Objective:To evaluate the application value of robost optimization of brachytherapy for cervical cancer.Methods:Twenty patients who completed radical treatment were recruited in this study. The dose volume histogram (DVH) parameters were statistically compared between the conventional and robust optimization plans, and the robustness between the conventional and robust optimization plans was evaluated using DVH and DVH bands. The robust optimization method utilized the worst dose distribution to consider the dose in the presence of uncertainties. In each optimization iteration, the dose distributin when the radioactive source shifted along the X, Y, and Z directions (±2 mm), and the dose distribution when the radioactive source was not shifted were calculated. The worst dose distribution for each voxel was the lowest dose in the target and the highest dose outside the target under all circumstances. The iterative objective function was calculated by the worst dose distribution.Results:In the scenario of no shifting of radioactive source position, the mean value of robust optimization was significantly lower and that of V 150% was significantly higher than those of conventional optimization (both P<0.05). When considering the shifting of radioactive source position, the worst dosimetric parameters of multiple dose distributions were statistically compared. The mean HR-CTV D 100% values did not significantly differ between the robust and conventional optimization plans, whereas the mean D 90% value (range: 0.02-0.03 Gy) of robust optimization was significantly higher than that of conventional optimization ( P<0.05). Robust optimization increased the D 2cm 3 of the bladder and small intestine, and the rectum dose was increased with the shifting of the radioactive source position in the robust optimization. The DVH bands did not significantly differ between the conventional and robust optimization plans for all patients. Conclusions:Robust optimization based on the worst dose distribution fails to significantly improve the robustness of brachytherapy for cervical cancer. Alternative methods are required to minimize the dosimetric effect of uncertainties in brachytherapy.

Objective: To compare the dosimetric differences of volumetric modulated arc therapy (VMAT) plans optimized with 3 different fluence smoothing parameters using Monaco treatment planning system. Methods: A total of 15 patients with middle and upper esophageal carcinoma were planned with Low fluence smoothing (Low), Medium fluence smoothing (Medium) and High fluence smoothing(High) during VMAT optimization. The dosimetric differences in D₉₅, D_mean, conformity index (CI), homogeneity index (HI) of targets, dose volume histogram (DVH) of organs at risk (OARs), and monitor unit (MU) were compared. Results: There were no significant differences in D₉₅, D_mean, CI and HI of targets, as well as in V₄₀ and D_mean of the heart, V₁₀, V₂₀ and D_mean of the lung , and segment number among plans optimized with different fluence smoothing techniques (P>0.05). Plans with high fluence smoothing achieved less V₃₀ of heart, D_max of cord PRV(t=-2.167, -0.999, P<0.05), lower MU (t=-3.148, -6.692, P<0.05), but increased V₅ of both lungs (t=1.306, -2.027, P<0.05) compared with plans with Medium and Low fluence smoothing. Plans with low fluence smoothing irradiated higher dose to the V₃₀ and D_mean to heart (t=0.411, 0.589, 0.013, P<0.05), but less V₅ of the lungs (t=0.423, P<0.05) compared with plans with medium fluence smoothing. Conclusions All VMAT plans with 3 different fluence smoothing can meet the clinical requirements. VMAT plans optimized with high fluence smoothing are recommended in the treatment of patients middle and upper thoracic esophageal carcinoma.

Objective: To investigate the Offset values of different applicators in afterloading brachytherapy. Methods: Six types of applicators were selected in this study which included stainless steel interstitial needle (Part#083.062), proguide round needle (Part#189.608), proguide sharp needle (Part#189.601), vaginal multi-channel applicator (Part#110.800), fletcher CT/MR applicator (Part#189.745) and henschke titanium applicator (Part#110.437). According to the sources imaging in the fluorography film, the distance of applicators between the first dwell position and the top could be measured. Marker was pasted on the surface of applicator corresponding to the first dwell position. And then the applicator was put into the pelvic phantom for a CT scan. During applicator reconstruction in the treatment planning system, the Offset values of all applicators could be acquired through adjusting the value of offset to superimpose the first dwell and the marker images. On account of the density of plastic material applicators were similar to human tissues, it was difficult to reconstruct the top of the applicator. With the help of stopper or simulation source, the value of offset could be acquired for plastic material applicators. Based on the measurement results, the differences were analyzed among different applicators. Results: The Offset values significantly differed among various applicators. The Offset value for stainless steel interstitial needle was -11.4 mm, -4.1 mm for proguide round needle, -3.5 mm for proguide sharp needle, 0 mm or -5.0 mm for vaginal multi-channel applicator, -6.5 mm for fletcher CT/MR applicator and -7.5 mm for henschke titanium applicator, respectively. Conclusion To adapt to the rapid development of precise radiotherapy, it is necessary to verify the Offset value in afterloading brachytherapy.

Objective: To report an implementation method and results of an independent brachytherapy dose verification software (DVS). Methods: The DVS was developed based on Visual C+ + and the modular structure design was adopted. The DICOM RT files exported from the treatment planning system (TPS) were automatically loaded into the DVS. The TG-43 formalism was employed for dose calculation. Six cervical cancer patients who underwent brachytherapy were retrospectively selected to test the DVS. Different applicators were utilized for each patient. Dosimetric parameters and γ analysis (0.1cm, 5%) were used to evaluate the dose difference between the DVS and the TPS. Results: Compared with the TPS dose, the γ pass rates of the doses calculated by the DVS were higher than 98%. For CTV, the dosimetric differences were less than 0.29% and 0.53% for D_100% and D_90%. For bladder, rectum and sigmoid, the agreement of D_0.1cm³, D_1cm³ and D_2cm³ within a 0.5% level. Conclusion With minimal human-computer interactions, the DVS can verify the accuracy of dose calculated by TPS for brachytherapy.

Objective:To report an implementation method and result of an inverse dose optimization algorithm (GBPO) that can control the dwell time variation in three-dimensional brachytherapy.Methods:The GBPO used a quadratic objective function. A dwell time modulation item was added to the objective function to restrict the dwell time variation, and a DTMF (dwell time modulation factor) was used to adjust the dwell time variation. A retrospective study was made of 15 cervical cancer patients treated using the Fletcher applicator. The relationship between the DTMF and dwell time deviation was analyzed. Dose-volume histogram (DVH) parameters of HR-CTV ( D100%, V150%) and organs at risk (OARs) ( D0.1 cm 3, D1 cm 3, D2 cm 3) were used to evaluate the difference between the GBPO plans and the commercial treatment plan system (using the IPSA algorithm) plans. Results:When the DTMF was less than 20, the dwell time deviation decreased quickly. However, after the DTMF increased to 100, and the dwell time deviation had no remarkable change. The D100% of GBPO plan was higher than that of IPSA plan (3.63±0.36 vs. 3.53±0.34, t=2.45, P<0.05), and the difference in other dosimetric parameters between the GBPO plans and the IPSA plans was not statistically significant ( P>0.05). Conclusions:The method reported in this study to control the dwell time variation was feasible. The GBPO plans have a comparable quality as the IPSA plans for the studied cervical cancer cases. The GBPO algorithm could be integrated into a three-dimensional brachytherapy treatment planning system.

Objective:To explore an implementation method and results of an inverse dose optimization algorithm (gradient-based planning optimization, GBPO) in three-dimensional brachytherapy.Methods:A standard quadratic objective function was used in the GBPO. The optimization code of GBPO was performed based on LBFGS (Limited memory Broyden Fletcher Goldberg Shanno). Seven cervical cancer patients using different applicators and 15 cervical cancer patients using the Fletcher applicator (Nucletron part#189.730) were retrospectively analyzed. The plan quality of GBPO was firstly assessed by isodose lines, then dose-volume histogram (DVH) parameters of CTV(D 100%, V 150%) and organs at risk(D 0.1cm 3, D 1.0cm 3, D 2.0cm 3) were used to evaluate the difference among the GBPO, IPSA and Graphic plans. Results:For the 7 patients using different applicators, GBPO could optimize the conformal dose distribution, and the DVH parameters of the target and organs at risk were basically the same among the GBPO, IPSA and Graphic plans. For 15 patients using the Fletcher applicator, the difference in DVH parameters between the GBPO and IPSA plans was not statistically significant. There was no remarkable difference in the DVH parameters between the GBPO and Graphic plans, but the D 100% of the GBPO plan was significantly higher ( P<0.01), and the V 150% was significantly lower ( P<0.01) than that of the Graphic plan. Conclusions:The quality of the GBPO plan is similar to that of the IPSA plan in terms of target coverage and organ protection. The inverse dose optimization algorithm GBPO can be integrated into a three-dimensional brachytherapy treatment planning system.

Objective To investigate effect of stanniocalcin-1 (STC1) gene on the proliferation,apoptosis and radiotherapy sensitivity of non-small cell lung cancer.Methods The STC1 siRNA (STC 1-siRNA) and the non-interfering siRNA (negative control group) were transfected into the human lung cancer A549 cells by LipofectamineTM2000,and the blank control group was established.The expression level of STC1 protein was detected after transfection for 48 h by Western blotting.Clone forming test was adopted to detect the proliferation of A549 cells after STC1-siRNA and irradiation treatment.CCK8 assay was performed to detect the cell viability after treatment with STC1-siRNA and STC1-siRNA+8 Gy.The cell apoptosis was detected by flow cytometry.The expression levels of Ki67,Bax,STAT3 and p-STAT3 proteins were quantitatively measured by Western blotting.Results The expression level of STC1 protein in the A549 cells transfected with STC1-siRNA was significantly down-regulated than that in the blank control group (P＜ 0.05).Compared with the blank control group,the sensitization ratio was significantly enhanced after STC1-siRNA transfection.Compared with the blank control group,the cell viability and the expression levels of Ki67 and p-STAT3 protein were significantly decreased,whereas the apoptosis rate and the expression of Bax protein were significantly increased in the STC1-siRNA group.Compared with the STC1-siRNA group,the cell viability and the expression levels of Ki67 and p-STAT3 proteins were significantly decreased,whereas the cell apoptosis rate and the expression of Bax protein were remarkably increased in the STC1-siRNA+ 8 Gy group (all P＜0.05).Conclusion Inhibition of STC1 gene expression can enhance the radiotherapy sensitivity and down-regulate the STAT3 signaling pathway in non-small cell lung cancer.

Objective To investigate the application value of a transmission reference stealth ionization chamber in the relative dosimetry of stereotactic radiotherapy.Methods The relative dosage of Varian (R) Novalis 6 MV photon rays equipped with Brainlab (R) conical applicators was determined by two different approaches in the IBA (R) Blue Phantom.One approach was designed to utilize IBA (R) SFD3G semiconductor ionization chamber alone in the "step by step" measurement mode,whereas the other method was to utilize IBA (R) SFD as the field detector combined with stealth ionization chamber as the reference detector in the "continuous" measurement mode.The central axial percentage depth dose (PDD) and off axis ratio (OAR) in a diameter of 4 and 15 mm were measured and the time spent on each measurement was recorded.Results The PDDs at the central axis and OARs at a depth of 10 cm for both conical applicators were in good agreement between the two measurement approaches with a dose difference of＜ 1％.The time spent on PDDs and OARs measurement with stealth ionization chamber was shortened by 13.1％ and 20.7％ compared with those without Stealth ionization chamber.Conclusion Stealth ionization chamber can be applied in the retative dosimetry of stereotactic radiotherapy with high dose accuracy and high efficiency.

Objective To compare dosimetric parameters between automated and manualvolumetric modulated arc therapy(VMAT) plans in the treatment of postoperative cervical cancer patients,and to investigatethe feasibility and dosimetric advantage of the automated VMAT planning.Methods Automated and manual VMAT plans were generated with Pinnacle3 treatment planning system (TPS) for twenty-three postoperative cervical cancer patients,including eight patients in stage Ⅱ A and fifteen in stage Ⅱ B,respectively.The differences in D D95,conformity index (CI) and homogeneity index (HI) of target,as well as dose volume histogram (DVH) of organs at risk (OAR),planning time,average optimization time and monitor unit (MU) were compared between automated and manual VMAT plans.Results The average D CI and HI of automated VMAT plans were better than those of manual VMAT plans (t=4.65-14.92,P ＜0.05).There was no significant difference in D95 (P ＞0.05).The automated VMAT plans achieved better average dosimetric parameters on OARs compared with the manual VMAT plans (t =3.30-14.42,P ＜ 0.05).Automated VMAT plans had a significantly shorter planning time (72 min,t =3.85,P ＜ 0.05) and interruption frequency (twice,t =5.41,P ＜ 0.05) than manual VMAT plans.However,automated VMAT plans had a higher average MU than manual VMAT plans with an average MU of 819 ± 53 and 638 ± 41 for automated and manual VMAT plans,respectively.Conclusions It is feasible to generate automated VMAT plans with Pinnacle3 TPS for postoperative cervical cancer patients.The automated VMAT plans increase the plan quality and reduce the optimization time compare with manual VMAT plans.Automated technique also eliminates the influence of human factors on the plan quality.

Objective To evaluate the effect of stainless steel applicator on dose distribution in GZP 60 Co brachytherapy source and to obtain the dosimetric parameters of the 60 Co source with stainless steel applicator. Methods Geant4 was employed to obtain the mean adsorption dose of the 60 Co brachytherapy source in the range of 0-10 cm, and the dosimetric parameters were calculated according to the formula proposed by AAPM reports TG43 and TG43U1. The 60 Co source was located in the center of a sphere water phantom with a radius of 30 cm. Results For channel 1 and 2 of GZP 60 Co source, the results of Λ with stainless steel applicator were 1. 014 cGyh-1 U-1( with a difference of 0. 5％ compared with non-applicator) , the results of Λ with stainless steel applicator for channel 3 were 0. 998 cGyh-1 U-1 ( with a difference of 0. 1％ compared with non-applicator) . The radial dose function in the range of 0. 5-10. 0 cm in a longitudinal direction was calculated and the fitting formula for the function was obtained. The polynomial function for the radial dose function and the anisotropy function with a of 0°-175° and an r of 0. 5-10. 0 cm were obtained. Conclusion The dosimetric parameters of the 60 Co source with stainless steel applicator are obtained, which provide more accurate reference data for clinical application. In clinical practice, the effect of stainless steel applicator on dose distribution should be considered.