Radiotherapy For Liver Cancer Research Articles

Paired conditional generative adversarial network for highly accelerated liver 4D MRI

Purpose. 4D MRI with high spatiotemporal resolution is desired for image-guided liver radiotherapy. Acquiring densely sampling k-space data is time-consuming. Accelerated acquisition with sparse samples is desirable but often causes degraded image quality or long reconstruction time. We propose the Reconstruct Paired Conditional Generative Adversarial Network (Re-Con-GAN) to shorten the 4D MRI reconstruction time while maintaining the reconstruction quality. Methods. Patients who underwent free-breathing liver 4D MRI were included in the study. Fully- and retrospectively under-sampled data at 3, 6 and 10 times (3×, 6× and 10×) were first reconstructed using the nuFFT algorithm. Re-Con-GAN then trained input and output in pairs. Three types of networks, ResNet9, UNet and reconstruction swin transformer (RST), were explored as generators. PatchGAN was selected as the discriminator. Re-Con-GAN processed the data (3D + t) as temporal slices (2D + t). A total of 48 patients with 12 332 temporal slices were split into training (37 patients with 10 721 slices) and test (11 patients with 1611 slices). Compressed sensing (CS) reconstruction with spatiotemporal sparsity constraint was used as a benchmark. Reconstructed image quality was further evaluated with a liver gross tumor volume (GTV) localization task using Mask-RCNN trained from a separate 3D static liver MRI dataset (70 patients; 103 GTV contours). Results. Re-Con-GAN consistently achieved comparable/better PSNR, SSIM, and RMSE scores compared to CS/UNet models. The inference time of Re-Con-GAN, UNet and CS are 0.15, 0.16, and 120 s. The GTV detection task showed that Re-Con-GAN and CS, compared to UNet, better improved the dice score (3× Re-Con-GAN 80.98%; 3× CS 80.74%; 3× UNet 79.88%) of unprocessed under-sampled images (3× 69.61%). Conclusion. A generative network with adversarial training is proposed with promising and efficient reconstruction results demonstrated on an in-house dataset. The rapid and qualitative reconstruction of 4D liver MR has the potential to facilitate online adaptive MR-guided radiotherapy for liver cancer.

400: Constructing high-quality enhanced 4D-MRI with personalized modeling for liver cancer radiotherapy

400: Constructing high-quality enhanced 4D-MRI with personalized modeling for liver cancer radiotherapy

Selection of HBV key reactivation factors based on maximum information coefficient combined with cosine similarity.

Hepatitis B Virus (HBV) reactivation is the most common complication for patients with primary liver cancer (PLC) after radiotherapy. How to reduce the reactivation of HBV has been a hot topic in the study of postoperative radiotherapy for liver cancer. To find out the inducement of HBV reactivation, a feature selection algorithm (MIC-CS) using maximum information coefficient (MIC) combined with cosine similarity (CS) was proposed to screen the risk factors that may affect HBV reactivation. Firstly, different factors were coded and MIC between patients was calculated to acquire the association between different factors and HBV reactivation. Secondly, a cosine similarity algorithm was constructed to calculate the similarity relationship between different factors, thus removing redundant information. Finally, combined with the weight of the two, the potential risk factors were sorted and the key factors leading to HBV reactivation were selected. The results indicated that HBV baseline, external boundary, TNM, KPS score, VD, AFP, and Child-Pugh could lead to HBV reactivation after radiotherapy. The classification model was constructed for the above factors, with the highest classification accuracy of 84% and the AUC value of 0.71. Comparing multiple feature selection methods, the results showed that the effect of the MIC-CS was significantly better than MIM, CMIM, and mRMR, so it has a very broad application prospect.

A Study of Applying Pix2Pix to Reduce the Cost and Damage of Radiotherapy of Cancerous Livers

Radiation therapy is widely used to treat cancerous cells; however, it is costly and has significant side effects if not properly used. During treatment, some organs, such as the liver, may shift slightly due to the patient’s respiration, making accurate real-time tracking and contouring essential to minimize damage to healthy tissues. Current tracking systems usually include precise real-time positioning and contouring of the treatment area, which require costly imaging technologies to run throughout the entire therapy session, increasing the overall treatment cost and limiting the availability of advanced equipment like MRIs to hospitals. This research studies the application of Pix2Pix, a Conditional Generative Adversarial Network (GAN), as an alternative to traditional contouring methods in liver cancer radiotherapy. The result shows that a well-trained Pix2Pix can help accurately track liver movement during respiration. With AI computing power becoming increasingly affordable, I anticipate that GANs like Pix2Pix can be industrialized to make cancer treatment more accessible and cost-effective.

Palliative radiotherapy for hepatic tumors: a narrative review of indications and recommendations.

Primary and metastatic liver cancer presents heterogeneously. New radiotherapy techniques have reduced toxicity concerns, leading to increased use of liver radiotherapy. This review synthesizes available evidence and offers recommendations for palliative radiotherapy for liver cancer. PubMed, Ovid Medline, Embase, Cochrane Central, and Web of Science were searched from from inception to December 28th, 2022. Articles reporting local control (LC), survival, toxicity, symptom control, and response after stereotactic body radiotherapy (SBRT), partial-liver, or whole-liver radiotherapy (WLRT) techniques were reviewed. We also identified nomograms identifying patients who may benefit from radiotherapy. Nine randomized-controlled trials were found, in addition to many retrospective, feasibility, and phase I or II studies. Patients with favorable prognosis may receive SBRT using 30-50 Gray (Gy) in 3-5 fractions for primary cancer and up to 60 Gy for metastases, provided normal-tissue constraints are met. Select patients with multiple (>5) or large (>10 cm) lesions or macrovascular invasion (MVI) may be considered, but with potentially reduced LC and increased toxicity. Lower SBRT doses (i.e., 25 Gy in 5 fractions) can be considered on a cautionary basis for patients with poorer liver function or health. Patients with larger tumor burden, poor performance status (PS), or inability to tolerate SBRT positioning or motion-management can consider partial-liver three-dimensional conformal radiotherapy (3DCRT). For patients with extremely guarded prognosis and/or extremely poor performance, WLRT provides pain and symptom relief over several weeks. Combining radiotherapy and systemic therapy may allow radiotherapy de-escalation while maintaining good outcomes. Radiotherapy has a definite role for palliation of liver cancer with practical research providing guidance in the use of techniques and different regimens in various patient subgroups. Future investigation, including randomized trials, is needed to optimize patient selection, radiotherapy techniques, and integration with other therapies.

Influence and optimization strategy of the magnetic field in 1.5 T MR-linac liver stereotactic radiotherapy

ObjectiveTo compare intensity reduction plans for liver cancer with or without a magnetic field and optimize field and subfield numbers in the intensity-modulated radiotherapy (IMRT) plans designed for liver masses in different regions.MethodsThis retrospective study included 62 patients who received radiotherapy for liver cancer at Shandong Cancer Hospital. Based on each patient's original individualized intensity-modulated plan (plan1.5 T), a magnetic field-free plan (plan0 T) and static intensity-modulated plan with four different optimization schemes were redesigned for each patient. The differences in dosimetric parameters among plans were compared.ResultsIn the absence of a magnetic field in the first quadrant, PTV Dmin increased (97.75 ± 17.55 vs. 100.96 ± 22.78)%, Dmax decreased (121.48 ± 29.68 vs. 119.06 ± 28.52)%, D98 increased (101.35 ± 7.42 vs. 109.35 ± 26.52)% and HI decreased (1.14 ± 0.14 vs. 1.05 ± 0.01). In the absence of a magnetic field in the second quadrant, PTV Dmin increased (84.33 ± 19.74 vs. 89.96 ± 21.23)%, Dmax decreased (105 ± 25.08 vs. 104.05 ± 24.86)%, and HI decreased (1.04 ± 0.25 vs. 0.99 ± 0.24). In the absence of a magnetic field in the third quadrant, PTV Dmax decreased (110.21 ± 2.22 vs. 102.31 ± 26)%, L-P V30 decreased (10.66 ± 9.19 vs. 5.81 ± 3.22)%, HI decreased (1.09 ± 0.02 vs. 0.98 ± 0.25), and PTV Dmin decreased (92.12 ± 4.92 vs. 89.1 ± 22.35)%. In the absence of a magnetic field in the fourth quadrant, PTV Dmin increased (89.78 ± 6.72 vs. 93.04 ± 4.86)%, HI decreased (1.09 ± 0.01 vs. 1.05 ± 0.01) and D98 increased (99.82 ± 0.82 vs. 100.54 ± 0.84)%. These were all significant differences. In designing plans for tumors in each liver region, a total number of subfields in the first area of 60, total subfields in the second zone of 80, and total subfields in the third and fourth zones of 60 or 80 can achieve the dose effect without a magnetic field.ConclusionIn patients with liver cancer, the effect of a magnetic field on the target dose is more significant than that on doses to organs at risk. By controlling the max total number of subfields in different quadrants, the effect of the magnetic field can be greatly reduced or even eliminated.

Evaluating the Use of SGRT and Abdominal Compression Device for Improved Patient Positioning in Liver Cancer Radiotherapy

To mitigate tumor displacement caused by respiratory movement and to enhance positioning accuracy in liver cancer patients during radiotherapy, abdominal compression fixation devices are commonly employed. However, the efficacy of using surface guided radiotherapy (SGRT) to further improve patient setup accuracy in combination with abdominal compression has not been fully established. Hence, we aimed to investigate this in our study. In this study, we analyzed data from 11 patients with liver cancer. The patients were positioned using isocentric skin markers and the abdominal compression fixture was placed on an accurate scale reading based on the records from CT simulation. A cone-beam CT (CBCT) scan was performed to assess setup errors. These setup errors represent data for the control group - Skin marker group. The patients were then adjusted to the correct treatment position based on CBCT correction and the SGRT system was activated for monitoring. Care was taken for the region of interest drawn to avoid the abdominal compression device for all patients. The reference surface used for monitoring was the captured VRT surface rather than DICOM. The six degrees of freedom values detected by the SGRT system were recorded, representing data for the test group - SGRT group. Both sets of data were analyzed using statistical software. The errors were presented as median (interquartile range) and the differences between the two groups were tested using paired Wilcoxon rank sum test, with P < 0.05 considered as significant. A total of 60 CBCT images were analyzed, the median values and interquartile ranges are presented in the Table. The results showed that the accuracy of the SGRT group in the x and y directions was significantly better than the skin marker group (P < 0.05). The median values for the x (transverse) direction were 0.25(0.09-0.43) cm and 0.09(0.05-0.19) cm for the skin marker and SGRT groups, respectively. The median values for the y (longitudinal) direction were 0.54 (0.29-0.79) cm and 0.14 (0.07-0.24) cm for the skin marker and SGRT groups, respectively. The results for the z (vertical) direction, Rz (rotation), Ry (roll) and Rx (pitch) rotation directions were also analyzed similarly. The findings of this study suggest that compared to skin markers, SGRT can improve the accuracy of patient positioning in liver cancer radiotherapy with abdominal compression, potentially reducing unnecessary radiation exposure from CBCT imaging due to inaccurate positioning. Further multicenter prospective clinical trials are required to confirm these results.

Radiotherapy for Liver Cancer: An International Multi-Centre Pooled Analysis of 925 Cases

Primary and secondary liver cancer incidence is growing and has a poor prognosis. The standard use of radiation has been hampered by studies with a wide range of patients, different management protocols and varied outcomes. To overcome this heterogeneity in the literature, larger and higher-level trials are warranted, but, so far, have been difficult to implement. Therefore, pooled analyses may offer the best way to determine the benefit of radiation, identify treatment parameters needed to optimize treatment techniques, and identify patient factors that allow for better patient selection. Patients with liver cancer treated by radiotherapy at centers in Canada, United States and Australia was pooled. Patient and treatment characteristics were noted, as well as the clinical outcomes of local control within 1 year, recurrence and mortality. Stepwise Cox proportional hazards models were used to identify significant predictors for recurrence and mortality. Patients were stratified by center, and primary versus metastatic disease. A total of 925 patients were included in this study. Mean age was 67 years, and 45% had a primary diagnosis of hepatocellular carcinoma. 1-year local control rate was 80%. Median survival was 1.8 years (1.9 years for primary liver cancer, and 1.4 years for metastatic liver cancer). Higher total dose and BED was associated with better survival. Median time to recurrence was 1.5 years. Higher total dose was associated with lower risk of recurrence CONCLUSION: As one of the largest pooled analyses in hepatic cancer, this international multi-center study provides pragmatic data on clinical outcomes of patients receiving radiotherapy for liver cancer. This database may assist in better selection of patients for future studies and answer questions such as what is the optimal dose and which patients benefit from treatment.

Optimizing the Imaging Scheme of Small-Dose Contrast Agent in 4D-CT Localization Enhancement Scan for Radiotherapy of Liver Cancer

The primary liver cancer radiation therapy 4D-CT-enhanced (CE-4DCT) scan can accurately reflect the state of the liver as it moves with respiration, and enables clear visualization of the tumor, providing a precise range for target area outlining. However, the CE-4DCT scan localization time of primary liver cancer is long, and the fixed delay time of diagnostic CT cannot obtain high-quality 4DCT images. To this end, we designed a randomized controlled study to investigate the ideal localization scan delay time parameters for primary liver cancer CE-4DCT. Patients with primary hepatocellular carcinoma who presented to our department for radiotherapy CT localization from January to December 2022 participated in this study. All subjects were randomly divided into two groups in a 1:1 ratio. CE-4DCT scans were performed using a high concentration of iodomepril (400 mg/ml) contrast agent with a contrast volume equal to the patient's body weight. The scanning parameters were set according to scheme A (flow rate 2.0 ml/s, delay time 30s) and B (2.0 ml/s, 35s) respectively. Before the CE-4D CT scan, CT plain scan was routinely performed, physicians measured the CT value (HU) of abdominal aorta, portal vein, left hepatic vein, middle hepatic vein, right hepatic vein, liver parenchyma and tumor lesion on CT40 time item and plain scan images respectively. The image quality was subjectively and qualitatively assessed. The image enhancement effect is divided into excellent, good, relatively poor and poor. A total of 18 patients were included in this study. Patient characteristics were well-balanced in both groups. There were statistical differences between the two groups (A vs B) in the abdominal aorta (226.66 ± 45.59 vs. 176.66 ± 32.84, p = 0.017), left hepatic vein (142.77 ± 24.41 vs. 164.88 ± 19.02, p = 0.048); in the portal vein, middle hepatic vein, right hepatic vein, liver parenchyma, and tumor lesions CT values were not statistically different. The comparison of all flat-scan images between the two groups was statistically significant. The comparison of all flat-scan images in both groups was statistically significant. The subjective qualitative assessment of the developing effect was excellent in 44.4% (33.3% vs. 11.1%), good in 16.7% (5.6% vs. 11.1%), and poor in 38.9% (16.7% vs. 22.2%) in both groups. image quality was slightly higher in group A than in group B, but did not reach statistical significance (χ2 = 1.088, p = 0.698). In patients with primary hepatocellular carcinoma with portal vein carcinoma thrombosis 83.33% subjectively evaluated poor results. Qualitatively acceptable enhanced images were obtained for primary hepatocellular carcinoma (CE-4DCT) localization scans with a delay time controlled at 30s when using the least amount of contrast agent and the same flow rate.

Investigation on cone-beam computed tomography-based liver cancer radiotherapy clinical target volume planning target volume margin and analysis of dosimetric differences

PurposeThis study aimed to calculate the margin from the clinical target volume (CTV) to the planning target volume (PTV) through online cone-beam computed tomography (CBCT) calibration and analyze the effects on the target area caused by setup errors and dose to organs at risk. MethodsThirty-five patients with liver cancer were selected, and CBCT images before radiotherapy were registered with positioning CT images to obtain couch shift values and calculate the CTV–PTV margin from the CTV to the PTV. The dose distribution was recalculated in the planning system based on the couch shift values, and the resulting data were assigned to the experimental group. Data before radiotherapy and CBCT were used as the control group. ResultsThe CTV–PTV margins were 4.70 mm, 4.50 mm, and 5.00 mm in the X, Y, and Z directions, respectively. The incidence rates of setup errors <3 mm and 3–5 mm in the X, Y, and Z directions were 74.62%,25.38%,and 78.36% and 21.64%, 73.13%,and 26.87%, respectively. The deviation in gross target volume dosimetric parameters was <5% in both the experimental and control groups. The deviations in dose uniformity and conformity of the PTV in the experimental group were 37.50% and 62.00%, respectively, and the target coverage of the PTV was <95%, which was below the clinical requirements. For the organs-at-risk KidL_V20, KidL_V30, KidR_V30, Eso_V45, and Eso_V50, the deviations in dosimetric parameters in the experimental group were −14.40%,-25.59%,6.74%,9.76%,and13.37%,respectively. ConclusionAlthough the setup error was <5 mm, the resulting deviation in dose cannot be neglected, and the CTV–PTV margin should be recalculated to ensure better protection of organs at risk while meeting prescribed clinical dose requirements in the target volume.

Applying mixed-integer linear programming to the non-coplanar beam angle optimization of intensity-modulated radiotherapy for liver cancer.

Currently, intensity-modulated radiation therapy (IMRT) is commonly used in radiotherapy clinics. However, designing a treatment plan with multiple beam angles depends on the experience of human planners, and is mostly achieved using a trial-and-error approach. It is preferrable but challenging to solve this issue automatically and mathematically using an optimization approach. The goal of this study is to develop a mixed-integer linear programming (MILP) approach for the beam angle optimization (BAO) of non-coplanar IMRT for liver cancer. MILP models for the BAO of both coplanar and non-coplanar IMRT treatment plans were developed. The beam angles of the IMRT plans were first selected by the MILP model built using mathematical optimization software. Next, the IMRT plans with the selected beam angles was created in a commercial treatment planning system. Finally, the fluence map and dose distribution of the IMRT plans were generated under pre-defined dose-volume constraints. The IMRT plans of 10 liver cancer patients previously treated at our institute were used to assessed the proposed MILP models. For each patient, both coplanar and non-coplanar IMRT plans with beam angles optimized by the MILP models were compared with the IMRT plan clinically approved by physicians. The MILP model-guided IMRT plans showed reduced doses for most of the organs at risk (OARs). Compared with the IMRT plans clinically approved by physicians, the doses for the spinal cord (28.5 vs. 36.1, P=0.001<0.05) and liver (27.6 vs. 29.1, P=0.005<0.05) decreased significantly in the IMRT plans with non-coplanar beams selected by the MILP models. The MILP model is an effective tool for the BAO in coplanar and non-coplanar IMRT treatment planning. It facilitates the automation of IMRT treatment planning for current high-precision radiotherapy.

Real-time 3D MRI reconstruction from cine-MRI using unsupervised network in MRI-guided radiotherapy for liver cancer.

Respiration has a major impact on the accuracy of radiation treatment for thorax and abdominal tumours. Instantaneous volumetric imaging could provide precise knowledge of tumour and normal organs' three-dimensional (3D) movement, which is the key to reducing the negative effect of breathing motion. Therefore, this study proposed a real-time 3D MRI reconstruction method from cine-MRI using an unsupervised network. Cine-MRI and setup 3D-MRI from eight patients with liver cancer were utilized to establish and validate the deep learning network for 3D-MRI reconstruction. Unlike previous methods that required 4D-MRI for network training, the proposed method utilized a reference 3D-MRI and cine-MRI to generate the training data. Then, a network was trained in an unsupervised manner to estimate the relationship between the cine-MRI acquired on coronal plane and deformation vector field (DVF) that describes the patient's breathing motion. After the training process, the coronal cine-MRI were inputted into the network, and the corresponding DVF was obtained. By wrapping the reference 3D-MRI with the generated DVF, the 3D-MRI could be reconstructed. The reconstructed 3D-MRI slices were compared with the corresponding phase-sorted cine-MRI using dice similarity coefficients (DSCs) of liver contours and blood vessel localization error. In all patients, the liver DSC had mean value >96.1% and standard deviation<1.3%; the blood vessel localization error had mean value <2.6mm, and standard deviation was <2.0mm. Moreover, the time for 3D-MRI reconstruction was approximately 100ms. These results indicated that the proposed method could accurately reconstruct the 3D-MRI in real time. The proposed method could accurately reconstruct the 3D-MRI from cine-MRI in real time. This method has great potential in improving the accuracy of radiotherapy for moving tumours.

Evaluation of a Tumor-Targeting Oligosaccharide Nanosystem in BNCT on an Orthotopic Hepatocellular Carcinoma Model.

Boron neutron capture therapy (BNCT) is becoming a promising radiation treatment technique dealing with tumors due to its cellular targeting specificity. In this article, based on the biocompatible chitosan oligosaccharide (COS), we designed a boron delivery system using carborane (CB) as a boron drug with cRGD peptide modification and paclitaxel (PTX) loaded in the hydrophobic core. The nanoparticles (cRGD-COS-CB/PTX) realized the boron delivery into tumor sites with an enhanced permeability and retention (EPR) effect and an active targeting effect achieved by the cRGD-integrin interaction on the surface of tumor cells. The uniform spherical nanoparticles can be selectively taken by hepatoma cells rather than normal hepatocytes. In vivo experiments showed that the nanoparticles had a targeting effect on tumor sites in both subcutaneous and orthotopic tumor models, which was an encouraging result for radiotherapy for liver cancer. To sum up, the nanoparticles we produced proved to be promising dual-functionalized nanoparticles for radiotherapy and chemotherapy.

The Expression of Connexin 26 Regulates the Radiosensitivity of Hepatocellular Carcinoma Cells through a Mitogen-Activated Protein Kinases Signal Pathway.

Connexin 26 (Cx26) is a protein that constitutes a gap junction and is widely expressed in the liver. Abnormal expression of Cx26 is one of the important mechanisms of liver cancer, and is closely related to the transmission of radiation damage signals between cells. In the present study, we investigated the radiosensitivity of hepatocellular carcinoma (HCC) cells HepG2, with low expression of Cx26, and SK-hep-1, with high expression of Cx26 after X-ray irradiation. The cell survival, micronucleus formation and protein expressions of the mitogen-activated protein kinases (MAPK) signaling pathway were detected. The expression level of Cx26 could affect the radiosensitivity of liver cancer cells by affecting the phosphorylation of p38 and ERK proteins and regulating the expression of downstream NF-κB. Cell lines with knock-out and overexpression of Cx26 were also built to confirm the findings. Our results suggested that Cx26 might play an important role in the radiosensitivity of liver cancer and could be a potential target for clinical radiotherapy of liver cancer.

The role transition of radiotherapy for the treatment of liver cancer in the COVID-19 era.

The uncontrollable COVID-19 crises in the SARS-CoV-2 high-prevalence areas have greatly disrupted the routine treatment of liver cancer and triggered a role transformation of radiotherapy for liver cancer. The weight of radiotherapy in the treatment algorithm for liver cancer has been enlarged by the COVID-19 pandemic, which is helpful for the optimal risk-benefit profile.

PD-0334 Feasibility of magnetic resonance-guided stereotactic ablative body radiotherapy of liver cancer

PD-0334 Feasibility of magnetic resonance-guided stereotactic ablative body radiotherapy of liver cancer

Simultaneous Image Reconstruction and Element Decomposition for Iodine Contrast Agent Visualization in Multienergy Element-Resolved Cone Beam CT.

Iodine contrast agent is widely used in liver cancer radiotherapy at CT simulation stage to enhance detectability of tumor. However, its application in cone beam CT (CBCT) for image guidance before treatment delivery is still limited because of poor image quality and excessive dose of contrast agent during multiple treatment fractions. We previously developed a multienergy element-resolved (MEER) CBCT framework that included x-ray projection data acquisition on a conventional CBCT platform in a kVp-switching model and a dictionary-based image reconstruction algorithm that simultaneously reconstructed x-ray attenuation images at each kilovoltage peak (kVp), an electron density image, and elemental composition images. In this study, we investigated feasibility using MEER-CBCT for low-concentration iodine contrast agent visualization. We performed simulation and experimental studies using a phantom with inserts containing water and different concentrations of iodine solution and the MEER-CBCT scan with 600 projections in a full gantry rotation, in which the kVp level sequentially changed among 80, 100, and 120 kVps. We included iodine material in the dictionary of the reconstruction algorithm. We analyzed iodine detectability as quantified by contrast-to-noise ratio (CNR) and compared results with those of CBCT images reconstructed by the standard filter back projection (FBP) method with 600 projections. MEER-CBCT achieved similar contrast enhancement as FBP method but significantly higher CNR. At 2.5% iodine solution concentration, FBP method achieved 170 HU enhancement and CNR of 2.0, considered the standard CNR for successful tumor visualization. MEER-CBCT achieved the same CNR but at ~6.3 times lower iodine concentration of 0.4%.

Kinsenoside Protects Against Radiation-Induced Liver Fibrosis via Downregulating Connective Tissue Growth Factor Through TGF-β1 Signaling.

Radiation-induced liver fibrosis (RILF) is a serious complication of the radiotherapy of liver cancer, which lacks effective prevention and treatment measures. Kinsenoside (KD) is a monomeric glycoside isolated from Anoectochilus roxburghii, which has been reported to show protective effect on the early progression of liver fibrosis. However, the role of KD in affecting RILF remains unknown. Here, we found that KD alleviated RILF via downregulating connective tissue growth factor (CTGF) through TGF-β1 signaling. Sprague-Dawley rats were administered with 20 mg/kg KD per day for 8 weeks after a single 30Gy irradiation on the right part of liver, and tumor-bearing nude mice were administered with 30 mg/kg KD per day after a single fraction of 10Gy on the tumor inoculation site. Twenty-four weeks postirradiation, we found that the administration of KD after irradiation resulted in decreased expression of α-SMA and fibronectin in the liver tissue while had no adverse effect on the tumor radiotherapy. Besides, KD inhibited the activation of hepatic stellate cells (HSCs) postirradiation via targeting CTGF as indicated by the transcriptome sequencing. Results of the pathway enrichment and immunohistochemistry suggested that KD reduced the expression of TGF-β1 protein after radiotherapy, and exogenous TGF-β1 induced HSCs to produce α-SMA and other fibrosis-related proteins. The content of activated TGF-β1 in the supernatant decreased after treatment with KD. In addition, KD inhibited the expression of the fibrosis-related proteins by regulating the TGF-β1/Smad/CTGF pathway, resulting in the intervention of liver fibrosis. In conclusion, this study revealed that KD alleviated RILF through the regulation of TGFβ1/Smad/CTGF pathway with no side effects on the tumor therapy. KD, in combination with blocking the TGF-β1 pathway and CTGF molecule or not, may become the innovative and effective treatment for RILF.

Impact on liver position under breath-hold by computed tomography contrast agents in stereotactic body radiotherapy of liver cancer.

BackgroundWe investigated variations in liver position relative to the vertebral bone for liver cancer treated with stereotactic body radiation therapy under expiratory phase breath-hold (BH) for treatment with contrast-enhanced-computed tomography (CECT), non-CECT, and cone-beam computed tomography (CBCT).Materials and methodsSeventeen consecutive patients using a contrast enhancement (CE) agent for the CT simulation session for this retrospective study were selected. The first computed tomography (CT) scan without the use of CE agent in the expiratory phase was used for treatment planning (pCT). The remaining three CT scans without a CE agent under expiratory phase BH were acquired successively without repositioning to evaluate the intra-fraction variation in liver position. Furthermore, a three-phase CT scan (arterial, portal, and late phases) accompanied by a CE agent under expiratory phase BH was acquired for target delineation. CBCT scans without the use of a CE agent under expiratory phase BH were acquired for treatment. Inter-fractional variations (non-CECT or CECT) in liver position were measured using the difference between CBCT and pCT or each 3 phase CECT images, respectively.ResultsThe average ± standard deviations for intrafractional, non-CECT interfractional variations, and CECT interfractional variations were 1.0 ± 1.3, 2.5 ± 2.6, and 6.4 ± 6.4 mm, respectively, in the craniocaudal (CC) direction. Intra- and inter-fractional variations in liver position were relatively small for non-CECT. However, significant inter-fractional liver position variations in CECT were observed in the expiratory phase BH. The position of the liver should be carefully considered when applying CECT images for image-guided radiotherapy.

Ion therapy guideline (Version 2020)

Ion therapy guideline (Version 2020)