Machine Learning-Based Multiomics Prediction Model for Radiation Pneumonitis.

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 < 1 were labeled as 0. The whole lung excluding clinical target volume (lung-CTV) was used as the region of interest (ROI). The radiomic and dosiomic features were extracted from the lung-CTV area's image and dose distribution. Besides, the equivalent dose of the 2 Gy fractionated radiation (EQD2) model was used to convert the physical dose to the isoeffect dose, and then, the EQD2-based dosiomic (eqd-dosiomic) features were extracted from the isoeffect dose distribution. Four machine learning (ML) models, including DVH, radiomics combined with DVH (radio + DVH), radiomics combined with dosiomics (radio + dose), and radiomics combined with eqd-dosiomics (radio + eqdose), were established to construct the prediction model via eleven different classifiers. The fivefold cross-validation was used to complete the classification experiment. The area under the curve (AUC) of the receiver operating characteristics (ROC), accuracy, precision, recall, and F1-score were calculated to assess the performance level of the prediction models. Results: Compared with the DVH, radio + DVH, and radio + dose model, the value of the training AUC, accuracy, and F1-score of radio + eqdose was higher, and the difference was statistically significant (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.

Critical Evaluation of Secondary Cancer Risk After Breast Radiation Therapy with Hybrid Radiotherapy Techniques.

Background: 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.

XBP1-elicited environment by chemotherapy potentiates repopulation of tongue cancer cells by enhancing miR-22/lncRNA/KAT6B-dependent NF-κB signalling.

BACKGROUND: Tumour repopulation initiated by residual tumour cells in response to cytotoxic therapy has been described clinically and biologically, but the mechanisms are unclear. Here, we aimed to investigate the mechanisms for the tumour-promoting effect in dying cells and for tumour repopulation in surviving tongue cancer cells. METHODS: Tumour repopulation in vitro and in vivo was represented by luciferase activities. The differentially expressed cytokines in the conditioned medium (CM) were identified using a cytokine array. Gain or loss of function was investigated using inhibitors, neutralising antibodies, shRNAs and ectopic overexpression strategies. RESULTS: We found that dying tumour cells undergoing cytotoxic therapy increase the growth of living tongue cancer cells in vitro and in vivo. Dying tumour cells create amphiregulin (AREG)- and basic fibroblast growth factor (bFGF)-based extracellular environments via cytotoxic treatment-induced endoplasmic reticulum stress. This environment stimulates growth by activating lysine acetyltransferase 6B (KAT6B)-dependent nuclear factor-kappa B (NF-κB) signalling in living tumour cells. As direct targets of NF-κB, miR-22 targets KAT6B to repress its expression, but long noncoding RNAs (lncRNAs) (XLOC_003973 and XLOC_010383) counter the effect of miR-22 to enhance KAT6B expression. Moreover, we detected increased AREG and bFGF protein levels in the blood of tongue cancer patients with X-box binding protein-1 (XBP1) activation in tumours under cytotoxic therapy and found that XBP1 activation is associated with poor prognosis of patients. We also detected activation of miR-22/lncRNA/KAT6B/NF-κB signalling in recurrent cancers compared to paired primary tongue cancers. CONCLUSIONS: We identified the molecular mechanisms of cell death-induced tumour repopulation in tongue cancer. Such insights provide new avenues to identify predictive biomarkers and effective strategies to address cancer progression.

4DCT ventilation function image-based functional lung protection for esophageal cancer radiotherapy.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 FL0.8­V30 correlation was the strongest (r = 0.819, P < 0.01). The FL-sparing planning had a target area conformity index and homogeneity index comparable to the non-sparing planning (P > 0.05). For FL, the FL-sparing planning achieved lower FL-MLD (6.30 ±â€¯2.14 Gy vs. 7.83 ± 2.70 Gy), V10 (17.13 ±â€¯7.70% vs. 27.40 ± 9.48%), and V20 (6.96 ±â€¯3.85% vs. 11.63 ± 7.19%) compared to the non-sparing planning (P < 0.05), while heart and spinal cord doses were not significantly different between the two planning groups. CONCLUSION: The 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.

Functional lung imaging in thoracic tumor radiotherapy: Application and progress.

Radiotherapy plays an irreplaceable and unique role in treating thoracic tumors, but the occurrence of radiation-induced lung injury has limited the increase in tumor target doses and has influenced patients' quality of life. However, the introduction of functional lung imaging has been incorporating functional lungs into radiotherapy planning. The design of the functional lung protection plan, while meeting the target dose requirements and dose limitations of the organs at risk (OARs), minimizes the radiation dose to the functional lung, thus reducing the occurrence of radiation-induced lung injury. In this manuscript, we mainly reviewed the lung ventilation or/and perfusion functional imaging modalities, application, and progress, as well as the results based on the functional lung protection planning in thoracic tumors. In addition, we also discussed the problems that should be explored and further studied in the practical application based on functional lung radiotherapy planning.

Different functional lung-sparing strategies and radiotherapy techniques for patients with esophageal cancer.

Background: Integration of 4D-CT ventilation function images into esophageal cancer radiation treatment planning aimed to assess dosimetric differences between different functional lung (FL) protection strategies and radiotherapy techniques. Methods: A total of 15 patients with esophageal cancer who had 4D-CT scans were included. Lung ventilation function images based on Jacobian values were obtained by deformation image registration and ventilation imaging algorithm. Several different plans were designed for each patient: clinical treatment planning (non-sparing planning), the same beam distribution to FL-sparing planning, three fixed-beams FL-sparing intensity-modulated radiation therapy (IMRT) planning (5F-IMRT, 7F-IMRT, 9F-IMRT), and two FL-sparing volumetric modulated arc therapy (VMAT) planning [1F-VMAT (1-Arc), 2F-VMAT (2-Arc)]. The dosimetric parameters of the planning target volume (PTV) and organs at risk (OARs) were compared and focused on dosimetric differences in FL. Results: The FL-sparing planning compared with the non-sparing planning significantly decreased the FL-Dmean, V5-30 and Lungs-Dmean, V10-30 (Vx: volume of receiving ≥X Gy), although it slightly compromised PTV conformability and increased Heart-V40 (P< 0.05). The 5F-IMRT had the lowest PTV-conformability index (CI) but had a lower Lungs and Heart irradiation dose compared with those of the 7F-IMRT and 9F-IMRT (P< 0.05). The 2F-VMAT had higher PTV-homogeneity index (HI) and reduced irradiation dose to FL, Lungs, and Heart compared to those of the 1F-VMAT planning (P< 0.05). The 2F-VMAT had higher PTV conformability and homogeneity and decreased FL-Dmean, V5-20 and Lungs-Dmean, V5-10 but correspondingly increased spinal cord-Dmean compared with those of the 5F-IMRT planning (P< 0.05). Conclusion: In this study, 4D-CT ventilation function image-based FL-sparing planning for esophageal cancer can effectively reduce the dose of the FL. The 2F-VMAT planning is better than the 5F-IMRT planning in reducing the dose of FL.

Functional Liver Imaging in Radiotherapy for Liver Cancer: A Systematic Review and Meta-Analysis.

Backgrounds: Functional liver imaging can identify functional liver distribution heterogeneity and integrate it into radiotherapy planning. The feasibility and clinical benefit of functional liver-sparing radiotherapy planning are currently unknown. Methods: A comprehensive search of several primary databases was performed to identify studies that met the inclusion criteria. The primary objective of this study was to evaluate the dosimetric and clinical benefits of functional liver-sparing planning radiotherapy. Secondary objectives were to assess the ability of functional imaging to predict the risk of radiation-induced liver toxicity (RILT), and the dose-response relationship after radiotherapy. Results: A total of 20 publications were enrolled in descriptive tables and meta-analysis. The meta-analysis found that mean functional liver dose (f-MLD) was reduced by 1.0 Gy [95%CI: (-0.13, 2.13)], standard mean differences (SMD) of functional liver volume receiving ≥20 Gy (fV20) decreased by 0.25 [95%CI: (-0.14, 0.65)] when planning was optimized to sparing functional liver (P >0.05). Seven clinical prospective studies reported functional liver-sparing planning-guided radiotherapy leads to a low incidence of RILD, and the single rate meta-analysis showed that the RILD (defined as CTP score increase ≥2) incidence was 0.04 [95%CI: (0.00, 0.11), P <0.05]. Four studies showed that functional liver imaging had a higher value to predict RILT than conventional anatomical CT. Four studies established dose-response relationships in functional liver imaging after radiotherapy. Conclusion: Although functional imaging modalities and definitions are heterogeneous between studies, but incorporation into radiotherapy procedures for liver cancer patients may provide clinical benefits. Further validation in randomized clinical trials will be required in the future.

Pelvic bone marrow sparing radiotherapy for cervical cancer: A systematic review and meta-analysis.

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.

Evaluation of automatic VMAT plans in locally advanced nasopharyngeal carcinoma.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Multi-path synergic fusion deep neural network framework for breast mass classification using digital breast tomosynthesis.

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.

Secondary cancer risk after radiation therapy for breast cancer with different radiotherapy techniques.

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.

Dosimetric evaluation of automatic and manual plans for early nasopharyngeal carcinoma to radiotherapy.

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.

RGD peptide-modified fluorescent gold nanoclusters as highly efficient tumor-targeted radiotherapy sensitizers.

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 αvß3 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.

An anthropomorphic abdominal phantom for deformable image registration accuracy validation in adaptive radiation therapy.

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.

Reduction in stray radiation dose using a body-shielding device during external radiation therapy.

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.

Disturbance of the let-7/LIN28 double-negative feedback loop is associated with radio- and chemo-resistance in non-small cell lung cancer.

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.

Analysis of setup error based on CTVision for nasopharyngeal carcinoma during IGRT.

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 (Σ), 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, Σ 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.

Optimal beam arrangement for pulmonary ventilation image-guided intensity-modulated radiotherapy for lung cancer.

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.

4D-CT reconstruction based on pulmonary average CT values.

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.

The feasibility of mapping dose distribution of 4DCT images with deformable image registration in lung.

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.