Objective:To conduct a systematic evaluation of prognostic factors for retreatment of esophageal cancer patients with locoregional recurrence after radical chemoradiotherapy, and provide a clinical reference for selecting individualized retreatment schemes and improving their survival.Methods:A retrospective analysis was performed on the clinical data of 85 patients with esophageal cancer who experienced locoregional recurrence at least 1 year after radical radiotherapy or chemotherapy at the Department of Radiation Oncology in the Fourth Hospital of Hebei Medical University from January 2008 to December 2017. The effects of different nutritional and immune status and retreatment schemes on survival were compared, and the prognostic factors for retreatment were subjected to comprehensive subgroup analysis.Results:As of December 2021, the follow-up rate for all patients was 93%. The 1-, 2-, 3-, and 5-year overall survival rates of all patients after retreatment were 31.5%, 18.6%, 10.6%, and 6.6%, respectively. For patients who received radiotherapy or chemoradiotherapy, the 1-, 2-, 3-, and 5-year overall survival rates were 36.8%, 22.3%, 13.0% and 9.3%, respectively. Multivariable analysis showed that the time interval between the first treatment and recurrence, the retreatment schemes after recurrence, the level of serum albumin before retreatment, and the prognostic nutritional index before retreatment were independent prognostic factors for survival after retreatment ( P<0.05). Subgroup analysis was performed on the combinations of peripheral blood hemoglobin level, albumin level, and prognostic nutritional index before retreatment, as well as systemic immune inflammation index and short-term curative effect after retreatment. The results showed that the comprehensive analysis of blood routine and serum albumin indicators could accurately predict the survival after retreatment. Conclusions:The nutritional and immune status of patients with locoregional recurrence of esophageal cancer after chemoradiotherapy can be used to predict the prognosis of retreatment. The time interval between the first treatment and recurrence and the retreatment scheme significantly affect the survival after retreatment. The retreatment scheme should be rigorously evaluated and appropriately selected to improve the benefit-risk ratio.

Objective:To analyze the local recurrence patterns after concurrent chemoradiotherapy (CCRT) for thoracic esophageal squamous cell carcinoma (ESCC) through image fusion, and to explore the risk factors of local recurrence and its relationships with dosimetric indices.Methods:A retrospective analysis was conducted for 209 thoracic ESCC patients who received radical CCRT in Fourth Hospital of Hebei Medical University during 2016-2019. For the patients diagnosed as the local recurrence of esophageal lesions, their CT images were fused with the original planning CT images using image registration software to identify the recurrence sites. Through 1∶1 propensity score matching (PSM) of the clinal data of patients with local recurrence (the recurrence group, nbefore = 81, nafter = 62) and those without local recurrence (the recurrence-free group, nbefore = 128, nafter=62), the dose and volume parameters of the treatment plans for the two groups were compared. Univariate and multivariate analyses were conducted using the Kaplan-Meier method and the Cox regression model to analyze the factors affecting the overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS). Results:All patients had 1-, 3-, and 5-year OS rates of 80.9%, 42.6%, and 33.0%, respectively, 1-, 3-, and 5-year PFS rates of 67.9%, 34.0%, and 27.9%, respectively, and 1-, 3-, and 5-year RFS rates of 71.3%, 39.2%, and 30.5%, respectively. T stage, N stage, and radiation dose were independent prognostic factors for the OS, PFS, and RFS ( HR = 1.42-1.87, P < 0.05) of the patients, respectively. Among 68 patients with local recurrence, 62 cases (91.2%) suffered recurrence within the gross tumor volume (GTV). The dose and volume parameters of patients with local recurrence, such as GTV- D95%, clinical target volume (CTV)- D95%, GTV- D50%, CTV- D50%, and planning target volume (PTV)- D50%, GTV- V60, CTV- V60, and PTV- V60, were significantly lower than those of patients free from the local recurrence ( t=1.90-2.15, P < 0.05). Conclusions:Local recurrence of patients with thoracic ESCC after radical CCRT occurs mainly within the GTV. Increasing radiation doses may contribute to their survival benefits. The D50% for each target volume in the radiotherapy plan may be related to local recurrence, and it is necessary to conduct further research.

Objective:To evaluate the effects of high mobility group protein box 1 (HMGB1) on clinical prognosis of esophagus squamous cell carcinoma (ESCC) patients treated with chemoradiotherapy and the radiosensitivity of xenograft in nude mice.Methods:A total of 90 endoscopic biopsy specimens were obtained from ESCC patients treated with chemoradiotherapy. The expression level of HMGB1 was determined by immunohistochemical staining. High expression level was defined when staining was observed on ≥50% of the tumor cells. All patients were divided into the high expression group ( n=48) and low expression group ( n=42), and their survival information was retrospectively analyzed. Cell transfection was performed with the plasmid carrying human HMGB1-shRNA to knockdown HMGB1 expression in ECA109 cells and xenograft mouse models were established. The tumor volume and mass were calculated after irradiation with a dose of 15 Gy. The cell apoptosis in xenograft tissues were detected. Survival analysis was performed using Kaplan-Meier method. Univariate prognostic analysis was conducted by log-rank test. Intergroup comparison was performed by analysis of variance (ANOVA). Results:The expression level of HMGB1 was significantly associated with gross tumor volume, longest diameter of tumor, T staging and distant metastasis ( χ2=9.663, 5.625, 4.068, 7.146, all P<0.05). In the low expression group, the overall survival (OS) ( χ2=4.826, P=0.028), progression-free survival (PFS) ( χ2=4.390, P=0.036) were longer compared with that in the high expression group. Further analysis of HMGB1-high expression patients showed that the radiation dose and the combination of chemoradiotherapy did not significantly affect the OS or PFS of ESCC patients. We observed that knockdown of HMGB1 slowed the growth rate of xenograft, decreased the tumor volume and increased the apoptosis rate after irradiation. Conclusions:ESCC patients with high expression level of HMGB1 obtain poor prognosis after chemoradiotherapy, which can be enhanced by increasing the sensitivity to radiotherapy and chemotherapy. HMGB1 knockdown can effectively increase the radiosensitivity of xenograft in ESCC nude mice.

Neoadjuvant radiotherapy and chemotherapy combined with surgery is the standard treatment for patients with locally advanced esophageal cancer, which has been widely applied in clinical practice. Clinical efficacy has also been recognized by clinicians. However, even after the completion of neoadjuvant radiotherapy and subsequent surgical treatment, some patients still have local regional recurrence or distant metastasis in a short period of time. Among them, distant metastasis has become the main failure mode of patients undergoing surgery after neoadjuvant radiotherapy and chemotherapy, indicating that this treatment remains to be further improved. Based on the experience of patients with rectal cancer benefiting from total neoadjuvant therapy, the feasibility and implementation of total neoadjuvant therapy for locally advanced esophageal cancer were discussed in this article.

Objective:To investigate the radiation dose and fractionation regimens for limited stage small cell lung cancer (LS-SCLC) in Chinese radiation oncologists.Methods:Over 500 radiation oncologists were surveyed through questionnaire for radiation dose and fractionation regimens for LS-SCLC and 216 valid samples were collected for further analysis. All data were collected by online questionnaire designed by WJX software. Data collection and statistical analysis were performed by SPSS 25.0 statistical software. The differences in categorical variables among different groups were analyzed by Chi-square test and Fisher's exact test. Results:Among 216 participants, 94.9% preferred early concurrent chemoradiotherapy, 69.4% recommended conventional fractionation, 70.8% preferred a total dose of 60 Gy when delivering conventional radiotherapy and 78.7% recommended 45 Gy when administering hyperfractionated radiotherapy.Conclusions:Despite differences in LS-SCLC treatment plans, most of Chinese radiation oncologists prefer to choose 60 Gy conventional fractionated radiotherapy as the main treatment strategy for LS-SCLC patients. Chinese Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN) and Chinese Medical Association guidelines or expert consensus play a critical role in guiding treatment decision-making.

Objective:To investigate the efficacy of camrelizumab combined with second-line therapy in patients with recurrent or metastatic esophageal squamous cell carcinoma (ESCC) in the real-world settings.Methods:Clinical data of 48 patients with esophageal cancer who met the inclusion criteria were retrospectively analyzed. The types of failure after first-line treatment, clinical efficacy, side effects and prognostic factors of second-line treatment were analyzed. SPSS 25.0 software was used for statistical analysis. Count data were expressed by composition ratio and analyzed by Chi-square test or Fisher's exact test. Survival analysis was conducted by Kaplan-Meier curve and log-rank test. Non-normally distributed data were recorded with the median, range and quartile. Results:There were 26, 14, and 4 cases of combined chemoradiotherapy, chemotherapy and radiotherapy in the treatment of second-line camrelizumab, and 4 cases received immunotherapy alone. The median duration of immunotherapy was 6 cycles (range, 2-39 cycles). After second-line treatment, the short-term efficacy of 17, 27 and 4 cases was partial remission (PR), stable disease (SD) and progressive disease (PD), respectively. The overall response rate (ORR) was 35.4% and disease control rate (DCR) was 91.7%. The 1- and 2-year OS rates were 42.9% and 22.5%, and 1- and 2-year PFS rates were 29.0% and 5.8%. The median OS and PFS were 9.0 months (95% CI=6.4-11.7) and 8.5 months (95% CI=1.5-5.6), respectively. Multivariate analysis showed that combined immunotherapy mode, number of cycles of immunotherapy and short-term efficacy were the independent prognostic indicators affecting OS in this group of patients ( HR=2.598, 0.222, 8.330, P=0.044, <0.001, <0.001). Lymphocyte count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), combined immunotherapy mode and short-term efficacy were the independent prognostic indicators affecting PFS in this group ( HR=3.704, 3.598, 6.855, 2.159, 2.747, P=0.009, 0.008, <0.001, 0.049, 0.012). Conclusions:Camrelizumab combined with second-line therapy can bring survival benefit to patients with recurrent or metastatic ESCC after first-line therapy, especially immunotherapy combined with chemoradiotherapy can significantly provide survival benefit. Peripheral blood inflammatory biomarkers are independent indicators affecting clinical prognosis of patients. Patients with better short-term efficacy also achieve better prognosis. The final conclusion remains to be validated by a large number of randomized controlled studies.

Objective:To investigate the prognostic value of Onodera's prognostic nutrition index (PNI) before treatment in patients with cervical and upper thoracic esophageal squamous cell carcinoma (CUTESCC) undergoing definitive chemoradiotherapy (dCRT) and its predictive value in the occurrence of ≥ grade 2 radiation esophagitis (RE).Methods:The data of 163 CUTESCC patients eligible for inclusion criteria admitted to the Fourth Hospital of Hebei Medical University from January 2012 to December 2017 were retrospectively analyzed. The receiver operating characteristic (ROC) curve was used to calculate the best cut-off value of PNI for predicting the prognosis of patients. The prognosis of patients was analyzed by univariate and Cox multivariate analyses. Logistics binary regression model was adopted to analyze the risk factors of ≥ grade 2 RE in univariate and multivariate analyses. The significant factors in logistic multivariate analysis were used to construct nomogram for predicting ≥ grade 2 RE.Results:The optimal cut-off value of PNI was 48.57 [area under the curve (AUC): 0.653, P<0.001]. The median overall survival (OS) and progression-free survival (PFS) were 26.1 and 19.4 months, respectively. The OS ( χ2=6.900, P=0.009) and PFS ( χ2=9.902, P=0.003) of patients in the PNI ≥ 48.57 group ( n=47) were significantly better than those in the PNI < 48.57 group ( n=116). Cox multivariate analysis showed that cTNM stage and PNI were the independent predictors of OS ( HR=1.513, 95% CI: 1.193-1.920, P=0.001; HR=1.807, 95% CI: 1.164-2.807, P=0.008) and PFS ( HR=1.595, 95% CI: 1.247-2.039, P<0.001; HR=2.260, 95% CI: 1.439-3.550, P<0.001). Short-term efficacy was another independent index affecting PFS ( HR=2.072, 95% CI: 1.072-4.003, P=0.030). Logistic multivariate analysis showed that the maximum transverse diameter of the lesion ( OR=3.026, 95% CI: 1.266-7.229, P=0.013), gross tumor volume (GTV) ( OR=3.456, 95% CI: 1.373-8.699, P=0.008), prescription dose ( OR=3.124, 95% CI: 1.346-7.246, P=0.009) and PNI ( OR=2.072, 95% CI: 1.072-4.003, P=0.030) were the independent factors affecting the occurrence of ≥ grade 2 RE. These four indicators were included in the nomogram model, and ROC curve analysis showed that the model could properly predict the occurrence of ≥ grade 2 RE (AUC=0.686, 95% CI: 0.585-0.787). The calibration curve indicated that the actually observed values were in good agreement with the predicted RE. Decision curve analysis (DCA) demonstrated satisfactory nomogram positive net returns in most threshold probabilities. Conclusions:PNI before treatment is an independent prognostic factor for patients with CUTESCC who received definitive chemoradiotherapy. The maximum transverse diameter of the lesion, GTV, prescription dose and PNI are the risk factors for ≥ grade 2 RE in this cohort. Establishing a prediction model including these factors has greater predictive value.

Objective:To investigate the influence of the depth of invasion on the prognosis of pT1 stage mid-thoracic esophageal cancer patients undergoing left thoracotomy.Methods:Retrospectively analyze the clinicopathological data of 139 patients with pT1N0M0 stage of mid-thoracic esophageal cancer who meet the enrollment criteria. Firstly, the prognosis and influencing factors of the whole group were analyzed. The differences in prognosis, local recurrence and distant metastasis between PT1A and PT1B patients were compared, and the influence of different infiltration depth on prognosis and treatment failure of patients was analyzed. SPSS 19.0 statistical software was used for statistical analysis.Results:The 1-year, 3-year and 5-year overall survival(OS) and disease-free survival(DFS) were 95.0%, 87.8%, 82.0% and 91.4%, 84.2%, 77.0%, respectively. There were significant differences in OS( χ2=7.500, P=0.006) and DFS( χ2=7.354, P=0.007) at 1, 3 and 5 years between pT1a and pT1b patients. Cox multivariate analysis showed that pT stage and pathological type were independent prognostic factors for OS and DFS( P<0.05). There were no significant differences in OS( χ2=0.734, P=0.693) and DFS( χ2=0.7690, P=0.681) of pT1a tumors with different invasion depths. There were significant differences in OS( χ2=15.368, P<0.001) and DFS( χ2=27.470, P<0.001) at 1, 3 and 5 years of pT1b tumors with different invasion depths. The recurrence rate of pT1b(23.8%) was significantly higher than that of pT1a(5.3%)( χ2=5.274, P=0.022). The distant metastasis rate of the former(10.9%) was also significantly higher than that of the latter(0)( χ2=4.494, P=0.034). There were significant differences in local recurrence rate( χ2=17.051, P<0.001) and distant metastasis rate( χ2=15.460, P<0.001) among pT1b patients with different infiltration depths. Logistic multivariate analysis showed that the depth of infiltration was an independent factor affecting the occurrence of local recurrence in stage pT1b patients after treatment( P<0.001). Pathological type( P=0.003) and infiltration depth( P=0.027) were independent factors affecting the occurrence of distant metastasis. Conclusion:pT1a period and pT1b period after the prognosis and treatment of patients with different failure modes, and pT1b period in patients with different infiltration depth and the prognosis of patients and its failure mode after treatment significantly related, infiltration depth of pT1b period after treatment in patients with the independence of the influencing factors of failure, suggest that clinical doctors should pay attention to pT1b period in patients with postoperative adjuvant therapy. This conclusion needs to be confirmed by large prospective studies of cases.

Objective:To evaluate the efficacy and prognostic factors of radiotherapy combined with immunotherapy as the first-line treatment for patients with locally advanced or metastatic esophageal squamous cell carcinoma (LA/M ESCC).Methods:A single-center, retrospective analysis was conducted for the recent efficacy, survival, prognostic factors, post-treatment failure modes, and treatment-related adverse reactions of 57 LA/M ESCC patients eligible for enrollment.Results:The entire group of patients had 1-, 2-, and 3-year overall survival (OS) of 86.0%, 57.5%, and 53.9%, respectively and 1-, 2-, and 3-year progression-free survival (PFS) of 61.4%, 31.0%, and 31.0%, respectively. The median OS was not reached, and the median PFS was 15.0 (95% CI: 10.77-19.23) months. These patients had an overall response rate (ORR) of 80.7% (46/57) and a disease control rate (DCR) of 94.7% (54/57). As indicated by the result of the multivariate analysis, the independent prognostic factors affecting the OS of the patients included their age, clinical stage, number of immunotherapy cycles, and recent efficacy ( HR = 0.25, 2.58, 0.35, 4.05, P < 0.05), and the independent factors influencing the PFS of the patients included their clinical stage and recent efficacy ( HR = 2.27, 1.97, P < 0.05). There were no statistically significant differences in the effects of irradiation ranges and the combination modes of immunologic drugs and chemoradiotherapy on both OS and PFS of the patients ( P > 0.05). A total of 32 patients suffered post-treatment failure. After the second treatment, they had 1- and 2-year OS of 55.7% and 25.3%, respectively, with median OS of 14.0 (95% CI: 5.17-22.83) months. A total of 26 cases experienced treatment-associated adverse reactions of grades 2 or higher during and after treatment. Conclusions:The combination of radiotherapy and immunotherapy is effective and safe as the first-line treatment for LA/M ESCC patients. The post-treatment failure modes still include local recurrence and distant metastasis. Therefore, such combination merits further investigation.

Objective:To evaluate the value of enhanced CT radiomics feature model for predicting 5-year overall survival (OS) of esophageal squamous cell carcinoma patients after radiotherapy.Methods:Clinical data of 218 patients with esophageal squamous cell carcinoma treated with radical chemoradiotherapy in the Fourth Hospital of Hebei Medical University from July 2016 to December 2017 were retrospectively analyzed. Patients were randomly divided into the training group ( n=153) or a validation group ( n=65) at a 7 vs. 3 ratio. Enhanced CT radiomics features were extracted. The data in the training group was used to construct the prediction model, and the data in the validation group were utilized to validate the efficiency of this model for predicting the 5-year OS of patients. The predictive performance of this model was assessed by the receiver operating characteristic (ROC) curve, consistency index (C-index), and decision curve analysis (DCA). Results:The 1-, 3-, 5-year OS rates were 67.0%, 33.4%, 24.9%. Five radiomic features were selected from extracted features in the training group to construct the radiomic signature (RS) for predicting 5-year OS. The area under the ROC curve (AUC) was 0.760 in the training group and 0.707 in the validation group, and the C-index was 0.680 and 0.684, respectively. The radiomics nomogram, which incorporated the RS with clinical risk factors, were established to predict the 5-year OS of esophageal squamous cell carcinoma patients after radiotherapy. The AUC was 0.782 in the training group and 0.751 in the validation group, and the C-index was 0.708 and 0.688, respectively. According to the optimal cutoff of the model, all patients were divided into the high risk and low risk groups. The 1-, 3-, 5-year OS rates were 86.5%, 65.4%, 28.9% in the low risk group, and 58.4%, 17.8%, 5.9% in the high risk group, and the differences were statistically significant (all P<0.001). Similar conclusions were obtained in the validation group (all P<0.001). Conclusion:Enhanced CT radiomics features can be utilized to construct the prediction model for 5-year OS of esophageal squamous cell carcinoma patients after radiotherapy, which can be applied in clinical practice.