ObjectiveTo analyze intrathoracic or extrathoracic recurrence pattern after surgical resection of thoracic esophageal squamous cell carcinoma (TESCC) and its help for further modify and improvement on the target of postoperative radiation therapy. Methods One hundred and ninety-five patients who had undergone resection of TESCC at the Cancer Hospital,Chinese Academy of Medical Sciences enrolled from April 1999 to July 2007.Sites of failure on different primary location of esophageal cancer were documented.Results Patients with upper or middle thoracic esophageal cancer had higher proportion of intrathoracic recurrence.Patients with lower thoracic esophageal cancer had more intrathoracic reccurence and abdominal lymph node metastatic recurrence.Histological lymph node status has nothing to do with intrathoracic recurrence,supraclavicular lymph node ( SLN ) metastasis or distant metastasis ( χ2 =1.58,0.06,0.04,P =0.134,0.467,0.489,respectively),whereas the chance of abdominal lymph node metastases in N positive patients was significantly higher than that in N0 patients (28.7％: 10.6％,χ2 =9.94,P =0.001 ),and so did in middle thoracic esophageal cancer ( 20.0％: 5.6％,χ2 =5.67,P =0.015). Anatomic recurrence rate of patients with proximal resection margin no more than 3 cm was significantly higher compared to those more than 3 cm (25.0％: 11.3％,χ2=5.65,P=0.019).ConclusionsMediastinum is the most common recurrence site.According to recurrence site,the following radiation targets are recommended:when tumor was located at the upper or middle thoracic esophagus with negative N status,the mediastinum,the tumor bed and the supraclavicular region should be included as postoperative RT target;when tumor was located at the middle thoracic esophagus with positive N or located at the lower thoracic esophagus,the abdominal lymph node should be added.If the proximal resection margin was no more than 3 cm,the anastomotic-stoma should be included.

Objective To investigate whether catalpol affects senile plaque formation and spatial learning and memory ability in the amyloid-β protein precursor/presenilin 1 (APP/PSI) double transgenic mice.Methods Three month-old APP/PS1 double transgenic mice were randomly divided into catalpoltreated and saline-treated groups (n =10),with C57 mice of the same age and genetic background as normal control group (n =10).The catalpol (in a dose of 5 mg · kg-1 · d-1) and the same amount of saline were peritoneally injected into Alzheimer' s disease (AD) model mice for 3 weeks.Immunohistochemical staining was performed to examine senile plaques in the brain of AD model mice,and Morris water maze was used to assess the spatial learning and memory abilities of the mice.Results Compared with the saline-treated AD model mice (6.0 ±0.6),the number of senile plaques of catalpol treated AD mice significantly decreased (2.3± 0.7; t =3.500,P =0.025); Mice in each groups had similar latency and path length to reach platform in visible platform test; In hidden platform test,catalpol-treated mice had a significant lesser latency and path length compared with saline-treated mice,furthermore,catalpol-treated mice had much more platform-crossing times (6.4 ± 0.8) than saline-treated mice (2.9 ± 0.4 ; t =5.592,P =0.001).Conclusion Catalpol can significantly decrease the senile plaque formation and improve the spatial learning and memory abilities of APP/PS1 double transgenic mice.

Objective:To investigate the relationship between histone deacetylase (HDAC) gene polymorphism and type 2 diabetes mellitus (T2DM) in Bai and Han populations in Dali of Yunnan province.Methods:A total of 148 patients with T2DM of Bai and Han nationalities who received treatment in Dali Bai Autonomous Prefecture People's Hospital from May 2019 to March 2021 were included in the T2DM group. An additional 100 healthy controls of Bai and Han nationalities who concurrently received physical examination in the same hospital from May 2019 to December 2020 were included in the normal control group. The susceptibility genes of T2DM were detected using the Taqman MGB probe method. The susceptibility gene loci were amplified using polymerase chain reaction. The whole sequence of susceptibility gene was sequenced.Results:There were no significant differences in the distribution frequencies of rs2530223 genotype, rs11741808 genotype, rs2547547 genotype, and rs1741981 genotype between Bai and Han populations (all P > 0.05). There was a significant difference in blood lipid level between four loci ( t = -1.06, -0.19, 0.39, -2.12, -2.04, 0.16, 1.47, < 0.01, -0.16, -3.17, -2.93, 0.69, -2.58, -2.33, all P < 0.05). There was a significant difference in homeostasis model assessment of insulin resistance between different states (all P < 0.05). The frequency distributions of each genotype and each allele did not differ significantly between healthy control people of Bai nationality and T2DM patients of Bai nationality and between healthy control people of Han nationality and T2DM patients of Han nationality (all P > 0.05). Logistic regression analysis showed that the polymorphism was not an independent risk factor for T2DM. Conclusion:The relationships between HDAC gene polymorphism and T2DM, obesity and dyslipidemia differ between Bai and Han populations.

Objective To analyze the clinical value of postoperative radiotherapy for node-positive middle thoracic esophageal squamous cell carcinoma ( TESCC ) and to modify the target volume .Methods A total of 286 patients with node-positive middle TESCC underwent radical surgery in Cancer Hospital, Chinese Academy of Medical Sciences, from 2004 to 2009.In addition, 90 of these patients received postoperative intensity-modulated radiotherapy.The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was used for survival difference analysis.The Cox model was used for multivariate prognostic analysis.The chi-square test was used for comparing the recurrence between patients receiving different treatment modalities.Results The 5-year overall survival ( OS) rates of the surgery alone ( S) group and surgery plus postoperative radiotherapy ( S+R) group were 22.9%and 37.8%, respectively, and the median OS times were 23.2 and 34.7 months, respectively ( P=0.003) .For patients with 1 or 2 lymph
node metastases (LNMs), the 5-year OS rates of the S group and S+R group were 27.3%and 44.8%, respectively ( P=0.017);for patients with more than 2 LNMs, the 5-year OS rates of the S group and S+R group were 16.7%and 25.0%, respectively (P=0.043).The peritoneal lymph node metastasis rates of N1 , N2 , and N3 patients in the S group were 2.9%, 10.9%, and 20.0%, respectively ( P=0.024) .The S+R group had a significantly lower mediastinal lymph node metastasis rate than the S group ( for patients with 1 or 2 LMNs:8.0%vs.35.3%, P=0.003;for patients with more than 2 LNMs, 10.0%vs.42.3%, P=0.001) , and had a prolonged recurrence time compared with the S group ( 25.1 vs.10.7 months, P=0.000) .However, for patients with more than 2 LNMs, the S+R group had a significantly higher hematogenous metastasis rate than the S group (46.7%vs.26.1%, P=0.039).Conclusions Patients with node-positive middle TESCC could benefit from postoperative radiotherapy.The target volume can be reduced for patients with 1 or 2 LNMs.Prospective studies are needed to examine whether it is more appropriate to reduce the radiotherapy dose than to reduce the target volume for patients with more than 2 LNMs.A high hematogenous metastasis rate warrants chemotherapy as an additional regimen.

[ Abstract] Objective To investigate the clinical efficacy of preoperative three-dimensional radiotherapy (3DRT) with or without concurrent chemotherapy for esophageal carcinoma.Methods We retrospectively analyzed 103 esophageal carcinoma patients who received preoperative 3DRT with or without concurrent chemotherapy from 2004 to 2014 in Cancer Hospital CAMS.The median radiation dose was 40 Gy, and the TP or PF regimen was adopted for concurrent chemotherapy if needed.The overall survival (OS) and disease-free survival ( DFS) were calculated by the Kaplan-Meier method, and the survival difference and univariate prognostic analyses were performed by the log-rank test.The Cox proportional hazards model was used for multivariate prognostic analysis.Results The number of patients followed at 3-years was 54.The 3-year OS and DFS rates were 61.1% and 54.9%, respectively, for all patients.There were no significant differences between the 3DRT and concurrent chemoradiotherapy (CCRT) groups as to OS (P=0.876) and DFS (P=0.521).The rates of complete, partial, and minimal pathologic responses of the primary tumor were 48.0%, 40.2%, and 11.8%, respectively.There were significant differences in OS and DFS between the complete, partial, and minimal pathologic response groups (P=0.037 and 0.003). No significant difference in pathologic response rate was found between the 3DRT and CCRT groups (P=0.953).The lymph node metastasis rate was 26.5%, and this rate for the complete, partial, and minimal pathologic response groups was 14%, 30%, and 67%, respectively, with a significant difference between the three groups (P=0.001).The OS and DFS were significantly higher in patients without lymph node metastasis than in those with lymph node metastasis (P=0.034 and 0.020).The surgery-related mortality was 7.8% in all patients.Compared with the 3DRT group, the CCRT group had significantly higher incidence rates of leukopenia (P=0.002), neutropenia (P=0.023), radiation esophagitis (P=0.008), and radiation esophagitis ( P=0.023).Pathologic response of the primary tumor and weight loss before treatment were independent prognostic factors for OS and DFS (P=0.030,0.024 and P=0.003,0.042). Conclusions Preoperative 3DRT alone or with concurrent chemotherapy can result in a relatively high complete pathologic response rate, hence increasing the survival rate.Further randomized clinical trials are needed to confirm whether preoperative CCRT is better than 3DRT in improving survival without increasing the incidence of adverse reactions.

Objective:To evaluate the clinical efficacy and failure patterns of prophylactic cranial irradiation (PCI) in patients with limited-stage small cell lung cancer (LS-SCLC) on the basis of modern chemoradiotherapy and diagnostic techniques.Methods:In this retrospective study, clinical data of 201 LS-SCLC patients treated with chemotherapy (EP/CE regimens, ≥4 cycles) and intensity-modulated radiotherapy (IMRT) in Cancer Hospital of Chinese Academy of Medical Sciences from 2006 to 2014 were reviewed. All patients were primarily managed with concurrent or sequential chemoradiotherapy and achieved complete response (CR) or partial response (PR). Ninety percent of patients were revaluated for brain metastasis (BM) by MRI and 10% by CT scan. Long-term survival and failure patterns were compared between the PCI ( n=91) and non-PCI groups ( n=110). Results:The median follow-up time was 77.3 months (95% CI 73.0-81.5 months). The median overall survival (OS), 2-and 5-year OS rates were 58.5 months, 72.5% and 47.7% in the PCI group, and 34.5 months, 61.7% and 35.8% in the non-PCI group ( P=0.075). The median progression-free survival (PFS), 2-and 5-year PFS rate were 22.0 months, 48.0% and 43.4% in the PCI group, significantly higher than 13.9 months, 34.4% and 26.7% in the non-PCI group ( P=0.002). The 2- and 5-year cumulative incidence of BM were 6.6% and 12.2% in the PCI group, and 30.0% , 31.0% in the non-PCI group ( P=0.001). The median time and rate of BM as an isolated first site of relapse were 11.9 months and 4.4% in the PCI group, and 8.7 months and 25.5% in the non-PCI group ( P<0.001). Multivariate analysis showed that response after chemoradiotherapy ( P<0.001) and PCI ( P=0.033) were the independent prognostic factors for PFS. Stratified analysis demonstrated that PCI significantly improved the 5-year PFS in patients who achieved CR (72.7% vs. 48.0%, P=0.013), while it did not improve the 5-year PFS in patients who obtained PR (26.1% vs. 20.2%, P=0.213). Conclusion:In the new era of standard chemoradiotherapy and more accurate diagnostic methods for BM, PCI was associated with improved PFS and lower incidence of BM in LS-SCLC patients.

Objective To investigate the clinical efficacy and prognosis of intensity-modulated radiotherapy(IMRT)combined with chemotherapy for limited-stage small cell lung cancer(LS-SCLC). Methods A retrospective analysis was performed on the clinical data of 484 LS-SCLC patients treated with chemoradiotherapy in our center from 2006 to 2014. The patients with partial or complete response to IMRT received prophylactic cranial irradiation(PCI). The Kaplan?Meier method was used to calculate survival rates, and the log-rank test and Cox regression were used for univariate and multivariate analyses, respectively. Results In all the patients, the follow-up rate was 93%;the median overall survival(OS) time was 23.8 months;the 2-,3-,and 5-year OS rates were 48.7%,39.8%,and 28.6%,respectively;the median progression-free survival(PFS)time was 14.1 months;the 2-, 3-, and 5-year PFS rates were 34.4%,30.5%, and 28.3%, respectively. The incidence rates of grade ≥3 bone marrow suppression, grade ≥2 radiation esophagitis, and grade ≥2 radiation pneumonitis were 26.9%, 24.8%, and 18.4%, respectively, in SCLC patients after IMRT. The objective response rate was 84.5%. The univariate analysis showed that age, smoking history, TNM stage, PCI, and the number of chemotherapy cycles before radiotherapy were prognostic factors for OS(P= 0.006, 0.001, 0.047, 0.000, and 0.046). The multivariate analysis showed that smoking history and PCI were independent prognostic factors(P=0.001 and 0.000).Conclusions IMRT combined with chemotherapy achieves satisfactory clinical outcomes in the treatment of LS-SCLC. Smoking history and PCI are independent prognostic factors for OS of LS-SCLC patients.

Objective To evaluate the dose distribution and clinical efficacy of hippocampal-sparing prophylactic cranial irradiation ( HS-PCI ) in patients with small cell lung cancer by using helical tomotherapy. Methods Clinical data of 49 patients with small cell lung cancer receiving HS-PCI using helical tomotherapy in Cancer Hospital between 2014 and 2017 were retrospectively analyzed. All patients received brain MRI to exclude the possibility of brain metastasis within 1 month after standard surgery or radio-and chemo-therapy. The prescription dose was 95% PTV,25 Gy in 10 fractions. The adverse reactions and cognitive functions of patients were observed before,6 months and 1 year after treatment,and the dose distribution in the hippocampal gyrus,survival rate and brain metastasis rate were analyzed. Results The median follow-up time was 16 months. The average dose in the hippocampal gyrus was 7. 23 Gy and 8. 46 Gy in the reduction region,which was reduced by 71. 88% and 66. 16% compared with the prescription dose. The maximum dose in the hippocampal gyrus was 10. 66 Gy and 15. 43 Gy in the reduction region. Among 49 patients,8 died,the 1-year survival rate was 85. 1% and the 2-year survival rate was 70. 3%.Nine patients (18. 3%) had brain metastases,and one of them with extensive multiple brain metastases (n＝13) presented with metastasis adjacent to the hippocampal gyrus. The main adverse reactions included mild headache, dizziness and brain edema,whereas no ≥ grade 2 adverse reactions occurred. At 6 months after treatment, the HVLT-R score was significantly decreased,and declined by 6. 78% at 12 months after treatment. The HVLT-R scores did not significantly differ in patients without brain metastasis before and 12 months after treatment ( P＞0. 05 ). Conclusion Application of HS-PCI using helical tomotherapy meets the dose requirement,effectively protects the cognitive function and yields slight adverse reactions.

Objective This study aimed to evaluate the impact of technical advancement of radiation therapy in patients with LA?NSCLC receiving definitive radiotherapy (RT). Methods Patients treated with definitive RT (≥50 Gy) between 2000 and 2010 were retrospectively reviewed. Overall survival ( OS) , cancer specific survival ( CSS) , locoregional progression?free survival ( LRPFS) , distant metastasis?free survival (DMFS) and progression?free survival (PFS) were calculated and compared among patients irradiated with different techniques. Radiation?induced lung injury ( RILI) and esophageal injury ( RIEI) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events 3.0 ( NCI?CTCAE 3.0) . Results A total of 946 patients were eligible for analysis, including 288 treated with two?dimensional radiotherapy ( 2D?RT) , 209 with three?dimensional conformal radiation therapy ( 3D?CRT) and 449 with intensity?modulated radiation therapy ( IMRT) respectively. The median follow?up time for the whole population was 84.1 months. The median OS of 2D?RT, 3D?CRT and IMRT groups were 15.8, 19.7 and 23.3 months, respectively, with the corresponding 5?year survival rate of 8. 7%, 13. 0% and 18. 8%, respectively ( P<0.001) . The univariate analysis demonstrated significantly inferior OS, LRPFS, DMFS and PFS of 2D?RT than those provided by 3D?CRT or IMRT. The univariate analysis also revealed that the IMRT group had significantly loger LRPFS and a trend toward better OS and DMFS compared with 3D?CRT. Multivariate analysis showed that TNM stage, RT technique and KPS were independent factors correlated with all survival indexes. Compared with 2D?RT, the utilization of IMRT was associated with significantly improved OS, LRPFS, DMFS as well as PFS. Compared with 3D?CRT, IMRT provided superior DMFS ( P=0.035), a trend approaching significance with regard to LRPFS (P=0.073) but no statistically significant improvement on OS, CSS and PFS in multivariate analysis. The incidence rates of RILI were significantly decreased in the IMRT group (29.3% vs. 26.6% vs.14.0%, P<0.001) whereas that of RIET rates were similar (34.7% vs. 29.7% vs. 35.3%, P=0.342) among the three groups. Conclusions Radiation therapy technique is a factor affecting prognosis of LA?NSCLC patients. Advanced radiation therapy technique is associated with improved tumor control and survival, and decreased radiation?induced lung toxicity.