This retrospective study was conducted to evaluate the efficacy and safety of elective nodal irradiation (ENI) and involved-field irradiation (IFI) for esophageal squamous cell carcinoma (ESCC) patients treated with intensity-modulated radiotherapy (IMRT).From January 2006 to December 2012, 644 patients (ENI = 157, IFI = 487) with stage I to IVa ESCC (AJCC 2010) at our institution were analyzed. Propensity score matching (PSM) was used to identify 471 (ENI = 157, IFI = 314) well-balanced patients for comparison. Overall survival (OS) was the primary outcome of the study.After PSM, the median OS was 26.8 (95% confidence interval [CI], 17.9–35.7) for the ENI arm versus 21.5 (95% CI: 17.9–25.1) months in the IFI arm. The 1-, 3-, 5-year OS were 77.1%, 42.0%, and 26.1% for the ENI arm versus 73.2%, 32.2%, and 19.0% for the IFI arm (P = .020). ENI was a significant independent predictor of 5-year OS (1.301 [1.052–1.609]; P = .015). Furthermore, patients with stage I/II ESCC or lymph node (LN) positivity in the ENI arm had significantly better 5-year OS than their counterparts in the IFI arm. In addition, for LN positivity patients treated with definitive radiotherapy alone, ENI tended to prolong OS compared with IFI (P = .035). The 2 arms were comparable in toxicities.Using IMRT, ENI is superior to IFI in improving OS of ESCC patients, with acceptable toxicities that were comparable to those to IFI, especially for LN positivity ESCC patients treated with definitive irradiation alone. These results should be confirmed in a large randomized study comparing these 2 modalities.

ObjectiveThis study aimed to analyze whether involved field irradiation (IFI) is associated with improving survival outcomes and reducing adverse events compared with elective nodal irradiation (ENI) in patients of esophageal cancer who underwent definitive radiotherapy or chemoradiotherapy.Summary background dataRadiotherapy plays an important role for not surgery patients. However, the role of radiation target size is still uncertain.MethodsWe searched Web of Science, Embase, PubMed, and Cochrane Central for English and non-English publications comparing esophageal cancer patients who received radiotherapy with IFI with those with ENI. Primary outcomes included overall survival (OS) and adverse events related to radiotherapy. The risk of bias was assessed using the Cochrane Risk of Bias tool for randomized studies and the Newcastle-Ottawa Scale and Agency for Healthcare Research and Quality Standard for non-randomized studies. We evaluated the certainty of evidence by Grading of Recommendations, Assessment, Development, and Evaluation.ResultsTotally, 23 studies with 4120 patients were included. IFI group demonstrated significant improvement in the OS rates at 5 years, but not at 1, 2, and 3 years, compared with the ENI group (pooled Risk Ratio [RR], 0.78; 95% confidence interval [CI], 0.68–0.90; P = 0.0004; high certainty). In addition, IFI demonstrated a significant decrease in the incidence of grade ≥2 acute esophagitis (AE) (pooled RR, 0.79; 95% CI, 0.69–0.90; P = 0.0005; high certainty) and grade ≥3 AE (pooled RR, 0.51; 95% CI, 0.38–0.69; P < 0.00001; high certainty) compared with ENI, but not in the incidence of grades ≥3 acute pneumonia, late esophagitis, and late pneumonia.ConclusionsCompared to ENI, IFI demonstrated significant improvement in OS at 5 years. The addition of intensity-modulated radiotherapy (IMRT) to IFI increased the 5-year OS; however, similar results were not observed with the addition of three-dimensional conformal radiotherapy to IFI and ENI. Furthermore, IFI demonstrated a significant decrease in grade ≥2 and grade ≥3 AE, while IMRT demonstrated no difference in the incidence of grade ≥3 AE. IFI and ENI do not differ in the incidence of grades ≥3 acute pneumonia, late esophagitis, and late pneumonia.

ObjectiveTo investigate the predictive value of Controlling Nutritional Status (CONUT) score and systemic inflammation (SIS) score in the prognosis, short-term efficacy, and immune-related side effects of patient with recurrent or metastatic esophageal squamous cell carcinoma (R/M ESCC) receiving immunotherapy as second line therapy combined with or without radiotherapy.MethodsForty-eight patients with R/M ESCC who received second-line therapy with Camrelizumab were retrospectively studied. They were divided into the high and low score groups according to the CONUT and SIS score. Univariate and multivariate analyses were used to analyze factors that might affect patient prognosis and the effects of different CONUT score and SIS on the short-term efficacy and immune-related toxic and side effects of patients.ResultsThe 1- and 2-year overall survival (OS) and progression-free survival (PFS) rates were 42.9% and 22.5%, and 29.0% and 5.8%, respectively. The CONUT score ranged from 0 to 6 (3.31 ± 1.43), whereas the SIS score ranged from 0 to 2 (1.19 ± 0.73). Multivariate analysis showed that treatment related toxicity, number of cycles of Camrelizumab used, short-term effect and SIS score were independent prognostic factors for OS (P=0.044, 0.021, 0.021, 0.030, respectively), whereas SIS and CONUT scores were independent prognostic factors for PFS (P=0.005, 0.047, respectively). Patients with low CONUT/SIS score had a low incidence rate of immune-related adverse reactions (X2 = 9.735, 5.693; P=0.002, 0.017) and better short-term efficacy (X2 = 4.427, 7.438; P=0.035, 0.006).ConclusionR/M ESCC patients with low CONUT/SIS score have better prognosis, higher objective response rate, lower incidence of immune-related toxic and side effects after receiving immunotherapy as second-line therapy. CONUT scores and SIS scores may be reliable prognostic indicators for patient receiving immunotherapy as second-line therapy for R/M ESCC.

Background To explore the effect of HMGB1 on the radio-sensitivity of esophageal cancer cells through regulating the PI3K/Akt/ATM pathway. Methods and results We observed the expression of HMGB1 and p-ATM in biopsies of esophageal cancer patients with immunohistochemical staining. Western blot and RT-qPCR were applied to detect the protein and RNA related to PI3K/Akt/ATM pathway, respectively. In addition, we inhibited the PI3K/Akt pathway with ly294002 and activated it with IGF1, then we explored the invasion, proliferation ability, and apoptosis of esophageal cancer cells in vitro by transwell, CCK8 assay, and flow cytometry respectively. In vivo, xenograft tumor model was established in nude mice to study the effect of HMGB1 on radioresistance via PI3K/AKT/ATM Signaling Pathway. The survival rate in patients with single positive/double negative expression of HMGB1 and p-ATM was significantly higher than in those with both positive expression of HMGB1 and p-ATM, the depletion of HMGB1 combined with ly294002 significantly inhibited cell proliferation and invasion ability, meanwhile, the addition of IGF1 reversed it. Meanwhile, depletion of HMGB1 and ly294002 promoted apoptosis and arrested the cancer cells in G0/G1 cell cycle with the decreased expression of Cyclin D1 and CDK4 and improved P16. We further validated these results in vivo, the application of HMGB1 silencing promoted apoptosis of xenograft tumors after radiation, especially combined with pathway inhibitor ly294002. Conclusions Esophageal cancer patients with high expression of HMGB1 and p-ATM have a poor prognosis after chemo-radiotherapy. Down-regulation of HMGB1 may promote the radio-sensitivity of esophageal cancer cells through regulating PI3K/Akt/ATM pathway.

ObjectiveThis systematic review and meta-analysis aimed to investigate the role of neoadjuvant immunochemotherapy with or without radiotherapy [NIC(R)T] compared to traditional neoadjuvant therapies, without immunotherapy [NC(R)T].Summary background dataNCRT followed by surgical resection is recommended for patients with early-stage esophageal cancer. However, it is uncertain whether adding immunotherapy to preoperative neoadjuvant therapy would improve patient outcomes when radical surgery is performed following neoadjuvant therapy.MethodsWe searched PubMed, Web of Science, Embase, and Cochrane Central databases, as well as international conference abstracts. Outcomes included R0, pathological complete response (pCR), major pathological response (mPR), overall survival (OS) and disease-free survival (DFS) rates.ResultsWe included data from 5,034 patients from 86 studies published between 2019 and 2022. We found no significant differences between NICRT and NCRT in pCR or mPR rates. Both were better than NICT, with NCT showing the lowest response rate. Neoadjuvant immunotherapy has a significant advantage over traditional neoadjuvant therapy in terms of 1-year OS and DFS, with NICT having better outcomes than any of the other three treatments. There were no significant differences among the four neoadjuvant treatments in terms of R0 rates.ConclusionsAmong the four neoadjuvant treatment modalities, NICRT and NCRT had the highest pCR and mPR rates. There were no significant differences in the R0 rates among the four treatments. Adding immunotherapy to neoadjuvant therapy improved 1-year OS and DFS, with NICT having the highest rates compared to the other three modalities.Systematic Review Registrationhttps://inplasy.com/inplasy-2022-12-0060/, identifier INPLASY2022120060.