Low dose volume histogram analysis of the lungs in prediction of acute radiation pneumonitis in patients with esophageal cancer treated with three-dimensional conformal radiotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the predictive value of low dose volume of the lung on acute radiation pneumonitis (RP) in patients with esophageal cancer treated with three-dimensional conformal radiotherapy (3D-CRT) only, and to analyze the relation of comprehensive parameters of the dose-volume V5, V20 and mean lung dose (MLD) with acute RP.</p><p><b>METHODS</b>Two hundred and twenty-two patients with esophageal cancer treated by 3D-CRT have been followed up. The V5-V30 and MLD were calculated from the dose-volume histogram system. The clinical factors and treatment parameters were collected and analyzed. The acute RP was evaluated according to the RTOG toxicity criteria.</p><p><b>RESULTS</b>The acute RP of grade 1, 2, 3 and 4 were observed in 68 (30.6%), 40 (18.0%), 8 (3.6%) and 1 (0.5%) cases, respectively. The univariate analysis of measurement data:The primary tumor length, radiation fields, MLD and lung V5-V30 had a significant relationship with the acute RP. The magnitude of the number of radiation fields, the volume of GTV, MLD and Lung V5-V30 had a significant difference in whether the ≥ grade 1 and ≥ grade 2 acute RP developed or not. Binary logistic regression analysis showed that MLD, Lung V5, V20 and V25 were independent risk factors of ≥ grade 1 acute RP, and the radiation fields, MLD and Lung V5 were independent risk factors of ≥ grade 2 acute RP. The ≥ grade 1 and ≥ grade 2 acute RP were significantly decreased when MLD less than 14 Gy, V5 and V20 were less than 60% and 28%,respectively. When the V20 ≤ 28%, the acute RP was significantly decreased in V5 ≤ 60% group. When the MLD was ≤ 14 Gy, the ≥ 1 grade acute RP was significantly decreased in the V5 ≤ 60% group. When the MLD was >14 Gy, the ≥ grade 2 acute RP was significantly decreased in the V5 ≤ 60% group.</p><p><b>CONCLUSIONS</b>The low dose volume of the lung is effective in predicting radiation pneumonitis in patients with esophageal cancer treated with 3D-CRT only. The comprehensive parameters combined with V5, V20 and MLD may increase the effect in predicting radiation pneumonitis.</p>

Relationship of gross tumor volume with lymph node metastasis and prognosis of esophageal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore whether there is a relationship between gross tumor volume (GTV) and pathologic lymph node metastasis or prognosis of esophageal carcinoma, and to provide a new prognosis reference for esophageal carcinoma (EC).</p><p><b>METHODS</b>Six hundred and seven patients received radical resection of thoracic esophageal carcinoma from May 2002 to June 2006 in our hospital, and their pre-operative CT images were transmitted to the three-dimensional conformal radiotherapy planning system by the network in digital format. Esophageal GTV targets were outlined and their GTV volumes were calculated. To analyze whether there is a relationship between GTV volume and pathologic lymph node metastasis or prognosis.</p><p><b>RESULTS</b>In the 607 cases of esophageal carcinoma, the GTV volume was (22.5 ± 16.8) cm(3) in 374 stage N0 EC patients, significantly different from that of (30.4 ± 20.1) cm(3) in 233 stage N1 EC cases (P < 0.001). There is a significant difference between the GTV volumes of the groups with and without lymph node metastasis (P < 0.05). There was a significant difference of the GTV volumes of EC patients with one lymph node metastasis and those with ≥ 4 lymph node metastasis (P < 0.05). There was a positive correlation between GTV volume and the number of lymph node metastasis (r = 0.230, P < 0.001). The 1-, 3-, 5-year survival rates since the surgery date were 83.8%, 53.5%, and 36.4%, respectively. There was a significant difference between the survival rates of stage N0 (48.5%) and stage N1 patients (18.2%, P < 0.001), and there was a significant difference between the survival rats of patients with 0, 1 and ≥ 2 lymph node metastasis (P < 0.01). Cox regression model analysis showed that GTV volume, number of lymph node metastasis, pathological type, and lesion site were independent prognostic factors (all P < 0.05).</p><p><b>CONCLUSION</b>The GTV volume of esophageal carcinoma is positively correlated with the number of pathologic lymph node metastasis, and it is an independent prognostic factor for this cancer.</p>

Prognostic analysis of clinicopathological factors in patients after radical resection of esophageal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore factors affecting the survival in patients after radical resection of esophageal carcinoma, and to provide a valuable reference for selecting treatment protocol after surgery.</p><p><b>METHODS</b>Clinicopathological data of 618 esophageal cancer patients who underwent radical resection at the Fourth Hospital of Hebei Medical University from May 2002 to June 2006 were collected and reviewed in this study. All patients had no cancer history, did not receive preoperative radiotherapy or chemotherapy, and had Karnofsky performance scores ≥ 70. Univariate analysis was performed by using log-rank test to determine predictors of survival, and multivariable analysis was performed by a Cox regression model.</p><p><b>RESULTS</b>The overall 1-, 3-, 5-year survival rates were 83.32%, 53.33%, 36.02%, respectively, and the median survival time was 38.33 months. The Cox regression analysis showed that operation mode, intraoperative findings of the extent of tumor invasion, pathological T stage, and the number of metastatic lymph nodes were significant predictors of survival. For patients with lymph node metastasis, the overall 1-, 3-, and 5-year survival rates did not significantly differ between the operation alone group and the postoperative prophylactic radiotherapy group. For patients without lymph node metastasis, the 1-, 3-, and 5-year survival rates were 94.34%, 51.55%, and 34.41%, respectively, in the postoperative radiotherapy group, significantly higher than those in the operation alone group (63.08%, 23.30% and 4.36%; χ(2) = 15.99, P < 0.01).</p><p><b>CONCLUSIONS</b>The independent prognostic factors of esophageal cancer patients after radical resection include the operation mode, intra-operative findings of the extent of tumor invasion, pathological T stage, the number of lymph node metastasis and the number of regions of lymph node metastasis. Postoperative prophylactic radiotherapy is beneficial for esophageal cancer patients with lymph node metastasis.</p>

Characteristics of the lymph node metastases and influencing factors and their value in target region delineation in postoperative radiotherapy for thoracic esophageal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the distribution of lymph node metastases, to analyze the cliniopathologic factors of thoracic esophageal carcinoma after curative resection, and to provide the criteria of irradiated region delineation in radiotherapy for esophageal carcinoma.</p><p><b>METHODS</b>The clinicopathological data of 763 patients who underwent esophagecotomy from Jun 2002 to Jun 2006 were retrospectively analyzed. The regularity of lymph node metastases of thoracic esophageal cancer and clinicopathological factors were stratified and analyzed with SPSS13.0 software.</p><p><b>RESULTS</b>Of the 763 patients, a total of 5846 lymph nodes were dissected with an average of 7.7 lymph nodes in each case. Metastatic lymph nodes were 711, the ratio of metastatic lymph node was 12.2%, and 297 patients had lymph node involved, the lymph node metastasis rate was 38.9%. The metastatic lymph nodes of upper-thoracic esophagus were mainly observed in the supraclavicular and paratracheal regions (P < 0.05), the metastatic lymph nodes of middle-third thoracic esophagus were bidirectional, and those of the lower-third thoracic esophagus mainly metastasized to the regions adjacent to the esophagus, gastric cardia and gastric artery (P < 0.05). Both the metastasis ratio and rate of lymph nodes adjacent to the gastric artery in the lower-thoracic esophageal cancer were significantly higher than those in the middle-third and upper-third thoracic esophageal cancers (P = 0.007, P = 0.001). The multiple factors logistic regression analysis showed that tumor length, depth of tumor invasion, vascular tumor emboli and distant metastasis were major factors for lymphatic metastasis (P < 0.01). For the whole group of patients the lymph node metastatic rate was 28.5% in upper-thoracic esophageal cancer, significantly lower than 38.8% of the lower-thoracic esophageal cancer (P = 0.039) and 43.4% in the middle-thoracic esophageal cancer (P = 0.010). However, the lymph node metastatic rates were 37.0%, 37.9% and 41.4% in the upper-, middle- and lower-thoracic esophageal cancers of the 592 cases receiving left chest notches, with a non-significant difference among them (P = 0.715).</p><p><b>CONCLUSION</b>The lesion length, depth of tumor invasion, vascular tumor embolus and distant metastasis are the most important parameters for lymph node metastases. Operative modes have obvious influence on the distribution of regional lymph node metastases. Therefore, in the clinical management, a postoperative prophylactic radiotherapy may be selected according to the tumor length, depth of tumor invasion, vascular tumor embolus and distant lymph node metastasis.</p>

Exploration of the classification of gross tumor volume and pathological staging of esophageal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Using the volume calculating function of treatment planning system of 3DCRT to work out the value of GTV standard classifications and to provide the reference for clinical staging of esophageal carcinoma.</p><p><b>METHODS</b>Six hundred and seven patients underwent radical resection of thoracic esophageal carcinoma in our hospital, and their pre-operative CT images were transmitted in digital format to the three-dimensional conformal radiotherapy planning system by the network. Esophageal lesion GTV targets were outlined, and their volumes were automatically computed by the planning system. Compared the differences of the GTV volumes in different pathological T stages, and analyzed the relationship between GTV volumes and pathological T stages. According to the median volume of GTV at different pathological T stages, divided the values of GTV volume corresponding to different T stages and selected the suitable classification standard of GTV volume.</p><p><b>RESULTS</b>The esophageal carcinoma GTV length, maximum diameter and volume were related to pathological T staging and with a positive correlation (all P < 0.001). The Spearman correlation coefficient (r) was 0.376, 0.466 and 0.464, respectively, P < 0.001. Except that the length, maximum diameter and volume of GTV in pathological T3 and T4 had no significant difference, other indicators of the pathological T stages showed significant differences between the groups (P < 0.001). According to the median volume of GTV at different pathological T stages, the GTV volumes were divided into three grades: <or= 5.0 cm(3), 5.1 - 13.0 cm(3), and > 13.0 cm(3). When compared them with pathological T1, T2, and T3-T4 stages, the coincidence rate was 73.8%. The consistency was good between the GTV volume grades and pathological T stages (Kappa = 0.40, P < 0.001). The overall 5-year survival rates of GTV grades 1, 2, 3 were 78.1%, 31.5% and 33.5%, respectively (P < 0.0001). If the GTVs were divided into four grades: <or= 5.0 cm(3), 5.1 - 13.0 cm(3), 13.1 - 39.0 cm(3), and > 39.0 cm(3), the coincidence rate of GTV volume grades and pathology T staging was only 54.7%, and the consistency was poor, Kappa = 0.24, P < 0.001. The overall 5-year survival rate of GTV 1, 2, 3, 4 were 78.1%, 31.5%, 36.2% and 27.5%, respectively (P < 0.0001).</p><p><b>CONCLUSION</b>The length, maximum diameter and volume of esophageal carcinoma GTV are related to pathological T staging with a positive correlation. The classification that esophageal carcinoma GTVs divided into three grades has a good coincidence with the pathological T staging.</p>

Short hairpin RNA-mediated MDC1 gene silencing enhances the radiosensitivity of esophageal squamous cell carcinoma cell line ECA109 / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effect of MDC1 gene silencing by RNA interference on the radiosensitivity of human esophageal carcinoma cell line ECA109.</p><p><b>METHODS</b>The vectors containing short hairpin RNA (shRNA) targeting MDC1 gene (pMDC1-shRNA) were cotransfected with pPACKH1-lentivector packaging system into 293T cells to package the lentivirus particles. Forty-eight hours after the transfection with specific or control lentiviral vectors, the stable integrants were selected using copGFP reporter gene; real-time RT-PCR and Western blotting were used to detect the expression levels of MDC1 mRNA and protein in the transfected ECA109 cells, respectively. The cell cycle distribution was measured with flow cytometry at 12, 24 and 48 h after a 5 Gy irradiation, and the radiosensitivity of esophageal carcinoma cell was evaluated by clone formation array.</p><p><b>RESULTS</b>Sequence analysis confirmed correct insertion of MDC1-shRNA construct into pSIH1-H1-copGFP. The percentage of G2/M phase ECA109/ MDC1 cells was lower than that of ECA109 and ECA109/negative cells. The value of D0, SF2 and Dq of ECA109/ MDC1 cells were 1.88 Gy, 0.84 and 1.20, respectively, lower than those of ECA109 cells (3.06 Gy, 0.91 and 1.59) and those of ECA109/negative cells (2.90 Gy, 0.89 and 1.47).</p><p><b>CONCLUSION</b>RNA interference can inhibit MDC1 gene expression and enhance the radiosensitivity of ECA109 cells in vitro.</p>

Expression of DNA damage checkpoint mediator 1 and p53-binding protein 1 in human esophageal cancer cell lines TE-1, TE-13, and Eca109 / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the expression of DNA damage checkpoint mediator 1 (MDC1) and p53-binding protein 1 (53BP1) at both mRNA and protein levels and their significance in different human esophageal cancer cell lines.</p><p><b>METHODS</b>In 3 human esophageal carcinoma cell lines, TE-1, TE-13 and Eca109 cells, the expressions of MDC1 and 53BP1 mRNA were detected with RT-PCR, and MDC1 and 53BP1 protein expressions were measured with immunohistochemistry, indirect immunofluorescence and Western blotting, respectively.</p><p><b>RESULTS AND CONCLUSIONS</b>MDC1 and 53BP1 expressions were observed for the first time in human esophageal carcinoma cell lines TE-1,TE-13 and Eca109 cells, at both the mRNA and protein levels. The expressions of MDC1 and 53BP1 proteins may be implicated in the radiosensitivity of human esophageal carcinoma.</p>

Effect on retardation of G2/M phase in esophageal carcinoma cells transfected with CHK1 and CHK2 shRNA after irradiation / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To observe the effect of RNA interference on CHK1 and CHK2 expression and change of G2/M phase arrest in esophageal carcinoma cells after irradiation.</p><p><b>METHODS</b>Four sequences short hairhip RNA (shRNA) of each CHK1 and CHK2 genes were constructed and connected with vector of pENTR/U6 plasmid, respectively, and then transfected into Eca109 cells with lipofectamine 2000 reagent. Protein and mRNA expression of CHK1 and CHK2 genes were detected with Western blotting and RT-PCR, respectively. Cell cycling was measured by flow cytometry after 5 Gy irradiation. Cell survival rate after 5 Gy irradiation was evaluated by clonegenetic assay.</p><p><b>RESULTS</b>Four shRNA vector each of CHK1 and CHK2 genes were successfully constructed and transfected into Ecal09 cells, respectively. Protein expression of CHK1 and CHK2 were obviously decreased. Their mRNA expressions were also decreased after transfected with shRNA of CHK1 and CHK2. Arrest of G2/M stage in Eca109 cells were obviously decreased only in cells transfected with CHK1 shRNA but not with CHK2 shRNA at 12 h after 5 Gy irradiation. In first progeny Eca109 cells transfected with CHK1 and CHK2 shRNA, expression of CHK1 and CHK2 protein was also decreased. The level of phosphorylated CHK2-T68 expression was decreased at 1 h after 5 Gy irradiation, and at 72 h only transfected with CHK2 shRNA but not with CHK1 shRNA. Phosphorylation level of CHK1-S345 was not increased after transfected with CHK1 or CHK2 shRNA, but arrest of G2/M stage still remained at 12 h after 5 Gy irradiation and at 72 h accordingly. The cell survival rate was decreased in Eca109 cells transfected with CHK1 or CHK2 shRNA after 5 Gy irradiation.</p><p><b>CONCLUSION</b>After transfected with shRNA of CHK1 or CHK2, their expressions of mRNA and protein in Ecal09 cells are markedly inhibited and this inhibition effect can be observed in their first progeny cells and at least hold for 3 days. Arrest of G2/M phase can be reduced after irradiation when teansfected with shRNA of CHK1 and the radiosensitivity of Ec109 cells can be increased.</p>

Influence of pathological characteristics on radiotherapeutic target area of esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Objective To investigation the pathological characteristics of esophageal squamous cell carcinoma to provide reference criteria for delineating the target area in radiotherapy.Methods Fifty-two patients from the Fourth Hospital of HeBei Medical University underwent resection whom all had been proved to have esophageal squamous cell carcinoma before operation.Chest CT was scanned and transmitted to the 3- dimensional conformal planning system for radiotherapy by VRX-16 scanner.The lesion of esophageal carcinoma was delineated in the 3-dimensional rebuild CT image and the lesion volume was computed by digital rebuild program.Every surgically resected specimen was made into pathologic giant section.The actual size of the specimen was obtained by calculating the size under the microscope with the shrinkage ratio.Multicentric carcinomatous lesion,severe dysplasia and direct intramural infiltration were observed in the giant section with a microscope and the order of such pathological characteristics were analysed statistically.Results 1.The tumor length by different method of preparation of operated specimens differed obviously.The longest was shown by CT. 2.Multicentric carcinomatous lesion was found in 15(29%)cases out of 52 patients.Proximal to the tumor,the mean distance between the multicentric carcinomatous lesion and the main lesion plus the length of the multicentric carcinomatous lesion was 3.02?1.45cm.Distal to the tumor,it was 2.60?2.44 cm.Severe dysplasia was found in 28 patients.Proximally,the mean distance between the severe dysplasia and the main lesion plus the length of the severe dysplasia was 2.45?1.30 cm.Distal to the tumor,it was 3.24?2.19 cm.Direct intramural infiltration was found in 41 patients,of which the mean length being 2.80?1.52 cm proximally and 2.02?1.51 cm distally. 3.Tumor thrombus was found in 6 patients and lymphoduct infiltration in 36 patients.Direct intramural infiltration was found at higher incidence in specimens complicated with lymphoduct infiltration(86%)and those complicated with tumor thrombus(91%).There were no apparent factors affecting severe dysplasia.The proximal distance to direct intra- mural infiltration was much longer than distally.Conclusions Multicentric carcinomatous lesion,severe dysplasia and direct intramural infiltration may be observed in esophageal squamous cell carcinoma.Multicentric carcinomatous lesion and direct intramural infiltration are obviously correlated with lymphoduct infiltration.To cover 95% of the microscopic extension,a margin of 5.0 cm is needed proximal to the base of gross tumor volume,and 7.5 cm distal to it.To cover 90% of the microscopic extension,a margin of 4.5 cm is needed proximally,and 5.0 cm distally.