Objective To investigate the effects of low dose of gamma knife irradiation on the expression of N-methyl-D-aspartate (NMDA) receptor subunits in cortex and hippocampus of epileptic rats. Methods The rats were randomly divided into 4 groups: control group, GK group, pentylenetetrazole (PTZ) group and GK+ PTZ group. The rats were injected intraperitoneally with PTZ to establish the epileptic models. Gamma knife irradiation was performed on bilateral frontal cortex of rats at a peripheral dose of 15Gy. After irradiation, the changes of the seizure and behaviors were observed and recorded. The rats were killed on the 12th week after irradiation, Immunohistochemstry and western blotting were used to detect the relative expression levels of NMDAR subunits (NR1, NR2A, and NR2B) in the cortex and hippocampus. Results There were no epileptic seizures in the control group and the GK group. Compared with the PTZ group, the epileptic seizures of rats in the GK+PTZ group were significantly reduced after low dose gamma knife irradiation (P<0.05). Compared with control group, the protein expression levels of NR1, NR2A and NR2B in the PTZ group increased significantly in the cortex and hippocampus, and so were the positive neurons and their average absorbance value (P<0.05). Compared with PTZ group, the protein expression levels of NR1, NR2A and NR2B of the GK+PTZ group decreased remarkably in the cortex and hippocampus (P<0.05). Protein expression levels of NR1, NR2A and NR2B were not significantly different between control group and GK group (P＞0.05). Conclusion Epileptic rats exhibited an increase in the protein expression levels of NR1, NR2A and NR2B in the cortex and hippocampus while low dose of gamma knife irradiation can decrease expression levels of NMDA receptor subunits in the cortex and hippocampus of epileptic rats, which might represent a possible mechanism underlying the therapeutic effects of gamma knife irradiation on epileptic seizure.

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.

Tumor-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is a rare paraneoplastic syndrome characterized by hypophosphatemia resulting from decreased tubular phosphate reabsorption, with a low or inappropriately normal level of active vitamin D. The culprit tumors of TIO could produce fibroblast growth factor 23 which plays a role in regulating renal Pi handling and 25-hydroxyvitamin D 1α-hydroxylase activity. Chronic hypophosphatemia could eventually lead to inadequate bone mineralization, presenting as osteomalacia. The diagnosis should be considered when patients manifest as hypophosphatemia and osteomalacia, or rickets and needs to be differentiated from other disorders of phosphate metabolism, such as the inhereditary diseases like X-linked hypophosphataemic rickets, autosomal dominant hypophosphataemic rickets, autosomal recessive hypophosphataemic rickets and acquired diseases like vitamin D deficiency. Localization of responsible tumors could be rather difficult since the vast majority are very small and could be everywhere in the body. A combination of thorough physical examination, laboratory tests and imaging techniques should be applied and sometimes a venous sampling may come into handy. The technology of somatostatin-receptor functional scintigraphy markedly facilitates the localization of TIO tumor. Patients undergoing complete removal of the causative neoplasm generally have favorable prognoses while a few have been reported to suffer from recurrence and metastasis. For those undetectable or unresectable cases, phosphate supplements and active vitamin D should be administrated and curative intended radiotherapy or ablation is optional.
Calcification, Physiologic ; Diagnosis ; Fibroblast Growth Factors ; Humans ; Hypophosphatemia ; Metabolism ; Neoplasm Metastasis ; Osteomalacia ; Paraneoplastic Syndromes ; Physical Examination ; Prognosis ; Radionuclide Imaging ; Radiotherapy ; Recurrence ; Rickets ; Vitamin D ; Vitamin D Deficiency

Objective To investigate the consensus and controversies on the delineation of radiotherapy target volume for patients with locally advanced non-small cell lung cancer (LA-NSCLC).Methods Questionnaires including 15 questions on the delineation of radiotherapy target volume of NSCLC were sent to 12 radiation departments in China in November 2015.A patient with LA-NSCLC was selected by Fudan University Shanghai Cancer Center, and simulation CT images and medical history data were sent to the 12 radiation departments.Twelve radiation oncologists from the 12 radiation departments showed and explained the delineation of radiotherapy target volume of their own, and the patient was discussed by all experts in the sixth multidisciplinary summit forum of precise radiotherapy and chemotherapy for tumor and lung cancer.Results All receivers of the questionnaire answered the questions.The standard lung window width/level for the delineation of lung cancer was 800-1600/-600 to-750 HU, and the mediastinum window was 350-400/20-40 HU.Respiratory movement was measured by stimulator, 4D-CT, and stimulator+4D-CT with 2-5 mm expansion based on experience.The primary clinical target volume (CTV) was defined as gross target volume (GTV) plus 5-6 mm for squamous carcinoma/5-8 mm for adenocarcinoma.The metastatic lesion of mediastinal lymph nodes was delineated as 5 mm plus primary lesion in 6 departments and as primary lesion in another 6 departments.Of the 12 departments, 10 applied 5 mm of set-up error, 1 applied 3 mm, and 1 applied 4-6 mm.For V20 of the lungs, 10 departments defined it as<30%, 1 as<35%, and 1 as 28%.Nine departments defined the radiation dose of concurrent chemoradiotherapy (CCRT) for LA-NSCLC as 60 Gy in 30 fractions, 62.7 Gy in 33 fractions in 1 department, 50-60 Gy in 25-30 fractions in 1 department, and 60-70 Gy in 25-30 fractions in 1 department.For the delineation of target volume for the LA-NSCLC patient treated with CCRT, the primary planning target volume (PTV) was defined as GTV plus organ movement (IGTV) and set-up error (GTV→IGTV→PTV) in 3 departments, as CTV plus organ movement (ITV) and set-up error (GTV→CTV→ITV→PTV) in 8 departments, and as CTV plus set-up error/IGTV plus 5-6 mm for squamous carcinoma/5-8 mm for adenocarcinoma (CTV) and set-up error (GTV→CTV→PTV/GTV→IGTV→CTV→PTV) in 1 department.For the delineation of PTV in the mediastinal lymph node, GTV→IGTV→PTV was performed in 3 departments, GTV→CTV→ITV→PTV in 8 departments, and GTV→CTV→PTV in 1 department.For 10%-100% patients with LA-NSCLC, the radiation field needed to be replanned when 38-50 Gy was completed.There was no unified standard for the optimal standardized uptake value (SUV) of positron emission tomography (PET)-computed tomography (CT) simulation and delineation.Seven departments had applied magnetic resonance imaging (MRI) simulation and 10 departments had applied stereotactic body radiation therapy (SBRT) for the treatment of early-stage NSCLC.For the delineation of PTV for early-stage NSCLC (T1-2N0M0), GTV→IGTV→PTV was performed in 5 departments, IGTV→PTV in 3 departments, and GTV→CTV→ITV→PTV in 2 departments.In all the 12 departments, peripheral early-stage NSCLC was given 6.0-12.5 Gy/fraction, 3-12 fractions and central early-stage NSCLC was given 4.6-10.0 Gy/fraction, 5-10 fractions.The results of discussion on the delineation of target volume for the patient were as follows:respiratory movements should be measured by 4D-CT or simulator;the lung window width/level is 1600/-600 HU and the mediastinal window width/level is 400/20 HU;the primary controversy is whether the involved-field irradiation or elective nodal irradiation should be used for the delineation of CTVnd in the mediastinal lymph node.Conclusions Basic consensus is reached for the delineation of target volume in LANSCLC in these aspects:lung window width/level, respiratory movements and set-up error, primary lesion delineation, the radiation dose in CCRT, and the optimal time for replanning the radiation field.There are controversies on the optimal SUV in the delineation of target volume based on PET-CT simulation, the optimal dose fractionation in SBRT for early-stage NSCLC, and the delineation of CTVnd.

Objective To evaluate the efficacy of rescue treatment for recurrent esophageal cancer after radical esophagectomy, and to provide insights into the development of comprehensive treatment for esophageal cancer.Methods The clinical data of 218 patients who were confirmed with recurrent metastatic esophageal cancer after R0 resection and received rescue treatment in our hospital from 2004 to 2014 were retrospectively reviewed.The survival rate was determined by the Kaplan-Meier method.Univariate and multivariate prognostic analyses were performed using the log-rank test and Cox proportional hazards model, respectively.Results The median post-recurrence follow-up time was 53 months.The 1-and 3-year overall survival (OS) rates after recurrence were 57.2% and 24.4%, respectively.Among the 163 patients with local recurrence, the 1-and 3-year OS rates were 70% and 42% for patients treated with chemoradiotherapy (n=40), 55% and 24% for those with radiotherapy alone (n=106), and 23% and 8% for those with supportive therapy (n=13)(chemoradiotherapy vs.radiotherapy alone P=0.045, radiotherapy alone vs.supportive therapy P=0.004;none of the patients who were treated with chemotherapy alone survived for one year or more).Univariate analysis showed that N staging, TNM staging, and post-recurrence rescue treatment regimen were independent prognostic factors for esophageal cancer (all P=0.001).On the other hand, multivariate analysis indicated that only rescue treatment regimen was the independent prognostic factor for esophageal cancer (P=0.013).Conclusions Rescue chemoradiotherapy or radiotherapy alone can bring significant survival benefits for patients with recurrent and metastatic, especially locally recurrent, esophageal cancer following radical esophagectomy.

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.

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.

OBJECTIVETo analyze the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) for patients with locally advanced non-small-cell lung cancer (LA-NSCLC).

METHODSClinical data of 251 patients with stage III (76 IIIA and 175 IIIB) NSCLC who received CCRT as initial treatment between Jan 2001 and Dec 2010 in our hospital were reviewed. A median total radiotherapy dose of 60 Gy (range, 50-74 Gy) were delivered. 174 patients were treated with IMRT, 51 with 3D-CRT and 26 with 2D-radiotherapy. EP chemotherapy regimen was administered in 112 patients, PC regimen in 99 patients, topotecan regimen in 18 patients and other regimens in the remaining 22 patients. The efficacy and toxicity of CCRT were retrospectively analyzed.

RESULTS244 patients were assessable for response, including 6 (2.5%) patients with CR, 183 (75.0%) with PR, 42 (17.2%) with SD and 13 (5.3%) with PD. At a median follow-up period of 20 months, the 1-, 3-, 5- year OS were 69.2%, 31.2%, 23.2%, respectively, and the median OS was 21 months. The 1-, 3-, 5- year PFS were 40.9%, 22.1%, 17.7%, respectively, and the median PFS was 10 months. Patients with stage IIIA NSCLC achieved better 5-year OS than that with IIIB NSCLC (29.2% vs. 20.7%, χ2=2.254, P=0.133). Failure pattern was assessable in 244 patients, including 61 (25.0%) locoregional progression alone, 55 (22.5%) distant metastasis alone and 77 (31.6%) with both. The rates of grade≥3 radiation pneumonitis, esophagitis and hematologic toxicity were 4.4%, 11.2% and 26.4%, respectively.

CONCLUSIONSCCRT provide stage III NSCLC patients favorable outcome with acceptable toxicity. CCRT is standard therapeutic approach for patients with unresectable locally advanced NSCLC.

Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; pathology ; therapy ; Chemoradiotherapy ; Cisplatin ; administration & dosage ; Cyclophosphamide ; administration & dosage ; Esophagitis ; etiology ; Humans ; Lung Neoplasms ; pathology ; therapy ; Neoplasm Staging ; Radiation Pneumonitis ; etiology ; Radiotherapy, Conformal ; Retrospective Studies ; Topotecan ; administration & dosage

Objective To explore the incidence and related predictive factors for acute symptomatic esophagitis in patients with locally advanced non?small cell lung cancer ( NSCLC ) treated with intensity?modulated radiation therapy ( IMRT) . Methods Data were collected retrospectively from 256 patients with inoperable or unresectable stage Ⅲ NSCLC treated in our hospital between January 2007 and December 2011. The radiotherapy target volume included primary lung cancer and lymphatic drainage area involved,with a median dose of 60 Gy in 30 fractions (50-70 Gy).Of all the patients,109 patients (42.6%) received concurrent chemotherapy. Grade ≥2 acute esophagitis ( AE ) ( symptomatic esophagitis ) which occurred during radiotherapy and within 3 months after completion of radiotherapy served as the outcome event. National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0( NCI?CTCAE3.0) was used to evaluate the grade of AE. The logistic regression model was used to analyze the predictive factors. Results A total of 174 patients ( 68%) had treatment?related grade ≥2 AE;154 patients ( 60. 2%) had grade 2 AE and 20 patients (7.8%) had grade 3 AE.The median dose when grade≥2 AE occurred was 30 Gy (11?68 Gy).For grade≥2 AE,multivariate analysis showed that esophageal V5?V60,mean dose,and age were independent predictive factors (P=0.021,0,0.010).For grade ≥3 AE,multivariate analysis showed that esophageal V50?V60 ,concurrent chemotherapy,and body mass index ( BMI) were independent predictive factors ( P= 0.010,0.003,0.019 ) . Old age and higher BMI were the protective factors for grade≥2 and ≥3 AE, respectively. Conclusions For patients with locally advanced NSCLC treated with IMRT, esophageal V50—V60 and concurrent chemotherapy are predictive factors for grade ≥3 AE,and esophageal V50 has a high predictive value for both grade ≥2 and ≥3 AE.

ObjectiveTo evaluate the value of the international union against cancer (UICC)stage,pathologic complete response (pCR),and the estimated treatment response as various means for prognostic stratifying patients after surgery in patients with squamous cell carcinoma of the esophagus who received preoperative radiotherapy (RT).MethodsA retrospective review was performed on 311 patients with esophageal squamous cell carcinoma who received RT before the esophagectomy. Data collected included the demographics,the RT details,the pathologic findings,and the survival.Prognostic survival was analyzed by Kaplan-Meier method and Logrank test.ResultsThe follow-up rate was 96.5％,89 and 43 patients,respectively were followed up more than 5 and 10 years.In univariate analysis,residual disease and the number of positive lymph node were predictors of the overall survival ( T-pCR,x2 =11.53,P =0.001 ;0,1 -3,≥4,x2=42.13,P=0.000,respectively).Further study found the 7th stage system of UICC cannot (can or cannot) entirely predict the prognosis of this group of patients.If categorizing the stages of their lymph nodes into three groups:N0(0),N1 (1-3) and N2(≥4)),and the modified UICC system can accurately distinguish ypStage Ⅰ with ypStage Ⅱ ( T0.3 N 1 M0 + T3 N0 M0 ) ( x2 =11.15,P =0.001 ) and ypStage Ⅱ with ypStage Ⅲ ( T4 N0-1 M0 and T0-3 N2 M0 ) ( x2 =23.39,P =0.000 ).ConclusionsThe pathologic post-radiotherapy T stage and the number of positive lymph node are predictors for esophageal squamous cell carcinoma receiving preoperative radiotherapy.The modified UICC stage system can be a better survival predictor than the 7th UICC stage system.