CNN-based multi-modal radiomics analysis of pseudo-CT utilization in MRI-only brain stereotactic radiotherapy: a feasibility study.

BACKGROUND: Pseudo-computed tomography (pCT) quality is a crucial issue in magnetic resonance image (MRI)-only brain stereotactic radiotherapy (SRT), so this study systematically evaluated it from the multi-modal radiomics perspective. METHODS: 34 cases (< 30 cm³) were retrospectively included (2021.9-2022.10). For each case, both CT and MRI scans were performed at simulation, and pCT was generated by a convolutional neural network (CNN) from planning MRI. Conformal arc or volumetric modulated arc technique was used to optimize the dose distribution. The SRT dose was compared between pCT and planning CT with dose volume histogram (DVH) metrics and gamma index. Wilcoxon test and Spearman analysis were used to identify key factors associated with dose deviations. Additionally, original image features were extracted for radiomic analysis. Tumor control probability (TCP) and normal tissue complication probability (NTCP) were employed for efficacy evaluation. RESULTS: There was no significant difference between pCT and planning CT except for radiomics. The mean value of Hounsfield unit of the planning CT was slightly higher than that of pCT. The Gadolinium-based agents in planning MRI could increase DVH metrics deviation slightly. The median local gamma passing rates (1%/1 mm) between planning CTs and pCTs (non-contrast) was 92.6% (range 63.5-99.6%). Also, differences were observed in more than 85% of original radiomic features. The mean absolute deviation in TCP was 0.03%, and the NTCP difference was below 0.02%, except for the normal brain, which had a 0.16% difference. In addition, the number of SRT fractions and lesions, and lesion morphology could influence dose deviation. CONCLUSIONS: This is the first multi-modal radiomics analysis of CNN-based pCT from planning MRI for SRT of small brain lesions, covering dosiomics and radiomics. The findings suggest the potential of pCT in SRT plan design and efficacy prediction, but caution needs to be taken for radiomic analysis.

Pretreatment patient-specific quality assurance prediction based on 1D complexity metrics and 3D planning dose: classification, gamma passing rates, and DVH metrics.

PURPOSE: Highly modulated radiotherapy plans aim to achieve target conformality and spare organs at risk, but the high complexity of the plan may increase the uncertainty of treatment. Thus, patient-specific quality assurance (PSQA) plays a crucial role in ensuring treatment accuracy and providing clinical guidance. This study aims to propose a prediction model based on complexity metrics and patient planning dose for PSQA results. MATERIALS AND METHODS: Planning dose, measurement-based reconstructed dose and plan complexity metrics of the 687 radiotherapy plans of patients treated in our institution were collected for model establishing. Global gamma passing rate (GPR, 3%/2mm,10% threshold) of 90% was used as QA criterion. Neural architecture models based on Swin-transformer were adapted to process 3D dose and incorporate 1D metrics to predict QA results. The dataset was divided into training (447), validation (90), and testing (150) sets. Evaluation of predictions was performed using mean absolute error (MAE) for GPR, planning target volume (PTV) HI and PTV CI, mean absolute percentage error (MAPE) for PTV D95, PTV D2 and PTV Dmean, and the area under the receiver operating characteristic (ROC) curve (AUC) for classification. Furthermore, we also compare the prediction results with other models based on either only 1D or 3D inputs. RESULTS: In this dataset, 72.8% (500/687) plans passed the pretreatment QA under the criterion. On the testing set, our model achieves the highest performance, with the 1D model slightly surpassing the 3D model. The performance results are as follows (combine, 1D, and 3D transformer): The AUCs are 0.92, 0.88 and 0.86 for QA classification. The MAEs of prediction are 0.039, 0.046, and 0.040 for 3D GPR, 0.018, 0.021, and 0.019 for PTV HI, and 0.075, 0.078, and 0.084 for PTV CI. Specifically, for cases with 3D GPRs greater than 90%, the MAE could achieve 0.020 (combine). The MAPE of prediction is 1.23%, 1.52%, and 1.66% for PTV D95, 2.36%, 2.67%, and 2.45% for PTV D2, and 1.46%, 1.70%, and 1.71% for PTV Dmean. CONCLUSION: The model based on 1D complexity metrics and 3D planning dose could predict pretreatment PSQA results with high accuracy and the complexity metrics play a leading role in the model. Furthermore, dose-volume metric deviations of PTV could be predicted and more clinically valuable information could be provided.

Optimal fractionation and timing of weekly cone-beam CT in daily surface-guided radiotherapy for breast cancer.

PURPOSE: Surface-guided radiotherapy (SGRT) has been demonstrated to be a promising supplement to cone-beam computed tomography (CBCT) in adjuvant breast cancer radiotherapy, but a rational combination mode is lacking in clinical practice. The aim of this study was to explore this mode and investigate its impact on the setup and dose accuracy. METHODS AND MATERIALS: Daily SGRT and weekly CBCT images were acquired for 23 patients with breast cancer who received conventional fractionated radiotherapy after lumpectomy. Sixteen modes were acquired by randomly selecting one (CBCT1), two (CBCTij), three (CBCTijk), four (CBCTijkl), and five (CBCT12345) images from the CBCT images for fusion with the SGRT. The CTV-PTV margins, OAR doses, and dose coverage (V95%) of PTV and CTV was calculated based on SGRT setup errors with different regions of interest (ROIs). Dose correlations between these modalities were investigated using Pearson and Spearman's methods. Patient-specific parameters were recorded to assess their impact on dose. RESULTS: The CTV-PTV margins decreased with increasing CBCT frequencies and were close to 5 mm for CBCTijkl and CBCT12345. For the ipsilateral breast ROI, SGRT errors were larger in the AP direction, and target doses were higher in all modes than in the whole breast ROI (P < 0.05). In the ipsilateral ROI, the target dose correlations between all modes increased with increasing CBCT time intervals, decreased, and then increased with increasing CBCT frequencies, with the inflection point being CBCT participation at week 5. The dose deviations in CBCT123, CBCT124, CBCT125, CBCTijkl, and CBCT12345 were minimal and did not differ significantly (P > 0.05). There was excellent agreement between CBCT124 and CBCT1234, and between (CBCTijkl, CBCT12345) and CBCT125 in determining the classification for the percentage of PTV deviation (Kappa = 0.704-0.901). In addition, there were weak correlations between the patient's Dips_b (ipsilateral breast diameter with bolus) and CTV doses in modes with CBCT participation at week 4 (R = 0.270 to 0.480). CONCLUSIONS: Based on weekly CBCT, these modes with ipsilateral ROI and a combination of daily SGRT and a CBCT frequency of ≥ 3 were recommended, and CBCT was required at weeks 1 and 2 for CBCTijk.

A novel dose fall-off index and preliminary application in brain and lung stereotactic radiotherapy.

BACKGROUND: Stereotactic radiotherapy (SRT) has been widely used for the treatment of brain metastases and early stage non-small-cell lung cancer (NSCLC). Excellent SRT plans are characterized by steep dose fall-off, making it critical to accurately and comprehensively predict and evaluate dose fall-off. PURPOSE: A novel dose fall-off index was proposed to ensure high-quality SRT planning. METHODS: The novel gradient index (NGI) had two different modes: NGIx V for three-dimensions and NGIx r for one-dimension. NGIx V and NGIx r were defined as the ratios of the decreased percentage dose (x%) to the corresponding isodose volume and equivalent sphere radii, respectively. A total of 243 SRT plans at our institution between April 2020 and March 2022 were enrolled, including 126 brain and 117 lung SRT plans. Measurement-based verifications were performed using SRS MapCHECK. Ten plan complexity indexes were calculated. Dosimetric parameters related to radiation injuries were also extracted, including the normal brain volume exposed to 12 Gy (V12 ) and 18 Gy (V18 ) during single-fraction SRT (SF-SRT) and multi-fraction SRT (MF-SRT), respectively, and the normal lung volume exposed to 12 Gy (V12 ). The performance of NGI and other common dose fall-off indexes, gradient index (GI), R50% and D2cm were evaluated using Spearman correlation analysis to explore their correlations with the PTV size, gamma passing rate (GPR), plan complexity indexes, and dosimetric parameters. RESULTS: There were statistically significant correlations between NGI and PTV size (r = -0.98, P < 0.01 for NGI50 V and r = -0.93, P < 0.01 for NGI50 r), which were the strongest correlations compared with GI (r = 0.11, P = 0.13), R50% (r = -0.08, P = 0.19) and D2cm (r = 0.84, P < 0.01). The fitted formulas of NGI50 V = 23.86V-1.00 and NGI50 r = 113.5r-1.05 were established. The GPRs of enrolled SRT plans were 98.6 ± 1.7%, 94.2 ± 4.7% and 97.1 ± 3.1% using the criteria of 3%/2 mm, 3%/1 mm, and 2%/2 mm, respectively. NGI50 V achieved the strongest correlations with various plan complexity indexes (|r| ranged from 0.67 to 0.91, P < 0.01). NGI50 V also showed the highest r values with V12 (r = -0.93, P < 0.01) and V18 (r = -0.96, P < 0.01) of the normal brain during SF-SRT and MF-SRT, respectively, and V12 (r = -0.86, P < 0.01) of the normal lung during lung SRT. CONCLUSIONS: Compared with GI, R50% and D2cm , the proposed dose fall-off index, NGI, had the strongest correlations with the PTV size, plan complexity and V12 /V18 of the normal tissues. These correlations established on NGI are more helpful and reliable for SRT planning, quality control, and reducing the risk of radiation injuries.

The role of image-guided radiotherapy in prostate cancer: A systematic review and meta-analysis.

Background: Image-guided radiotherapy (IGRT) has gradually been widely promoted in clinical procedure. However, there has been no consensus on the effects of IGRT on toxicity and survival, and no clear level 1 evidence has even been promulgated. Methods: Medline, EMBASE, PubMed, Cochrane databases and ClinicalTrials.gov were searched for studies comparing IGRT vs non-IGRT or higher frequency IGRT vs lower frequency IGRT during prostate radiotherapy, indexed from database inception to April 2022. Results: The review included 18 studies (3 randomized clinical trial and 15 cohort studies) involving 6521 men, with a median duration of patient follow-up of 46.2 months in the IGRT group vs 52.7 months in the control group. The meta-analysis demonstrated that IGRT significantly reduced acute GU (risk ratio [RR], 0.78; 95 % confidence interval [CI], 0.69-0.88; P < 0.001 [9 studies]) and GI toxicity (RR, 0.49; 95 % CI, 0.35-0.68; P < 0.001 [4 studies]) and late GI toxicity (HR, 0.25; 95 % CI, 0.07-0.87; P = 0.03 [3 studies]) compared with non-IGRT. Meanwhile, compared with prospective studies, retrospective studies showed that IGRT had a more significant effect in reducing the late GI toxicity. Compared with non-daily IGRT, daily IGRT significantly improved 3-year PRFS (HR, 0.45; 95 % CI, 0.28-0.72; P = 0.001 [2 studies]) and BFFS (HR, 0.57; 95 % CI, 0.39-0.83; P = 0.003 [3 studies]). Furthermore, high-frequency daily IGRT could lead to greater 3-year BFFS benefit in prostate cancer patients than weekly IGRT. However, no significant effects of IGRT on acute rectal toxicity, late GU toxicity, 5-year OS and SCM were found. Conclusions: For men receiving prostate radiotherapy, IGRT was associated with an improvement in biochemical tumor control and a reduction in GI and acute GU toxicity, but did not significantly improve 5-year OS or increase 5-year SCM.

Pseudo-siamese network combined with dosimetric and clinical factors, radiomics features, CT images and 3D dose distribution for the prediction of radiation pneumonitis: A feasibility study.

Purpose: Radiation pneumonitis (RP)(grade ≥ 2) can have a considerable impact on patient quality-of life. In previous studies, the traditional method commonly used radiomics and clinical factors for RP prediction. This study aims to develop and evaluate a novel pseudo-siamese network (PSN) to assist radiologists predict RP before radiotherapy based on combination of dosimetric and clinical factors, radiomics features, CT (computed tomography) images, and dose distribution (hybrid model). Method: One hundred and ten patients with lung cancer (19 RP ≥ 2) who received radiotherapy between 2016 and 2020 were retrospectively enrolled in this study. Dosimetric factors were calculated from DVH (dose-volume histogram), such as lung mean dose, lung V5, and prescription dose. Clinical characteristics were recorded, such as age, sex, smoking status, TN stage, and overall stage. A total of 1419 radiomics features were extracted. Cluster analysis was used for detecting radiomics features that associated with RP. Patients were randomly split into a training set (90 %, 85 non-RP, and 14 RP) and a validation set (10 %, 6 non-RP, and 5 RP). A PSN architecture was designed for combining 1D (dosimetric and clinical factors, radiomics) and 3D (CT images, 3D dose distribution) features. 5-fold cross-validation procedure for estimating the skill of the model on new data. Results: For cluster analysis, totally of 106 radiomics features with high correlation were selected. The accuracy was 0.727, 0.636, 0.545, and 0.727 for input dosimetric and clinical factors, dose distribution, CT images, and radiomics features, respectively. The accuracy of hybrid model was 0.818. The sensitivity of hybrid model was 0.800 (95 % confidence interval (CI) [0.299, 0.989]), and specificity was 0.833(95 % CI [0.364, 0.991]). The areas under the receiver operating characteristic curves (AUCs) result in 5-fold cross-validation was 0.77-0.90(mean AUC ± std was 0.85 ± 0.05). Conclusion: This study firstly propose method that the combination of high dimensional and low dimensional features for RP prediction. The results confirm the feasibility of multi-dimensional features predict RP.

Gross Tumor Volume Segmentation for Stage III NSCLC Radiotherapy Using 3D ResSE-Unet.

INTRODUCTION: Radiotherapy is one of the most effective ways to treat lung cancer. Accurately delineating the gross target volume is a key step in the radiotherapy process. In current clinical practice, the target area is still delineated manually by radiologists, which is time-consuming and laborious. However, these problems can be better solved by deep learning-assisted automatic segmentation methods. METHODS: In this paper, a 3D CNN model named 3D ResSE-Unet is proposed for gross tumor volume segmentation for stage III NSCLC radiotherapy. This model is based on 3D Unet and combines residual connection and channel attention mechanisms. Three-dimensional convolution operation and encoding-decoding structure are used to mine three-dimensional spatial information of tumors from computed tomography data. Inspired by ResNet and SE-Net, residual connection and channel attention mechanisms are used to improve segmentation performance. A total of 214 patients with stage III NSCLC were collected selectively and 148 cases were randomly selected as the training set, 30 cases as the validation set, and 36 cases as the testing set. The segmentation performance of models was evaluated by the testing set. In addition, the segmentation results of different depths of 3D Unet were analyzed. And the performance of 3D ResSE-Unet was compared with 3D Unet, 3D Res-Unet, and 3D SE-Unet. RESULTS: Compared with other depths, 3D Unet with four downsampling depths is more suitable for our work. Compared with 3D Unet, 3D Res-Unet, and 3D SE-Unet, 3D ResSE-Unet can obtain superior results. Its dice similarity coefficient, 95th-percentile of Hausdorff distance, and average surface distance can reach 0.7367, 21.39mm, 4.962mm, respectively. And the average time cost of 3D ResSE-Unet to segment a patient is only about 10s. CONCLUSION: The method proposed in this study provides a new tool for GTV auto-segmentation and may be useful for lung cancer radiotherapy.

The factors of fiducial marker motions and individual margin assessment in postoperative breast cancer radiotherapy.

Background: As a surrogate for the breast tumor bed, individual fiducial markers frequently move during radiotherapy. This study aimed to classify the motions and calculate the individualized target margin. Methods: The mammary basal diameters (D) and heights (H) were measured to represent breast sizes for 15 patients after breast-conserving surgery. The clinical target volume (CTV) was divided into 4 quadrants by a coordinate system with the center of mass of the tumor bed as the origin. The lateral, anteroposterior, and craniocaudal motions of markers were calculated (MLR, MAP, MSI) based on the difference of the setup errors between the spine matching and the fiducial markers matching. The distances between markers and the innermost, foremost, and uppermost borders of CTV (DSLR, DSAP, DSSI) were recorded. Results: In the first quadrant, MAP was strongly correlated with D×H (r>0.80) when D×H <99.89 cm2. Both MLR and MAP were positively linearly related to DSLR, DSAP, DSSI (r>0.85, R2>0.75). MSI was also positively linearly correlated with DSAP and DSLR (r>0.90, R2>0.80). In the fourth quadrant with D×H <90.71 cm2, only MLR and DSLR showed a linear positive correlation (r>0.90, R2>0.75), whereas the others showed linear negative correlations (r>-0.90, R2>0.80). The planning target volume (PTV) margin varied significantly between the first and fourth quadrant (P<0.05), and the largest margin was 12.4 mm in the craniocaudal direction of the first quadrant with D×H ≥99.89 cm2. Conclusions: Fiducial motion is susceptible to breast size and fiducial position, and the individualized PTV margins should take the above factors into account.

Dosimetric impacts of cone-beam computed tomography (CBCT)-based anatomic changes in intensity-modulated radiotherapy for cervical cancer.

Background: To evaluate the effects of dose to tumors and organs at risk (OARs) on inter-fractional anatomic changes. Methods: We evaluated nine patients with cervical cancer treated with intensity-modulated radiotherapy (IMRT) (45 Gy in 25 fractions) using kV cone-beam computed tomography (CBCT) image guidance once or twice a week before treatment. For each patient, the original plan on the computed tomography (CT) image was copied to merged images, and then the fractional doses were calculated. Subsequently, deformable accumulated doses were obtained by summing the fractional absolute doses into a single dose in MIM Maestro software. The volume changes in the target and OARs were compared between the original CT and merged CBCT images, and the differences in the fractional and accumulated doses were also evaluated. Results: Sixty-nine merged CBCT images were obtained and analyzed in this study. For the target areas, the volume changes in the clinical target volume (CTV) and planning target volume (PTV) reached -18.05% and -24.11% at most, respectively. The fractional D2% of the CTV and PTV was generally higher than the original plans, and the accumulated deviations were 2.27%±0.82% (P<0.01) and 2.42%±1.28% (P<0.01), respectively. The fractional D98% of the PTV was underdosed up to 18.28% for 78% of patients, and the accumulated deviations were -2.06% to -17.29% (P<0.05). For the OARs, the bladder volume changes were the most dramatic, reducing up to 93.60%. The fractional Dmean and D2cc of the bladder were generally higher than the original plans, and there were significant differences in their accumulated values (P<0.05). There was no obvious trend of rectal volume change with -69.65% to 74.20%. The rectum Dmean and D2cc of the accumulated were not significantly different from the planned dose (P>0.05). Conclusions: For patients with cervical cancer, the changes in bladder and rectal volume were greater than in the target volume. Although the volume changes in the bladder and rectum had no significant effect on D98% of the CTV and PTV, they had a significant effect on their own D2cc and the D2% of the CTV and PTV. More attention should be paid to the volume changes in the bladder and rectum in clinical work.

Correlation between the γ passing rates of IMRT plans and the volumes of air cavities and bony structures in head and neck cancer.

BACKGROUND: Both patient-specific dose recalculation and γ passing rate analysis are important for the quality assurance (QA) of intensity modulated radiotherapy (IMRT) plans. The aim of this study was to analyse the correlation between the γ passing rates and the volumes of air cavities (Vair) and bony structures (Vbone) in target volume of head and neck cancer. METHODS: Twenty nasopharyngeal carcinoma and twenty nasal natural killer T-cell lymphoma patients were enrolled in this study. Nine-field sliding window IMRT plans were produced and the dose distributions were calculated by anisotropic analytical algorithm (AAA), Acuros XB algorithm (AXB) and SciMoCa based on the Monte Carlo (MC) technique. The dose distributions and γ passing rates of the targets, organs at risk, air cavities and bony structures were compared among the different algorithms. RESULTS: The γ values obtained with AAA and AXB were 95.6 ± 1.9% and 96.2 ± 1.7%, respectively, with 3%/2 mm criteria (p > 0.05). There were significant differences (p < 0.05) in the γ values between AAA and AXB in the air cavities (86.6 ± 9.4% vs. 98.0 ± 1.7%) and bony structures (82.7 ± 13.5% vs. 99.0 ± 1.7%). Using AAA, the γ values were proportional to the natural logarithm of Vair (R2 = 0.674) and inversely proportional to the natural logarithm of Vbone (R2 = 0.816). When the Vair in the targets was smaller than approximately 80 cc or the Vbone in the targets was larger than approximately 6 cc, the γ values of AAA were below 95%. Using AXB, no significant relationship was found between the γ values and Vair or Vbone. CONCLUSION: In clinical head and neck IMRT QA, greater attention should be paid to the effect of Vair and Vbone in the targets on the γ passing rates when using different dose calculation algorithms.

Dynamic Changes in Bladder Morphology Over Time in Cervical Cancer Patients.

OBJECTIVES: Continuous surveillance of bladder volume (BV) is beneficial during the treatment of various urogenital diseases because the bladder is always changing its position, size and even shape at different filling phases. For this purpose, we quantified the motion of the urinary bladder. METHODS: Daily ultrasound measurements and weekly cone-beam computed tomography scans were obtained from 89 patients in the supine position. BV, bladder centroid positions, and triaxial lengths in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions were compared across different time points. RESULTS: BV linearly increased over time, and the mean urinary filling rate (vtot) was correlated with the patients' age and water consumption. The greatest bladder centroid motion occurred longitudinally, with less movement observed laterally. The maximum bladder centroid movement was 18.8 ± 2.2 mm inferiorly and 1.8 ± 0.9 mm posteriorly for every 10% decrease in BV. The rates of changes in triaxial lengths differed across the 4 filling phases. The rate was the largest at a BV range of 10-80 mL, especially in the LR direction, with values of 5.9 ± 1.0, 3.6 ± 1.0, and 3.9 ± 1.0 mm per every 10-mL BV increase for LR, AP, and SI, respectively. With bladder filling (<80 mL), the maximum increase in triaxial length was observed in the SI direction and the rates of all changes considerably decreased, especially at BV > 600 mL. CONCLUSION: The vtot could be used to evaluate the temporal changes in the bladder. The spatial changes should be assessed according to different filling phases based on the centroid position and triaxial lengths.

Efficacy and Toxicity of Whole Pelvic Radiotherapy Versus Prostate-Only Radiotherapy in Localized Prostate Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: There is little level 1 evidence regarding the relative efficacy and toxicity of whole pelvic radiotherapy (WPRT) compared with prostate-only radiotherapy (PORT) for localized prostate cancer. METHODS: We used Cochrane, PubMed, Embase, Medline databases, and ClinicalTrials.gov to systematically search for all relevant clinical studies. The data on efficacy and toxicity were extracted for quality assessment and meta-analysis to quantify the effect of WPRT on biochemical failure-free survival (BFFS), progression-free survival (PFS), distant metastasis-free survival (DMFS), overall survival (OS), gastrointestinal (GI) toxicity, and genitourinary (GU) toxicity compared with PORT. The review is registered on PROSPERO, number: CRD42021254752. RESULTS: The results revealed that compared with PORT, WPRT significantly improved 5-year BFFS and PFS, and it was irrelevant to whether the patients had undergone radical prostatectomy (RP). In addition, for the patients who did not receive RP, the 5-year DMFS of WPRT was better than that of PORT. However, WPRT significantly increased not only the grade 2 or worse (G2+) acute GI toxicity of non-RP studies and RP studies, but also the G2+ late GI toxicity of non-RP studies. Subgroup analysis of non-RP studies found that, when the pelvic radiation dose was >49 Gy (equivalent-doses-in-2-Gy-fractions, EQD-2), WPRT was more beneficial to PFS than PORT, but significantly increased the risk of G2+ acute and late GU toxicity. CONCLUSIONS: Meta-analysis demonstrates that WPRT can significantly improve BFFS and PFS for localized prostate cancer than PORT, but the increased risk of G2+ acute and late GI toxicity must be considered. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021254752.

Impact of high-dose rate radiotherapy on B and natural killer (NK) cell polarization in peripheral blood mononuclear cells (PBMCs) via inducing non-small cell lung cancer (NSCLC)-derived exosomes.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most commonly diagnosed solid tumor. While it has been established that stereotactic body radiotherapy for NSCLC plays an important role in antitumor immune response, the possible effects of the dose rate on this response has not been fully clarified. METHODS: In vitro, A549 cells were irradiated on a Varian TrueBeam® Linear Accelerator with dose and dose rate escalation using the flattening filter-free (FFF) technique, which was followed by coculturing with peripheral blood mononuclear cells (PBMCs). The exosomes from irradiated A549 cells were isolated and then cocultured with PBMCs. Flow cytometry was performed to analyze the proportion of lymph cell clusters in PBMCs. RESULTS: The proportion of CD3- immune cell clusters in PBMCs was significantly higher in the 10 Gy treatment group than in the nonirradiated group and other lower-dose (2, 6 Gy) treatment groups at the dose rate of 1,000 MU/min. However, no influence was observed on the proportion of CD3+ T cell subsets. Further results showed that both natural killer (NK) and B cell proportions reached peaks in the 14 Gy treatment group when a dose rate of 1,200 MU/min was used. Notably, the peak values of these two cell proportions were reached at a lower radiation dose of 10 Gy when a greater dose rate, ranging from 1,600 to 2,400 MU/min, was used. We further found that a single, high dose of irradiation (10 Gy), as compared with a single, low dose of irradiation (2 Gy), could markedly stimulate the A549-related exosome secretion in a radiation dose rate-dependent manner. The ultrahigh dose rate radiation-derived exosomes contributed to the polarization of B and NK cell subsets in PBMCs. CONCLUSIONS: The optimized radiation regime, which depends on the appropriate radiation dose and dose rate, results in the production of exosomes derived from NSCLC cells and eventually the redistribution of immune cells in PBMCs.

Dose-time fractionation schedules of preoperative radiotherapy and timing to surgery for rectal cancer.

Chemoradiotherapy (CRT) is extensively used prior to surgery for rectal cancer to provide significantly better local control, but the radiotherapy (RT), as the other component of CRT, has been subject to less interest than the drug component in recent years. With considerable developments in RT, the use of advanced techniques, such as intensity-modulated radiotherapy (IMRT) in rectal cancer, is garnering more attention nowadays. The radiation dose can be better conformed to the target volumes with possibilities for synchronous integrated boost without increased complications in normal tissue. Hopefully, both local recurrence and toxicities can be further reduced. Although those seem to be of interest, many issues remain unresolved. There is no international consensus regarding the radiation schedule for preoperative RT for rectal cancer. Moreover, an enormous disparity exists regarding the RT delivery. With the advent of IMRT, variations will likely increase. Moreover, time to surgery is also quite variable, as it depends upon the indication for RT/CRT in the clinical practices. In this review, we discuss the options and problems related to both the dose-time fractionation schedule and time to surgery; furthermore, it addresses the research questions that need answering in the future.

Clinical Impact of the Bolus in Intensity-Modulated Radiotherapy and Volumetric-Modulated Arc Therapy for Stage I-II Nasal Natural Killer/T-Cell Lymphoma.

INTRODUCTION: To estimate the clinical impact of bolus in intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for stage I-II nasal natural killer/T-cell lymphoma (NNKTCL), including target quality, organs at risk (OARs) sparing, and tumor control probability (TCP). METHODS: Two different treatment plans were designed in IMRT and VMAT for 10 stage I-II NNKTCL patients. The clinical plans added bolus perfectly contacting the nose skin, similar to common clinical planning design practices. The edited bolus plans resulted from dose recalculation with the edited bolus, which simulated the actual shape of a commercial flat bolus during treatment. All the plans were with no beam passing through the couch avoiding beam attenuation caused by the couch. Differences between both types of plans in target quality, OARs sparing, and TCP were evaluated. RESULTS: Compared with clinical plans, the D98%, D2%, Dmean, and TCP of edited bolus plans with IMRT slightly decreased (p = 0.002, 0.015, 0.000, and 0.000), the homogeneity index increased 8.33% (p = 0.024), and the doses to a small number of OARs slightly changed. Similar results were obtained for VMAT. CONCLUSION: The bolus deformation in practical clinical treatment resulted clinically in tiny changes with respect to the target coverage, OARs sparing, and TCP in both IMRT and VMAT for stage I-II NNKTCL. This implied that the clinical impact of the boluscan be negligible when utilizing it to increase the dose to irregularly shaped tumors in the nasal area.

Estimation of radiotherapy modalities for patients with stage I-II nasal natural killer T-Cell lymphoma.

PURPOSE: The objective of this study is to estimate radiotherapy (RT) modalities for patients with stage I-II nasal natural killer T-Cell lymphoma (NNKTCL), including plan quality, radiation delivery efficiency, cost of RT and excess absolute risk (EAR). MATERIALS AND METHODS: Twenty-four representative patients with stage I-II NNKTCL treated with fix-field intensity-modulated radiotherapy (FF-IMRT) were re-planned for volumetric modulated arc therapy (VMAT), TomoDirect (TD) and TomoHelical (TH) on the TomoHDA system, respectively. Plan characteristics, cost of RT and EAR were compared. RESULTS: Compared with IMRT, TD and TH showed significant improvement in terms of D98%, D2%, cold spot volume and homogeneity index (HI) of planning target volume (PTV), while achieving worse Dmean and conformity index (CI). The mean dose of oropharynx, thyroid and left salivary, and the maximum dose of right salivary by TD (249.20%, p=0.000; 52.94%, p=0.000; 160.23%, p=0.022; 122.67%, p=0.027), VMAT (15.76%, p=0.000; 23.53%, p=0.000; 34.09%, p=0.000; 31.33%, p=0.000) and TH (250.32%, p=0.000; 58.82%, p=0.000; 120.45%, p=0.020; 117.33%, p=0.032) increased significantly compared to IMRT. VMAT reduced treatment time (p=0.000; 0.000; 0.000) and monitor units (MUs) (p=0.000; 0.000; 0.000) obviously compared with IMRT, TD and TH. The cost of RT for TD and TH increased 150% compared with IMRT and VMAT. IMRT obtained the lowest EAR to oropharynx, thyroid, left and right salivary gland in the four treatment modalities. CONCLUSION: The results show that both TD and TH can achieve higher conformal target quality while getting worse organs at risk (OARs) sparing and EAR to some organs than IMRT for patients with stage I-II NNKTCL. IMRT delivers the lowest dose to most OARs, VMAT requires the lower cost of RT and shortest delivery time, and TH obtained the optimal target coverage. The results could provide direction for selecting proper RT modalities for different cases.

Impact of CT slice thickness on volume and dose evaluation during thoracic cancer radiotherapy.

INTRODUCTION: Accurate delineation of targets and organs at risk (OAR) is required to ensure treatment efficacy and minimize risk of normal tissue toxicity with radiotherapy. Therefore, we evaluated the impacts of computed tomography (CT) slice thickness and reconstruction methods on the volume and dose evaluations of targets and OAR. PATIENTS AND METHODS: Eleven CT datasets from patients with thoracic cancer were included. 3D images with a slice thickness of 2 mm (2-CT) were created automatically. Images of other slice thickness (4-CT, 6-CT, 8-CT, 10-CT) were reconstructed manually by the selected 2D images using two methods; internal tumor information and external CT Reference markers. Structures and plans on 2-CT images, as a reference data, were copied to the reconstructed images. RESULTS: The maximum error of volume was 84.6% for the smallest target in 10-CT, and the maximum error (≥20 cm3) was 10.1%, 14.8% for the two reconstruction methods, internal tumor information and external CT Reference, respectively. Changes in conformity index for a target of <20 cm3 were 5.4% and 17.5% in 8-CT. Changes on V30 and V40 of the heart were considerable. In the internal tumor information method, volumes of hearts decreased by 3.2% in 6-CT, while V30 and V40 increased by 18.4% and 46.6%. CONCLUSION: The image reconstruction method by internal tumor information was less affected by slice thickness than the image reconstruction method by external CT Reference markers. This study suggested that before positioning scanning, the largest section through the target should be determined and the optimal slice thickness should be estimated.

Cancer risk assessment in modern radiotherapy workflow with medical big data.

Modern radiotherapy (RT) is being enriched by big digital data and intensive technology. Multimodality image registration, intelligence-guided planning, real-time tracking, image-guided RT (IGRT), and automatic follow-up surveys are the products of the digital era. Enormous digital data are created in the process of treatment, including benefits and risks. Generally, decision making in RT tries to balance these two aspects, which is based on the archival and retrieving of data from various platforms. However, modern risk-based analysis shows that many errors that occur in radiation oncology are due to failures in workflow. These errors can lead to imbalance between benefits and risks. In addition, the exact mechanism and dose-response relationship for radiation-induced malignancy are not well understood. The cancer risk in modern RT workflow continues to be a problem. Therefore, in this review, we develop risk assessments based on our current knowledge of IGRT and provide strategies for cancer risk reduction. Artificial intelligence (AI) such as machine learning is also discussed because big data are transforming RT via AI.

Dosimetric comparison of helical tomotherapy, VMAT, fixed-field IMRT and 3D-conformal radiotherapy for stage I-II nasal natural killer T-cell lymphoma.

BACKGROUND: The aim of this study was to compare radiotherapy plans for Stage I-II nasal natural killer/T-cell lymphoma (NNKTL) using helical tomotherapy (HT), volumetric-modulated arc therapy (VMAT), Fixed-Field intensity-modulated radiotherapy (IMRT), and three-dimensional conformal radiotherapy (3D-CRT). METHODS: Eight patents with Stage I-II NNKTL treated with IMRT were re-planned for HT, VMAT (two full arcs), and 3D-CRT. The quality of target coverage, the exposure of normal tissue and the efficiency of radiation delivery were analyzed. RESULTS: HT showed significant improvement over IMRT in terms of D98%, cold spot volume and homogeneity index (HI) of planning target volume (PTV). VMAT provided best dose uniformity (p = 0.000) to PTV, while HT had best dose homogeneity among the four radiotherapy techniques (p = 0.000) to PTV. VMAT obviously reduced treatment time (p = 0.010; 0.000) compared to HT and IMRT. Mean dose of left and right optic nerve was significantly reduced by IMRT compared to HT (19.86%, p = 0.000; 21.40%, p = 0.002) and VMAT (8.97%, p = 0.002; 9.35%, p = 0.001), and maximum dose of left lens of VMAT increased over the HT (36.25%, p = 0.043) and IMRT (40.65%, p = 0.001). CONCLUSION: The unexpected results show that both HT and VMAT can achieve higher conformal treatment plans while getting worse organs at risk (OARs) sparing than IMRT for patients with Stage I-II NNKTL. VMAT requires the shortest delivery time, and IMRT delivers the lowest dose to most OARs. The results could provide guidance for selecting proper radiation technologies for different cases.

A parameterized model for mean urinary inflow rate and its preliminary application in radiotherapy for cervical cancer.

Forty-nine patients with stage IIb cervical cancer were included to investigate the changes in bladder volume in response to different approaches to maintaining consistent bladder filling. The impacts of age (P age), water consumption (P wat ), and body mass index (BMI, P bmi ) on the mean urinary inflow rate (v tot ) were analysed. The bladder volume (BV) increased linearly over time. A large variation in v tot among individuals was observed, ranging from 0.19 to 5.13 ml/min. The v tot was correlated with P age (R = -0.53, p = 0.01) and P wat (R = 0.84, p = 0.00), and no correlation between v tot and P bmi was found (p > 0.05). Therefore, v tot could be parameterized using two methods: multivariable linear regression and iterative fitting. There was no statistically significant difference between the two methods. The model accuracy was successfully assessed with several validation tests for patients with good compliance (79.2% of all patients), and the proportion of radiotherapy (RT) fractions with zero wait time (one ultrasound (US) scan) increased from 6.5% to 41.2%. The optimal US scanning number and RT time could be provided using this model. This adaptive RT approach could reduce patient discomfort caused by holding onto urine and reduce technician labour as well as cost.