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.
ObjectiveTo investigate the impact of clinicopathological factors on the prognosis of patients with single-organ oligometastasis of esophageal cancer (soOMEC) following surgery and to develop prognostic nomograms.MethodsThis was a retrospective analysis of 144 patients with soOMEC after surgery in a single center who met the inclusion criteria. First, Cox univariate and multivariate models were used to analyze (SPSS 25.0 statistical software) the characteristics of patients, and independent prognostic factors for postoperative overall survival (OS) and OS after oligometastasis (OM-OS) were determined. Prognosis was analyzed using R language software, nomograms were created based on the Cox multivariate analysis results, a bootstrap method (b=200) was used for internal validation, and receiver operating characteristic (ROC) and calibration curves were used to validate the models.ResultsFrom January 2014 to December 2017, a total of 1595 patients with esophageal cancer received R0 resection. As of the end of the follow-up period, 144 patients had single-organ oligometastasis (soOM). The median time to oligometastasis (TTO) in the whole group of patients was 14.2 months, and the 1-, 3-, and 5-year OS rates were 75.7%, 28.2%, and 13.3%, respectively. The median OS was 25.0 months (95% confidence interval (CI): 21.8-28.2); the 1-, 2-, and 3-year OS rates after distant metastasis (DM-OS) were 25.5%, 13.3%, and 7.2%, respectively, and the median DM-OS was 5.5 months (95% CI: 3.9-7.1). The Cox multivariate analysis results showed that three indicators, i.e., TNM stage (hazard ratio (HR)=2.192, 95% CI: 1.441-3.336, P=0.000), TTO (HR=0.119, 95% CI: 0.073-0.194, P=0.000), and treatment after DM (HR=0.784, 95% CI: 0.970-0.025, P=0.025) were independent prognostic factors affecting the OS of patients; TTO (HR=0.669, 95% CI: 0.455-0.984, P=0.041) and treatment after DM (HR=0.713, 95% CI: 0.559-0.910, P=0.007) were independent prognostic factors affecting the DM-OS of patients. Using the Cox multivariate analysis results, prediction nomograms for total OS and DM-OS of patients were established. In the validation of the nomogram models, the areas under the curve (AUCs) for the 1-, 3-, and 5-year total OS were 0.930, 0.927, and 0.928 in the training set and 0.705, 0.856, and 1 in the validation set, respectively; the AUCs for the 1-, 2-, and 3-year DM-OS were 0.904, 0.923, and 0.908 in the training set and 0.928, 0.842, and 0.895 in the validation set, respectively. The results showed that the two models have strong discriminative ability and good clinical promotion and application value.ConclusionsAggressive local therapy combined with systemic chemotherapy can benefit patients with soOMEC after surgery, and for patients with OM appearing at 1 year after surgery, aggressive radiotherapy or combined chemotherapy is expected to improve the prognosis and prolong OS. The nomogram models developed in this study demonstrated strong predictive performance in internal validation and hold potential as clinical tools for estimating the prognosis of patients and assisting in treatment decision-making. However, their true clinical utility and generalizability require further validation through larger, multicenter, and prospective studies.
Background:Among cancers, lung cancer has the second highest incidence rate and the highest mortality rate in the world. Identifying suitable biomarkers to assist in the prognostic prediction of lung cancer is crucial for developing individualized treatment plans. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score has been applied to predict patient prognosis across a variety of cancers. This study aimed to investigate the predictive value of the HALP score for the prognosis of patients with stage III squamous cell lung cancer. Methods:The clinical data of patients with stage III squamous lung cancer who had undergone radical radiotherapy at the Department of Radiotherapy of The Fourth Hospital of Hebei Medical University from January 2011 to December 2020 were retrospectively analyzed. The optimal cutoff values for continuous variables were determined using X-Tile software. A Cox proportional hazards model was used for univariate and multivariate analysis, the Kaplan-Meier method was used for survival analysis, and log-rank test was used to check for differences. Results:A total of 206 patients were included in this study, and the cutoff value for the HALP score was 24.3. There were statistically significant differences between the high- and low-HALP-score groups in terms of alcohol consumption history, tumor-node-metastasis (TNM) stage, prognostic nutritional index (PNI) score, and systemic immune-inflammation index (SII) score. The median overall survival (OS) was 11.0 and 22.0 months in the low- and high-HALP-score groups, respectively (P<0.001), and the median progression-free survival (PFS) was 8.0 and 13.0 months, respectively (P=0.002). Univariate analysis showed that a low HALP score was significantly associated with OS [hazard ratio (HR) =1.698, 95% confidence interval (CI): 1.261-2.286; P<0.001] and PFS (HR =1.584, 95% CI: 1.176-2.132; P=0.002) in patients with stage III lung squamous carcinoma, while the multivariate analysis showed that a low HALP score was the most important factor in OS (HR =1.538, 95% CI: 1.137-2.079; P=0.005) and PFS (HR =1.399, 95% CI: 1.033-1.895; P=0.03) as independent predictors of poor prognosis. Conclusions:In patients with stage III squamous cell lung cancer treated with radical radiotherapy, low baseline HALP score is associated with its poorer OS and PFS and may thus be valuable prognostic factor.
Background:Surgery is commonly used to treat stage I lung cancer patients, whereas radiotherapy is applied to treat stage III lung cancer patients. However, few advanced-stage lung cancer patients benefit from surgery. This study aimed to investigate the efficacy of surgery for stage III-N2 non-small cell lung cancer (NSCLC) patients.Methods:A total of 204 patients with stage III-N2 NSCLC were included and divided into surgery (n=60) and radiotherapy (n=144) groups. The clinical characteristics [tumor node metastasis (TNM) stage, and adjuvant chemotherapy] and basic information (gender, age, and smoking/family history) of the included patients were evaluated. Furthermore, the patients' Eastern Cooperative Oncology Group (ECOG) scores and comorbidities were also evaluated, and the Kaplan-Meier approach was utilized to analyze their overall survival (OS). A multivariate Cox proportional hazards model was generated to analyze OS.Results:There was a significant difference in disease stages (IIIa and IIIb) between the surgery and radiotherapy groups (P<0.001). Compared with the surgery group, there were more patients with ECOG scores of 1 and 2 and fewer patients with ECOG scores of 0 in the radiotherapy group (P<0.001). Moreover, there was a significant difference in comorbidities between the stage III-N2 NSCLC patients in the two groups (P=0.011). The OS rate was higher significantly in stage III-N2 NSCLC patients in the surgery group compared to that in the radiotherapy group (P<0.05). Kaplan-Meier analysis demonstrated that the OS of III-N2 NSCLC was markedly better in the surgery group compared to the radiotherapy group (P<0.05). The multivariate proportional hazards model showed that age, T stage, surgery, disease stage, and adjuvant chemotherapy were independent prognostic predictors for OS in stage III-N2 NSCLC patients.Conclusions:Surgery is associated with improved OS in stage III-N2 NSCLC patients and is recommended to treat these patients.
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.
Radiotherapy acts by damaging DNA and hindering cancer cell proliferation. H2AX is phosphorylated to produce γH2AX that accumulates in a response to DNA double-strand breaks. Non-coding RNA can influence DNA damage response and enhance DNA repair, which show potential for cancer treatment. The study aimed to observe the influence of SPI1 on the radiosensitivity of lung squamous cell carcinoma (LUSC) and to investigate the mechanisms. SPI1, TPX2, and RNF2 were overexpressed in LUSC tissues and radioresistant cells comspared with adjacent tissues and parental cells, respectively. The binding between SPI1 and TPX2 or RNF2 promoter was investigated using ChIP-qPCR and dual-luciferase assays. SPI1 bound to TPX2 and RNF2 promoters and activated their transcription. SPI1 downregulation increased the radiosensitivity of LUSC cells, which was compromised by TPX2 or RNF2 overexpression. Meanwhile, SPI1 downregulation elevated the protein expression of γH2AX at the late stage of DNA damage response and suppressed DNA damage repair in LUSC cells, which were compromised by TPX2 or RNF2. These results indicate that SPI1 silencing potentiates radiosensitivity in LUSC cells by downregulating the transcription of TPX2 and RNF2, which provides a potential target for the radiotherapy in LUSC.
PurposeThe prognostic effect of postoperative radiotherapy (PORT) on pathological T3N0M0 (pT3N0M0) esophageal squamous cell carcinoma (ESCC) remains inconclusive. This study aimed to retrospectively investigate patterns of failure and whether PORT after R0 resection improves survival in patients with pT3N0M0 ESCC, compared with surgery alone.Patients and methodsThe clinical data of 256 patients with pT3N0M0 ESCC from January 2007 to December 2010 were retrospectively reviewed. The included patients were classified into two groups: the surgery-plus-postoperative radiotherapy group (S + R) and the surgery-alone group (S). Propensity score matching (PSM) was used to create comparable groups that were balanced across several covariates (n = 71 in each group). Statistical analyses were performed using the Kaplan–Meier method and Chi-squared test.ResultsIn the study cohort, the 5- and 10-year overall survival (OS) rates in the S + R group were 53.4% and 38.4%, and those in the S group were 50.3%, 40.9% (p = 0.810), respectively. The 5- and 10-year disease-free survival (DFS) rates in the S + R group were 47.9% and 32.9%, and those in the S group were 43.2%, 24.0% (p = 0.056), respectively. The results were coincident in the matched samples (p = 0.883, 0.081) after PSM. Subgroup analysis showed that patients with upper thoracic lesions in the S + R group had significantly higher OS than patients in the S group (p = 0.013), in addition, patients with upper and middle thoracic lesions in the S + R group had significantly higher DFS than patients in the S group (p = 0.018, 0.049). The results were also confirmed in the matched samples after PSM. The locoregional recurrence between the two groups were significantly different before and after PSM (p = 0.009, 0.002). The locoregional control rate (LCR) in the S + R group was significantly higher than that in the S group before and after PSM (p = 0.015, 0.008).ConclusionPostoperative radiotherapy may be associated with a survival benefit for patients with pT3N0M0 upper thoracic ESCC. A multicenter, randomized phase III clinical trial is required to confirm the results of this study.
ObjectiveTo analyze and compare the efficacy and safety of simultaneous integrated boost intensity-modulation radiation therapy (SIB-IMRT) combined with systematic and standardized management for esophageal cancer.MethodsFrom January 2012 to January 2019, 200 patients with esophageal cancer who received radical chemoradiotherapy in our hospital were treated with lymphatic drainage area radiation prevention combined with systematic and standardized management. According to difference in radiotherapy methods, the patients were divided into local lesion 92 patients treated with simultaneous integrated boost intensity-modulation radiation therapy (SIB-IMRT) combined with systematic standardized management (SIB-IMRT group), and late course boost intensity-modulation radiation therapy (LCB-IMRT) combined with systematic standardized management 108 patients (LCB-IMRT group). The short-term eficacy of the two groups were compared. The dose volume parameters of the organ in danger are evaluated based on the dose volume histogram. The related adverse reactions during chemoradiotherapy were compared between two groups. The local control rate and survival rate were compared between the two groups.ResultsThe recent total effective rates of rats in the SIB-IMRT group and LCB-IMRT group were 95.65% and 90.74%, respectively, and there was no significant difference between the two groups (p > 0.05). The mean doses to left and right lung, heart and spinal cord in the SIB-IMRT group were significantly lower than that in the LCB-IMRT group (p < 0.05). There was no significant difference in the incidence of adverse reactions such as radiation esophagitis, radiation pneumonitis, radiation tracheitis, gastrointestinal reaction and bone marrow suppression between the SIB-IMRT group and LCB-IMRT groups (p > 0.05). The one-year and three-year overall survival rates in the SIB-IMRT group and LCB-IMRT groups were 82.61%, 42.39% and 77.78%, 34.26%, respectively, and the median survival times were 38 and 29 months, respectively. The local control rates in the SIB-IMRT group and LCB-IMRT group in one and three years were 84.78%, 56.52% and 75.93%, 41.67%, respectively. The 3-year local control rate in the SIB-IMRT group was higher than that in the LCB-IMRT group (p < 0.05), but there was no significant difference in the 1-and 3-year overall survival rates between the two groups (p > 0.05).ConclusionSIB-IMRT combined with systematic and standardized management in the treatment of esophageal cancer can reduce the amount of some organs at risk and improve the local control rate of the lesion.
Background: Papillary Thyroid Carcinoma (PTC) represents the most common thyroid cancer. Until recently, treatment options for PTC patients are limited. Nilotinib is the second-generation tyrosine kinase inhibitor, and has been widely used in the treatment of Chronic Myeloid Leukemia (CML). Objectives: We aimed to explore whether nilotinib is effective for the suppression PTC cancer progression and the underlying mechanisms. Methods: In this study, the three human PTC cell lines (KTC-1, BCPAP, and TPC1) were used to verify the effects of nilotinib on cell growth. The half maximal inhibitory concentration (IC50) was calculated according to the growth curve post nilotinib treatment at different concentrations. Cell counting kit-8 and colony formation analysis were used to monitor cell growth after nilotinib treatment. Cell apoptosis and autophagy related proteins and phosphorylation of PI3K/Akt/mTOR were detected by Western blotting analysis. Results: Nilotinib treatment could effectively inhibit PTC cell growth, which was accompanied by an increase in apoptosis and induction of autophagy. Mechanistically, nilotinib treatment repressed the phosphorylation of the PI3K/Akt/mTOR pathway. Conclusion: Collectively, our results demonstrated that nilotinib may display anti-tumor effect against PTC via inhibiting PI3K/Akt/mTOR pathway and inducing apoptosis and autophagy.
Objective: Angiogenesis plays an important role in the growth and metastasis of non-small cell lung cancer (NSCLC). Bevacizumab is a humanized monoclonal antibody that mainly acts on vascular endothelial growth factor A (VEGFA). Kinase insert domain receptor (KDR) is the most important target of VEGFA. The aim of present study was to investigate the influence of KDR genetic variation on the efficacy and safety of patients with advanced NSCLC receiving first-line bevacizumab plus chemotherapy regimen. Methods: A total of 169 patients with advanced NSCLC who received bevacizumab combined with chemotherapy were recruited in this study. Clinical outcome of the regimens was evaluated in the hospital. Peripheral blood and biopsy tissue specimens of patients were collected for the genotyping of KDR genetic variation and KDR mRNA expression, respectively. The association between KDR genotype status and other variables were analyzed. Univariate analysis of genotype status and prognosis was implemented using the Kaplan-Meier survival analysis method. Multivariate Cox regression analysis was performed to adjust the confounding factors. Results: Of the polymorphisms analyzed, only V297 L was of clinical significance. The prevalence of V297 L among the study population were as follows: CC genotype 123 cases (72.8%), CT genotype 41 cases (24.3%), TT genotype 5 cases (2.9%). The minimum allele frequency is 0.15. The distribution frequencies of the 3 genotypes corresponded with Hardy-Weinberg equilibrium (P = 0.489). Patients with TT and CT genotypes were merged in the subsequent comparison of clinical outcomes. The analysis of efficacy exhibited that the objective response rates (ORR) of patients with CC genotype and CT/TT genotypes were 52.8% and 47.8% (P = 0.561), respectively. Prognosis indicated that the median progression free survival (PFS) of patients with CC genotype and CT/TT genotype were 8.9 and 5.5 months, respectively (P = 0.006). The median OS of the 2 genotypes were 20.0 and 14.9 months, respectively (P = 0.021). Adjusted in multivariate Cox regression analysis of PFS, CT/TT genotypes were an independent factor for PFS [hazard ratio (HR) = 1.59, P = 0.011). Safety profile according to genotype status of V297 L failed to find significant difference. Interestingly, the expression of KDR mRNA of patients with CT/TT genotype was significantly higher than that of patients with CC genotype in the 58 cancer tissue specimens (P < 0.001). Conclusion: The clinical comes of patients with advanced NSCLC receiving first-line bevacizumab plus chemotherapy regimens might be impacted by polymorphism V297 L through mediating the mRNA expression of KDR.
目的:观察食管癌患者放疗过程中系统免疫炎症指数(systemic immune-infammation index,SII)的变化趋势,并且分析SII与预后的相关性.方法:收集2013—2017年在河北医科大学第四医院接受根治性放疗的符合病例选择标准的106例食管癌患者的临床资料,根据放疗前、放疗期间每周以及放疗结束时的血常规检查结果,计算SII,按照受试者工作特征(receiver operating characteristic,ROC)曲线得到SII最佳临界值,对患者进行分组,评估SII的变化趋势.应用Kaplan-Meier法计算生存率,COX风险回归模型分析食管癌放疗患者的预后影响因素.结果:应用ROC曲线确定放疗前SII最佳临界值为646.8.放疗前SII与TNM分期相关(P=0.028),与血清前白蛋白(prealbumin,PAB)和白蛋白(albumin,ALB)呈负相关(P=0.002和P<0.001).SII在放疗期间呈上升趋势.106例患者1年、3年和5年总生存率分别为76.4%、36.6%和22.9%,中位生存期为24.2个月(95%置信区间:18.974~29.426).放疗前高SII组患者1年、3年和5年总生存率分别为62.7%、26.3%和15.0%,低SII组患者1年、3年和5年总生存率分别为89.1%、46.4%和30.2%,2组的差异有统计学意义(P=0.003).单因素分析结果显示,病变部位、TNM分期、放疗方式、放疗处方剂量、化疗和SII是食管癌患者总生存的影响因素(P<0.05).多因素分析结果显示,TNM分期、放疗处方剂量和SII是食管癌患者总生存的独立影响因素(P<0.05).高SII组患者≥2级放射性食管炎和放射性肺炎的发生率均高于低SII组患者(P<0.05).结论:SII在放疗期间呈上升趋势,是食管癌放疗患者预后的独立影响因素.
目的 探讨C反应蛋白与白蛋白比值(CAR)对接受根治性放疗的老年食管鳞癌患者生存的预测价值.方法 回顾性分析136例接受根治性放疗且年龄≥60岁食管鳞癌患者的临床资料,计算患者放疗前CAR,根据受试者工作特征曲线(ROC)确定最佳临界值,分为高CAR组和低CAR组,比较两组的临床资料和总生存期(OS)的差异,采用Kaplan-Meier法计算生存率并行Log-rank检验,Cox风险比例回归模型进行多因素预后分析.结果 ROC曲线确定CAR最佳临界值为0.073,分为高CAR组(≥0.073)和低CAR组(<0.073).CAR与T分期、临床分期、中性粒细胞计数、前白蛋白、中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)和单核细胞与淋巴细胞比值(MLR)有关(P<0.05).全组患者1、3、5年生存率分别为72.1%、31.5%、19.1%;高CAR组的1、3、5年生存率分别为66.3%、20.9%、11.4%,明显低于低CAR组的82.0%、49.4%、32.1%(P=0.001).单因素分析显示,年龄、病变部位、临床分期、放疗方式、处方剂量、是否联合化疗、NLR、PLR、CAR与OS有关(P<0.05);多因素Cox回归分析显示,临床分期、病变部位和CAR水平是影响OS的独立因素.结论 CAR是接受根治性放疗的老年食管鳞癌患者预后的影响因素,可作为预测生存的指标.
Abstract Background The preoperative prognostic nutritional index (PNI) is associated with postoperative complications and long-term survival of various cancers. However, its role in esophageal squamous cell carcinoma (ESCC) is inconclusive. The aim of this study was to identify the prognostic value of PNI in predicting survival in ESCC patients undergoing radical radiotherapy. Methods We retrospectively reviewed 354 ESCC patients undergoing radical radiotherapy. The time-dependent receiver operating characteristics was used to determine the optimal cutoff value. The association between PNI and survival was determined by Kaplan-Meier method and Cox regression model. Propensity score matching was applied to balance the baseline characteristics. Results PNI was positively correlated with hemoglobin (P < 0.001) and prealbumin (P < 0.001). The optimal cutoff value of PNI was set at 50.5. The 5-year overall survival (OS) in low PNI group and high PNI group were 20.8% and 34.0%, respectively (P < 0.001). The 5-year progression free survival in patients with low PNI and high PNI were 15.2% and 28.5%, respectively (P = 0.001). Multivariate analysis showed that PNI was a significant predictor for OS (P = 0.038). In the PSM analysis, PNI still remained an independent predictor for OS (P = 0.015). Conclusions The PNI is a significant and independent predictor for OS of ESCC patients undergoing radical radiotherapy.
Objective: This study was set out to inquire into the expression and clinical significance of lncRNA activated by transforming growth factor β (LncRNA-ATB) and in cancer tissues of patients with non-small cell lung cancer (NSCLC). Methods: LncRNA-ATB in cancer tissues and adjacent tissues of 89 NSCLC patients was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and its clinical diagnostic value in NSCLC was determined by receiver operating characteristic (ROC) curves. Based on the median expression of LncRNAATB in NSCLC tissues, 89 patients were allocated into high- and low-expression groups. The 3-year survival rate was calculated using Kaplan-Meier method and logrank test, and compared between lncRNA-ATB high and low expression groups by Log-rank test. Cox regression quantitatively analyzed the correlation between lncRNA-ATB and the clinical prognosis of NSCLC patients. Results: LncRNAATB presented notably higher expression in NSCLC tissues as compared to adjacent tissues (P < 0.05), and was linked to smoking history, TNM stage and greatest tumor diameter (GTD) (P < 0.05). The cut-off value, sensitivity and specificity, as well as the area under the curve (AUC) of NSCLC diagnosed by LncRNA-ATB were 2.103, 73.77%, 83.15% and 0.836, respectively. Patients with high lncRNA-ATB expression (40.00%) showed statistically lower than those with low lncRNA-ATB expression (63.36%). TNM stage, differentiation degree and lncRNA-ATB expression were independent variables affecting patient prognosis. Conclusions: LncRNA-ATB, with increased expression profiles in NSCLC tissues, is involved in NSCLC progression and associated with unfavourable prognosis of patients, which can be a plausible tumor marker for NSCLC patients.
Anaplastic thyroid cancer (ATC) is a rare type of thyroid cancer (TC) with no effective therapeutic strategy. Although surgery, chemotherapy and radiation are all available for ATC treatment, the median survival for ATC patients is less than 6 months. In this study, we aimed to study on resistant mechanisms to B-Raf proto-oncogene serine/threonine kinase (BRAF) inhibitor and identify effective combinational therapy for ATC patients. TC cells were treated with Vemurafenib and cell apoptosis and viability were analyzed by flow cytometry and MTT assay. Monolayer and sphere cells were isolated from ATC cells to detect the mRNA level of stem cell markers and differentiation markers by RT-PCR. Phosphor-STAT3 level in sphere and monolayer cells was tested by Western blotting. The xenotransplantation animal model has established to analyze the anti-tumor effect of Vemurafenib and Stattic combinational therapy. Undifferentiated TC cells were resistant to Vemurafenib treatment. Sphere cells isolated from ATC showed no significant change in cell viability and apoptosis upon Vemurafenib treatment, and expressed a high level of stem cell marker and phosphor-STAT3. STAT3 inhibition enhanced the tumorigenic capacity and increased Vemurafenib sensitivity in ATC cell lines. Stattic significantly enhanced anti-tumor effect of Vemurafenib in mouse model. Our findings demonstrate that the combinational therapy of Vemurafenib and Stattic is an effective therapeutic treatment for ATC patients.
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.
目的 探讨影响Ⅱ~Ⅲ期食管癌根治性切除术后患者预后的因素.方法 回顾性分析2007年1月—2010年12月行食管癌根治性切除术且术后病理分期为Ⅱ~Ⅲ期共716例患者的临床资料.选择可能影响预后的临床病理资料及术后治疗情况进行单因素和多因素分析.结果 716例患者1、3、5年总生存率分别为79.85%、58.27%、49.73%.多因素分析显示:性别、术中粘连程度、术后阳性淋巴结数目、T分期及术后辅助治疗是影响患者总生存时间(OS)的独立预后因素(均P<0.05).对术后辅助治疗方式进行分层分析显示:Ⅱa期(342例)患者术后化疗组OS优于单纯手术组和术后放疗组(χ2分别为9.301、4.422,P<0.05或P<0.01);Ⅱb(75例)及Ⅲ期(299例)患者术后放化疗组及术后放疗组OS均优于单纯手术组(Ⅱb期:χ2分别为3.926、4.605,P<0.05;Ⅲ期:χ2分别为8.504、7.435,P<0.01).716例患者1、3、5年无进展生存率分别为71.23%、49.32%、38.26%.多因素分析显示:性别、术中粘连程度、TNM分期及术后辅助治疗是影响患者无进展生存时间(PFS)的独立预后因素(均P<0.05).对术后辅助治疗方式进行分层分析显示:Ⅱa期患者术后化疗组PFS优于单纯手术组(χ2=7.481,P<0.01);Ⅱb及Ⅲ期患者术后放化疗组PFS均优于单纯手术组(χ2分别为6.684、5.741,P<0.05).结论 根治术后辅助治疗为影响Ⅱ~Ⅲ期食管癌患者预后的重要因素.Ⅱa期患者可仅行术后化疗,而Ⅱb~Ⅲ期患者接受辅助放疗或放化疗可获得更优预后.
Objective:To evaluate the recurrence patterns of esophageal squamous cell carcinoma (ESCC) after radical surgery and analyze the predictors of post-recurrence survival (PRS).Methods:A total of 382 ESCC patients who developed recurrence after radical surgery were retrospectively reviewed from January 2007 to December 2011. All of them received salvage treatment after recurrence. The Univariate analysis was determined using the Kaplan-Meier method and log-rank test. Multivariate prognostic analysis was determined using the Cox proportional hazard model.Results:The 1-, 3-, 5-year overall survival (OS) rates were 80.9%, 35.6% and 20.4%, respectively. The median survival time and recurrence time were 29.2 months and 15.0 months. The 1-, 3-, 5-year PRS rates were 37.7%, 14.6% and 11.9%, respectively. The median PRS time was 10.2 months. Locoregional recurrence was noted at 462 sites among 382 patients including 20.5% (95/462) of sites in supraclavicular LN (lymph node), 10.0% (46/462) in anastomosis, 56.1% (259/462) in mediastinal regional LN and 13.4% (62/462) in upper abdominal LN. There were 156, 43, 82 and 101 patients treated with salvage radiotherapy, chemotherapy, chemoradiotherapy and palliative care after recurrence, respectively. The univariate analysis showed that T stage, N stage, TNM stage, recurrence site, number of recurrent regions and treatment regimen after recurrence were significantly correlated with PRS ( χ2=5.336, 4.292, 8.067, 7.482, 4.093, 76.426, P<0.05). Patients receiving salvage radiotherapy with the median dose of 60 Gy, were divided into <60 Gy group and ≥ 60 Gy group. The ≥60 Gy group had a better PRS than <60 Gy group ( χ2=8.320, P<0.05). Multivariate analysis showed that number of recurrent regions and treatment regimen were independent prognostic factors of PRS. Conclusions:Mediastinal and supraclavicular regions were the most common sites of recurrence in ESCC patients after radical surgery. Salvage radiotherapy and chemoradiotherapy could significantly improve PRS in recurrent ESCC patients.
Objective To analyze the risk factors for abdominal lymph node recurrence after radical surgery in patients with middle thoracic esophageal squamous cell carcinoma (TE-SCC),and to design the target volume for postoperative radiotherapy based on the results.Methods A retrospective study was performed among 913 patients with middle TE-SCC undergoing radical surgery who were admitted to our hospital from 2007 to 2012.Influencing factors were analyzed for abdominal lymph node recurrence after treatment.The efficacy was compared between different treatment methods in the high-risk population.Comparison of categorical data was made by chi-square test.The overall survival rates (OS) were calculated by the Kaplan-Meier method and analyzed by the univariate log-rank analysis.The influencing factors for abdominal lymph node recurrence were analyzed by the multivariate logistic regression equation.Results After treatment,37 patients had abdominal lymph node recurrence,yielding a recurrence rate of 4.1%.A total of 53 recurrent sites were found.The univariate analysis showed that no/low differentiation,pT3+4 stage,no less than 3 positive postoperative lymph nodes,and positive postoperative abdominal lymph nodes were influencing factors for abdominal lymph node recurrence (P =0.032,0.001,0.009,0.000).The multivariate regression analysis showed that pathological T staging and positive postoperative abdominal lymph nodes were influencing factors for abdominal lymph node recurrence (P=0.011,0.000).For patients with pT3+4 stage disease and positive postoperative abdominal lymph nodes,postoperative radiotherapy improved OS and local control rates but failed to reduce the distant metastasis-free rate.Conclusions T staging and positive postoperative abdominal lymph nodes are important risk factors for abdominal lymph node recurrence after radical surgery in patients with middle TE-SCC.Postoperative adjuvant therapy is recommended for patients with pT3+4 stage disease and positive postoperative abdominal lymph nodes.
Objective To analyze the failure patterns and prognostic factors of radical surgery in patients with T1-4N0-1M0 thoracic esophageal squamous cell carcinoma (TESCC),and the implications for the target area design of postoperative therapy.Methods We retrospectively analyzed 1 191 patients with TESCC who underwent radical surgery at our institution.The failure patterns,the prognostic factors,as well as the effects of lesion locations and N stage on the failure patterns were analyzed.Results The thoracic-region recurrence rate and the distant metastasis rate was 31.7% and 16.4% in all patients.The multivariate analysis showed that the lesion locations,the degree of inflammatory adhesion,T staging,N staging and the rate of lymph nodes metastasis were independent factors affecting the regional recurrence (P < 0.05).Gender,tumor differentiation and the rate of lymph nodes metastasis were independent factors affecting distant metastasis (P < 0.05).The intrathoracic lymph nodes recurrence rate of upper/middle TESCC was significantly higher than that of the lower TESCC (x2 =6.179,P =0.046),while the abdomen lymph nodes recurrence rate of the lower was significantly higher than that of upper/middle TESCC (x2 =15.853,P < 0.05).The recurrence rate and distant metastasis rate of stage N1 patients were significantly higher than that of N0 patients (x2 =7.764-56.495,P < 0.05).The abdomen lymph nodes recurrence rate of stage N1 patients was significantly higher than that of N0 in upper TESCC (x2 =7.905,P <0.05).The supraclavicular and intrathoracic lymph nodes recurrence rates of stage N1 patients were significantly higher than that of N0 patients in middle TESCC (x2 =12.506,18.436,P < 0.05).The supraclavicular lymph nodes,anastomosis and abdomen lymph node recurrence rates of stage N1 were significantly higher than that of N0 patients in lower TESCC (x5 =5.272,4.878,18.006,P < 0.05).The anastomotic recurrence rate of stage T3+4 was higher than that of T1+2 in middle/lower TESCC (x2 =4.341,7.154,P < 0.05),and the abdominal lymph nodes recurrence rate of stage T3 +4 was higher than that of T1 +2 in lower TESCC (x2 =5.366,P < 0.05).Conclusions The lymphatic drainage regions for postoperative radiotherapy (PORT) are selective.We suggest that abdominal lymph nodes drainage area should be noted for the stage N1 patients with upper TESCC,and the supraclavicular lymph nodes drainage area should be noted for the N1 patients with lower TESCC.In addition,the anastomosis is suggested to be included in PORT target area for stage T3/T4 middle/lower TESCC patients.