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Objective. The study aims to establish and validate an effective CT-based radiation pneumonitis (RP) prediction model using the multiomics method of radiomics and EQD2-based dosiomics. Materials and Methods. The study performed a retrospective analysis on 91 nonsmall cell lung cancer patients who received radiotherapy from 2019 to 2021 in our hospital. The patients with RP grade ≥1 were labeled as 1, and those with RP grade p < 0.05 . Besides, the average value of the precision and recall of radio + eqdose was higher, but the difference was not statistically significant p > 0.05 . Conclusion. The performance of using the ML-based multiomics method of radiomics and eqd-dosiomics to predict RP is more efficient and effective.

Quanbin Zhang,1 Yu Zeng,2 Yingying Peng,1 Hui Yu,1 Shuxu Zhang,1 Shuyu Wu1 1Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Stomatology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Shuxu Zhang; Shuyu Wu, Email gthzsx@163.com; wsyeasy@outlook.comBackground: As hybrid radiotherapy technique can effectively balance dose distribution between targets and organs, it is necessary to evaluate the late effects related to radiotherapy. The aim of the study was to calculate and provide individual estimates of the risks for hybrid radiotherapy techniques in breast cancer patients.Methods: Whole-breast irradiation was performed in 43 breast cancer patients by using 3D conformal, intensity-modulated and hybrid techniques. The excess absolute risk (EAR), lifetime attributable risk (LAR) and normal tissue complication probability (NTCP) were calculated to estimate risks in organs. The risk variability in contralateral breast was assessed by using the patient’s anatomic parameters.Results: Compared with IMRT and FinF, hybrid techniques achieved satisfactory dose distribution and comparable or lower estimated risks in organs. The LAR was estimated to be up to 0.549% for contralateral lung with advantages of tangential techniques over H-VMAT. For ipsilateral lung, the LAR was estimated to be up to 9.021%, but lower in H-VMAT and FinF without significant difference. The risk of thyroid was negligible in overall estimation. For contralateral breast, the LAR was estimated to be up to 0.865% with advantages of MH-IMRT and H-VMAT over TF-IMRT. The fraction of individual variability could be explained by using anatomic parameters of minimum breast distance (MBD) and minimum target concave angle (θMTCA). NTCP for all analyzed endpoints was significantly higher in TF-IMRT relative to FinF and hybrid techniques, while TH-IMRT and H-VMAT were presenting lower toxicity risk. However, MH-IMRT presented a higher probability of toxicity in lung. For most cases, H-VMAT demonstrated a benefit for contralateral breast, heart and lung sparing.Conclusion: The optimal treatment should be performed individually according to anatomic parameters and balances between EAR and NTCP. Individual assessment may assist in achieving optimal balances between targets and organs as well as supporting clinical decision-making processes.Keywords: secondary cancer risk, hybrid techniques, individual assessment, breast cancer, radiotherapy

Backgrounds Concurrent chemo-radiotherapy in patients with locally advanced cervical cancer has significant hematologic toxicities (HT), leading to treatment disruption and affecting patient prognosis. We performed the meta-analysis to assess the clinical benefit of pelvic (active) bone marrow (BM) sparing radiotherapy. Methods A systematic methodological search of six primary electronic databases was performed. This systematic review mainly assessed the differences in pelvic (active) BM dose-volume parameters (DVP), hematologic toxicity of pelvic (active) BM sparing versus non-sparing radiotherapy plans. The secondary objective was to explore optimal dose limitation regimens and evaluate other radiation-induced toxicities (gastrointestinal and urological toxicity (GT/UT)). Random-effects models were used for meta-analysis. Results Final 65 publications that met inclusion criteria were included in the meta-analysis and descriptive tables. Meta-analysis of mean pelvic BM-DVP differences showed that pelvic BM-V10,20,40,50 (Vx: volume of BM receiving ≥ X Gy) were reduced by −4.6% [95% CI: −6.6, −2.6], −10.9% [−13.2, −8.6], −7.3% [−9.5, −5.2] and −3.4% [−4.3, −2.4] in pelvic BM-sparing plans. Pelvic BM sparing radiotherapy decreased G2/3+ HT [odds ratio (OR) 0.31, (0.23, 0.41)/0.42, (0.28, 0.63)], without increasing GT [G2/3+: OR 0.76, (0.51, 1.14)/0.90, (0.47, 1.74)] and UT [G2/3+: OR 0.91, (0.57, 1.46)/0.54, (0.25, 1.17)]. Pelvic active BM sparing radiotherapy also reduced HT [G2/3+ HT: OR 0.42, (0.23, 0.77)/0.34, (0.16, 0.72)]. There were significant variations between publications in dose restriction regimens. Conclusion The pelvic BM protection radiotherapy can decrease BM dose and HT. Moreover, it does not increase GT and UT. The clinical benefit of pelvic active BM protection needs to be further validated in randomized controlled trials.

This study aimed to evaluate the quality of locally advanced nasopharyngeal carcinoma (NPC) radiotherapy plans generated by the automated planning module of a commercial treatment planning system (TPS). Data of 30 patients with locally advanced NPC were retrospectively investigated. For each patient, volumetric modulated arc therapy (VMAT) plans with double arcs were generated manually by experienced physicists and automatically in the Pinnacle3 Auto-Planning module (Philips Medical Systems, Fitchburg, WI, USA). The anatomic distance between the second clinical target volume (CTV2) and the pons of the brainstem, and the T category of disease were factored into the evaluation. Dosimetric verification was evaluated in terms of gamma pass rate. Target coverage, sparing of organs at risk (OARs), and monitor units were evaluated and compared between the manual and automatic VMAT plans. Not all treatment plans fully met the dose objectives for planning target volumes (PTVs) and OARs, particularly in T4 patients. Overall, automatic VMAT provides a comparable or superior plan quality to manual VMAT in most cases. In stratified analysis, plan quality is mainly independent on T category but is also affected by anatomic distance. If the anatomic distance is less than 5 mm, the automatic VMAT plan quality is equal or even inferior to manual VMAT performed by experienced physicists. Conversely, if the anatomic distance is greater than 5 mm, the automatic VMAT plan quality is superior to manual VMAT. Gamma pass rates for quality assurance are similar between manual and automatic VMAT plans for the former case, but significantly higher in automatic VMAT for the latter. The selection of manual versus automatic VMAT planning in locally advanced NPC should be made individually based on the anatomic distance, rather than blindly and habitually, since automatic VMAT is not good enough to completely replace manual VMAT.

4DCT (four-dimensional computed tomography) can effectively obtain functional lung ventilation images for patients and integrate them into radiotherapy treatment planning. Studies have not been performed on esophageal cancer, and there is no clear consensus on the optimal functional lung threshold for functional lung.Functional lung images were generated for 11 patients with esophageal cancer. The correlation between the dose-volume parameters of functional lung (FL) as defined by different thresholds and the change of PFT/PDFT (pulmonary [diffusion] function test) metrics before and after radiotherapy were evaluated. FL-sparing planning was generated for each patient to preserve the functional lung and compared to conventional anatomical CT (non-sparing) planning.There was a significant positive correlation between the FL0.8 (defined Jacobian value ≤ 0.8), FL0.84, and FL0.9 dose-volume parameters and ΔFEV1/FVC (reduction before and after radiotherapy), and the FL0.8‑VThe 4DCT-based FL irradiation dose for esophageal cancer was significantly associated with a decrease in FEV1/FVC. The optimal FL defined as a Jacobian value ≤ 0.8 or about 21% of the whole lung volume may be a good choice. FL-sparing planning significantly reduced the FL dose without compromising target area coverage.

ObjectiveTo investigate the impact of different dose algorithms and calculation angle intervals (DCAI) on the in vivo dose (IVD) verification of small-field arc therapy in stereotactic body radiation therapy (SBRT).MethodsWe made an exit-dose-measuring and positioning device (EDPD) for the SRS MapCHECK (SMC) using polymethyl methacrylate (PMMA). Computed tomography data for the anthropomorphic head phantom, SMC, and EDPD combination were acquired with 1 mm slice thickness and spacing. SBRT partial arc plans were created using an SBRT cone, block, and a small square open field, with a gantry rotation angle of 60°. The dose distribution was calculated using three different dose algorithms [Pencil Beam (PB), CC Convolution (CCC), and Monte Carlo (MC)], with 1 mm isotropic resolution. We also used three different DCAIs (1°, 3°, 5°) with the PB and CCC algorithms to calculate the dose distribution of each plan three times. The uncertainty of each control point for the MC algorithm was set to 1%. The SMC was used to measure the exit dose outside the phantom for IVD verification, the detector plane was located 182.5 mm outside the scan center.ResultsWithin the phantom, the minimum passing rate of 3D gamma analysis (1%/1 mm) for the dose distributions calculated at different DCAIs was 99.1%, and the maximum relative deviation (RD) of the central point dose (CPD) was 90% for the CCC algorithm at 1° DCAI.ConclusionThe DCAI for exit-dose calculations should be ≤1° using the CCC algorithm. Furthermore, among the three algorithms verified in the current study, the MC algorithm showed the highest accuracy, followed by CCC, with the PB algorithm having the worst performance. The PB algorithm is thus not suitable for exit-dose calculation or IVD verification of SBRT.

Radiotherapy is a leading treatment approach of cancer therapy. While it is effective in killing tumor cells, it can also cause serious damage to surrounding normal tissue. Targeted radiotherapy with gold nanoparticle-based radiosensitizers is actively being investigated, and considered as a promising means to enhance the efficacy of radiotherapy against tumors under a relatively low and safe radiation dose. In this work, we report a green and one-step strategy to synthesize fluorescent gold nanoclusters by using a commercialized cyclic arginine-glycine-aspartic acid (c(RGDyC)) peptide as the template. The nanoclusters inherit special properties of both the Au core (red/NIR fluorescence emission and strong radiosensitizing effect) and c(RGDyC) shell (active cancer cell-targeting ability and good biocompatibility), and can be applied as fluorescent probes to stain αvβ3 integrin-positive cancer cells, as well as radiosensitizing agents to boost the killing efficacy of radiotherapy. Our data suggest that the as-designed gold nanoclusters have excellent biocompatibility, bright red/NIR fluorescence, active tumor targeting property, and strong radiosensitizing effect, making them highly promising towards potential clinical translation.

The aim of this study was to estimate the radiation-related secondary cancer risks in organs during the treatment of breast cancer with different radiotherapy techniques, such as three-dimensional conformal radiotherapy (3D-CRT), intensity modulated radiotherapy (IMRT), and volumetric modulated arc therapy (VMAT). The treatment plans for 26 patients with breast cancer who received whole-breast irradiation at a dose of 50 Gy included tangential field 3D-CRT with hard-wedges (W-TF), tangential field IMRT (2F-IMRT), multiple field IMRT (6F-IMRT), and double partial arcs (VMAT). Patients were divided into three groups according to the distance between the contralateral breast (CB) and the body of the sternum. Setup error was simulated by moving the isocenter, and the dose distribution was then recalculated without changing the field fluency distribution. Based on the linear-exponential, the plateau, and the full mechanistic dose-response models, the organ equivalent dose and excess absolute risk were calculated from dose-volume histograms to estimate the secondary cancer risks in organs. Compared with 3D-CRT, IMRT and VMAT showed excellent results regarding tumor conformity and homogeneity; however, the low dose volume to organs was considerably higher in 6F-IMRT and VMAT. Secondary cancer risks for 2F-IMRT were comparable or slightly lower than for W-TF, but considerably lower than for 6F-IMRT or VMAT. After setup error simulation, there was a small increase in secondary cancer risk for 2F-IMRT and an increase of 159% and 318% for 6F-IMRT and VMAT, respectively, compared with W-TF. Although these results were obtained in most patients, they did not necessarily apply to every individual. The secondary cancer risks in the CB decreased significantly in correlation with increased distance for all alternative techniques, although they were higher in VMAT and lower in 2F-IMRT regardless of the distance. After setup error simulation, the increased changes in secondary cancer risks in the CB were comparable between 2F-IMRT, 6F-IMRT, and VMAT, suggesting that the secondary cancer risks in the CB mainly depend on radiotherapy techniques and distance, although the effect of setup error cannot be ignored. In the contralateral lung (CL), the secondary cancer risks were almost independent from distance and depended mainly on radiotherapy techniques; they were rarely affected by setup error. VMAT was associated with a higher secondary cancer risk in the CL. For the ipsilateral lung (IL), the secondary cancer risks were higher than those in other organs because the IL receives high doses to achieve tumor control, and they were relatively lower in VMAT. This warrants special consideration when estimating the secondary cancer risk to the IL. The study results suggested that the optimal radiotherapy method for breast cancer should be determined on an individual basis and according to the balance between secondary cancer risks related to anatomic diversity and setup error, which can prevent blind selection of techniques.

To investigate dosimetric differences and plan qualities between manual plans and automatic plans for nasopharyngeal carcinoma (NPC) in early stage, and provide better options to maximize the benefits. Sixteen cases diagnosed with early NPC were retrospectively investigated. Conventional step and shoot IMRT with 7-fields and full arc volumetric-modulated arc therapy (VMAT) with double arcs were manually generated by experienced planners and automatically generated by Auto-Planning module in Pinnacle3 respectively, such as IMRT manual-planning (mIMRT), IMRT auto-planning (aIMRT), VMAT manual-planning (mVMAT), and VMAT auto-planning (aVMAT) for each patient. Target coverage, organs at risk sparing, monitor units, and planning times were compared and evaluated. All parameters of plans are able to fulfill International Commission on Radiation Units and Measurements repor (ICRU) 83 recommendations. Automatic plans are comparable or superior to manual plans without time-consuming planning process. The CI and HI for PTVs are better in aVMAT when compared with aIMRT and mVMAT, but those are similar between aIMRT and mVMAT. Automatic plans not only have superior dose homogeneity and conformity in PTVs, but also have better sparing for spinal cord or slightly reduce the doses received by other OARs, while the VMAT plans have better sparing for brain stem, especially the aVMAT plans. However, Dmax, V30, and V40 of brain stem are similar between aIMRT and mVMAT without significant difference. The monitor units and planning time for treatment plans have been significantly decreased through automatic planning technique. The automatic VMAT plan has greater clinical advantages and should be recommended to a better option for treating NPC in early stage, while automatic IMRT would be preferentially considered instead of manual VMAT.

Objective. To develop and evaluate a multi-path synergic fusion (MSF) deep neural network model for breast mass classification using digital breast tomosynthesis (DBT). Methods. We retrospectively collected 441 patients who had undergone DBT in which the regions of interest (ROIs) covering the malignant/benign breast mass were extracted for model training and validation. In the proposed MSF framework, three multifaceted representations of the breast mass (gross mass, overview, and mass background) are extracted from the ROIs and independently processed by a multi-scale multi-level features enforced DenseNet (MMFED). The three MMFED sub-models are finally fused at the decision level to generate the final prediction. The advantages of the MMFED over the original DenseNet, as well as different fusion strategies embedded in MSF, were comprehensively compared. Results. The MMFED was observed to be superior to the original DenseNet, and multiple channel fusions in the MSF outperformed the single-channel MMFED and double-channel fusion with the best classification scores of area under the receiver operating characteristic (ROC) curve (87.03%), Accuracy (81.29%), Sensitivity (74.57%), and Specificity (84.53%) via the weighted fusion method embedded in MSF. The decision level fusion-based MSF was significantly better (in terms of the ROC curve) than the feature concatenation-based fusion (p< 0.05), the single MMFED using a fused three-channel image (p< 0.04), and the multiple MMFED end-to-end training (p< 0.004). Conclusions. Integrating multifaceted representations of the breast mass tends to increase benign/malignant mass classification performance and the proposed methodology was verified to be a promising tool to assist in clinical breast cancer screening.

To date, commercial 4D-CT systems typically depend on an external respiratory monitoring device. Immobilizing patients in a thermoplastic mask while receiving radiotherapy may result in a failure of 4D-CT reconstruction. The aim of this study is to investigate the feasibility of 4D-CT reconstruction based on a method using pulmonary average CT values (ACV) without an external respiratory monitoring device. The ACV of the whole lung assumes cyclical variation during respiration. Phases of CT images were identified by calculating the ACV over time. Subsequently, five sets of 4D-CT images based on a Real-time Position Management (RPM) system were selected to verify the ACV method. The entire lung CT datasets of another sixteen free-breathing patients were acquired in Cine scan mode for multiple couch positions. The phase of every CT image was identified and re-sorted into different phase 4D-CT volumes by analyzing the time dependence of the corresponding ACVs. This paper demonstrates the ACV method using the 4D-CT data sets based on the RPM system. Convenient and reliable 4D-CT reconstruction can be accomplished without any external respiratory monitoring device using ACVs.

Calculating an accurate cumulative dose through individual phases for four-dimensional computed tomography (4DCT) images from the lung is time-consuming. Although the dose distribution of different phases is similar, copying the dose distribution of one phase directly to another phase would yield a dosimetric error of approximately 4% without further optimization. To reduce the dosimetric error, three-dimensional B-spline elastic deformable image registration (DIR) was used to quickly obtain a relatively accurate cumulative dose of 4DCT images acquired from ten lung cancer patients. The dose distribution of the end-expiration phase was mapped to the end-inspiration phase using DIR. The mapped dose in the end-inspiration phase was then compared with the directly copied dose by analysis (3cm/3%) and the t-test. The results showed that optimization using DIR was significantly better in the average pass rate (by 0.6-4.7%). Our results indicate it is feasible to map the dose distribution of 4DCT images in lung with DIR, and that the motion amplitude of individual respiratory and different DIR algorithms affect the differences between the mapped and actual dose.

Early detection of skull base invasion in nasopharyngeal carcinoma (NPC) is crucial for correct staging, assessing treatment response and contouring the tumor target in radiotherapy planning, as well as improving the patient's prognosis. To compare the diagnostic efficacy of single photon emission computed tomography/computed tomography (SPECT/CT) imaging, magnetic resonance imaging (MRI) and computed tomography (CT) for the detection of skull base invasion in NPC. Sixty untreated patients with histologically proven NPC underwent SPECT/CT imaging, contrast-enhanced MRI and CT. Of the 60 patients, 30 had skull base invasion confirmed by the final results of contrast-enhanced MRI, CT and six-month follow-up imaging (MRI and CT). The diagnostic efficacy of the three imaging modalities in detecting skull base invasion was evaluated. The rates of positive findings of skull base invasion for SPECT/CT, MRI and CT were 53.3%, 48.3% and 33.3%, respectively. The sensitivity, specificity and accuracy were 93.3%, 86.7% and 90.0% for SPECT/CT fusion imaging, 96.7%, 100.0% and 98.3% for contrast-enhanced MRI, and 66.7%, 100.0% and 83.3% for contrast-enhanced CT. MRI showed the best performance for the diagnosis of skull base invasion in nasopharyngeal carcinoma, followed closely by SPECT/CT. SPECT/CT had poorer specificity than that of both MRI and CT, while CT had the lowest sensitivity.

CD133 is a pivotal marker of cancer stem cells (CSCs), which is involved in tumorigenesis and cancer progression. Recent studies have identified CD133 to be a prognostic factor for cancer rested with its expression and genetic variants. Here, we hypothesized that the single nuclear polymorphisms (SNPs) in CD133 may be associated with lung cancer risk and prognosis. Based on three independent case-control analyses with a total of 2332 lung cancer cases and 2457 controls, the gene-based association analysis with 13 polymorphisms of CD133 suggested that CD133 is a susceptible gene for lung cancer (P = 0.043) and that the SNP rs2240688AC in the 3'-untranslated region of CD133 is the most significant associated SNP with the risk of lung cancer (P = 0.020); further analysis showed that the rs2240688C variant genotypes (CA+CC) harbored a decreased risk of lung cancer (odds ratio = 0.80; 95% confidence interval (CI) = 0.72-0.90) and conferred a favorable survival for lung cancer patients (median survival time: 15 months) compared with AA genotype (median survival time: 11 months, log-rank test: P = 3.31 × 10(-6); Cox model: hazards ratio = 0.81, 95% CI = 0.70-0.94). Functional assays revealed that the rs2240688A to rs2240688C transition gained a new binding of the microRNA hsa-miR-135a/b and decreased the CD133 expression. Our data suggest that the functional polymorphism rs2240688AC in CD133 is associated with lung cancer risk and survival. This SNP may be a functional biomarker to predict risk and prognosis of lung cancer.

Purpose To design and construct a three-dimensional (3D) anthropomorphic abdominal phantom for geometric accuracy and dose summation accuracy evaluations of deformable image registration (DIR) algorithms for adaptive radiation therapy (ART). Method Organ molds, including liver, kidney, spleen, stomach, vertebra, and two metastasis tumors, were 3D printed using contours from an ovarian cancer patient. The organ molds were molded with deformable gels made of different mixtures of polyvinyl chloride (PVC) and the softener dioctyl terephthalate. Gels with different densities were obtained by a polynomial fitting curve that described the relation between the Hounsfield unit (HU) and PVC-softener blending ratio. The rigid vertebras were constructed by molding of white cement and cellulose pulp. The final abdominal phantom was assembled by arranging all the fabricated organs inside a hollow dummy according to their anatomies, and sealed by deformable gel with averaged HU of muscle and fat. Fiducial landmarks were embedded inside the phantom for spatial accuracy and dose accumulation accuracy studies. Two channels were excavated to facilitate ionization chamber insertion for dosimetric measurements. Phantom properties such as deformable gel elasticity and HU stability were studied. The dosimetric measurement accuracy in the phantom was performed, and the DIR accuracies of three DIR algorithms available in the open source DIR toolkit-DIRART were also validated. Results The constructed deformable gel showed elastic behavior and was stable in HU values over times, proving to be a practical material for the deformable phantom. The constructed abdominal phantom consisted of realistic anatomies in terms of both anatomical shapes and densities when compared with its reference patient. The dosimetric measurements showed a good agreement with the calculated doses from the treatment planning system. Fiducial-based accuracy analysis conducted on the constructed phantom demonstrated the feasibility of applying the phantom for organ-wise DIR accuracy assessment. Conclusions We have designed and constructed an anthropomorphic abdominal deformable phantom with satisfactory elastic property, realistic organ density, and anatomy. This physical phantom can be used for routine validations of DIR geometric accuracy and dose accumulation accuracy in ART.

Radio- and chemo-resistance represent major obstacles in the therapy of non-small-cell lung cancer (NSCLC) and the underlying molecular mechanisms are not known. In the present study, during induction of radio- or chemo-resistance in NSCLC cells, dynamic analyses revealed that decreased expression of let-7 induced by irradiation or cisplatin resulted in increased expression of its target gene LIN28, and increased expression of LIN28 then contributed to further decreased expression of let-7 by inhibiting its maturation and biogenesis. Moreover, we showed that down-regulation of let-7 and up-regulation of LIN28 expression promoted resistance to irradiation or cisplatin by regulating the single-cell proliferative capability of NSCLC cells. Consequently, in NSCLC cells, let-7 and LIN28 can form a double-negative feedback loop through mutual inhibition, and disturbance of the let-7/LIN28 double-negative feedback loop induced by irradiation or chemotherapeutic drugs can result in radio- and chemo-resistance. In addition, low expression of let-7 and high expression of LIN28 in NSCLC patients was associated significantly with resistance to radiotherapy or chemotherapy. Therefore, our study demonstrated that disturbance of the let-7/LIN28 double-negative feedback loop is involved in the regulation of radio- and chemo-resistance, and that let-7 and LIN28 could be employed as predictive biomarkers of response to radiotherapy or chemotherapy in NSCLC patients.

With the purpose of reducing stray radiation dose (SRD) in out‐of‐field region (OFR) during radiotherapy with 6 MV intensity‐modulated radiation therapy (IMRT), a body‐shielding device (BSD) was prepared according to the measurements obtained in experimental testing. In experimental testing, optimal shielding conditions, such as 1 mm lead, 2 mm lead, and 1 mm lead plus 10 mm bolus, were investigated along the medial axis of a phantom using thermoluminescent dosimeters (TLDs). The SRDs at distances from field edge were then measured and analyzed for a clinical IMRT treatment plan for nasopharyngeal carcinoma before and after shielding using the BSD. In addition, SRDs in anterior, posterior, left and right directions of phantom were investigated with and without shielding, respectively. Also, the SRD at the bottom of treatment couch was measured. SRD decreased exponentially to a constant value with increasing distance from field edge. The shielding rate was 50%–80%; however, there were no significant differences in SRDs when shielded by 1 mm lead, 2 mm lead, or 1 mm lead plus 10 mm bolus (P>0.05). Importantly, the 10 mm bolus absorbed back‐scattering radiation due to the interaction between photons and lead. As a result, 1 mm lead plus 10 mm bolus was selected to prepare the BSD. After shielding with BSD, total SRDs in the OFR decreased to almost 50% of those without shielding when irradiated with IMRT beams. Due to the effects of treatment couch and gantry angle, SRDs at distances were not identical in anterior, posterior, left and right direction of phantom without BSD. As higher dose in anterior and lower dose in posterior, SRDs were substantial similarities after shielding. There was no significant difference in SRDs for left and right directions with or without shielding. Interestingly, SRDs in the four directions were similar after shielding. From these results, the BSD developed in this study may significantly reduce SRD in the OFR during radiotherapy, thus decreasing the risk of secondary cancers.

Metformin, one of the most widely used antidiabetic drugs, has recently been associated with potential antitumorigenic effects. In this study, we evaluated the possible cytotoxic impact of combined low doses of metformin and ionizing radiation (IR) on 2 human hepatoma cell lines. The cytotoxic effect of metformin combined with IR was subsequently determined by clonogenic survival and cell cycle assays, assessment of mitochondrial complex I and lactate dehydrogenase (LDH) activity, measurement of cellular adenosine triphosphate (ATP) levels, comet assay and analyses of the formation and disappearance of phosphorylated histone H2AX (γ-H2AX) protein. The combination of metformin and IR caused a much stronger cytotoxicity than the treatment with metformin or IR alone, leading to an ~80% decrease in cell viability and ~35% increase in the accumulation of cells in the G2/M phase of the cell cycle in the 2 hepatoma cell lines. In addition, a reduction in mitochondrial complex I activity (~70%) and a significant increase in LDH activity, as well as lactate production were observed in the cells exposed to metformin. Interestingly, a severe depletion in ATP, increased olive tail moment and the delayed disappearance of γ-H2AX expression were detected in the hepatoma cells treated by metformin plus IR. These findings show that the combination of a low concentration of metformin and IR results in the considerable enhancement of cytotoxic effects in human hepatoma cell lines, leading to decreased DNA repair by reducing ATP production. The data provided in this study may elucidate the remarkable efficiency of this combination treatment and suggest that metformin may be used as a potential adjunct to the radiotherapy of hepatocellular carcinoma.

The purpose of this study is to evaluate the dosimetric gain of the adaptive radiotherapy (ART) over conventional intensity modulated radiation therapy (IMRT) by using as the deformable image registration technique for dose mapping and summation to assess the dosimetric difference on target and organs at risk (OARs) dose. We retrospectively collected planning CT images and fractional CT images from nine lung cancer patients who were treated with adaptive IMRT. During fractional treatments, new tumor and organ contours are generated using the deformable image registration and a new IMRT plan is generated for the follow up treatments for each patient. The resulting deformation moving vector fields are also used to map and accumulate dose from the first 20 fractions to the sequential 10 fractions for final total dose calculation. The organs at risk (OARs) and the tumor of dosimetric parameters are compared between the ART and conventional IMRT plan. The evaluation results showed that when using the ART technique, the mean GTV volume is reduced by 53.2%, the mean tumor dose is increased by 0.41Gy, the mean lung V20 and V30 are decreased by 2.17% and 3.32%, the mean heart V30 and V40 are decreased by 1.14% and 2.98%, respectively, and the maximum dose of spinal cord is decreased by 1.21Gy when compared with the conventional IMRT. This work demonstrated the feasibility of ART to achieve better target coverage and OARs sparing over the conventional IMRT, and it will potentially reduce the radiation side effect and increase the local control rate.

To realize dose deformation and accumulation using image registration technology, and evaluate the anatomic changes and corresponding dosimetric variations for patients with nasopharyngeal carcinoma (NPC). 15 patients with NPC treated with IMRT were selected in this study, the original treatment plan(Plan1(CT1)) based on the first CT scan(CT1) and the second plan(Plan2(CT2)) based on the repeated CT scan(CT2) were calculated using the planning system Raystation Version 4.5 (RaySearch Laboratories AB, Stockholm, Sweden). Plan1(CT2) was acquired by deforming the dose of Plan1(CT1) to CT2 using the hybrid deformation image registration method, which express to perform the original plan without re-planning. Assessing the dose distribution and deciding whether to modify the plan, if need it, Plan2(CT2) was planned based on CT2 images, Plan1+2(CT2) that expressing the actual exposure dose after modification was generated by accumulating the dose of Plan1(CT2) and Plan2(CT2). The dose distribution was compared among Plan1(CT1), Plan2(CT2) and Plan1+2(CT2). Compared with CT1, the volume of GTVnx, GTVnd and CTV2 in CT2 decreased by 36.3%, 36.3% and 49.8% respectively, and the left and right parotid gland decreased in volume by 34.6% and 34.6%. Compared with Plan1(CT1), due to the changes of organ size and location, the dose to target organ were significantly decreased in Plan1(CT2) (the dose received by 95% of the target (D95) to GTVnx, GTVnd and CTV2 were decreased by 2.9%, 6.2% and 3.3%, respectively), and the dose to normal tissue were increased (the dose to right parotid gland, brain stem and spinal cord were increased by 5.5%, 1.4% and 8.9%, respectively). With repeated CT and re-planning after 20 times as shown in Plan1+2(CT2), the dose delivered to target were significantly increased (Compared with Plan1(CT2), the dose in Plan1+2(CT2) received by 95% of the target (D95) to GTVnx, GTVnd and CTV2 were increased by 2.9%, 3.3% and 3.7%, respectively), and at the same time the dose to normal tissue were decreased as much as possible (the mean dose to the left and right parotid gland were decreased by 3.0% and 7.4%, and the max dose to the brain stem and spinal cord were decreased by 14.1% and 7.7%). During the course of adaptive radiotherapy, the volume of parotid gland and target significantly decreased. Re-planning after 20 times could ensure adequate dose to target and safe dose to the normal tissues.

The aim of the present study was to investigate the role of CTVision in interfractional setup errors during intensity‐modulated radiation therapy (IMRT) in 12 nasopharyngeal carcinoma (NPC) patients. The trend of setup errors as a function of time during a fractionated radiotherapy course was investigated, and the influence of reconstructive thickness on image reconstruction for setup errors was analyzed. The appropriate planning target volume (PTV) margin and planning risk volume (PRV) margin were defined to provide a reference for the design of IMRT for NPC. Based on CTVision, online CT was performed weekly for each patient. Setup errors were measured by registration between the CT reconstructed image and reference image. Mean of setup errors, estimated population systematic (:), and population random (σ) errors were calculated using SPSS (v15.0). Optimum PTV and PRV margins were calculated. In the clinical data, for the LR (left–right), SI (superior–inferior), and AP (anterior–posterior) directions, : was 0.8, 0.8, and 1.0 mm, respectively, and σ was 1.0, 1.3, and 0.8 mm, respectively. In the LR, SI, and AP directions, PTV margins were at least 2.7, 2.9, and 3.0 mm, respectively, and PRV margins were at least 1.5, 1.7, and 1.7 mm, respectively. No significant differences in setup errors were observed during the fractionated radiotherapy course (p>0.05). However, CT image reconstruction with different thicknesses affected the accuracy of measurements for setup errors, particularly in the SI direction. The application of CTVision to correct setup errors is important and can provide reasonable margins to guarantee the coverage of PTVs and spare organs at risk. A thickness of 3 mm in the reconstructed image is appropriate for the measurement of setup errors by image registration. PACS number(s): 87.55.Qr

Background The principal aim of this study was to evaluate the feasibility of incorporating four-dimensional (4D)-computed tomography (CT)-based functional information into treatment planning and to evaluate the potential benefits of individualized beam setups to better protect lung functionality in patients with non-small cell lung cancer (NSCLC). Methods Peak-exhale and peak-inhale CT scans were carried out in 16 patients with NSCLC treated with intensity-modulated radiotherapy (IMRT). 4D-CT-based ventilation information was generated from the two sets of CT images using deformable image registration. Four kinds of IMRT plans were generated for each patient: two anatomic plans without incorporation of ventilation information, and two functional plans with ventilation information, using either five equally spaced beams (FESB) or five manually optimized beams (FMOB). The dosimetric parameters of the plans were compared in terms of target and normal tissue structures, with special focus on dose delivered to total lung and functional lung. Results In both the anatomic and functional plans, the percentages of both the functional and total lung regions irradiated at V5, V10, and V20 (percentage volume irradiated to >5, >10 and >20 Gy, respectively) were significantly lower for FMOB compared with FESB (P < 0.05), but there was no significant difference for V30 (P > 0.05). Compared with FESB, a greater degree of sparing of the functional lung was achieved in functional IMRT plans with optimal beam arrangement, without compromising target volume coverage or the irradiated volume of organs at risk, such as the spinal cord, esophagus, and heart. Conclusions Pulmonary ventilation image-guided IMRT planning with further optimization of beam arrangements improves the preservation of functional lung in patients with NSCLC.

Deformable image registration (DIR) was widely used in radiation therapy, such as in automatic contour generation, dose accumulation, tumor growth or regression analysis. To achieve higher registration accuracy and faster convergence, an improved 'diffeomorphic demons' registration algorithm was proposed and validated. Based on Brox et al.'s gradient constancy assumption and Malis's efficient second-order minimization (ESM) algorithm, a grey value gradient similarity term and a transformation error term were added into the demons energy function, and a formula was derived to calculate the update of transformation field. The limited Broyden-Fletcher-Goldfarb-Shanno (L-BFGS) algorithm was used to optimize the energy function so that the iteration number could be determined automatically. The proposed algorithm was validated using mathematically deformed images and physically deformed phantom images. Compared with the original 'diffeomorphic demons' algorithm, the registration method proposed achieve a higher precision and a faster convergence speed. Due to the influence of different scanning conditions in fractionated radiation, the density range of the treatment image and the planning image may be different. In such a case, the improved demons algorithm can achieve faster and more accurate radiotherapy.

The aims of this study were to evaluate the volume and dosimetric variations during IMRT for locally advanced NPC and to identify the benefits of a two-phase adaptive IMRT method. Twenty patients with locally advanced NPC having received IMRT treatment were included. Each patient had both an initial planning CT (CT-1) and a repeated CT scan (CT-2) after treatment at a dose of 40 Gy. Three IMRT planning scenarios were compared: (1) the initial plan on the CT-1 (plan-1); (2) the hybrid plan recalculated the initial plan on the CT-2 (plan-2); (3) the replan generated on the CT-2 being used to complete the course of IMRT (plan-3). The mean gross target volume and mean volumes of the positive neck lymph nodes, high-risk clinical target volume, and the left and right parotid glands significantly decreased by 30.2%, 45.1%, 21.1%, 14.7% and 18.2%, respectively on the CT-2. Comparing plan-2 with plan-1, the dose coverage of the targets remained unchanged, whereas the dose delivered to the parotid glands and spinal cord increased significantly. These patients with locally advanced NPC might benefit from replanning because of the sparing of the parotid glands and spinal cord.

The present paper is to verify the accuracy of DPM, a Monte Carlo-based dose calculation algorithm, in homogeneous and inhomogeneous tissues. DPM was applied to calculate (1) depth dose curves and off-axis ratios at a depth of 10 cm in water using a 6 MeV photon beam with a 3 cm x 3 cm field and phase space file simulated Varian 60 degrees C medical linear accelerator with a 10 cm x 10 cm field at SSD = 100 (cm); (2) depth dose curves using 6 MeV photon beam in inhomogeneous tissues, such as water (6 cm)/lung (6 cm)/water (8 cm) with a 3 cm x 3 cm field and water (6 cm)/ bone (2 cm)/water (12 cm) with a 10 cm x 10 cm field; (3) depth dose curves using 6 MeV photon beam based on the CT data of a patient's head and abdomen. The doses based on DPM are compared to the doses calculated by DOSXYZnrc under the same condition. The error was within 3% in water phantom while the error was within 3% in inhomogeneous tissues, except a few points. It has been concluded that the DPM can accurately predict the dose to homogeneous and inhomogeneous tissues.

Objective: To investigate the feasibility of a four-dimensional computerized tomography (4D-CT) reconstruction method based on the similarity principle of spatial adjacent images and mutual information measure. Methods: The CT data of patient underwent free breathing were acquired in Cine mode by a GE Light Speed 16 CT scanner, the Cine during time was equal to the breathing period of the patient plus one second (about 4-6s) and 8 to 15 slices CT image were acquired by a row CT detector in every Cine scan. A software program was developed by using VC++ and VTK software tools to re-sort the CT data and reconstruct the 4D-CT. Then all of the CT data with same phase were sorted by the program into a same series based on the similarity principle of spatial adjacent images and mutual information measure among them, and 3D reconstruction of different phase CT data were completed by using the software. Results: All of the CT data were sort accurately into different series based on the similarity principle of spatial adjacent images and mutual information measures among them. Compared with the unsorted CT data, the motion artifacts in the 3D reconstruction of sorted CT data were reduced significantly, and all of the sorted CT series result in a 4D-CT that reflected the characteristic of the free breathing. Conclusion: Time-resolved 4D-CT reconstruction can be implemented with any general multi-slice CT scanners based on the similarity principle of spatial adjacent images and mutual information measure, the process of the 4D--CT data acquisition and reconstruction were not restricted to the hardware or software of the CT scanner and has the feasibility and extensive applicability.

Objective: To investigate the feasibility of delineating individual gross target volume (GTV) for tumors moving with respiration by using AIP/MIP CT instead of 4D-CT. Methods: CT data of three patients were acquired in Cine mode. The Cine duration time for each couch position is 4~6s, which equals to one breathing cycle plus 1s. The acquired CT data were input to a 4D-CT reconstruction system made in house to reconstruct AIP/MIP and 4D-CT. Then, the characteristics of motion tumor in AIP/MIP and 4D-CT were analyzed. The influences of window width/level on the appearance of periodical motion target in AIP/MIP CT were investigated by using a periodical motion phantom. Results: The GTV in AIP (GTVAIP) and MIP CT (GTVMIP) was bigger than that in extra-inhale phase 4D-CT (GTV4D-in) or extra-exhale phase 4D-CT (GTV4D-ex). The ratios of GTVAIP to GTV4D-in for two patients were 1.30 and 1.07, and the ratios of GTVMIP to GTV4D-ex were 1.57 and 1.21, respectively. AIP/MIP CT with appropriate window width/level can be used to derive the individual target motion envelope. Conclusions: AIP/MIP CT could be used to quickly delineate individual GTV for moving tumor, which may significantly reduce the target delineation laboring. It can be used to replace 4D-CT to derive the individual GTVs for tumors moving with respiratory.

MKK4 is a candidate tumor suppressor, which acts as a critical mediator of Epstein–Barr Virus (EBV)-induced c-Jun N-terminal kinase (JNK) activation. Functional polymorphism MKK4 −1304T>G has been showed to be protective in colorectal cancer or lung cancer. We hypothesized that genetic variants in the MKK4 promoter were associated with the risk of nasopharyngeal carcinoma (NPC). Two common polymorphisms in MKK4, −1304T>G and −1044A>T were genotyped in two independent case-control panels of Eastern and Southern Chinese populations, totally containing 1237 NPC and 1328 controls. We found that compared to the most common −1304TT genotype, carriers of variant genotypes (−1304TG+GG) were associated with a significantly reduced risk for NPC in total subjects (adjusted OR = 0.78; 95%CI = 0.67–0.94). Further stratification analysis showed that the protective effect was more pronounced in EBV negative status (adjusted OR = 0.51; 95%CI = 0.41–0.68) but restrained in those with EBV infection (adjusted OR = 1.05; 95%CI = 0.88–1.26), and that the −1304GG variant genotypes interacted with EBV negative status on reducing cancer risk (p = 0.011). However, no significant association was observed between the −1044A>T polymorphism and risk of NPC. Our data suggest that the protective role of genetic variant MKK4 −1304T>G is restrained in NPC with EBV infection. These findings implicate the role of EBV and MKK4 −1304 T>G interaction as a causative factor for the NPC.

Linear accelerator accurate simulation is the prerequisite of Monte Carlo dose calculation algorithm. The study simulated 6MV photon beam produced by Varian 600C medical linear accelerator to derive the mean energy and the full-width half-maximum(FWHM) of incident electron beam intensity distribution (assumed Gaussian distribution) with BEAMnrc and DOSXYZnrc by matching calculated and measured depth dose curves and off-axis ratios at a depth of 10.0cm in water. Depth dose curve is sensitive to the mean energy, insensitive to radial intensity distribution, while off-axis ratio is dramatically affected by mean energy and radial intensity distribution. Depth dose curves and off-axis ratios were performed past the depth of maximum dose within 1.5% of relative error and at 10.0cm depth within 30% of relative error, respectively.

Deformable image registration is currently widely used in four-dimensional (4D) radiotherapy applications including internal anatomy motion tracking, delineating and dose tracking. In this work, two optical flow based deformable registration algorithm are studied, and we have designed two experiments to evaluate their efficiency. In the first study, deformation fields are calculated between reference phases and other phases in 4D CT images, and the contours on the reference phase are deformed to corresponding phases. In the second study, motion fields between distinct phases: end-inspiration and end-expiration are interpolated to generate images in other phases. The algorithms are validated by quantitative comparison, and visual inspections of the positions and shapes of these deformed contours agree well with human judgment. Furthermore, the deformable registration methods have significant potential for phase prediction to reduce the amount of cine data acquisition in 4D CT.

Using an IMRT MatriXX, which is used to measure intensity maps in 2D, is a promising method for the dosimetric verification of external beam, megavoltage radiation therapy. From MatriXX images, two dimensional dose distributions inside a phantom or patient can be obtained. Whereas, the lateral X-ray scatter within the MatriXX makes the accuracy in dose reconstruction dissatisfactory. Therefore, a more accurate correction for the lateral scatter contribution has to be considered. In this study, a scatter kernel was introduced to correct the dose values determined with the MatriXX. The model requires the primary dose component at the position of the MatriXX. A parametrized description of the lateral scatter within the MatriXX was obtained from measurements with an ionization chamber in a miniphantom. This yielded a good description of the lateral scatter within the MatriXX on the central axis. This is relevant since the treatment outcome critically depends on the dose delivered to the tumor (usually close to the isocenter). There is an excellent agreement between the dose values measured with the ionization chamber in a miniphantom and those obtained from the MatriXX after the scatter correction with the kernel. It can be concluded that the scatter correction is able to improve the accuracy of the MatriXX dose values on the central axis.

The FDK algorithm is one of the most widely referenced and used algorithm for cone-beam CT reconstruction in circular trajectory because of its simplicity of implementation and computational efficiency. However, images reconstructed by the FDK algorithm of real projection data may be blurred without electronic correction and geometric calibration, and are often plagued by deleterious ring artifacts and shading artifacts. In this paper, images reconstructed with and without detector correction are compared base on computer experiment of real biological object. Furthermore, Algorithms for shading artifacts reduction and fast ring artifacts reduction are also introduced. The experimental simulation shows that these algorithms are effective in reducing ring and shading artifacts without compromising the image resolution, and produce satisfactory results.