Objective To test intraoperative radiotherapy with mobile photon beam using the INTRABEAM system ( Germany) , and to analyze the dosimetric characteristics of low?energy photon beam using X?ray source and spherical applicators and explore its potential limitations in clinical application. Methods A special water phantom, a parallel?plate ionization chamber, and an electrometer were used to measure the depth dose rates and isotropy of dose distribution in x/y plane of X?ray source and different spherical applicators in the INTRABEAM system. Those data were then compared with the system data. Results For the X?ray source, the deviation of observed depth dose rate and isotropy in the x/y plane from the system data were-2.16%± 1. 36% and-1.9%~ 2. 1%, respectively. For applicators with different diameters, the deviation of observed depth dose rate, transfer coefficient, and isotropy in x/y plane from the system data were-10.0%~2. 3%,-8.9%~4. 2%, and-1.6%~2. 6%, respectively. Surface dose rate and dose gradient became larger with the decrease in the diameter of the spherical applicator. The measurement of depth dose rate and isotropy of X?ray source and spherical applicators showed good repeatability. The influencing factors for measurement accuracy included the positioning error of ionization chamber, energy response, noise current, and correction factor f ’ ( R ) . Conclusions This study reveals the dosimetric characteristics of the INTRABEAM system, verifies the accuracy of the system data, and obtains the data for clinical application and routine quality assurance. However, large dose gradient and small therapeutic range may limit its wide clinical application.

Objective To explore the predictive value of primary tumor site for loco?regional recurrence ( LRR) in early breast cancer patients with one to three positive axillary lymph nodes after radical surgery. Methods The clinical data of 656 patients pathologically diagnosed with pT1?2 N1 M0 breast cancer who received radical surgery without postoperative radiotherapy in our hospital from 1998 to 2010 were retrospectively analyzed. In those patients, 156 had primary tumor located in the inner quadrant, 45 in the central quadrant, and 455 in the outer quadrant. LRR and local recurrence?free survival ( LRFS) were end points. The Kaplan?Meier method was used to estimate LRR and LRFS rates. The log?rank test was used for survival difference analysis and univariate prognostic analysis. Multivariate analysis was performed using the Cox regression model. Results The 5?and 10?year sample sizes were 416 and 191, respectively. The 5?and 10?year LRR rates were 8?6% and 12?9%, respectively, while the 5?and 10?year LRFS rates were 86?2%and 76?4%, respectively. The univariate analysis indicated that age, pT stage, Ki67 level, molecular classification, and primary tumor in the inner quadrant were significant influencing factors for LRR ( P=0?000,0?006,0?017,0?004,0?000). The multivariate analysis showed that age no greater than 35 years, primary tumor in the inner quadrant, and non?luminal subtype in molecular classification were independent prognostic factors for LRR and LRFS ( P=0?0012,0?012,0?005) . With an increasing number of risk factors ( ≥ 2 ) , patients with primary tumor in the inner quadrant had a dramatically increased LRR rate and a reduced LRFS rate, while patients with primary tumor in the outer or central quadrant kept the same LRR and LRFS rates. Conclusions The primary tumor site holds promise for prediction of LRR and LRFS in patients with pT1?2N1M0 breast cancer after radical surgery. Patients with primary tumor located in the inner quadrant have a high LRR rate and a low LRFS rate, which provides an excellent predictor for the risk of recurrence in patients with high?risk breast cancer.

Objective To investigate the feasibility of the scheme of target volume delineation with extended involved?field intensity?modulated radiotherapy (IMRT) for patients with early?stage nasal NK/ T?cell lymphoma (NC?NKTL). Methods Twenty?one patients with stage IE?IIE NC?NKTL were treated with short?course chemotherapy combined with radiotherapy from 2011 to 2013. The majority of patients received the GELOX regimen. All patients received extended involved?field IMRT with a dose of 54?? 6 Gy in 26 fractions for gross tumor volume, 50?? 7 Gy in 26 fractions for high?risk clinical target volume (CTV), and 45?? 5 Gy in 26 fractions for low?risk CTV. The dose distribution, short?term treatment outcomes, and adverse reactions were analyzed. Results The 2?year sample size was 12. The 2?year follow?up rate was 100%. The 2?year local control rate ( LRC) was 100%. The 2?year overall and progression?free survival rates were 90?? 5% and 90?? 5%, respectively. The median coverage rates of planning target volumes with 90% of the prescribed doses of 54?? 6 Gy, 50?? 7 Gy, and 45?? 5 Gy were 99?? 8%, 99?? 6%, and 99?? 7%, respectively. No grade 3 or 4 adverse reactions were observed in patients. Conclusions The scheme of target volume delineation and dose configuration in our study not only achieves excellent target volume coverage, but also reduces adverse reactions in patients, which achieves a 2?year LRC ideal for patients with early?stage NC?NKTL.

Objective At present,nasopharyngeal carcinoma (NPC) is a head and neck cancer with special geographical distribution and biological behavior.Studies have shown that 18 F-FDG PET/CT parameters have certain prognostic values in patients with NPC in high-incidence areas.The aim of this study is to investigate the prognostic values of 18 F-FDG PET/CT parameters in patients with NPC in low-incidence areas.Methods The clinical data of 83 NPC patients who were diagnosed and treated in Beth Israel Medical Center, Albert Einstein Medical College from January 2003 to December 2013 were analyzed retrospectively.Based on 18 F-FDG PET/CT images,gross tumor volume (GTV) was delineated using the gradient method to obtain 18 F-FDG PET/CT parameters:maximum standardized uptake value (SUVmax ), metabolic tumor volume ( MTV),and total lesion glycolysis ( TLG).Results The number of patients followed was 37 at 3-years time.For all patients,the 3-year failure-free survival,locoregional relapse-free survival,and metastasis-free survival rates were 74%,88%,and 85%,respectively.The univariate analysis showed that SUVmax of the primary tumor (P=0.004) and TLG (P=0.014) were prognostic factors for 3-year locoregional relapse-free survival rate,and SUVmax of the primary tumor (P=0.024) and TLG (P=0.033) were prognostic factors for 3-year failure-free survival rate.The multivariate analysis showed that SUVmax of the primary tumor was the independent prognostic factor for 3-year failure-free survival rate. Conclusion SUVmax of the primary tumor before treatment is the independent prognostic factor for failure-free survival in patients with NPC.

Objective To investigate the maximum-tolerated dose (MTD) of cisplatin in docetaxel,cisplatin,and fluorouracil (TPF) induction chemotherapy followed by intensity-modulated radiotherapy (IMRT) and concomitant chemotherapy as well as the safety and short-term efficacy of TPF induction chemotherapy in the treatment of locally advanced nasopharyngeal carcinoma (NPC).Methods Thirtythree patients with locally advanced NPC were enrolled in this trial.The MTD of cisplatin was determined by dose escalation study,and the short-term efficacy and toxicities were evaluated.Results When the doses of docetaxel and fluorouracil were 60 mg/m2 d1 and 550 mg/m2 d1-5,respectively,the MTD of cisplatin was 65 mg/m2 d1.In this regimen (repeated every 3 weeks),grade 3-4 toxicities included neutropenia (67％),febrile neutropenia (9％),diarrhea (21％),and oral mucositis (6％).Except those who experienced dose-limited toxicity,other patients completed the whole treatment schedule.After TPF induction chemotherapy,the overall response rate was 97％,and the complete response rate was 21％.Conclusions In the endemic areas of NPC,induction chemotherapy with docetaxel (60 mg/m2 d1),cisplatin (65 mg/m2 d1),and fluorouracil (550 mg/m2 d1-5),which is repeated every 3 weeks,is proved safe and effective for Asian patients with locally advanced NPC.

Objective To analyze the clinical factors for pathologic complete response ( pCR) after preoperative neoadjuvant chemoradiotherapy ( neo?CRT) for locally advanced rectal cancer. Methods From 2005 to 2012, 297 patients with locally advanced rectal cancer and complete clinical data were enrolled as subjects. Those patients were diagnosed with biopsy and treated with neo?CRT ( radiotherapy by 3?dimonsional conformal radiotherapy or volumetric?modulated arc therapy) followed by radical surgery. The logistic regression model was used for the multivariate analyses of the correlation of pCR with age, gender, distance between tumor and the anal verge, serum level of carcinoembryonic antigen ( CEA ) before treatment, hemoglobin level before treatment, cT staging, and cN staging. Results In all patients, 78 ( 26?7%) patients had pCR after treatment. The numbers of patients with pCR were 42( 34?4%) in patients with stage T1?T3 disease and 37(21?1%) in patients with stage T4 disease. In the patients with serum CEA levels no higher than 5?33 ng/ml, 55(36?4%) had pCR after treatment, while in the patients with serum CEA levels higher than 5?33 ng/ml, only 24( 16?4%) had pCR. The univariate analysis revealed that age, gender, distance between tumor and the anal verge, anemia before treatment, or cN staging were not related to pCR. The multivariate analysis showed that stage cT1?T3 and a serum CEA level no higher than 5?33 ng/ml before treatment were influencing factors for pCR after neo?CRT for locally advanced rectal cancer ( P=0?031,P=0?000) . Conclusions The clinical staging and the serum CEA level before treatment are influencing factors for pCR after neo?CRT for locally advanced rectal cancer. The serum CEA level before treatment can be considered as a predictor of pCR after neo?CRT for locally advanced rectal cancer.

Objective To examine the application of On-Board Imaging (OBI) system-based image-guided radiotherapy (IGRT) in the improvement of the precision of intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma.Methods Ten patients with nasopharyngeal carcinoma were treated with IMRT using the OBI system. The IGRT images after positioning, position adjustment, and treatment were observed and recorded to investigate the image difference between CT simulation and IGRT. Results The deviations in the x (lateral), y (cranial-caudal), and z (ventral-dorsal) directions between CT simulation and IGRT images were 0.22±1.00 mm,-0.37±1.28 mm, and 0.04±1.36 mm, respectively, after positioning, 0.29±0.76 mm,-0.04±0.78 mm, and -0.01±0.92 mm, respectively, after position adjustment, and 0.20±0.78 mm, 0.16±0.80 mm, and 0.05±0.92 mm, respectively, after treatment. The probabilities of a ≤1 mm deviation in the x, y, and z directions were 81.0%, 77.6%, and 88.2%, respectively, after positioning, 92.5%, 96.4%, and 96.4%, respectively, after position adjustment, and 91.7%, 94.9%, and 96.8%, respectively, after treatment. Conclusions The application of OBI system-based IGRT is very important in the improvement of the precision of fractionated IMRT for patients with nasopharyngeal carcinoma. The position of the patient should be adjusted based on the IGRT image after positioning in order to correct set-up error and effectively increase the precision of fractionated IMRT.

Objective:To evaluate the accuracy of measurement of the output factor of high-energy photon small field (Scp) using commercial semi-diodes and ionization chambers in small fields in accordance with the IAEA-483 report, which has been proposed that all kinds of detectors should be revised for small field Scp measurement in clinical practice.Methods:EGSnrc of Monte Carlo (MC) software was utilized to simulate the treatment head of Varian Novalis Tx linear accelerator, and the profile curve and relative dose value were generated by simulation in DOSXYZnrc based on derived phase space file. Measurement of PDD and Profiles was used to adjust and validate the simulation mode. Detectors including ionization chambers A16, A14 sL, CC01, CC13, PFD and EFD and semi-diodes PFD, EFD and Razor under different radiation field settings (0.5 cm to 10.0 cm) were employed to measure the profile curves and Scp of FWHM equivalent rectangular fields, which were compared with data of Monte-Carlo simulation. The measurement of Scp was revised by data given in the IAEA-483 report. The data with or without correction were compared with the data of MC simulation.Results:A curve deviation o F<2.0% between MC simulation and PFD measurement was accepted. MC simulated Profiles were consistent with PFD, EFD and Razor measurements, when the field was<3.0 cm. Razor response in the out-field region was 2.3% higher than those of MC and PFD, and it increased with the increment of field and was 3.0% at 10.0 cm. The maximum 20.0%-80.0% penumbra width was detected as 3.0 mm for CC13 at 10.0 cm rectangular field. With the decrease of the radiation field, the deviation relative to MC simulation was increased as for Scp mean values of 7 detectors before correction. The standard deviation (SD) of the measured value was increased rapidly when it was close to 1.0 cm, ranging from 0.009-0.014 for the field of 5.0 cm-1.5 cm to 0.030-0.089 for the field of 1.0 cm-0.5 cm. The mean value of SD for the whole measurement before correction was 0.030. The mean SD of Scp measured by the six probes was 0.008, 0.013 at 0.8 cm and 0.021 at 0.6 cm after correction. When the equivalent field was ≥1.0 cm, the corrected Scp and MC simulation deviation was ranged from -3.6% to -0.5%. The error was between -6.9% and -1.3% when the radiation field was<1.0 cm. Conclusion:The SD of Scp measured by different detectors after correction in accordance to the IAEA-483 report is small, which is in good agreement with the data of MC simulation, suggesting that it could be applied in clinical dosimetry.

Objective To quantitatively compare the γ-H2AX foci formation between DNA-PKcs+/+and DNA-PKcs-/-mouse embryonic fibroblast(MEF)cells,and to investigate the dynamic changes in DNA double-strand breaks(DSBs)in human nasopharyngeal carcinoma SUNE-1 cells exposed to X-ray radiation. Methods The expression of DNA-PKcs was determined by Western blot. The γ-H2AX foci formation induced by 5 Gy X-ray radiation was detected by cell immunofluorescence. The ImageJ software was used to quantitatively analyze the γ-H2AX foci formation. Results The expression of DNA-PKcs was silenced in DNA-PKcs-/-MEF cells and normal in DNA-PKcs+/+MEF cells. According to the dynamic analyses of the numbers of γ-H2AX foci/cell and γ-H2AX foci/mm2, a similar tendency was observed in DSB formation in DNA-PKcs+/+MEF cells, DNA-PKcs-/-MEF cells,and SUNE-1 cells exposed to X-ray radiation. A large number of γ-H2AX foci formed at 0.5-1.0 h after radiation. DSBs were repaired at 6 h after radiation in DNA-PKcs+/+MEF cells and 24 h after radiation in DNA-PKcs-/-MEF cells and SUNE-1 cells. The peak values of γ-H2AX foci/cell and γ-H2AX foci/mm2were observed at 1.0 and 0.5 h after radiation, respectively. Compared with DNA-PKcs+/+MEF cells, DNA-PKcs-/-MEF cells had different numbers of γ-H2AX foci/cell at 0.5, 1.0, 3.0, 6.0, and 12.0 h after radiation, as well as different numbers of γ-H2AX foci/mm2at 3.0, 6.0, and 12.0 h after radiation. Conclusions Quantitative measurement of the number of γ-H2AX foci/cell or γ-H2AX foci/mm2by cell immunofluorescence provides new insights into the quantitative and dynamic study of DSB damage and repair.