Liver Stereotactic Body Radiation Therapy Research Articles

Daily Diagnostic Quality Computed Tomography-on-Rails (CTOR) Image Guidance for Abdominal Stereotactic Body Radiation Therapy (SBRT)

Background/Objectives: Stereotactic body radiation therapy (SBRT) for abdominal targets faces a variety of challenges, including motion caused by the respiration and digestion and a relatively poor level of contrast between the tumor and the surrounding tissues. Breath-hold treatments with computed tomography-on-rails (CTOR) image guidance is one way of addressing these challenges, allowing for both the tumor and normal tissues to be well-visualized. Using isodose lines (IDLs) from CT simulations as a guide, the anatomical information can be used to shift the alignment or trigger a replan, such that normal tissues receive acceptable doses of radiation. Methods: This study aims to describe the workflow involved when using CTOR for pancreas and liver SBRT and demonstrates its effectiveness through several case studies. Results: In these case studies, using the anatomical information gained through diagnostic-quality CT guidance to make slight adjustments to the alignment, resulted in reductions in the maximum dose to the stomach. Conclusions: High-quality imaging, such as CTOR, and the use of IDLs to estimate the doses to OARs, enable the safe delivery of SBRT, without the added complexity and resource commitment required by daily online adaptive planning.

Comparative analysis of clinical treatment outcomes: Breath-hold vs. free-breathing techniques in liver stereotactic body radiotherapy.

The aim of this study was to clarify the safety and efficacy of breath-hold irradiation in liver stereotactic body radiotherapy (SBRT). A retrospective analysis was conducted on 57 consecutive patients who received SBRT for hepatocellular carcinoma or liver metastases between 2013 and 2021. Breath-hold irradiation was implemented for patients treated after April 2020. The median follow-up period for all patients was 16.4 months (IQR: 7.36-20.9). The 2-year overall survival rate was 64.4% (95% CI: 47.4-77.2), and the local control rate was 84.3% (95% CI: 69.7-92.3) for all patients. The 1-year overall survival was 80.0% (95% CI: 60.8-90.5) versus 82.0% (95% CI: 53.5-93.9) in the free-respiratory (FR) group versus the breath-hold (BH) group, respectively (P = 0.60). The 1-year local control rates were 78.1% (95% CI: 57.5-89.5) in the FR group and 95.7% (95% CI: 72.9-99.4) in the BH group, respectively (P = 0.16). Radiation-induced liver injury, defined by an escalation of ≥2 in Child-Pugh score, was observed in four patients within each group (FR 13% vs. BH 15%). There were no gastrointestinal adverse events of Grade 3 or higher. Breath-hold irradiation can be safely administered and has demonstrated clinical potential in improving local control. Further research into dose escalation using breath-hold techniques is warranted.

Application of motion prediction based on a long short-term memory network for imaging dose reduction in real-time tumor-tracking radiation therapy

PurposeTo demonstrate the possibility of using a lower imaging rate while maintaining acceptable accuracy by applying motion prediction to minimize the imaging dose in real-time image-guided radiation therapy. MethodsTime-series of three-dimensional internal marker positions obtained from 98 patients in liver stereotactic body radiation therapy were used to train and test the long-short-term memory (LSTM) network. For real-time imaging, the root mean squared error (RMSE) of the prediction on three-dimensional marker position made by LSTM, the residual motion of the target under respiratory-gated irradiation, and irradiation efficiency were evaluated. In the evaluation of the residual motion, the system-specific latency was assumed to be 100 ms. ResultsExcept for outliers in the superior–inferior (SI) direction, the median/maximum values of the RMSE for imaging rates of 7.5, 5.0, and 2.5 frames per second (fps) were 0.8/1.3, 0.9/1.6, and 1.2/2.4 mm, respectively. The median/maximum residual motion in the SI direction at an imaging rate of 15.0 fps without prediction of the marker position, which is a typical clinical setting, was 2.3/3.6 mm. For rates of 7.5, 5.0, and 2.5 fps with prediction, the corresponding values were 2.0/2.6, 2.2/3.3, and 2.4/3.9 mm, respectively. There was no significant difference between the irradiation efficiency with and that without prediction of the marker position. The geometrical accuracy at lower frame rates with prediction applied was superior or comparable to that at 15 fps without prediction. In comparison with the current clinical setting for real-time image-guided radiation therapy, which uses an imaging rate of 15.0 fps without prediction, it may be possible to reduce the imaging dose by half or more. ConclusionsMotion prediction can effectively lower the frame rate and minimize the imaging dose in real-time image-guided radiation therapy.

Analysis of intra-fractional positioning correction performed by cone beam computed tomography in SBRT treatments

PurposeThis study aims to evaluate the positioning correction extracted from Intra-fraction Cone Beam (IF-CBCT) images obtained during Stereotactic Body Radiotherapy (SBRT) treatments, and to assess whether its magnitude justifies its acquisition. In addition, the results obtained in lung, liver, and pancreas SBRTs with two deep inspiration breath-hold systems (DIBH), and for prostate with/without ultrasound (US) monitoring were compared. Methods1449 treatments, performed with two linear accelerators (LINACs) were retrospectively analyzed. DIBH were performed either with a spirometry-based device or a surface-guidance system and one LINAC was equipped with US monitoring system for prostate. Significance tests were used to account for differences between units. ResultsGroup systematic error (M) was approximately –0.7 mm for DIBH treatments in superior-inferior (SI) direction with no difference (p > 0.7) between LINACs. Moreover, there was a SI difference of 0.5 mm for prostate treatments (p = 0.008), in favor of the US monitored one. In anterior-posterior (AP) direction, only liver treatments exhibited differences between LINACs, with the spirometer-based system being 0.8 mm inferior (p = 0.003). M<0.4 mm in left–right (LR) direction was found for all locations and LINACs. The spirometer-based system resulted in lower standard deviation of systematic and random errors in most components and locations, with a greater effect observed in liver SBRTs. ConclusionsThe corrections made with IF-CBCT during SBRT treatments were not negligible. Both DIBH systems were effective in managing respiratory movements. However, the spirometry-based system was slightly more accurate. In addition, US monitoring of the prostate appeared to be useful in reducing target shift.

Lung and Liver Stereotactic Body Radiation Therapy During Mechanically Assisted Deep Inspiration Breath-Holds: A Prospective Feasibility Trial

PurposeRadiation therapy of tumours subject to breathing-related motion during breath-holds (BH) has the potential to substantially reduce the irradiated volume. Mechanically-assisted and non-invasive ventilation (MANIV) could ensure the target repositioning accuracy during each BH while facilitating treatment feasibility through oxygen supplementation and a perfectly replicated mechanical support. However, there is currently no clinical evidence substantiating the use of MANIV-induced BH for moving tumours. The aim of this work was therefore to evaluate the technique performances under real treatment conditions. Methods and MaterialsPatients eligible for lung or liver stereotactic body radiotherapy were prospectively included in a single-arm trial. The primary endpoint corresponded to the treatment feasibility with MANIV. Secondary outcomes comprised intrafraction geometrical uncertainties extracted from real-time imaging, tolerance to BH and treatment time. ResultsTreatment was successfully delivered in 92.9% (13/14) of patients: one patient with a liver tumour was excluded due to a mechanically-induced gastric insufflation displacing the liver cranially by more than 1 cm. In the Left-right/Anteroposterior/Craniocaudal directions, the recalculated safety margins based on intrafraction positional data were 4.6 mm / 5.1 mm / 5.6 mm and 4.7 mm / 7.3 mm / 5.9 mm for lung and liver lesions, respectively. Compared to the free-breathing internal target volume and mid-position approaches, the average reduction in the planning target volume with MANIV reached -47.2±15.3 %, p<0.001 and -29.4±19.2 %, p=0.007 for intra-thoracic tumours and -23.3±12.4 %, p<0.001 and -9.3±15.3 %, p=0.073 for upper abdominal tumours, respectively. For one liver lesion, large caudal drifts of occasionally more than one centimetre were measured. The total slot time was 53.1 ± 10.6 minutes with a BH comfort level of 80.1±10.6%. ConclusionsMANIV enables high treatment feasibility within a non-selected population. Accurate intrafraction tumour repositioning is achieved for lung tumours. Due to occasional intra-BH caudal drifts, pre-treatment assessment of BH stability for liver lesions is however recommended.

Clinical application of real-time tumor-tracking for stereotactic volumetric modulated arc therapy for liver tumors

Real-time tumor-tracking volumetric modulated arc therapy (RT-VMAT) enabling beam-gating based on continuous X-ray tracking of the three-dimensional position of internal markers is relevant for moving tumors. Dose-volume characteristics and treatment time were evaluated in ten consecutive patients who underwent liver stereotactic body radiation therapy with RT-VMAT. Target dose conformity and sparing of the stomach and the intestine were improved comparing RT-VMAT with RT-3D conformal radiotherapy. The mean treatment time for each fraction was less than 10 min. RT-VMAT could be effective, especially for targets located adjacent to organs at risk.

Diffeomorphic transformer-based abdomen MRI-CT deformable image registration.

Stereotactic body radiotherapy (SBRT) is a well-established treatment modality for liver metastases in patients unsuitable for surgery. Both CT and MRI are useful during treatment planning for accurate target delineation and to reduce potential organs-at-risk (OAR) toxicity from radiation. MRI-CT deformable image registration (DIR) is required to propagate the contours defined on high-contrast MRI to CT images. An accurate DIR method could lead to more precisely defined treatment volumes and superior OAR sparing on the treatment plan. Therefore, it is beneficial to develop an accurate MRI-CT DIR for liver SBRT. To create a new deep learning model that can estimate the deformation vector field (DVF) for directly registering abdominal MRI-CT images. The proposed method assumed a diffeomorphic deformation. By using topology-preserved deformation features extracted from the probabilistic diffeomorphic registration model, abdominal motion can be accurately obtained and utilized for DVF estimation. The model integrated Swin transformers, which have demonstrated superior performance in motion tracking, into the convolutional neural network (CNN) for deformation feature extraction. The model was optimized using a cross-modality image similarity loss and a surface matching loss. To compute the image loss, a modality-independent neighborhood descriptor (MIND) was used between the deformed MRI and CT images. The surface matching loss was determined by measuring the distance between the warped coordinates of the surfaces of contoured structures on the MRI and CT images. To evaluate the performance of the model, a retrospective study was carried out on a group of 50 liver cases that underwent rigid registration of MRI and CT scans. The deformed MRI image was assessed against the CT image using the target registration error (TRE), Dice similarity coefficient (DSC), and mean surface distance (MSD) between the deformed contours of the MRI image and manual contours of the CT image. When compared to only rigid registration, DIR with the proposed method resulted in an increase of the mean DSC values of the liver and portal vein from 0.850±0.102 and 0.628±0.129 to 0.903±0.044 and 0.763±0.073, a decrease of the mean MSD of the liver from 7.216±4.513mm to 3.232±1.483mm, and a decrease of the TRE from 26.238±2.769mm to 8.492±1.058mm. The proposed DIR method based on a diffeomorphic transformer provides an effective and efficient way to generate an accurate DVF from an MRI-CT image pair of the abdomen. It could be utilized in the current treatment planning workflow for liver SBRT.

Dosimetric comparison of proton therapy and CyberKnife in stereotactic body radiation therapy for liver cancers

Stereotactic body radiation therapy (SBRT) has been increasingly used for the ablation of liver tumours. CyberKnife and proton beam therapy (PBT) are two advanced treatment technologies suitable to deliver SBRT with high dose conformity and steep dose gradients. However, there is very limited data comparing the dosimetric characteristics of CyberKnife to PBT for liver SBRT. PBT and CyberKnife plans were retrospectively generated using 4DCT datasets of ten patients who were previously treated for hepatocellular carcinoma (HCC, N = 5) and liver metastasis (N = 5). Dose volume histogram data was assessed and compared against selected criteria; given a dose prescription of 54 Gy in 3 fractions for liver metastases and 45 Gy in 3 fractions for HCC, with previously published consensus-based normal tissue dose constraints. Comparison of evaluation parameters showed a statistically significant difference for target volume coverage and liver, lungs and spinal cord (p < 0.05) dose, while chest wall and skin did not indicate a significant difference between the two modalities. A number of optimal normal tissue constraints was violated by both the CyberKnife and proton plans for the same patients due to proximity of tumour to chest wall. PBT resulted in greater organ sparing, the extent of which was mainly dependent on tumour location. Tumours located on the liver periphery experienced the largest increase in organ sparing. Organ sparing for CyberKnife was comparable with PBT for small target volumes.

Feasibility of a portable respiratory training system with a gyroscope sensor.

A portable respiratory training system with a gyroscope sensor (gyroscope respiratory training system [GRTS]) was developed and the feasibility of respiratory training was evaluated. Simulated respiratory waveforms from a respiratory motion phantom and actual respirator waveforms from volunteers were acquired using the GRTS and Respiratory Gating for Scanners system (RGSC). Respiratory training was evaluated by comparing the stability and reproducibility of respiratory waveforms from patients undergoing expiratory breath-hold radiation therapy, with and without the GRTS. The stability and reproducibility of respiratory waveforms were assessed by root mean square error and gold marker placement-based success rate of expiratory breath-hold, respectively. The absolute mean difference for sinusoidal waveforms between the GRTS and RGSC was 2.0%. Among volunteers, the mean percentages of errors within ±15% of the respiratory waveforms acquired by the GRTS and RGSC were 96.1% for free breathing and 88.2% for expiratory breath-hold. The mean root mean square error and success rate of expiratory breath-hold (standard deviation) with and without the GRTS were 0.65 (0.24) and 0.88 (0.89) cm and 91.0% (6.9) and 89.1% (11.6), respectively. Respiratory waveforms acquired by the GRTS exhibit good agreement with waveforms acquired by the RGSC. Respiratory training with the GRTS reduces inter-patient variability in respiratory waveforms, thereby improving the success of expiratory breath-hold radiation therapy. A respiratory training system with a gyroscope sensor is inexpensive and portable, making it ideal for respiratory training. This is the first report concerning clinical implementation of a respiratory training system.

Comparison between Volumetric Modulated arc Therapy based Coplanar and Noncoplanar Planning for Stereotactic Body Radiation Therapy of Liver

The study aims to investigate potential dosimetric benefits between non-coplanar and coplanar beam arrangements of Volumetric-Modulated Arc Therapy (VMAT) plans for liver stereotactic body radiotherapy (SBRT). Thirteen patients who had undergone liver SBRT treatment in our department were chosen retrospectively for the study. Two sets of SBRT-VMAT plans namely, non-coplanar (NC-VMAT) and Coplanar (C-VMAT) were generated in Monaco(v5.11) planning system for Elekta Versa HD Linac using unflatten 6MV photon. The NC-VMAT plans were created by two/three non-coplanar partial arcs with couch rotation of ±150 and had an arc span of 1300 to 1600 whereas the C-VMAT plans consisted of a full arc. Both plans were compared by statistically analyzing various dosimetric and technical parameters. There is no statistically significant difference observed between the C-VMAT and NC-VMAT plans for planning target volume (PTV) coverage. However, the spine dose (D1cc) was much less in the NC-VMAT plan compared to the C-VMAT plan, with mean values of 6.127 ± 3.08Gy and 9.058 ± 4.76Gy, respectively (p-value=0.002). The low dose spillage to the healthy tissue was compared by the volume receiving 5Gy (V5Gy) and 10Gy (V10Gy). V5Gy of the NC-VMAT plan was 2399.23±1870.76cc while that of C-VMAT plans was 2835.36±1930.20cc with the p-value <0.001. Moreover, the monitor units(MU) were less with NC-VMAT than with C-VMAT SBRT plans (p=0.015). The plan quality of NC-VMAT plans was favorable compared to C-VMAT plans for liver SBRT especially in reducing spine dose, low dose spillage to healthy tissue, and MU.

Modeling of Gamma Index for Prediction of Pretreatment Quality Assurance in Stereotactic Body Radiation Therapy of the Liver.

The purpose of this study was to develop a predictive model to evaluate pretreatment patient-specific quality assurance (QA) based on treatment planning parameters for stereotactic body radiation therapy (SBRT) for liver carcinoma. We retrospectively selected 180 cases of liver SBRT treated using the volumetric modulated arc therapy technique. Numerous parameters defining the plan complexity were calculated from the DICOM-RP (Radiotherapy Plan) file using an in-house program developed in MATLAB. Patient-specific QA was performed with global gamma evaluation criteria of 2%/2 mm and 3%/3 mm in a relative mode using the Octavius two-dimensional detector array. Various statistical tests and multivariate predictive models were evaluated. The leaf speed (MILS) and planning target volume size showed the highest correlation with the gamma criteria of 2%/2 mm and 3%/3 mm (P < 0.05). Degree of modulation (DoM), MCSSPORT, leaf speed (MILS), and gantry speed (MIGS) were predictors of global gamma pass rate (GPR) for 2%/2 mm (G22), whereas DoM, MCSSPORT, leaf speed (MILS) and robust decision making were predictors of the global GPR criterion of 3%/3 mm (G33). The variance inflation factor values of all predictors were <2, indicating that the data were not associated with each other. For the G22 prediction, the sensitivity and specificity of the model were 75.0% and 75.0%, respectively, whereas, for G33 prediction, the sensitivity and specificity of the model were 74.9% and 85.7%%, respectively. The model was potentially beneficial as an easy alternative to pretreatment QA in predicting the uncertainty in plan deliverability at the planning stage and could help reduce resources in busy clinics.

Radiomodulating Properties of Superparamagnetic Iron Oxide Nanoparticle (SPION) Agent Ferumoxytol on Human Monocytes: Implications for MRI-Guided Liver Radiotherapy.

Superparamagnetic iron oxide nanoparticles (SPION) have attracted great attention not only for therapeutic applications but also as an alternative magnetic resonance imaging (MRI) contrast agent that helps visualize liver tumors during MRI-guided stereotactic body radiotherapy (SBRT). SPION can provide functional imaging of liver parenchyma based upon its uptake by the hepatic resident macrophages or Kupffer cells with a relative enhancement of malignant tumors that lack Kupffer cells. However, the radiomodulating properties of SPION on liver macrophages are not known. Utilizing human monocytic THP-1 undifferentiated and differentiated cells, we characterized the effect of ferumoxytol (Feraheme®), a carbohydrate-coated ultrasmall SPION agent at clinically relevant concentration and therapeutically relevant doses of gamma radiation on cultured cells in vitro. We showed that ferumoxytol affected both monocytes and macrophages, increased the resistance of monocytes to radiation-induced cell death and inhibition of cell activity, and supported the anti-inflammatory phenotype of human macrophages under radiation. Its effect on human cells depended on the duration of SPION uptake and was radiation dose-dependent. The results of this pilot study support a strong mechanism-based optimization of SPION-enhanced MRI-guided liver SBRT for primary and metastatic liver tumors, especially in patients with liver cirrhosis awaiting a liver transplant.

SBRT-SG-01: final results of a prospective multicenter study on stereotactic body radiotherapy for liver metastases.

This study aimed to assess the efficacy and tolerability of stereotactic body radiation therapy (SBRT) for the treatment of liver metastases. Patients with up to 5 liver metastases were enrolled in this prospective multicenter study and underwent SBRT. Efficacy outcomes included in-field local control (LC), progression-free survival (PFS), and overall survival (OS). Acute and late toxicities were evaluated using CTCAE v.4.0. A total of 52 patients with 105 liver metastases were treated between 2015 and 2018. The most common primary tumor was colorectal cancer (72% of cases). Liver metastases were synchronous with the primary tumor diagnosis in 24 patients (46.2%), and 21 patients (40.4%) presented with other extrahepatic oligometastases. All patients underwent intensity-modulated radiation therapy (IMRT)/volumetric-modulated arc therapy (VMAT) with image-guided radiation therapy (IGRT) and respiratory gating, and a minimum biologically effective dose (BED10Gy) of 100Gy was delivered to all lesions. With a median follow-up of 23.1months (range: 13.4-30.9months) since liver SBRT, the median actuarial local progression-free survival (local-PFS) was not reached. The actuarial in-field LC rates were 84.9% and 78.4% at 24 and 48months, respectively. The median actuarial liver-PFS and distant-PFS were 11 and 10.8months, respectively. The actuarial median overall survival (OS) was 27.7months from SBRT and 52.5months from metastases diagnosis. Patients with lesion diameter ≤ 5cm had significantly better median liver-PFS (p = 0.006) and OS (p = 0.018). No acute or late toxicities of grade ≥ 3 were observed. This prospective multicenter study confirms that liver SBRT is an effective alternative for the treatment of liver metastases, demonstrating high rates of local control and survival while maintaining a low toxicity profile.

SBRT for Liver Tumors: What the Interventional Radiologist Needs to Know.

This review summarizes the clinical evidence supporting the utilization of stereotactic body radiotherapy (SBRT) for liver tumors, including hepatocellular carcinoma, liver metastases, and cholangiocarcinoma. Emerging prospective evidence has demonstrated the benefit and low rates of toxicity across a broad range of clinical contexts. We provide an introduction for the interventional radiologist, with a discussion of underlying themes such as tumor dose-response, mitigation of liver toxicity, and the technical considerations relevant to performing liver SBRT. Ultimately, we recommend that SBRT should be routinely included in the armamentarium of locoregional therapies for liver malignancies, alongside those liver-directed therapies offered by interventional radiology.

SBRT with ipilimumab and nivolumab to metastatic MSS colorectal and pancreatic cancer: A pooled analysis of four prospective phase II trials.

752 Background: The role of immunotherapy (IO) in microsatellite stable (MSS) pancreatic and colorectal cancer is limited. Stereotactic body radiation therapy (SBRT) is increasingly used in the limited metastatic setting, however its use with IO remains an area of investigation for both target response and overall systemic response. Here we evaluate the local failure rate of irradiated target lesions with and without IO. Methods: We pooled four prospective phase II single-arm studies of patients with metastatic MSS colorectal or pancreatic cancer treated with SBRT alone or with IO. Those in the first study (NCT01239381) received ablative liver SBRT to a maximum biologically effective dose (BED) of 48-100 Gy. Patients in the remaining studies received low dose SBRT to liver, lung, or nodal metastases with 24 Gy in 3 fractions to a BED of 43.2 Gy in combination with Ipilimumab and Nivolumab during the first (NCT04361162, NCT04575922) or second (NCT03104439) cycles. Local failure rates at the time of first progression were estimated by the cumulative incidence with non-target progression only and death as competing risks and compared using Gray’s test. The best response at the target was measured with the RECIST 1.1 criteria using the largest reduction in target size during follow up. Fisher’s exact test was used to compare objective response (ORR) and disease control rates (DCR), while the Wilcoxon rank sum test was performed to compare target size and percentage of tumor reduction. Results: Across all four studies there were 154 evaluable patients including 50 who received ablative SBRT and 104 patients who received low dose SBRT with IO. There were 92 patients with colorectal and 62 with pancreatic cancer. Median target size was 3.7 cm in the ablative SBRT group and 2.8 cm in the IO group (P=0.04). The 6-month, 1-year, and 2-year local failure rates were 10%, 18%, and 20% respectively following ablative SBRT and 24%, 25%, and 26% following low dose SBRT with IO (P=0.32). The ORR was 50.0% with SBRT alone and 23.1% with the addition of IO (P=0.001). There was no significant difference in the DCR (80.0% vs. 68.3%, P=0.18). The percent decrease in size was significantly higher in those with ablative SBRT (median -53.0% vs. -10.6%, p=0.02). There was no difference in the percent tumor response with respect to primary tumor type (P=0.13), KRAS (P=0.11) or TP53 (P=0.27) status. Conclusions: Despite the use of low dose SBRT with immune checkpoint inhibitors, there was no significant difference in local failure rates compared to ablative SBRT. Ablative SBRT dosing yielded a significantly higher depth of response. As clinical and preclinical studies suggest liver metastases are less responsive to IO, understanding dose and fractionation schemas for optimal local control is critical. Further studies are needed to explore the radiation dose with regards to local control when delivered with IO.

Four-dimensional dose evaluation for the liver stereotactic body radiotherapy with lipiodol retention after transcatheter arterial chemoembolization

PurposeTo evaluate the effect of lipiodol on the four-dimensional accumulated dose of liver stereotactic body radiotherapy (SBRT) after transcatheter arterial chemoembolization (TACE). Material and methodsTen patients who underwent liver SBRT with lipiodol retention after TACE were retrospectively analyzed. Free-breathing three-dimensional (3D) computed tomography (CT) and respiration-based four-dimensional (4D) CT scans were used. The tumor tissue and lipiodol region were delineated within the gross tumor volume (GTV). Volumetric modulated arc therapy plans were created using the X-ray Voxel Monte Carlo (XVMC), a fast MC algorithm. For 4D accumulated dose assessments, the dose was recalculated after copying the plan into each CT phase, and a deformable registration was used with the 3D CT as a reference. Additionally, dose variation due to tumor irradiation at the lipiodol location through motion was simulated by density override of planning target volume using tumor tissue density followed by dose recalculation. ResultsDose to the lipiodol region increased after density override with tumor density. In eight out of ten patients, 4D doses covering 98% of the GTV and tumor tissue increased compared to 3D doses. Notably, for both 3D and 4D cases, doses to the tumor tissue exceeded those of the GTV. Attention to GTV coverage in 3D planning for liver SBRT without considering lipiodol was deemed sufficient. The similar 19.2 Gy-liver volume for 3D and 4D allowed for liver evaluation using the 3D plan as a quick substitute. ConclusionsIn liver SBRT cases involving lipiodol after TACE, the XVMC planning system revealed higher 4D doses to tumor tissue compared to GTV, with 4D doses surpassing 3D. However, results were limited by XVMC accuracy, unable to reflect lipiodol's dose enhancement. For precise CT-based dose calculations involving lipiodol in the GTV, incorporating lipiodol's material information in the MC calculations is crucial.

Evaluation of liver segmental dose threshold for hepatocyte regeneration following liver stereotactic body radiation therapy.

There is limited evidence studying the relationship of liver segmental dose and segmental volume changes. The segmental dose thresholds could potentially allow for segmental regeneration after liver stereotactic body radiation therapy (SBRT). Given improved survival in hepatocellular cancer (HCC) and liver metastases and more salvage therapy options, this has become an important clinical question to explore. This study assesses the impact of liver segmental dose on segmental volume changes (gain or loss) after SBRT. Liver segmental contours were delineated on baseline and serial follow up triphasic computed tomography scans. The volumes of total liver and doses to total liver, uninvolved liver and individual segments were noted. A correlation was evaluated between liver/segmental volume and dose using Pearson's correlation. Furthermore, receiver operator's curve (ROC) analysis was performed to find the segmental dose, i.e . predictive for liver volume loss. A total of 140 non-tumour liver segments were available for analysis in 21 participants. Overall, 13 participants showed loss of overall liver volume and eight showed gain of overall liver volume. The median dose in segments reporting an increase in volume was 9.1 Gy (7-36 Gy). The median dose in segments losing volume was 15.5 Gy (1-49 Gy). On ROC analysis, segmental dose >11 Gy was associated with volume loss. On univariate analysis, only liver segmental dose contributed to a significant segmental volume loss. We propose from the findings of this study that in SBRT for large hepatocellular cancer or liver metastases, liver segments should be individually delineated. Furthermore, 3-5 liver segments may be preferentially subjected to <9 Gy to facilitate hepatocyte regeneration. Preferential sparing of uninvolved liver segments may improve outcomes in liver stereotaxyas lower segmental doses were associated with liver regeneration. This may have implications on future liver SBRT planning where segmental doses may be as important as the mean dose.

Finite Element Method-Based Hybrid MRI/CBCT Generation to Improve Liver Stereotactic Body Radiation Therapy Targets Localization Accuracy

Finite Element Method-Based Hybrid MRI/CBCT Generation to Improve Liver Stereotactic Body Radiation Therapy Targets Localization Accuracy

Biochemical Safety of SBRT to Multiple Intrahepatic Lesions for Hepatocellular Carcinoma.

We aim to better characterize stereotactic body radiation therapy (SBRT)-related hepatic biochemical toxicity in patients with multiple intrahepatic lesions from hepatocellular carcinoma (HCC). We conducted a retrospective analysis of patients with HCC who underwent SBRT for 2 or more synchronous or metachronous liver lesions. We collected patient characteristics and dosimetric data (mean liver dose [MLD], cumulative effective volume [Veff], cumulative volume of liver receiving 15 Gy [V15Gy], and cumulative planning target volume [PTV]) along with liver-related toxicity (measured by albumin-bilirubin [ALBI] and Child-Pugh [CP] scores). A linear mixed-effects model was used to assess the effect of multi-target SBRT on changes in ALBI. There were 25 patients and 56 lesions with median follow-up of 29 months. Eleven patients had synchronous lesions, and 14 had recurrent lesions treated with separate SBRT courses. Among those receiving multiple SBRT courses, there were 7 lesions with overlap of V15Gy (median V15Gy overlap: 35 mL, range: 0.5-388 mL). There was no association between cumulative MLD, Veff, V15Gy, or PTV and change in ALBI. Four of 25 patients experienced non-classic radiation-induced liver disease (RILD), due to an increase of CP score by ≥2 points 3 to 6 months after SBRT. Sixteen of 25 patients experienced an increase in ALBI grade by 1 or more points 3 to 6 months after SBRT. Comparing the groups that received SBRT in a single course versus multiple courses revealed no statistically significant differences in liver toxicity. Liver SBRT for multiple lesions in a single or in separate courses is feasible and with acceptable risk of hepatotoxicity. Prospective studies with a larger cohort are needed to better characterize safety in this population.

Stereotactic body radiotherapy with volumetric intensity-modulated arc therapy and flattening filter-free beams: dosimetric considerations.

The present study comparatively evaluates the impact of energy-matched flattening filter-free (FFF) photon beams with different energy levels on the physical-dosimetric quality of lung and liver stereotactic body radiotherapy (SBRT) treatment plans. For this purpose, 54different lung and liver lesions from 44patients who had already received SBRT combined with volumetric modulated arc therapy (VMAT) were included in this retrospective planning study. Planning computed tomography scans already available were used for the renewed planning with 6MV, 6MV-FFF, 10MV, and 10MV-FFF under constant planning objectives. The treatment delivery data, dosimetric distributions, and dose-volume histograms as well as parameters such as the conformity index and gradient indices were the basis for the evaluation and comparison of treatment plans. Asignificant reduction of beam-on time (BOT) was achieved due to the high dose rates of FFF beams. In addition, we showed that for FFF beams compared to flattened beams of the same energy level, smaller planning target volumes (PTV) require fewer monitor units (MU) than larger PTVs. An equal to slightly superior target volume coverage and sparing of healthy tissue as well as organs at risk in both lung and liver lesions were found. Significant differences were seen mainly in the medium to lower dose range. We found that FFF beams together with VMAT represent an excellent combination for SBRT of lung or liver lesions with shortest BOT for 10MV-FFF but significant dose savings for 6MV-FFF in lung lesions.