all strongly correlated with OS. We recommend a triple therapy regimen for select CEC patients based on the findings of the current study, although this recommendation should be further confirmed by prospective studies with large sample sizes.</p

Additional file 1: of Single-cell RNA-seq of esophageal squamous cell carcinoma cell line with fractionated irradiation reveals radioresistant gene expression patterns

Figure S1. Quality control of basic gene expression statistics. a. Replicate sequencing showed high repeatability (r = 0.96) of expression level. b. The expression distribution after depth normalization revealed similar medians for all cells analyzed. c. The expression data of discrete genes suggested a correlation of increased expression with decreased discrete degree. Therefore, we could not include genes with a normalized count ratio of less than 2 log2. d. The RSDs of gene expression assayed by duplicate sequencing appear highly linear (r = 0.98). Figure S2. Heatmap of DEGs in the three treatment groups (0 Gy controls, 12 Gy, and 30 Gy). Four gene expression patterns are seen among all DEGs. Pattern 1 shows a slight upregulation after radiation, with two subpopulations of 12 Gy cells. Pattern 2 shows a strong downregulation after 30 Gy. Pattern 3 was similar to pattern 1, but no subpopulations were observed. Finally, pattern 4 shows many slightly downregulated genes. Four cells in the 12 Gy group had a completely different expression pattern, and were excluded as outliers after sequencing depth checking. Figure S3. qPCR validation of DEGs in five radioresistant-related pathways in Fig. 4 by new treated KYSE-180 cells, KYSE-180-12 Gy cells and KYSE-180-30 Gy cells. * means P < 0.05; ** represents P < 0.01. Figure S4. qPCR validation of DEGs in five radioresistant-related pathways in Fig. 4 by KYSE-150 cells, KYSE-150-12 Gy cells and KYSE-150-30 Gy cells. * means P < 0.05; ** represents P < 0.01. Figure S5. Radioresistance-associated cellular phenotypic evidences of KYSE-150 cells. a. Transwell assay showed invasion of KYSE-150, KYSE-150-12 Gy and KYSE-150-30 Gy. b. FACS analysis with Annexin V-PE and 7-AAD showing apoptosis results of KYSE-150, KYSE-150-12 Gy and KYSE-150-30 Gy. c. Surviving KYSE-150 cells with and without FIR exposure identified by CCK-8 assay. * means P < 0.05; ** represents P < 0.01. (PDF 28921 kb

Additional file 2: of Single-cell RNA-seq of esophageal squamous cell carcinoma cell line with fractionated irradiation reveals radioresistant gene expression patterns

Table S1. Basic pathways and Cancer-related genes. Table S2. Four patterns of DEGs. Table S3. Key DEGs of sub of KYSE-180 12Gy. Table S4. Disease ontology of 1.5 fold DEGs. Table S5. KEGG of DEGs-obtained. Table S6. Key DEGs of bulk cell. Table S7. qPCR primer sequences of mRNA. Table S8. The enrichment GO analysis of four patterns of DEGs. (XLS 302 kb

Supplementary Data from Cancer-associated Fibroblast–promoted LncRNA <i>DNM3OS</i> Confers Radioresistance by Regulating DNA Damage Response in Esophageal Squamous Cell Carcinoma

Supplementary Figure. S5 DNM3OS inhibited irradiation-induced DNA damage in esophageal cancer cells by FCM analysis.</p

Supplementary Data from Cancer-associated Fibroblast–promoted LncRNA <i>DNM3OS</i> Confers Radioresistance by Regulating DNA Damage Response in Esophageal Squamous Cell Carcinoma

Supplementary Figure. S1. The expression of DNM3OS in esophageal cancer cells after transfection with DNM3OS siRNA.</p

Supplementary Data from Cancer-associated Fibroblast–promoted LncRNA <i>DNM3OS</i> Confers Radioresistance by Regulating DNA Damage Response in Esophageal Squamous Cell Carcinoma

Supplementary Figure. S6. DNM3OS regulated DNA damage response in KYSE-150R cells.</p