RESUMEN
Objective:To investigate the value of radiotherapy in patients with stage Ⅳ B thoracic esophageal squamous cell carcinoma (ESCC) at initial diagnosis. Methods:A total of 199 patients with stage Ⅳ B thoracic ESCC at initial diagnosis (according to UICC/AJCC Eighth Edition Esophageal and Esophagogastric Junction Cancer TNM Staging) who were treated in the Fourth Hospital of Hebei Medical University between January 2010 to December 2016 were recruited. Winthin the whole group, 130 patients (65.3%) had distant lymph node metastases alone, 51 cases (25.6%) of solid organ metastases alone and 18 cases (9.0%) of solid organ complicated with distant lymph node metastases. Among them, 16 patients (8.0%) were treated with chemotherapy alone, 50 cases (25.1%) of radiotherapy alone, 133 cases (66.8%) of radiochemotherapy (81 patients treated with concurrent radiochemotherapy and 52 patients treated with sequential radiochemotherapy). The survival rate was calculated by Kaplan-Meier method and the difference was analyzed by log-rank test. Clinical prognosis was assessed by multivariate Cox regression model. Results:The median overall survival (OS) of the entire cohort was 12.3 months (95% CI: 10.6-15.4m), and the 1-, 2-, 3-and 5-year OS rates were 52.1%, 25.2%, 19.1%, and 11.5%, respectively. Multivariate analysis showed that tumor length, the number of metastatic organs, and treatment modalities were the independent prognostic factors for OS. There was no significant difference in OS between concurrent radiochemotherapy and sequential radiochemotherapy ( P=0.955). The OS of patients in the radiotherapy dose of ≥6000 cGy group was significantly longer than that of their counterparts in the 4500-5039 cGy and 5040-6000 cGy groups (both P<0.001). Conclusions:For stage Ⅳ B thoracic ESCC patients at initial diagnosis, tumor length ≤3cm, single organ metastasis, and radiochemotherapy strategy are significantly correlated with longer OS. For stage Ⅳ ESCC patients with good physical status, radiotherapy can be supplemented on the basis of systemic chemotherapy. Concurrent or sequential radiochemotherapy needs to be individualized. If patients are tolerable, radiochemotherapy is recommended to the primary tumor or non-regional metastatic lymph nodes, aiming to prolong the OS of patients.
RESUMEN
Objective To analyze the clinical efficacy,toxicity and survival prognosis of patients diagnosed with Siewert type Ⅱ and Ⅲ locally advanced adenocarcinoma of esophagogastric junction (AEG) undergoing preoperative involved-field irradiation with concurrent chemotherapy. Methods A total of 45 cases were recruited in this prospective clinical trial. Prior to surgery, patients received 2 cycles of chemotherapy with XELOX and concurrent radiotherapy ( a total of 45 Gy in 25 fractions,5 times weekly). After 6-8 weeks,they underwent surgical resection. After the surgery,patients received 6 cycles of adjuvant chemotherapy. The completion of preoperative neoadjuvant chemoradiotherapy, postoperative pathological status,TNM down-staging effect and adverse reactions were observed. Kaplan-Meier method was applied to estimate survival analysis. Results All 45 patients completed preoperative neoadjuvant chemoradiotherapy. Among them, 39 patients completed 2 cycles of chemotherapy, and 6 patients completed 1 cycle of chemotherapy. The median time of surgical interval was 6 weeks. The R0resection rate was 96%.The pathological complete response (pCR) rate was 22%. The TNM down-staging rate was 69%.The incidence of acute radiation-induced esophagitis or gastritis was 44% and the incidence of radiation-induced pneumonitis was 7%. The incidence of grade 1-3 leukocytopenia,thrombocytopenia and neutropenia was 78%,47% and 44%,respectively. In terms of gastrointestinal reactions,the incidence of nausea,vomiting and loss of appetite was 62%,24% and 71%,respectively. No hematologic or nonhematologic adverse effects was observed at grade 4 or 5.The median follow-up time was 30 months. 11 patients died of cancer,1 patient was treatment-related death in the perioperative period and 1 patient died of pneumonia. The 1-,2-and 3-year progression-free survival (PFS) rates were 90%,70% and 67%,respectively. The 1-,2-and 3-year overall survival rates were 95%,80% and 75%,respectively. The 1-,2-and 3-year local control rates were 95%,84% and 84%, respectively. The 1-, 2-and 3-year distant metastasis rates were 7%, 25% and 25%, respectively. Conclusions Preoperative involved-field irradiation with concurrent chemotherapy yields relatively high clinical efficacy and is well tolerated by patients with Siewert typeⅡandⅢlocally advanced AEG.Patients are recommended to receive 4 cycles of adjuvant chemotherapy following neoadjuvant chemoradiotherapy and surgery.
RESUMEN
postoperative pathological examination results and radiotherapy toxicities. Results All the 45 patients completed preoperative concurrent chemoradiotherapy and surgery, with two cycles of chemotherapy in 39 patients and one cycle in 6 patients. The rates of R0resection and pathological complete response(pCR) were 95.6%(43/45)and 22.2%(10/45), respectively. There were 10(22.2%), 17(37.8%), 15 (33.3%),and 3(6.7%)patients with tumor regression grades 0,1,2,3,respectively. The rate of lymph node metastasis was 37.8%(17/45),and the lymph node ratio was 4.33%(46/1 062). The postoperative pathological examination showed that T and N downstaging after surgery was observed in 24 and 26 patients, respectively;the proportions of patients with T3-T4tumors and positive lymph nodes after surgery declined by 51.1%(P=0.000)and 42.2%(P=0.000), respectively. The overall incidence of radiation esophagitis/gastritis was 44.4%(20/45), and the incidence rates of grade 1, 2, and 3 radiation esophagitis/gastritis were 18%,22%,and 4%,respectively. The incidence of acute radiation pneumonitis was 6.7%(3/45), all in grades 1 and 2. There was one perioperative treatment-related death. Conclusions Two cycles of XELOX chemotherapy combined with concurrent 45 Gy radiotherapy before surgery in patients with locally advanced Siewert type Ⅱ and Ⅲ AEG can achieve a relatively high pCR rate,effectively reduce the lymph node metastasis rate, achieve downstaging, and increase R0resection rate. This regimen has many good advantages,including low incidence of acute toxicities,good tolerability,and acceptable rate of perioperative treatment-related deaths. The target volume delineation involving metastatic lymph nodes is feasible.
RESUMEN
Objective To examine the effects of different pre-treatment nutritional status and inflammatory markers on acute adverse reactions in esophageal cancer patients during concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy.Methods The acute adverse reactions of 338 eligible esophageal cancer patients who received concurrent IMRT and chemotherapy in our hospital from 2006 to 2014 were reviewed.The effects of different pre-treatment nutritional status, such as body mass index level (BMI), albumin level (ALB), total lymphocyte count (TLC), the presence or absence of anemia, and inflammatory indicators including neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR), on acute adverse reactions in the patients were examined.Data were analyzed using the chi-square test with continuity correction and logistic regression analysis.Results The incidence rate of malnutrition in the patients based on their nutritional status was 5.62%-54.14%.The incidence rate of grade≥2 acute radiation esophagitis (RE) was significantly higher in the low ALB group than in the normal ALB group (P=0.000).The incidence rate of adverse reactions in the hematologic system increased as TLC decreased (P=0.006), but the incidence rate of acute radiation pneumonitis (RP) was reduced as TLC decreased (P=0.001).In addition, the incidence rate of grade ≥2 acute RE was significantly higher in the anemia group than in the non-anemia group.Inflammatory marker analysis demonstrated that the incidence rate of acute RE was significantly higher in the high NLR group and high PLR group than in the low NLR group and low PLR group (P=0.000 and P=0.024, respectively).Logistic regression analysis of nutritional status and inflammatory markers showed that TLC was an independent risk factor for acute adverse reactions in the hematologic system (P=0.001), and ALB and PLR were independent risk factors for acute RE (P=0.017 and P=0.011,respectively).Conclusions Nutritional status and inflammatory markers are associated with concurrent chemoradiotherapy-induced acute adverse reactions in esophageal carcinoma patients, and hence may be valuable indicators of acute adverse reactions during treatment.In addition, nutritional treatment and support care should be actively provided to the patients to prevent the development of acute adverse reactions during treatment.
RESUMEN
Objective To investigate the clinical effect of induction chemotherapy plus concurrent radiochemotherapy in the treatment of locally advanced non-small cell lung cancer (NSCLC) through a meta-analysis.Methods CBM, CNKI, Cochrane Library, PubMed, and EMbase were searched for the articles on comparison between induction chemotherapy plus concurrent radiochemotherapy and concurrent radiochemotherapy for patients with locally advanced NSCLC.According to the inclusion and exclusion criteria, the data on short-term outcome and survival were collected.A Meta-analysis was performed to evaluate the clinical effect of induction chemotherapy followed by concurrent radiochemotherapy.Results A total of 5 articles were included, which involved 845 patients.The results showed that the short-term outcome and the 2-and 3-year survival rates were similar between patients receiving induction chemotherapy plus concurrent radiochemotherapy and those receiving concurrent radiochemotherapy ( OR=0.875, 95% CI 0.507-1.510, P=0.631;HR=0.770, 95% CI 0.515-1.151, P=0.203;HR=0.809, 95% CI 0.559-1.172, P=0.262), but the patients receiving induction chemotherapy plus concurrent radiochemotherapy showed a significantly higher incidence rate of grade ≥ 3 leukopenia than those receiving concurrent radiochemotherapy alone ( OR=0.637, 95% CI 0.435-0.931, P=0.020).Conclusions Induction chemotherapy plus concurrent radiochemotherapy shows no significant advantages over concurrent radiochemotherapy alone in the short-term outcome and 2-and 3-year survival rates, but it significantly increases myelosuppression.Since there are few studies involving a limited number of cases included in this analysis, more multicenter randomized trials are needed to provide more detailed data and further clarify the clinical value of induction chemotherapy plus concurrent radiochemotherapy.
RESUMEN
Objective To observe the efficacy and adverse reactions of intensity-modulated radiotherapy (IMRT) with or without chemotherapy in the treatment of esophageal carcinoma,and to explore the influencing factors for prognosis.Methods The short-term outcomes and acute adverse reactions in 349 patients with esophageal carcinoma who received IMRT with or without chemotherapy from 2006 to 2012 were retrospectively analyzed.The 1-,3-,and 5-year local control (LC) rates and overall survival (OS) rates were calculated with the Kaplan-Meier method.The influencing factors for survival were analyzed using the Cox regression model.Results The sample sizes at 3 and 5 years were 174 and 63,respectively.For all patients,the 1-,3-,and 5-year LC rates were 72.9％,61.2％,and 58.4％,respectively,and the 1-,3-,and 5-year OS rates were 66.5％,39.1％,and 24％,respectively.According to the results of subgroup analysis,the 1-,3-,and 5-year LC and OS rates in patients with a tumor volume of ＜ 54.73 cm3 were significantly higher than those in patients with a tumor size of ≥54.73 cm3 (P =0.001 and 0.000).There were no significant differences in 1-,3-,and 5-year LC rates between patients with and without lymph node metastasis (P =?).However,the 1-,3-,and 5-year OS rates were significantly lower in patients with lymph node metastasis than in patients without lymph node metastasis (62.7％ vs.83.1％;35.9％ vs.53.3％;20.4％ vs.38.3％;P =0.003).There were significant differences in the 1-,3-,and 5-year LC and OS rates between patients with complete response,partial response,and no response (P =0.000 and 0.000).The incidence rates of grade ≥ 2 acute radiation pneumonitis and grade ≥ 3 acute radiation esophagitis were 11.3％ and 9.0％,respectively.The tumor volume,short-term outcome,and lymph node metastasis were the influencing factors for OS (P =0.038,0.000,and 0.008).Conclusions IMRT with or without chemotherapy is effective and safe in the treatment of esophageal carcinoma.The prognosis becomes poor along with increased tumor volume and regional lymph node metastasis.The evaluation of short-term outcomes is closely correlated with LC and OS.
RESUMEN
Objective To analyze the patterns and distribution of lymph node metastasis in patients with adenocarcinoma of the esophagogastric junction ( AEG). Methods The pathological data of 393 patients with AEG from 2006 to 2009 were analyzed. The patterns and distribution of lymph node metastasis were analyzed in patients with different Siewert subtypes, depths of tumor invasion, and maximum diameters of the tumor, and the high?risk lymphatic drainage areas were investigated. Between?group comparison was performed by χ2 test. Results The metastatic rate and ratio of abdominal lymph nodes in AEG were 69?? 2%and 31?? 31%, respectively. The incidence rates of lymph node metastasis in the cardia, lesser curvature, left gastric artery, splenic artery, splenic hilum, mesenteric root, and abdominal aorta were the highest. The metastatic rate and ratio of mediastinal lymph nodes were 16?? 4% and 8?? 3%, respectively. The incidence rates of lymph node metastasis in the lower paraesophageal, esophageal hiatus, and superior diaphragmatic areas were the highest. Compared with Siewert type II and type III AEG, Siewert type I AEG had a significantly higher mediastinal lymph node metastatic rate (P= 0?? 003) and a significantly lower abdominal lymph node metastatic ratio (P= 0?? 002).The metastatic ratios of lymph nodes in multiple abdominal regions were higher in patients with stage T3+T4 AEG and a maximum tumor diameter of ≥6 cm than in the control group, while the metastatic ratios of mediastinal lymph nodes in groups with different maximum tumor diameters were similar. The metastatic ratios of lymph nodes in the greater curvature, hepatoduodenal ligament, and inferior diaphragmatic areas were lower than 10% in all groups. Conclusions In radiotherapy for AEG, the abdominal high?risk lymphatic drainage areas involve the cardia, lesser curvature, left gastric artery, splenic artery, splenic hilum, mesenteric root, and abdominal aorta, while the mediastinal high?risk lymphatic drainage areas involve the lower paraesophageal, esophageal hiatus, and superior diaphragmatic areas. In addition, the personalized target volume design should be based on the patterns of lymph node metastasis with different Siewert subtypes and clinical pathological characteristics.
RESUMEN
<p><b>OBJECTIVE</b>To explore the patterns and influencing factors of lymph node metastasis in limited esophageal small cell carcinoma (PESCC).</p><p><b>METHODS</b>A total of 98 limited stage PESCC patients who underwent surgery were selected for this study. The lymph node metastasis ratio at different sites, depth of invasion, tumor length and other factors were analyzed to assess their influence on lymph node metastasis.</p><p><b>RESULTS</b>Among the 98 PESCC cases, 46 cases had lymph node metastasis (46.9%). 100 out of 833 lymph nodes had metastasis, with a metastasis ratio of 12.0%. For upper thoracic esophageal small cell carcinomas, lymph node metastasis ratios were 42.9%, 12.5%, 0 and 0 in the superior mediastinum, middle mediastinum, inferior mediastinum and abdominal cavity, respectively. In the middle thoracic PESCCs, the lymph node metastasis ratios were 18.8%, 7.7%, 15.7%, and 15.3%, respectively. In the lower thoracic PESCCs, the lymph node metastasis ratios were 0, 0, 27.3% and 23.5%, respectively. Lymph node metastasis rates in PESCCs at stages T1, T2, T3, T4 were 15.4%, 42.3%, 63.9%, and 80.0%, respectively. The lymph node metastasis ratios in PESCCs at stages T1, T2, T3, T4 were 2.0%, 8.3%, 17.8% and 25.0%, respectively. Lymph node metastasis rate and lymph node metastasis ratio at different T stages were of significant difference (P<0.05 for all). Lymph node metastasis rates in patients with tumor <3 cm, 3-5 cm, and >5 cm were 30.6%, 46.9% and 66.7%, respectively, and lymph node metastasis ratios were 5.4%, 11.0% and 21.1%, respectively. Lymph node metastasis rate and lymph node metastasis ratio in patients with different tumor length had significant differences (P<0.05 for all). Lymph node metastasis ratio was 11.6% in the Chr-A negative and weak positive group, much higher than 4.3% in the Chr-A positive group (P=0.013). There was a tendency that lymph node metastasis ratio of NSE-positive group was higher than that of NSE-negative and weak positive group (P=0.069). The logistic univariate analysis did not find high risk factors of distant lymph node metastasis (all P>0.05). Logistic multivariate analysis found that only depth of invasion was a risk factor of lymph node metastasis in limited PESCC (P=0.002).</p><p><b>CONCLUSIONS</b>Esophagus small cell carcinomas sometimes have early lymph node metastases in many sites and distant range. The middle thoracic PESCCs tend to have extensive metastasis quite common in the upper mediastinal lymph nodes. Lower mediastinal and abdominal lymph node metastases are often seen in lower thoracic PESCCs. The depth of invasion and tumor length are main factors influencing mediastinal lymph node metastasis. The depth of invasion is an independent risk factor for lymph node metastasis.</p>
Asunto(s)
Humanos , Cavidad Abdominal , Carcinoma de Células Pequeñas , Patología , Neoplasias Esofágicas , Patología , Ganglios Linfáticos , Patología , Metástasis Linfática , Mediastino , Análisis Multivariante , Invasividad Neoplásica , Factores de RiesgoRESUMEN
<p><b>OBJECTIVE</b>To investigate the effects of HIF-1α on adhesion and invasion of human nasopharyngeal carcinoma CNE-1 cells under hypoxia and underlying molecular mechanisms.</p><p><b>METHODS</b>CoCl₂was used to mimic tumor hypoxic microenvironment. mRNA and protein expressions of HIF-1α, E-cadherin and CXCR4 in CNE-1 cells at different hypoxic time phases were detected by RT-PCR and ELISA respectively. The influences of silencing HIF-1α using RNA interference on E-cadherin and CXCR4 expressions were evaluated. Adhesion test Transwell invasion test were used to evaluate the effects of HIF-1α gene silencing on cell adhesion and invasion.</p><p><b>RESULTS</b>Under hypoxia, HIF-1α mRNA expression in CNE-1 cells was stable, but its protein expression increased obviously (P<0.05). Both mRNA and protein expressions of E-cadherin were decreased significantly with prolonged hypoxia, while mRNA and protein expressions of CXCR4 increased significantly (P<0.05). After silencing HIF-1α gene, expression of E-cadherin protein was up-regulated, but with down-regulated expression of CXCR4 protein, with a decrease significantly in adhesion rate or invasive cell number of CNE-1 cells (P<0.05).</p><p><b>CONCLUSIONS</b>Hypoxia can increase HIF-1α protein expression in nasopharyngeal carcinoma cell line CNE-1. Silencing HIF-1α by RNA interference can reduce inhesion and invasion abilities of CNE-1 cells, which may be mediated by down-regulating E-cadherin expression and up-regulating CXCR4 expression.</p>
Asunto(s)
Humanos , Cadherinas , Genética , Metabolismo , Carcinoma , Hipoxia de la Célula , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Subunidad alfa del Factor 1 Inducible por Hipoxia , Genética , Metabolismo , Neoplasias Nasofaríngeas , Genética , Patología , Interferencia de ARN , ARN Mensajero , Receptores CXCR4 , Genética , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To explore the expression of hypoxia inducible factor-1α(HIF-1α) in esophageal squamous cell carcinoma and its correlation with clinicopathological features.</p><p><b>METHODS</b>Original literatures in foreign languages regarding correlation between HIF-1α and esophageal squamous cell carcinoma were identified from Cochrane Library, PubMed, EMbase database, and Chinese original literatures were from CBM, CNKI. All analyses were performed by Stata 11.0 software. Histological grade, degree of differentiation, T stage, lymph node metastasis, tumor stage, lymphatic invasion and vascular invasion were analyzed using pooled odds ratio (OR) with 95% confidence interval (CI).</p><p><b>RESULTS</b>A total of 14 studies including 1 121 patients were enrolled in this meta analysis. Comparing with normal tissue, the expression of HIF-1α in esophageal squamous cell carcinoma was significantly enhanced (OR = 0.088, 95% CI: 0.061-0.129, P = 0.000); HIF-1α was significantly associated with T stage and lymph node metastasis (OR = 0.421, 95% CI: 0.222-0.798, P = 0.008; OR = 0.387, 95% CI: 0.207-0.725, P = 0.003). High expression of HIF-1α was correlated with an increased depth of tumor invasion, more lymph node metastasis and advanced tumor stage, whereas there was no relation to the degree of differentiation, histological grade, tumor stage, lymphatic invasion and vascular invasion.</p><p><b>CONCLUSIONS</b>High expression of HIF-1α protein correlates with an increased risk of esophageal squamous cell carcinoma. HIF-1α may be an indicator for T stage, lymph node metastasis and tumor stage, but further studies are needed.</p>
Asunto(s)
Humanos , Biomarcadores de Tumor , Metabolismo , Carcinoma de Células Escamosas , Metabolismo , Patología , Intervalos de Confianza , Neoplasias Esofágicas , Metabolismo , Patología , Subunidad alfa del Factor 1 Inducible por Hipoxia , Metabolismo , Metástasis Linfática , Oportunidad RelativaRESUMEN
Objective To study the effect of UHRF1 expression inhibition by RNA interference on the radiosensitivity of esophageal cancer cell line TE-1 and its mechanism.Methods Short hairpin RNA (shRNA) targeting UHRF1 gene was introduced into TE-1 cells by lentivector-mediated transfer.The cells were divided into three groups:non-transfected group,negative control (NC)-shRNA-transfected group,and UHRF1-shRNA-transfected group.The mRNA and protein expression levels of UHRF1 in TE-1 cells were measured by RT-PCR and Western blot before and after transfection.After transfection and X-ray radiation,the radiosensitivity of TE-1 cells was evaluated by colony formation assay; the cell cycle and cell apoptosis were determined by flow cytometry; the γ-H2AX (as a marker of DNA damage) level was measured by Western blot.Results After transfection with UHRF1-shRNA,the mRNA and protein expression levels of UHRF1 were significantly decreased in TE-1 cells,as compared with those in the NC-shRNA-transfected group and non-transfected group (0.11 vs 0.96 and 0.98,F =124.21,P =0.000;0.10 vs 0.89 and 0.94,F =125.25,P =0.000).The UHRF1-shRNA-transfected group had sensitization enhancement ratios of 1.53 (D0 ratio) and 1.95 (Dq ratio).X-ray radiation could cause G2/M arrest and increase apoptotic rate and γ-H2AX expression in TE-1 cells.Compared with the two control groups,the UHRF1-shRNA-transfected group showed significantly less G2/M arrest (F =500.15,P =0.000),a significantly higher apoptotic rate (F =100.10,P =0.000),and significantly higher residual γ-H2AX expression (F =61.00,P =0.000) at 24 hours after X-ray radiation.Conclusions RNA interference can effectively inhibit the UHRF1 expression and enhance the radiosensitivity of TE-1 cells.The mechanism may be related to cell cycle regulation,cell apoptosis,and DNA damage repair.
RESUMEN
Objective To investigate the local-regional recurrence in thoracic esophageal cancer after radical surgery including two-field lymph node dissection and provide evidence for postoperative radiotherapy. Methods We reviewed local-regional recurrence for 134 cases with esophageal squamous cell carcinoma after radical surgery from 2004 to 2009. Results In 134 cases, lymph node metastasis rate,anastomosis recurrence rate and tumor bed recurrence rate was 94. 0%, 9. 7% and 3.7%, respectively. As to the 126 cases with lymph node metastasis, significant difference was detected between mediastinal metastasis, supraclavicular metastasis and abdominal lymph node metastasis (80. 2%, 43.7% and 13.5%,respectively, χ2= 113. 15, P = 0. 000). Furthermore, the relative metastasis rate in upper mediastinum,middle mediastinum and the lower mediastinum was 73.8%, 39.7% and 1.6%, respectively, the difference was statistically significant ( χ2 = 139. 11, P = 0. 000 ). Significant difference was identified between right and left supraclavicular lymph node metastasis (31.7% vs 16. 7%, χ2= 7. 81, P = 0. 005 ).To confirm the analysis above,lymph node metastasis rate of left recurrent laryngeal nerve nodes, (including region 1L, 2L, 4L and 5) ,right recurrent laryngeal nerve nodes, azygos nodes, subcarinal nodes, and 2R region was 38.9%, 43.7%, 15.1%, 34.1% and 25.4%, respectively. Conclusions The main characteristics of local-regional recurrence may be lymph node metastasis for esophageal squamous cell carcinoma after radical surgery. On the contrary, tumor bed recurrence is rare. Dangerous regions include supraclavicular nodes, recurrent laryngeal nerve nodes, azygos nodes as well as subcarinal nodes.