BackgroundThis large retrospective study aimed to compare the long-term survival outcomes of esophageal squamous cell carcinoma (ESCC) patients with stage T4N0-3M0 treated with surgery followed by adjuvant chemoradiotherapy (S+CRT) versus definitive chemoradiotherapy (dCRT).MethodsPatients with T4N0-3M0 ESCC who received S+CRT or dCRT at our institution between January 2011 and December 2018 were included in the study.ResultsA total of 490 patients with stage T4N0-3M0 ESCC met the enrollment criteria, with 108 in the S+CRT group and 382 in the dCRT group. Overall survival (OS) and progression-free survival (PFS) were significantly better in S+CRT group compared to the dCRT group (P = 0.000, 0.003). After propensity score matching (PSM) analysis, 138 patients in the dCRT group and 81 patients in the S+CRT group were successfully matched. OS and PFS were again significantly better in the S+CRT group compared to the dCRT group (P = 0.002, 0.019).ConclusionsS+CRT is more likely to improve the overall prognosis of patients with T4N0-3M0 ESCC compared to dCRT. Treatment plan should be made based on a thorough consideration of both the patient’s condition and tumor characteristics, leading to individualized decisions.

This study investigates the functional role of FUNDC1 in the progression of esophageal squamous cell carcinoma (ESCC). Transcriptomic analysis using the Cancer Genome Atlas (TCGA) dataset revealed that FUNDC1 is significantly overexpressed in ESCC tissues and is associated with unfavourable patient prognosis. In vitro assays demonstrated that silencing FUNDC1 suppresses ESCC cell proliferation, migration, and invasion. Mechanistically, FUNDC1 knockdown was found to be associated with mitochondrial morphologic features suggestive of reduced fission and inhibits the epithelial-mesenchymal transition (EMT) process, both of which are critical for tumour metastasis. Further investigation revealed that FUNDC1 modulates EMT through the HMGB1/PI3K/Akt signaling pathway. Collectively, these findings indicate that FUNDC1 contributes to ESCC progression by regulating mitochondrial dynamics and EMT. Thus, FUNDC1 may represent a mechanistically relevant factor in ESCC progression and warrants further investigation as a therapeutic target. To this end, further studies involving clinical validation, in vivo models, and pharmacological inhibition are warranted to fully explore the therapeutic implications of targeting FUNDC1 in ESCC.

INTRODUCTION:As one of the most important treatments of Esophageal Squamous Cell Carcinoma (ESCC), the therapeutic effect of radiotherapy is still limited. FUN14 DomainContaining 1 (FUNDC1), a key regulator of mitophagy, has been implicated in tumor progression in several malignancies. However, its role in ESCC remains unclear. This study investigated the role of FUNDC1 in mitochondrial morphology, mitophagy, and radiosensitivity in ESCC cells. MATERIALS AND METHODS:We evaluated FUNDC1 expression in ESCC using bioinformatics and immunohistochemistry. The effects of FUNDC1 knockdown on malignant behavior were assessed through CCK-8, wound healing, and transwell assays. Flow cytometry analyzed cell cycle and apoptosis. Radiosensitivity was determined by colony formation assays with survival curve fitting using the Linear-Quadratic (LQ) model. DNA damage was assessed by γH2AX foci formation. Mitochondrial morphology and mitophagy were examined using live cell staining and immunofluorescence. Western blotting measured protein expression. RESULTS:FUNDC1 expression was elevated in multiple cancers. High FUNDC1 expression was associated with advanced tumor stage and showed an unfavorable survival trend in ESCC patients. In our clinical cohort, a significant association with overall survival was observed in the M0 subgroup. FUNDC1 knockdown inhibited proliferation, migration, and invasion, particularly after irradiation. It also enhanced IR-induced G2/M arrest, γH2AX foci formation, and apoptosis. Mechanistically, FUNDC1 knockdown attenuated IR-induced mitochondrial fission and mitophagy-related changes, accompanied by increased cytochrome c release and apoptosis. In addition, FUNDC1 knockdown was associated with reduced total HMGB1 expression, impaired HMGB1 nuclear-to-cytoplasmic translocation, and suppressed RAGE/ERK activation, and these changes were partially reversed by 14-3-3σ overexpression. DISCUSSION:Our findings suggest that FUNDC1 promotes malignant behavior and radioresistance in ESCC cells. FUNDC1 knockdown was accompanied by reduced mitochondrial fission, attenuated mitophagy-related changes, and enhanced apoptosis after irradiation. FUNDC1 may also modulate HMGB1/RAGE/ERK signaling through a mechanism involving 14-3-3σ, although the precise causal relationships remain to be established. CONCLUSION:FUNDC1 knockdown inhibited malignant behavior and enhanced radiosensitivity in ESCC cells, associated with altered mitochondrial morphology, reduced mitophagy-related changes, and suppression of HMGB1/RAGE/ERK signaling. FUNDC1 may serve as a potential target for radiosensitization in ESCC.

BACKGROUND:The current standard treatment for limited-stage small cell lung cancer (LS-SCLC) is concurrent chemoradiotherapy (cCRT) plus consolidation immunotherapy, with or without prophylactic cranial irradiation (PCI). However, it remains unknown whether administering immunotherapy concurrently with chemoradiotherapy confers additional benefit. This clinical trial is designed to investigate the efficacy and safety using durvalumab with chemoradiotherapy for LS-SCLC. METHODS:In this single-arm phase 2 study, patients with LS-SCLC received three (1-4) cycles of etoposide, cisplatin, or carboplatin, and durvalumab every 3 weeks, following by thoracic radiotherapy of 60.0 Gy to the gross tumor volume and 54.0 Gy to the planning target volume in 30 once-daily fractions and chemoimmunotherapy. After cCRT plus durvalumab, patients received durvalumab consolidation therapy every 3 weeks for a minimum of 1 year. PCI was recommended to patients with partial or complete response when chemoradiotherapy completed. Efficacy and adverse events were assessed. RESULTS:Overall, 51 patients were enrolled from March 1, 2021, to April 30, 2024, with a median follow-up of 32.0 months. The 1-, 2-, and 3-year progression-free survival (PFS) rates were 56.9%, 35.9%, and 28.2%, respectively, and the median PFS was 17.0 months. The 1-, 2-, and 3-year overall survival (OS) rates were 88.1%, 68.6%, and 49.6%, respectively, and the median OS was 32.0 months. There were 17 (33.4%) patients with grade 3 or 4 adverse events, 7 of which were immune‑related. CONCLUSIONS:These results suggest that the addition of durvalumab to chemoradiotherapy was well tolerated and showed encouraging efficacy, supporting further investigation in patients with LS-SCLC eligible for radical chemoradiotherapy.

Background The optimal integration of radiotherapy (RT) and immune checkpoint inhibitors (ICI) for esophageal squamous cell carcinoma (ESCC) remains undefined. This study aimed to evaluate treatment patterns, hematologic dynamics, and prognostic factors in patients receiving combined RT and ICI.Methods We conducted a multicenter retrospective analysis of 426 patients with unresectable ESCC treated with RT and ICI, with and without chemotherapy. Survival outcomes were compared between concurrent and Interval (chemo)radiotherapy ((C)RT) and ICI strategies. Hematologic parameters, including lymphocyte counts and the systemic inflammation score (SIS), were dynamically assessed at baseline, during RT, and post-RT. Prognostic factors for overall survival (OS) and progression-free survival (PFS) were analyzed using univariate and multivariate Cox regression models.Results Concurrent and Interval (C)RT-ICI strategies demonstrated comparable OS and PFS. Concurrent (C)RT-ICI was associated with a more pronounced decline in lymphocyte counts and a slightly higher incidence of adverse events, though generally manageable. Patients with isolated lymph node metastases achieved survival similar to those without metastasis and significantly better than those with organ metastases. During concurrent(C)RT-ICI, lymphocyte counts showed the most significant decline but gradually recovered 1-2 months after radiotherapy. Notably, SIS measured 1-2 months after RT emerged as a superior independent prognostic indicator for OS.Conclusions In real-world practice, concurrent (C)RT-ICI is a safe and feasible treatment option for ESCC, though associated with greater lymphocyte suppression. During ICI treatment, SIS assessed after RT may serve as a simple and reliable prognostic biomarker. Patients with isolated nodal metastases appear to derive substantial benefit from (C)RT-ICI, warranting further validation in prospective randomized trials.

BACKGROUND:Radioresistance is the primary cause of treatment failure in esophageal squamous cell carcinoma, emphasizing the importance of identifying effective radiosensitizers. OBJECTIVES:This study aimed to explore the effects and potential mechanisms of Eg5 inhibitor K858 on the radiosensitivity of esophageal squamous cell carcinoma TE-1 and KYSE150 cell lines, as well as xenografts (TE-1 cells). METHODS:Cellular function was assessed using CCK8, wound healing, and transwell invasion assays. Radiosensitivity parameters were derived from colony formation assays. Cell apoptosis and cell cycle were assessed using flow cytometry, whereas protein expression levels were detected using western blotting and immunohistochemistry. The xenograft model was used to observe the growth of tumors. RESULTS:K858 inhibited the malignant functions of TE-1 and KYSE150 cell lines. Radiosensitivity parameters were reduced after K858 treatment. The combination of K858 and irradiation markedly suppressed cell proliferation, induced apoptosis, and stimulated cell cycle arrest during the irradiation-sensitive phase. Additionally, K858, combined with irradiation, significantly increased the expression of the epithelial-mesenchymal transition marker E-cadherin and decreased the expression of N-cadherin, vimentin, MMP2, and MMP9. K858, combined with irradiation, significantly inhibited tumor growth in xenograft models. CONCLUSION:K858 enhanced the radiosensitivity of esophageal squamous cell carcinoma and affected the expression of epithelial-mesenchymal transition-related markers.

This study aimed to assess the effectiveness, safety, and recurrence patterns of first-line immunotherapy combined with chemoradiotherapy in esophageal squamous cell carcinoma (ESCC) patients. A retrospective analysis of 79 eligible ESCC patients was conducted. Primary outcomes included overall survival (OS) and progression-free survival (PFS), with secondary outcomes being objective response rate (ORR), disease control rate (DOR), treatment-related adverse events (trAEs), and treatment failure patterns. The median follow-up was 29.4 months, with median OS unreached and median PFS of 14.6 months (95% CI 10.7–18.5). ORR was 82.3%, and DOR was 96.2%. Factors affecting OS were clinical stage, immunotherapy cycles, immunotherapy and chemoradiotherapy sequence, radiation coverage, mid-treatment lymphocyte count, and short-term efficacy (HR = 2.254, 0.374, 2.653, 2.957, 2.309, 2.789; P = 0.030, 0.019, 0.009, 0.004, 0.001, 0.014). Factors impacting PFS were clinical stage, immunotherapy and chemoradiotherapy, and post-treatment lymphocyte count (HR = 2.135, 2.048, 1.911; P = 0.007, 0.010, 0.001). Among the cohort, 46.8% experienced treatment failure, with 33 receiving second-line treatment, resulting in a median OS of 14.17 months (95% CI 7.303–21.037) and 1- and 2-year OS rates of 56.7% and 24.3%. Notably, 36.7% experienced grade ≥ 2 trAEs, bone marrow suppression most commonly happened, and 5.1% developed esophageal fistulas. Immunotherapy combined with chemoradiotherapy demonstrates strong anti-tumor activity and tolerability in ESCC patients, The radiation for all leisions, sequential immunotherapy combined with chemoradiotherapy, and higher levels of lymph node cell counts are associated with a better prognosis. Large-scale randomized controlled trials are needed for further validation.

Actin-like protein 6A (ACTL6A) is thought to be associated with the survival and prognosis of patients with a variety of human cancers. This study investigates the effect of ACTL6A knockdown on ESCC radiosensitivity and explores molecular mechanisms that may enhance radiotherapy efficacy. The ACTL6A expression level was increased in esophageal squamous carcinoma cells after radiation irradiation. The protein expression level of ACTL6A in tumor tissue samples of clinical esophageal squamous cell carcinoma patients was analyzed by immunohistochemistry, and it was found that the prognosis of the high expression group was worse than that of the low expression group. Further knocking down the ACTL6A gene in esophageal squamous cell carcinoma cells, it was found that ACTL6A could regulate the proliferation, migration, invasion, DNA damage repair, cell cycle, and apoptosis of esophageal squamous cell carcinoma cells, which further affected the radiosensitivity of esophageal squamous cell carcinoma cells. Through functional enrichment analysis of gene set enrichment and validation of the mechanism using the Wnt pathway inhibitor XAV939, it was shown that ACTL6A is involved in the regulation of the Wnt/β-catenin signaling pathway. Knockdown of ACTL6A can inhibit the activity of this pathway, thereby increasing the radiosensitivity of esophageal squamous cell carcinoma. ACTL6A may become an important therapeutic target for esophageal squamous cell carcinoma, providing a necessary theoretical basis for future treatment strategies.

BACKGROUND:Definitive chemoradiotherapy is the standard treatment for unresectable, locally advanced esophageal cancer. However, radiotherapy (RT) often affects the immune system of patients. One of the possible mechanisms of lymphopenia after RT is that a large number of circulating lymphocytes in the systemic and pulmonary circulation will be killed by more sessions of low-dose radiation. The impact of dose-volume parameters of organs at risk (OARs) on absolute lymphocyte count (ALC) and the relationship between the extent of lymphocyte count reduction and survival prognosis in patients with middle and lower thoracic esophageal squamous cell carcinoma (ESCC) both remain difficult to determine. AIM:To determine the relationship between RT parameters, lymphocyte count and survival prognosis of esophageal cancer patients. METHODS:The clinical data of 112 patients with stage I-III ESCC who received definitive RT were analyzed retrospectively. The ALC values before RT, weekly during RT, and within 1 month after RT were determined. Logistic regression was used to evaluate the correlation between the parameters of radiation OARs and the lowest point of the ALC. Kaplan-Meier and Cox regression analyses were used to evaluate the relationship between the lowest point of the ALC and patient survival during RT. RESULTS:The median value of the ALC before treatment was 1.57 × 109 cells/L, and 32 patients (28.6%) showed grade 4 ALC reduction during RT. The reduction in G4 ALC during RT was significantly associated with poor overall survival (OS) and progression-free survival. Multivariate analysis showed that stage III tumors (P = 0.003), high heart V10 (P = 0.046), high lung V5 (P = 0.048), and high lung V20 (P = 0.031) were associated with G4 ALC reduction during RT. CONCLUSION:The reduction in G4 ALC is related to OS. Joint evaluation of the tumor stage and dose volume parameters has predictive value for G4 ALC reduction and OS.

This study aimed to investigate the role of immunotrophic inflammatory markers in assessing the prognosis and treatment-related toxicity in patients with esophageal squamous cell carcinoma (ESCC) undergoing first-line radiotherapy and chemotherapy combined with immunotherapy. We retrospectively enrolled 67 patients with ESCC and determined the optimal cutoff values for prognostic nutrition index (PNI), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) using receiver operating characteristic (ROC) curve analysis. Statistical analysis was performed using SPSS 25.0. The one-, two-, and three-year overall survival (OS) rates were 88.1%, 62.3%, and 57.6%, respectively. The overall effective rate was 82.1% (55/67). ROC curve analysis revealed optimal cutoff values for PNI, NLR, and PLR as 48.35, 3.84, and 150.49, respectively. Patients in the high PNI group, low NLR group and PLR group exhibited significantly higher mOS and mPFS time compared to the control group. Notably, the incidence of grade 2 toxicity and side effects in the PNI ≥ 48.35 group was significantly lower than that in the PNI < 48.35 group. Our findings suggest that pretreatment values of PNI, NLR, and PLR can serve as valuable biomarkers for evaluating the prognosis of ESCC patients undergoing first-line radiotherapy and chemotherapy combined with immunotherapy. Further studies with larger cohorts are warranted to validate these results.

BACKGROUND:This study aimed to compare the efficacies of neoadjuvant chemoradiotherapy (NCRT), chemotherapy (NCT), and chemoimmunotherapy (NCIT) in patients with locally advanced esophageal squamous cell carcinoma (LAESCC). The primary objective was to assess the overall survival (OS) among the three treatment groups. METHODS:A retrospective cohort of 625 patients treated at the Fourth Hospital of Hebei Medical University between 2016 and 2022 was analyzed. Patients received NCRT, NCT, or NCIT followed by radical esophagectomy. To adjust for confounding factors, inverse probability of treatment weighting (IPTW) was employed. Chi-square tests, Fisher's exact tests, and multivariate Cox survival analyses were used to assess prognostic factors and survival outcomes. RESULTS:Before IPTW, significant differences in baseline characteristics were observed among the three groups. After IPTW adjustment, differences were mitigated, allowing for a balanced comparison. NCIT demonstrated superior 4-year OS rate (91.4%) compared with NCRT (60.4%) and NCT (62.5%). The addition of adjuvant therapy further improved survival outcomes. CONCLUSIONS:NCIT may offer superior survival benefits over NCRT and NCT in patients with LAESCC, particularly when combined with adjuvant chemoimmunotherapy (ACIT). These findings underscore the potential of immunotherapy in multimodal treatment of LAESCC and warrant further investigation in prospective clinical trials.

BACKGROUND:Radiotherapy (RT) has been identified as a vital treatment for esophageal squamous cell carcinoma (ESCC), while the development of radioresistance remains a major obstacle in ESCC management. The aim of this study was to investigate the effect of NIMA-related kinase 2 (NEK2) on radioresistance in ESCC cells and to reveal potential molecular mechanisms.METHODS:Human esophageal epithelial cells (HEEC) and human ESCC cell lines were obtained from the Research Center of the Fourth Hospital of Hebei Medical University (Shijiazhuang, China). Cell Counting Kit-8 (CCK-8) and flow cytometry assays were applied to assess the proliferation ability, cell cycle, apoptosis rates, and ROS production of ESCC cells. The colony-forming assay was used to estimate the effect of NEK2 on radiosensitivity. Autophagy was investigated by western blotting analysis, GFP-mRFP-LC3 fluorescence assay, and transmission electron microscopy (TEM).RESULTS:In the present study, our results showed that NEK2 was associated with radioresistance, cell cycle arrest, apoptosis, ROS production, and survival of ESCC. NEK2 knockdown could significantly inhibit growth while enhancing radiosensitivity and ROS production in ESCC cells. Interestingly, NEK2 knockdown inhibited ESCC cell autophagy and reduced autophagic flux, ultimately reversing NEK2-induced radioresistance. Mechanistically, NEK2 bound to and regulated the stability of tripartite motif-containing protein 21 (TRIM21). The accumulation of NEK2-induced light chain 3 beta 2 (LC3B II) can be reversed by the knockdown of TRIM21.CONCLUSION:These results demonstrated that NEK2 activated autophagy through TRIM21, which may provide a promising therapeutic strategy for elucidating NEK2-mediated radioresistance in ESCC.

Abstract Background Oesophageal squamous cell carcinoma is one of the most commonly diagnosed carcinomas in China, and postoperative radiotherapy plays an important role in improving the prognosis of patients. Carcinomas in different locations of the oesophagus could have different patterns of lymph node metastasis after surgery. Methods In this multicentric retrospective study, we enrolled patients with middle thoracic oesophageal squamous cell carcinomas from 3 cancer centres, and none of the patients underwent radiotherapy before or after surgery. We analysed the lymph node recurrence rates in different stations to explore the postoperative lymphatic recurrence pattern. Results From January 1st, 2014, to December 31st, 2019, 132 patients met the criteria, and were included in this study. The lymphatic recurrence rate was 62.1%. Pathological stage (P = 0.032) and lymphadenectomy method (P = 0.006) were significant predictive factors of lymph node recurrence. The recurrence rates in the supraclavicular, upper and lower paratracheal stations of lymph nodes were 32.6%, 28.8% and 16.7%, respectively, showing a high incidence. The recurrence rate of the subcarinal node station was 9.8%, while 8.3% (upper, middle and lower) thoracic para-oesophageal nodes had recurrences. Conclusions We recommend including the supraclavicular, upper and lower paratracheal stations of lymph nodes in the postoperative radiation field in middle thoracic oesophageal carcinomas. Subcarinal station is also potentially high-risk, while whether to include thoracic para-oesophageal or abdominal nodes needs careful consideration.

Cervical and upper thoracic esophageal cancer (ESCA) presents treatment challenges due to limited clinical evidence. This multi-center study (ChC UES) explores radical radio(chemo)therapy efficacy and safety, especially focusing on radiation dose. We retrospectively analyzed clinical data from 1,422 cases across 8 medical centers. According to the radiation dose for primary gross tumor, patients were divided into standard dose radiotherapy (SD, 50–55 Gy) or high dose (HD, > 55 Gy) radiotherapy. HD was further subdivided into conventional- high-dose group (HD-conventional, 55–63 Gy) and ultra-high-dose group (HD-ultra, ≥ 63 Gy). Primary outcome was Overall Survival (OS). The median OS was 33.0 months (95

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 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.

Objectives The NEK2 (never in mitosis gene A-related kinase 2), a serine/threonine kinase involved in chromosome instability and tumorigenesis. Hence, this study aimed to explore the molecular function of NEK2 in esophageal squamous cell carcinoma (ESCC). Methods By available transcriptome datasets (GSE53625 cohort, GSE38129 cohort, and GSE21293 cohort), we analyzed the differentially expressed genes in invading and non-invading ESCC. Subsequently, we evaluated the association between NEK2 expression level and clinical outcomes through Kaplan–Meier analysis method. The quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB) analyses were performed to determine the expression levels of NEK2 mRNA and protein, respectively. We knocked down the NEK2 expression in ESCC cells (ECA109 and TE1), and evaluated the NEK2 biology function associated with ESCC cell proliferation, migration, invasion, and colony formation abilities. Finally, the downstream pathway of NEK2 was analyzed through Gene Set Enrichment Analysis (GSEA) and validated the regulatory mechanism of NEK2 on the potential pathway through WB. Results We found that NEK2 was highly expressed in ESCC cells compared with human esophageal epithelial cells (HEEC) (P < 0.0001), and high NEK2 expression was remarkably associated with poor survival (P = 0.019). Knockdown of NEK2 showed the significant inhibitory effect for tumorigenesis, and suppressed the ESCC cells proliferation, migration, invasion, and formation of colonies abilities. Additionally, GSEA revealed that Wnt/β-catenin pathway was a downstream pathway of NEK2. WB results further validated the regulatory mechanism of NEK2 for Wnt/β-catenin signaling. Conclusions Our results indicated that NEK2 promotes ESCC cell proliferation, migration and invasion by activating the Wnt/β-catenin pathway. NEK2 could be a promising target for ESCC.

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.

目的 探讨治疗前小野寺预后营养指数(PNI)对接受根治性放化疗颈胸上段食管鳞癌(CUTESCC)患者预后的影响和对≥2级放射性食管炎发生的预测价值.方法 回顾性分析河北医科大学第四医院2012年1月至2017年12月符合入组条件的163例CUTESCC患者的资料.应用受试者操作特征(ROC)曲线计算PNI预测患者预后的最佳截止值,对患者的预后进行单因素和Cox多因素分析.logistic二元回归模型用于单因素和多因素分析≥2级放射性食管炎(RE)的危险因素,将logistic多因素分析中具有统计学意义的因素用来构建预测≥2级RE的列线图.结果 PNI的最佳截止值为48.57[曲线下面积(AUC)=0.653,P＜0.001].全组患者中位总生存(OS)和无进展生存(PFS)期分别为26.1、19.4个月.PNI≥48.57组(47例)患者的 OS(x2=6.900,P=0.009)和 PFS(x2=9.902,P=0.003)均显著优于PNI＜48.57组(116例).Cox多因素分析显示,患者cTNM分期和PNI为影响患者OS(HR=1.513,95％CI为 1.193～1.920,P=0.001;HR=1.807,95％CI为 1.164～2.807,P=0.008)和PFS(HR=1.595,95％CI为 1.247～2.039,P＜0.001;HR=2.260,95％CI为 1.439～3.550,P＜0.001)的独立性预测指标,近期疗效为影响患者PFS的另一独立性指标(HR=2.072,95％CI为1.072～4.003,P=0.030).logistic多因素分析显示,病变最大横径(OR=3.026,95％CI 为 1.266～7.229,P=0.013)、大体肿瘤体积(GTV)(OR=3.456,95％CI为 1.373～8.699,P=0.008)、处方剂量(OR=3.124,95％CI为 1.346～7.246,P=0.009)和 PNI(OR=2.072,95％CI为1.072～4.003,P=0.030)是影响患者出现≥2级RE的独立性因素.将这4项指标纳入列线图模型:ROC曲线分析显示,该模型可以较好地预测患者≥2级RE的发生(AUC=0.686,95％CI为0.585～0.787);校正曲线显示,实际观测值与预测RE之间具有良好的一致性;决策曲线分析显示,在大多数阈值概率中列线图正净收益令人满意.结论 治疗前小野寺PNI为接受根治性放化疗颈胸上段食管鳞癌患者的独立性预后影响因素;病变最大横径、GTV、处方剂量和PNI这4项指标为本组患者出现≥2级放射性食管炎的危险因素,建立包含这些因素的预测模型,预测价值更大.

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.