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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Small cell lung cancer (SCLC) is highly malignant, aggressive and prone to brain metastasis. Several guidelines recommend prophylactic cranial irradiation (PCI) as the standard treatment for SCLC patients who have achieved complete remission after initial systemic treatment. However, in the modern era, magnetic resonance imaging (MRI) has been commonly applied in the diagnosis of brain metastasis, while radiotherapy combined with immunotherapy and molecular targeted therapy are widely adopted in the treatment of lung cancer. The value of PCI in SCLC has been questioned and challenged. In addition, the application of hippocampal avoidance and drugs to reduce the damage of neurocognitive function after PCI has also become a research hotspot. In this article, the research progress on PCI was reviewed with the latest literature, aiming to provide reference for selecting the most suitable individualized treatment for patients receiving PCI.
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Objective:To investigate the relationship between systemic immune-inflammation index (SII) and the prognosis of esophageal cancer patients treated with radical radiotherapy and to predict the prognosis of the patients using the SII combined with clinical staging.Methods:A retrospective analysis was conducted for 248 patients with esophageal cancer who were admitted to the Department of Radiotherapy in the Fourth Hospital of Hebei Medical University between 2014 and 2016. These patients included 146 males and 102 females, with a median age of 67 years. Among them, 134 patients received concurrent chemotherapy and 114 patients received radiotherapy alone. The SII before radiotherapy was defined as platelet count × neutrophil count/lymphocyte count. The patients were divided into a low-SII group and a high-SII group according to the optimal cutoff value of pretreatment SII determined by the receiver operating characteristics (ROC) curve. Survival analysis was calculated using the Kaplan-Meier method, and the Cox proportional hazards model was used for multivariate analysis. For these patients, the prognosis effects and the predictive value for survival of different SII levels combined with TNM staging were compared.Results:According to the ROC curves, the optimal cutoff value of SII before radiotherapy was 740.80. Based on this number, the patients were divided into a low-SII group (< 740.80, 150 cases) and a high-SII group (≥ 740.80, 98 cases). The objective response rate of the low-SII group was significantly higher than that of the high-SII group (86.0% vs 75.5%, χ2=4.39, P=0.036). The 1-, 3-, and 5-year overall survival (OS) rates of the low-SII group were 78.6%, 45.6%, and 32.3%, respectively. These rates were significantly higher than the corresponding rates of the high-SII group, which were 71.0%, 28.3%, and 16.4% ( χ2=11.22, P=0.001), respectively. Moreover, the 1-, 3- and 5-year progression-free survival (PFS) rates of the low-SII group were 67.0%, 36.9%, and 32.0%, respectively. Again, these rates were significantly higher than those of the high-SII group, which were 45.5%, 17.5%, and 12.5% ( χ2=15.38, P < 0.001), respectively. Multivariate analysis showed that TNM staging, treatment method, and SII were independent prognostic factors for OS and PFS ( HR=1.39-1.60, P<0.05). Patients with low SII and early clinical staging had a better prognosis than other subgroups ( χ2=13.68, 13.43, P=0.001). The area under curve (AUC) of SII combined with TNM staging (0.70) was higher than that of SII (0.63) and TNM staging (0.62) ( Z=2.48, 2.57, P < 0.05). Conclusions:Pretreatment SII has a high predictive value for the prognosis of esophageal cancer after radiotherapy, and higher SII indicates a worse prognosis. Thus, combining SII with TNM staging can improve the prediction accuracy of the prognosis of esophageal cancer patients.
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Objective:To investigate the effects of the systemic immune-inflammation index (SII)on the long-term survival in esophageal cancer patients treated with radiotherapy.Methods:Aretrospective review was conducted for the clinical data of 303 patients with esophageal squamous cell carcinoma(ESCC)who received radical radiotherapy in the Fourth Hospital of Hebei Medical University from 2011 to 2017. These patients were divided into a high-SII group and a low-SII group according to their SII before radiotherapy. The correlation between SII and survival was determined using the Kaplan-Meier method and Cox regression model. Propensity score matching (PSM) was applied to reduce bias from measured confounding.Results:The SII of patients before radiotherapy was correlated significantly with T stage ( χ2=8.015, P=0.018) and TNM stage ( χ2=8.619, P=0.013). The 1-, 3-, 5-year overall survival (OS) rates in the high-SII group were 64.9%, 27.1%, and 19.4%, respectively. They were significantly lower than those in the low-SII group, which were 84.9%, 43.9%, and 30.5%, respectively (χ 2=13.443, P<0.001). The 1-, 3-, 5-year progression-free survival (PFS) rates in the high-SII group were 46.4%, 20.3%, and 13.3%, respectively. They were significantly lower than those in the low-SII group, which were 67.8%, 34.8%, and 26.5%, respectively (χ 2=12.383, P<0.001). The multivariate analysis indicated that the independent factors influencing the OS and PFS included T stage, lymph node metastasis, chemotherapy, and SII.After PSM was applied, the OS and PFS in the high-SII group were still lower than those in the low-SII group(χ 2OS=4.264, P=0.039; χ 2PFS=5.376, P=0.020), and the multivariate analysis showed that SII was a significant predictor for OS and PFS( HROS=1.357, P=0.037; HRPFS=1.393, P=0.022). Conclusions:SII is a significant independent influencing factor of the OS and PFS inESCC patients treated with received radiotherapy. Based on simple and inexpensive standard laboratory measurements, SII can be a promising marker for ESCC patients.
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Objective:To investigate the recurrence-free survival (RFS) and influencing factors of intensity-modulated radiotherapy±chemotherapy (IMRT±C) for the upper thoracic esophageal cancer.Methods:The medical records of 168 patients with cervical and upper thoracic esophageal cancer who met the inclusion criteria from January 2011 to December 2015 were retrospectively analyzed. The RFS was calculated by the Kaplan-Meier method. Multivariate prognostic analysis was performed by Cox models. The recurrence factors were identified by the Logistics model. Results:The 1-, 3-, and 5-year RFS rates were 67.8%, 38.0%, and 20.4%, respectively, and the median RFS was 21.9 months. The locoregional recurrence rate was 47.6%(80/168). The recurrence sites were local esophagus ( n=63), regional lymph nodes ( n=7), and local esophagus+ regional lymph node recurrence ( n=10). Multivariate analysis showed that hoarseness, cTstaging, combined with chemotherapy, 95%PTV 1 exposure dose and GTV average exposure dose were the influencing factors of RFS ( P=0.029, <0.001, 0.031, 0.038, 0.020). Logistics model showed that cTstaging, cNstaging, short-term efficacy, irradiationmethod, GTV maximum transverse diameter and PTV average exposure dose were the influencing factors of recurrence ( P=0.046, 0.022, 0.001, <0.001, 0.012, 0.001). Conclusions:Patients with cervical and upper thoracic esophageal cancer treated with radical IMRT combined with/without chemotherapy have a higher locoregional recurrence rate, and the recurrence rate is mainly the esophagus. The independent factors that affect RFS are different from the risk factors of recurrence.
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Objective:To study the prognostic impact of prognostic nutritional index (PNI) before radiotherapy in clinical stage Ⅲ esophageal cancer patients.Methods:We retrospectively reviewed 125 esophageal cancer patients with clinical stage Ⅲ undergoing definitive radiotherapy in Fourth Hospital of Hebei Medical University from 2013 to 2017. The PNI and nutritional risk index (NRI) were calculated before radiotherapy. The optimal cutoff value of PNI was determined by time-dependent receiver operating characteristics (ROC) at 49.925.The patients were divided into low PNI group(PNI<49.925) and high PNI group (PNI≥49.925). Based on NRI, the patients were divided into normal NRI group (NRI≥100) and abnormal NRI group (NRI<100). Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS) and to perform univariate analysis. The mutlivariate analysis was performed by Cox regression model.Results:PNI was positively correlated with hemoglobin ( r=0.505, P<0.001) and NRI ( r=0.594, P<0.001). The 1-, 3- and 5-year OS rates in the low PNI group were significantly lower than those of the high PNI group (67.5%, 27.3%, 11.4% vs. 85.4%, 45.8%, 27.4%, respectively, χ2=8.569, P<0.05). Moreover, the 1-, 3- and 5-year PFS rates in the low PNI group were obviously higher than those in the high PNI group (59.7%, 23.2%, 4.9% vs. 79.2%, 35.4%, 24.9%, respectively, χ2=6.715, P<0.05). Univariate analysis showed that GTV, radiotherapy dose, chemotherapy, albumin, NRI and PNI were significantly correlated with OS and PFS (OS: χ2=6.822, 4.326, 4.474, 13.123, 8.846, 8.569, P<0.05: PFS: χ2=7.869, 4.636, 5.874, 10.911, 8.544, 6.715, P<0.05). Multivariate analysis showed that GTV, radiotherapy dose and PNI were independent prognostic factors for OS ( P<0.05). And GTV, radiotherapy dose, chemotherapy and PNI were independent prognostic factors for PFS ( P<0.05). Conclusions:The PNI before radiotherapy is a significant and independent predictor for survival of clinical stage Ⅲ esophageal cancer patients. Based on simple and inexpensive standard laboratory measurements, PNI could be a promising prognostic biomarker for esophageal cancer patients.
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Objective:To analyze the therapeutic effects and prognosis after radiotherapy (chemotherapy) of patients with postoperative recurrent esophageal cancer.Methods:This study analyzed 501 patients with postoperative recurrent esophageal cancer who were treated in the Radiotherapy Department of the Fourth Hospital of Hebei Medical University and met enrollment conditions. Among them, 274 patients received concurrent chemotherapy and radiotherapy. The analyses in this study focused on the survival after the retreatment, postoperative recurrence patterns, prognosis of retreatment, and prognostic factors affecting the retreatment. Meanwhile, statistical analysis was conducted using the software SPSS Statistics 19.0.Results:The time of postoperative recurrence was 0.3-87.4 months, with a median number of 11.6 months. The median survival time was 12.1 months after the retreatment. Among all the patients, 344 patients suffered from only local recurrence, while the remaining 157 patients experienced distant metastasis. According to multivariate analysis result, independent prognostic factors included gender, pN stage, lymph node positive logarithmic ratio (LODDS), the number of chemotherapy cycles, time of recurrence, and distant metastasis ( P < 0.05). Meanwhile, prognostic factors affecting the 344 patients with only local recurrence included the time of recurrence, the number of chemotherapy cycles, and prescription dose ( χ2=22.605, 13.957, 10.446; P< 0.05). The remaining 157 patients suffered from distant metastasis. The 1-, 3-, and 5-year survival rates of them were 43.3%, 9.1%, and 5.5%, respectively, and those of the patients with only local recurrence were 53.6%, 22.6%, and 16.4%, respectively. The differences were statistically significant (χ 2=10.786, P< 0.05). Conclusions:Radiotherapy (chemotherapy) is safe and effective for the treatment of recurrent esophageal cancer. However, it features poor prognosis for male patients with a late pN stage, a high LODDS, the number of chemotherapy cycles ≤ 2, the time of recurrence≤ 24 months, and distant metastasis.
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Objective:To evaluate the effects of different irradiation doses on postoperative local recurrence in patients with esophageal cancer after radio (chemo) therapy.Methods:Clinical data of 331 esophageal cancer patients presenting with postoperative local recurrence admitted to our hospital from 2009 to 2014 were collected. The recurrence site, the effects of different radiotherapy doses on the prognosis of patients and the independent prognostic factors were retrospectively analyzed. The survival rate was calculated by Kaplan-Meier method. Univariate prognostic analysis was performed by log-rank test. Multivariate prognostic analysis was conducted by Cox proportional hazard regression model.Results:The 1-, 3-and 5-year overall survival rates were 54.3%, 23.2% and 16.6%, respectively. The median overall survival was 13.4 months (95% CI: 11.7-15.0). The median survival of patients with radiotherapy doses< 60 Gy and ≥60 Gy was 10.8 and 13.9 months ( P=0.013). Stratified analysis showed that patients with age< 60 years, no smoking history, no drinking history, no family history, upper thoracic segment, left thoracotomy, N 0 staging, log odds of positive lymph nodes (LODDS)< 0.030, recurrence time ≥ 13.1 months and recurrence site ≥ 2 had better prognosis when receiving radiotherapy dose ≥ 60 Gy ( P=0.038, 0.033, 0.001, 0.003, 0.018, 0.010, 0.041, 0.039, 0.043 and 0.007). Moreover, the short-term clinical efficacy of patients treated with ≥60 Gy dose was significantly better than that of those with<60 Gy dose ( P<0.001), which did not increase the incidence of ≥grade 2 radiation-induced gastritis ( P=0.977) or radiation-induced pneumonitis ( P=0.444). Cox multivariate analysis showed that the LODDS size, prescription dose and short-term efficacy were the independent factors affecting clinical prognosis of patients ( P=0.006, 0.008 and<0.001). Conclusions:The recommended dose for esophageal cancer patients with local recurrence after radiotherapy (chemotherapy) is greater than or equal to 60 Gy. The results of this study need to be confirmed by prospective studies with a large sample size.
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Objective:To explore the benefit groups of patients with locoregional recurrence of esophageal thoracic squamous cell carcinoma who received radiotherapy or chemoradiotherapy with different patterns of irradiation.Methods:Clinical data of 344 esophageal thoracic squamous cell carcinoma patients with postoperative recurrence who received intensity conformal radiotherapy or concurrent chemoradiotherapy in the Fourth Hospital of Hebei Medical University from 2009 to 2014 were retrospectively analyzed. The distribution of recurrence sites and prognostic factors were analyzed. A stratified analysis was carried out on the benefit groups of patients receiving the elective nodal irradiation (ENI) and involved field irradiation (IFI).Results:276 cases (80.2%) recurred at a single site and 68 cases (19.8%) recurred at more than two sites. The follow-up rate was 96.2%. The 1-, 3-and 5-year overall survival rates were 53.6%, 22.6% and 16.4%, respectively, with a median of 12.8 months (95% CI: 11.3-14.3 months). The 1-, 3-and 5-year local recurrence-free survival rates were 46.5%, 16.9% and 12.0%, respectively, with a median of 11.0 months (95% CI: 9.6-12.4 months). The 1-, 3-and 5-year progression-free survival rates were 39.8%, 11.3% and 6.7%, respectively, with a median of 7.9 months (95% CI: 5.8-10.0 months). Multivariate analysis showed that gender, the log odds of metastatic lymph nodes (LODDS) and the number of chemotherapy cycles were the independent prognostic factors ( P=0.003, <0.001, <0.001). Subgroup univariate analysis demonstrated that patients with an esophageal lesion length<5.0 cm, N 0 stage, the number of surgically-dissected lymph nodes of ≤9, the number of postoperative positive lymph node metastasis site of 0, and LODDS≤0.030 obtained benefits from ENI ( P=0.032, 0.012, 0.001, 0.012 and 0.014). Patients with the number of surgically-dissected lymph nodes of ≥16 achieved benefits from IFI ( P=0.035). Conclusions:Radiotherapy is an effective treatment mode for patients with local recurrence after esophageal cancer surgery. For patients with preoperative esophagography showing shorter esophageal lesions, earlier postoperative pathological N stage, lower LODDS score, and fewer surgically-dissected lymph nodes probably obtain more benefits from ENI than IFI. However, patients with more surgically-dissected lymph nodes may obtain more benefit from IFI compared with ENI.
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Objective:To examine the effect of FAM83D knockdown on proliferation, survival ability and invasion of human esophageal squamous cell carcinoma after X-ray radiation, and explore the mechanism.Methods:The expression of FAM83D, E-cadherin and vimentin in tumor tissues was detected in 69 cases of esophageal squamous cell cancer by using immunohistochemical method. The siRNA based on the sequences of the FAM83D mRNA were synthesized to transfect into the cultured ECA109 cells as FAM83D shRNA group. The effect of silencing FAM83D gene was evaluated to determine the protein levels of FAM83D in the human oesophageal squamous cell carcinoma ECA109 and KYSE30 cells using western blotting. MTS, clone formation, and Transwell assay were employed to examine the proliferation, survival ability and invasion of ECA109 and KYSE30 cells in vitro, respectively. We used flow cytometry assay to analyze distribution of cell apoptosis in different groups. Western blotting was used to examine the expression of cell metastasis-related molecules and apoptosis-related protein. Results:The strong expression rates of FAM83D, E-cadherin, and vimentin were 55%(38/69), 36%(25/69) and 61%(42/69) in the tumor tissues, respectively. FAM83D protein expression was significantly and negatively correlated with the expression of E-cadherin ( r=-0.350, P<0.01), and positively with the expression of vimentin ( r=0.470, P<0.01). Western blotting results demonstrated that silencing FAM83D gene significantly reduced the FAM83D protein expression ( P<0.01). MTS data demonstrated that FAM83D knockdown after irradiation significantly inhibited the proliferation of esophageal squamous cell carcinoma ECA109 and KYSE30 cells ( P<0.05). The data from the clone formation assay revealed that the radiosensitivity was increased after downragulation of FAM83D expression ( P<0.01). In addition, the invasive abilities of oesophageal carcinoma cells transfected with FAM83D shRNA after irradiation were significantly inhibited compared with those of the NC group ( P<0.01), followed by the downregulation of N-cadherin, vimentin, Snail, p-Akt and p-GSK-3β expression, and the upregulation of E-cadherin expression ( P<0.01). The apoptosis rate of tumor cells in FAM83D shRNA group after irradiation was markedly increased ( P<0.01), followed by a decrease of Bcl-2 and Mcl-1 expression and an increase of Cleaved caspase-3 expression ( P<0.01). Conclusions:FAM83D expressions was found to be closely related to the invasion and development of ESCC. Furthermore, siRNA interference technology inhibited the expression of FAM83D gene in oesophageal squamous cell carcinoma cells, reduced the proliferation, invasion of cells, induced cell apoptosis, and increased radiosensitivity, which may be associated with regulating the epithelial-mesenchymaltransition via Snail/Akt/GSK-3β signaling pathways.
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Objective:To investigate the relationship between Onodera′s prognostic nutritional index (PNI) and prognosis of patients with esophageal squamous cell carcinoma (ESCC) after definitive chemoradiotherapy or radiotherapy, aiming to provide a convenient, effective and accurate predictive indicator for evaluating the long-term survival of patients after treatment.Methods:Clinical data of 231 ESCC patients treated with definitive chemoradiotherapy or radiotherapy at the Fourth Hospital of Hebei Medical University from 2013 to 2015 were retrospectively analyzed. The PNI values of each patient at different radiotherapy periods were calculated and the ROC curve was used to determine the optimal cutoff value of PNI before radiotherapy, 231 patients were divided into the better-nourishment group ( n=86) and worse-nourishment group ( n=145). Kaplan- Meier method was used for survival analysis. Cox proportional hazards model was utilized to analyze the relationship between different nutritional status and prognosis. The short-term clinical efficacy and incidence of acute toxicities were statistically compared between two groups. Results:The mean values of PNI before, at week 3, week 6 and 1 month after radiotherapy were48.68±5.08, 39.68±4.87, 43.74±4.89 and48.31±4.92, respectively. The optimal cutoff value of pretreatment PNI was 49.25, the area under the curve (AUC) was 0.655, the sensitivity and specificity were 68.6% and 60.9%, respectively. The 5-year overall survival (OS) and progression-free survival (PFS) rates in the better-nourishment group (PNI≥49.25) were 36.0% and 31.3%, significantly better than 19.3% and 18.6% in the worse-nourishment group (PNI<49.25)( P=0.001, P=0.039). Multivariate analysis showed PNI before the therapy was an independent prognostic factor for OS ( P=0.021). Stratified analysis demonstrated that Stage Ⅰ/Ⅱ and concurrent chemotherapy patients in the better-nourishment group all obtained significantly better OS than their counterparts in the worse-nourishment group ( P=0.007, P=0.004). In addition, the objective response rate in the better-nourishment group was significantly higher than that in the worse-nourishment group ( P=0.047), whereas the incidence of ≥3 grade radiation esophagitis was lower than that in the worse-nourishment group ( P=0.060). Conclusions:Pretreatment PNI is a convenient and reliable indicator for predicting the long-term survival of ESCC patients after definitive chemoradiotherapy or radiotherapy. Patients with higher PNI have relatively better prognosis and radiotherapy tolerance, especially in those with early stage or concurrent chemotherapy.
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Objective To study the relationship between the dose-volume indexes and acute toxicity of intrathoracic stomach in esophageal cancer patients receiving radiotherapy after esophagectomy.Methods A total of 104 patients treated with postoperative radiotherapy followed by radical esophagectomy were enrolled.The dose-volume indexes of intrathoracic stomach were collected from treatment planning system.The ROC curve and logistic regression were performed to analyze the relationship between acute toxicity of intrathoracic stomach and clinical parameters,dose-volume indexes.Results A total of 29 patients (27.88 ％) suffered from grade 2 or above acute toxicity.The ROC curve analysis showed that the dose-volume indexes including D D L5-L45 and V5-V50were associated with occurrence of grade 2 or above acute toxicity,The univariate analysis showed that location,D D L5-L45 and V5-V50 were significantly correlated with the incidence of grade 2 or above acute toxicity (P＜0.05).The multivariate analysis showed that location,L5 and V35 were independent factors for incidence of grade 2 or above acute toxicity.The ROC curve analysis showed that cut-off values of L5 and V35 were 14.00 cm and 44.00％,respectively.And the rates of Grade 2 or above acute toxicity were 20.00％ for L5＞ 14.00 cm and 38.64％ for L5 ≥ 14.00 cm (x2 =4.473,P＜0.05),14.08％ for V35＜44.00％ and 57.58％ for V35 ≥44.00％ (x2 =7.263,P＜0.05),respectively.The incidence of grade 2 or above acute toxicity was significantly higher in post-mediastinum stomach group than the other two groups (x2 =12.881,P＜0.05).Conclusions Dosevolume index may be indicator to predict acute toxicity of intrathoracic stomach.It is recommended that post-mediastinum stomach should be chosen carefully if esophageal cancer patients require postoperative radiotherapy.